Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
Radiographic findings consistent with non-small cell lung cancer, including lesions with ground glass opacities with a solid component of 50% or greater; those with ground glass opacities and < 50% solid component will be excluded
WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product
Stage T3 or T4a, histologically-confirmed NPNSCC requiring orbital or skull base resection:\r\n* Stages T3 and T4a disease will be included regardless of nodal status (N0 or N1-3), provided that surgical therapy would require orbital or skull base resection\r\n* The surgical oncologist in each institution will determine the need for resection of the orbit OR base of skull at baseline for patients on both Arms A and B and following neo-adjuvant chemotherapy for patients on Arm B\r\n** Resection of skull base will be deemed necessary according to skull base bone erosion by CT or marrow involvement by MRI is noted; for any disease abutting the skull base\r\n** Resection of orbital contents will be deemed necessary according to skull base society guidelines, based on involvement of periorbital fat documented by MRI imaging
Patients must be deemed surgically resectable by the surgical teams at each institution and must have a determination of degree of anticipated structure preservation of orbit and skull base; this needs to be determined prior to randomization
Have non-epithelial ovarian tumors (e.g., germ cell tumors, sex cord stromal tumors)
Have known sensitivity to any component of bevacizumab
Have known sensitivity to any component of paclitaxel
Participants must be purified protein derivative (PPD) negative; alternatively, the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay can be used; an individual is considered positive for M. tuberculosis infection if the IFN-gamma response to tuberculosis (TB) antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control); the result must be obtained within 12 weeks prior to enrollment; PPD positive (or Quantiferon assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
Participants with clinical or radiographic evidence of pancreatitis are excluded
Participant has >= grade 2 diarrhea (participants with grade 1 diarrhea are eligible provided stool for ova/parasites and stool cryptosporidium studies are negative)
Criteria for Solid Tumor Expansion and Lymphoma Cohorts:\r\n* Inclusion and exclusion criteria for this cohort are the same as above, with the following rule for CD4 count based on tolerability in Phase I; if, participants with lymphocyte T CD4 count between 100-200/mm^3 (Stratum 2) are shown to tolerate treatment in the Phase I dose de-escalation portion at the same dose level as those with CD4 counts > 200/mm^3 (Stratum 1), participants in the expansion cohort with CD4 counts >= 100/mm^3 are permitted; otherwise, the expansion is open to all solid tumor patients except those whose tumors are known not to respond to nivolumab (pancreas, prostate and MSS colon cancer); for the relapsed refractory HIV-cHL cohort, participants with CD4 count >= 100/mm^3 are permitted
Patients must have biopsy-proven newly diagnosed polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is:\r\n* CD20 positive\r\n* EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ hybridization (preferred) and/or LMP immunoperoxidase staining
Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
Burkitt morphology
Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following: \r\n* Bone marrow (including pancytopenia without any detectable B-cell proliferation) \r\n* Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)\r\n* Lungs (interstitial pneumonitis with or without pleural effusions)\r\n* Gastrointestinal hemorrhage
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Medulloblastoma:\r\n* Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (FFPE or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis\r\n* Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis\r\n* Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
Histologic diagnosis is mandatory for all patients prior to study entry; study eligibility will be based on institutional pathology; however, performance (and ultimate submission for Central Pathology review) of immunohistochemically (IHC) stained slides for INI11 (to rule out CNS AT/RT), GFAP, EMA, neuronal markers (synaptophysin) for all tumors, as well as a reticulin stain for medulloblastomas displaying any degree of desmoplasia on conventional microscopy, is required; in addition, requested, but not required, are IHC slides for P53 and MIB-1/Ki-67 for all tumors
Adequate Bone Marrow Function defined as:\r\n* Peripheral absolute phagocyte count (APC) > 1000/ µL; APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count.\r\n* Platelet Count > 100,000/µL (transfusion independent)\r\n* Hemoglobin > 8 gm/dL (may have received RBC transfusions)
Participants must have previously untreated HIV-classical HL (cHL), with the exception of up to 14 consecutive days of steroids, emergency radiation, or 1 prior cycle of cyclophosphamide to reduce tumor burden and improve hyperbilirubinemia in the setting of lymphoma related liver involvement
Cirrhosis secondary to any cause will be excluded
Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up
Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks
Concurrent neuromuscular disorder that is associated with the potential of elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Patients must have measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days PRIOR TO STUDY ENTRY
Unsuitable for resection or transplant or radiofrequency ablation (RFA)
Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):\r\n* Technical contraindications: arteriovenous fistula, including surgical portosystemic shunt or spontaneous portosystemic shunt\r\n* Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion\r\n* Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease\r\n* Presence of extrahepatic disease\r\n* No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry\r\n* Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry\r\n* Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen.
Willing to avoid pregnancy or fathering children.
No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Lactating females who plan to breastfeed their infants
Radical or partial nephrectomy with lymphadenectomy in select participants
Bilateral synchronous tumors with inheritable forms of RCC including von Hippel-Lindau
Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
Only first and second recurrences of GBM are eligible
Participants may not have a dependency on IV hydration or total parenteral nutrition (TPN)
Current participation in another therapeutic clinical trial
Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
Refractory anemia with ringed sideroblasts (RARS)
Refractory cytopenia with multilineage dysplasia (RCMD)
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine metaiodobenzylguanidine [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Eligible Ages in Australia and Canada; 2 years to 21 years
Systemic steroid pretreatment without presteroid WBC documentation
CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)
CRLF2 rearrangement without JAK mutation
Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R) fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or without CRLF2 rearrangement
Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
BCR-ABL1-rearranged (Ph+) ALL
Subject is between 18 years old and 75 years old, inclusive
Subjects must have histologically proven GBM or AA and:
Must be in first or second recurrence (including this recurrence)
Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ? 80% resection of enhancing region
The subject has a KPS ? 70
Known 1p/19q co deletion
Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences);
Associated with either diffuse subependymal or leptomeningeal dissemination; or
> 5 cm in any dimension
For inclusion into optional exploratory genetic and biomarker research, patients must fulfill the following criteria:\r\n* Provision of informed consent for genetic research\r\n* Provision of informed consent for biomarker research\r\n** If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient; the patient will not be excluded from other parts of the study
Dependency on IV hydration > 1 day per week within the screening period
Previous enrollment in the present study
Willingness and ability to consent (and assent if under age 18) for self to participate in study
Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide (refer to Section 2.6.1.3) and to not donate sperm during the study and for at least 180 days following last dose of TRC105 or pazopanib
Medulloblastoma or medulloblastoma variants including posterior fossa primitive neuroectodermal tumor (PNET) as documented by an institutional pathologist
EXERCISE INTERVENTION:
Must be at least 5 years old and enrolling on SJMB12
Must be capable of performing the exercise intervention at the time of baseline assessment as determined by the treating physician
Eligible participants will be asked to sign a separate consent form for this optional study at the time they are enrolling on SJMB12; participants will then be randomly assigned to either the standard-of-care control group or the exercise intervention group
NEUROCOGNITIVE REMEDIATION INTERVENTION
At least 5 years old at time of consent to remediation intervention
No significant cognitive impairment operationalized as either an intelligence quotient (IQ) < 70 for children with SJMB12 baseline testing or based on clinician judgment in the case of missing baseline IQ
No major sensory or motor impairment that would preclude valid cognitive testing (e.g., unresolved posterior fossa syndrome, blindness, poorly controlled seizures/photosensitive epilepsy, psychosis) or a major psychological condition that would preclude completion of the intervention (e.g., significant oppositionality, autism spectrum disorder, severe anxiety or depressive symptoms)
Eligible participants will be asked to sign a separate consent form for this optional study; participants will then be randomly assigned to either the standard-of-care control group or the Cogmed computerized intervention group
Participants must be Stratum S (SHH)
Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation
Participant must have a confirmed germline deleterious BRCA mutation; participants with a BRCA1 or BRCA2 classified as “variant, suspected deleterious” by Myriad Genetics are also eligible for the trial; participants with only a BRCA1 or BRCA2 VUS (variant of uncertain significance) are not eligible for this study; if a potential subject is considered high risk for carrying a BRCA1/BRCA2 mutation by National Comprehensive Cancer Network (NCCN) criteria but does not have insurance coverage for testing or if results from available testing options will not be ready in time for enrollment in the study Myriad Genetic Laboratories may cover the cost of the test; genetic testing does not have to be performed by Myriad Genetic Laboratories but a study-specific test request form is available for tests submitted to Myriad; this form may also be used for genetic testing which will be covered by the participant’s insurance and may lead to more expedited testing
Any condition that would prohibit administration of corticosteroids
T1 and T2 (< 3.5 cm), N0, M0, confirmed by clinical, cytological or histological examination
No supraventricular arrhythmia on electrocardiogram (EKG)
Patients with known cardiopulmonary disease are not eligible; cardiopulmonary disease is defined as:\r\n* Cardiomyopathy other than chemotherapy related changes in cardiac function that meet the eligibility requirements\r\n* Clinically significant arrhythmia:\r\n** History of polymorphic ventricular fibrillation or torsade de pointes,\r\n** Permanent atrial fibrillation (a fib), defined as continuous a fib for >= 6 months,\r\n** Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening,\r\n** Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and\r\n** Patients with paroxysmal a fib or < grade (Gr) 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\r\n* Implantable cardioverter defibrillator;\r\n* Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing);\r\n* Pulmonary hypertension\r\n* Congestive heart failure class III or IV
Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
Glycosylated hemoglobin measurement (HbA1c) < 7.0%
Unilateral, bilateral, unifocal, or multifocal DCIS
ADH/borderline DCIS
A patient who has had a lumpectomy with positive margins as part of their treatment for a current DCIS diagnosis is eligible (post-excision mammogram required at enrollment to establish a new baseline)
Absence of invasion or microinvasion
HER2 0, 1+, or 2+ by IHC if HER2 testing is performed
At least two sites of biopsy for those cases where mammographic extent of calcifications exceeds 4 cm, with second biopsy benign or both sites fulfilling pathology eligibility criteria
Amenable to follow up examinations
Male DCIS
Papillary or micropapillary DCIS
Documented mass on examination or imaging at site of DCIS prior to biopsy yielding diagnosis of DCIS, with exception of fibroadenoma at a distinct/separate site from site of DCIS. In cases of uncertainty about whether the mass was present on physical examination prior to biopsy, the following criteria should be applied: if mammogram noting abnormal findings is diagnostic MMG = symptomatic/if mammogram noting abnormal findings is screening MMG = asymptomatic
Bloody nipple discharge
History of and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications.
If a patient is currently receiving denosumab, this must be discontinued prior to enrollment. Substitution with biphosphonates are acceptable.
Patients must have had a bilateral mammogram within 12 months prior to registration, unless the initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required; (subjects with bilateral total mastectomies do not require imaging)
Surgical margins must be clear of invasive carcinoma; if there is microscopic residual ductal in situ disease present at lumpectomy or total mastectomy margins, further excision is highly recommended; if further excision is not undertaken, the subject may still be entered on study, provided that in addition to breast or chest wall irradiation, a boost to the tumor bed is delivered; in situ lobular disease at the margin is acceptable
COMORBID CONDITIONS
Self-reported ability to walk at least 2 blocks (at any pace)
As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy
Conditions that would prohibit administration of corticosteroids
INTRA-OPERATIVE REGISTRATION/RANDOMIZATION CRITERIA
POST-OPERATIVE REGISTRATION/RANDOMIZATION CRITERIA
Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic hormone (ACTH) values within the institutional normal ranges OR cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days prior to registration
Diagnosis of rectal adenocarcinoma
Clinical T4 tumors
Primary surgeon indicates need for abdominoperineal (APR) at baseline
Patients must have adequate tissue available and must agree to have specimens submitted for germline BRCA deoxyribonucleic acid (DNA) sequencing and other correlative studies\r\n* NOTE: Blood for BRCA mutation testing is to be collected and submitted after registration but before treatment
As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution’s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study had been entered in the system
Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol
Tissue acquisition: patient must agree to provide the required research biopsies at baseline, week 4 and at surgery for integral and integrated biomarker and correlative studies
Premenopausal status
SCREENING/PRE-SCREENING REGISTRATION:
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
SUB-STUDY REGISTRATION:
As part of the OPEN registration process the treating institution’s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the system
No prior mediastinal or thoracic radiotherapy
Mutation results:\r\n* All patients must have molecular testing performed in a Clinical Laboratory Improvement Act (CLIA) certified lab which includes which includes KRAS and NRAS gene and exon 15 of BRAF gene (BRAF V600E mutation); patients with any known activating mutation in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61) and exon 4 (codons 117 and 146) of KRAS/NRAS genes and in exon 15 (BRAFV600E mutation) of BRAF gene are not eligible
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patients must have HER-2 amplification as determined by central testing (3+ or 2+ by immunohistochemistry and HER-2 gene amplification by in situ hybridization with a ratio of HER-2 gene signals to centromere 17 signals >= 2.0)
STEP 2 RANDOMIZATION: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; the notification from the Alliance registration/randomization office will serve as a confirmation of this eligibility criteria; after sites receive the confirmation e-mail from Alliance they can register the patient
Re-registration: ANC >= 1,500/mm^3
Re-registration: TSH WNL; supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible
Patients must have BRAF V600 mutation, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Act (CLIA)-certified lab; if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Active collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
Patients with new symptoms of congestive heart failure (CHF), cardiomyopathy, myocarditis, myocardial infarction (MI), or exposure to cardiotoxic medications must have a cardiology consultation, creatinine phosphokinase (CPK), and troponin testing at prestudy and as clinically indicated
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Albumin, alkaline phosphatase, bicarbonate, blood urea (BUN), chloride, glucose, phosphorus, and total protein must be assessed within 28 days of registration
Within 2 weeks prior to registration: Serum calcium (absolute or albumin corrected), magnesium and potassium >= lower limit of normal (LLN)\r\n* NOTE: serum calcium, magnesium and potassium can be replaced if values are below LLN
Patients must be offered participation in specimen banking; with patient consent, pretreatment specimens must be collected and submitted via the SWOG Specimen Tracking System
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
ARM B (AZACITIDINE + NIVOLUMAB)
ARM C (AZACITIDINE + MIDOSTAURIN)
Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C); tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve)
Presence of deficient (d) DNA mismatch repair (dMMR); MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR; dMMR may be determined either locally or by site-selected reference lab; Note: loss of MLH1 and PMS2 commonly occur together; formalin-fixed paraffin-embedded (FFPE) tumor tissue is required for subsequent retrospective central confirmation of dMMR status
Tumors must have been completely resected; in patients with tumor adherent to adjacent structures, en bloc R0 resection must be documented in the operative report or otherwise confirmed by the surgeon; near or positive radial margins are acceptable so long as en bloc resection was performed. Proximal or distal margin positivity is not permitted
Based upon the operative report and other source documentation, the location of the primary tumor will be categorized as proximal or distal to the splenic flexure (distal includes), and further categorization will be as follows: cecum/ascending, descending, sigmoid colon, or rectosigmoid colon
>= 11 and < 25 years old at enrollment
Followed for cancer or survivorship care at one of the following institutions: \r\n* Dana Farber/Harvard Cancer Center\r\n* Hospital for Sick Children\r\n* Children’s Hospital of Eastern Ontario\r\n* Oregon Health and Science University\r\n* Seattle Children’s Hospital\r\n* Yale University
Has experienced prior or ongoing hearing impairment due to chemotherapy or radiotherapy as defined by one of the following: \r\n* Society of Pediatric Oncology (SIOP) grade 1 hearing loss\r\n* Subjective (patient-reported) hearing difficulties\r\n* Subjective (patient-reported) tinnitus
Lactating females who plan to breastfeed their infants
NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient may not be randomized until site has been notified that the central determination of p53 mutation status of the surgical tumor tissue has been completed and site has been notified of assay completion
In both the above cases, the lesion considered at highest risk for recurrence based on the investigator's discretion will be used for eligibility determination
Documented germline mutation in BRCA1 or breast cancer 2, early onset (BRCA2) that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function); local germline (g)BRCA testing results, if available, will be used for establishing eligibility; if local gBRCA testing results are not available, central testing will be provided for those patients who otherwise appear to be eligible
Patients who do not have deleterious or suspected deleterious gBRCA1 and/or 2 mutations but only have BRCA1 and/or BRCA2 mutations that are considered to be non-detrimental (e.g., “variants of uncertain clinical significance” or “variant of unknown significance” or “variant, favor polymorphism” or “benign polymorphism” etc.)
Previous randomization in the present study
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Ability to lie still for imaging
Prior radiotherapy to the abdomen or pelvis
Gynecologic Oncology Group (GOG) performance status 0, 1, 2
PRE-REGISTRATION
Negativity for the Philadelphia chromosome must be established by conventional cytogenetics, fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR); patients who are negative for the Philadelphia chromosome by conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude occult translocations
Patient must not have intercurrent organ damage or medical problems that will jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy)
ELIGIBLE SITES:\r\n* Extremities: upper (including shoulder) and lower (including hip)\r\n* Trunk: body wall
All patients are required to be pre-registered to A061402 in order to submit post-radiation therapy (RT) bone marrow aspirate specimens to Roswell Park for MRD detection by flow cytometry; this submission is required prior to registration to confirm eligibility
Lactating females who plan to breastfeed their infants are not eligible
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
It is recommended that the starting and maintenance dose of rosuvastatin (due to BCRP inhibition by osimertinib) should be as low as possible and should be guided by the statin label; monitoring of low-density lipoprotein (LDL) cholesterol levels is advised; if the subject experiences any potentially relevant adverse events suggestive of muscle toxicity including unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, the statin should be stopped, creatine kinase (CK) levels should be checked, and any appropriate further management should be taken
Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as confirmed at time of prostatectomy; prostatectomy must have been performed =< 365 days (1 year) prior to step 1 registration any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted; (please note: Prior ablative treatment for benign prostatic hypertrophy or focal high-intensity focused ultrasound therapy [HIFU] prior to prostatectomy is allowed)
Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on DECIPHER GRID platform\r\n* Please note: If a patient already has a Decipher risk score and meets all of the other eligibility criteria, the patient is eligible to be registered; however, the Decipher risk report will need to be submitted to GenomeDx for validation
Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is allowed; prior focal HIFU or treatment for benign prostatic hypertrophy is allowed
Lactating females are not eligible unless they have agreed not to breastfeed their infant
Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction: \r\n* Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 BM MRD < 0.01%\r\n* With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 bone marrow (BM) MRD >= 0.01%\r\n* Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria
Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131: \r\n* Intrachromosomal amplification of chromosome 21 (iAMP21)\r\n* Mixed-lineage leukemia (MLL) rearrangement\r\n* Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81) \r\n* Induction failure (M3 BM at day 29)\r\n* Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD >= 0.01%
DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; Note: microsatellite instability high (MSI-H) diagnosed by microsatellite instability (MSI) testing (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) is not eligible unless dMMR is confirmed by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers including MLH1, MSH2, PMS2 and MSH6
Known DPD (dihydro pyrimidine dehydrogenase) deficiency
Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index\r\n* “Favorable” genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above\r\n* “Unfavorable” genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)\r\n* Only patients with MYCN non-amplified tumors are eligible for this study
Patients with evidence of metastatic disease will be excluded; any evidence of non-contiguous spread beyond the primary site as determined by pre or post-operative magnetic resonance (MR) imaging of brain, pre or post-operative MR imaging of the spine, and post-operative cerebrospinal fluid (CSF) cytology obtained from the lumbar CSF space (the requirement for lumbar CSF examination may be waived if deemed to be medically contraindicated); CSF cytology from a ventriculostomy or permanent ventriculoperitoneal (VP) shunt that reveals the presence of tumor cells is indicative of metastatic disease
Lactating females may not participate unless they have agreed not to breastfeed a child while on this study
Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) and with proliferation rate determination, using Ki-67 or MIB-1 immunohistochemistry (=< 30% versus > 30% versus “indeterminate” Ki-67 index)
Institution has received results from Adaptive Biotechnologies as defined by one of the following criteria:\r\n* Patients are “MRD Indeterminate”: ClonoSEQ ID molecular marker assessment did not identify any unique clonal immunoglobulin DNA sequence OR\r\n* ClonoSEQ ID molecular marker assessment identified unique clonal immunoglobulin DNA sequence and MRD assessment is completed
With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
Lactating females who plan to breastfeed
If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible
Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
Lactating females who plan to breastfeed their infants are excluded
Infants must be > 36 weeks gestational age at the time of enrollment
Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
Lactating females who plan to breastfeed
United States (US) and Canadian sites:\r\n* This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible
Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
Patients must have paraffin tissue from the diagnostic or relapse biopsy available to be submitted for central pathology review and integral molecular subtyping; this review is mandatory prior to registration to confirm eligibility and should be initiated as soon as possible; determination of cell-of-origin subtype will be performed using the lymphoma subtyping test (LST) assay
Determination of activated B-cell–like (ABC) subtype by pre-registration central review
Patients must be newly diagnosed and have a confirmed molecular diagnosis of classical histologic type (non large cell/anaplastic [LC/A]) WNT medulloblastoma from rapid central pathology screening review on APEC14B1 (immunohistochemistry [IHC]/molecular screening [positive nuclear beta (B)-catenin by IHC and positive for catenin beta 1 [CTNNB1] mutation) and confirmation of =< 1.5 cm^2 maximal cross-sectional area of residual tumor from rapid central imaging review
Patient must have negative lumbar cerebrospinal fluid (CSF) cytology; CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study\r\n* Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Subjects may receive palliative radiotherapy for symptomatic metastases prior to enrollment provided that there is at least one other non-irradiated lesion amenable to LCT at the time of enrollment.
Metastases located within 3 cm of previously irradiated (< 3Gy per fraction) structures if not a candidate for surgery for these lesions and if:\r\n* Spinal cord previously irradiated to > 40 Gy\r\n* Brachial plexus previously irradiated to > 50 Gy\r\n* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy\r\n* Brainstem previously irradiated to > 50 Gy\r\n* Lung previously irradiated with prior V20 Gy > 35%
Tumor tissue must be available for submission for central pathology review\r\n* Timing requirements:\r\n** If MGMT has been assessed locally by LabCorps or MD Anderson Cancer Center Molecular Diagnostics Lab (MDACC-MDL):\r\n*** Tissue for central pathology review and central MGMT assessment and the official LabCorps or MDACC-MDL MGMT result must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 40\r\n*** The site’s local MGMT report from LabCorp or MDACC-MDL will then be used to stratify the patient; a post-stratification MGMT central review will be performed, but step 2 registration and protocol treatment can proceed without central review of MGMT\r\n*** Patients whose tissue for central pathology review and official LabCorps or MDACC-MDL MGMT result cannot be received by NRG Oncology Biospecimen Bank on or before 40 calendar days after surgery may NOT enroll on this trial\r\n** If MGMT has not been assessed locally by LabCorps or MDACC-MDL:\r\n*** Tissue for central pathology review and central MGMT assessment must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 30\r\n*** Central MGMT analysis will be performed at MDACC-MDL and used for patient stratification; results will be conveyed to NRG Oncology within 10 business days of receipt of the tissue\r\n*** Patients who have not had local MGMT assessment by LabCorps or MDACC-MDL and whose tissue for central pathology review cannot be received by NRG Oncology Biospecimen Bank on or before 30 calendar days after surgery may NOT enroll on this trial\r\n* Tissue Requirements:\r\n** Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; in total, at least 1 cubic centimeter of tissue composed primarily of tumor must be present\r\n** Submission of an accompanying hematoxylin and eosin H&E slide(s) is MANDATORY\r\n** Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy and cavitronic ultrasonic surgical (CUSA) techniques are not allowed
As of Amendment 2, if the registering site is a photon center (registering patients to group I), the patient must agree to participate in the advanced imaging sub-study
Recurrent or multifocal malignant gliomas
Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives
As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Lactating females are not eligible unless they have agreed not to breastfeed their infants
There are no restrictions on distance between the metastases
Metastases with indistinct borders making targeting not feasible\r\n* NOTE: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician’s judgment will be required
Metastases located within 3 cm of the previously irradiated structures:\r\n* Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)\r\n* Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)\r\n* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)\r\n* Brainstem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)\r\n* Whole lung previously irradiated with prior V20Gy > 30% (delivered in =< 3 Gy/fraction)\r\n* Primary tumor irradiated with SBRT\r\n* Metastasis irradiated with SBRT
Exudative, bloody, or cytological proven malignant effusions
Pregnancy; lactating females must cease expression of milk prior to signing consent to be eligible
pN0 or pNx
Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one or more of the following criteria:\r\n* Patient has persistent or recurrent high-grade Ta/CIS urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses)\r\n* Patient has high grade T1 urothelial carcinoma after induction BCG (>= 5 doses) only or after induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses)\r\n* Patient is disease-free at 6 months after starting BCG (i.e., complete response) but then experiences a high-grade recurrence within 6 months after the last BCG dose
As a part of the oncology patient enrollment network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or retrograde pyelograms
Patients must be PPD negative within 90 days prior to registration; PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml); for PPD readings done outside of 48-72 hour window, patients must have PPD test and reading repeated to confirm eligibility
Patient must have stage I-III malignant pleural mesothelioma that is deemed resectable and must be planning to undergo pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP)
Patient must have epithelioid or biphasic histology (sarcomatoid histology is excluded); histologic diagnosis and typing of mesothelioma will require at least a core needle biopsy or surgical biopsy of the pleura via thoracoscopy and small thoracotomy; cytology only will not be regarded as sufficient for the diagnosis
Patient must have consultation with a surgeon within 21 days prior to step 1 registration; the surgeon must confirm that the patient’s disease is resectable by pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) and that the patient is an appropriate candidate for the surgical procedures
Patient must be offered the opportunity to participate in tissue and blood banking for future studies
As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patient may have discontinued RT early due to toxicity or other reasons
Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: patients must also be assessed for CD20 positivity and other markers; positivity for CD22 and CD20 is defined as baseline expression of the CD22 or CD20 antigen in more than 20% of leukemic cells using local multiparameter flow-cytometric immunophenotyping with the use of CD45 expression as a marker to gate the ALL blast population, according to recommendations from the European LeukemiaNet
No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater than 25% lymphoblasts) will not be eligible to be randomized\r\n* Rating: M0, M1; Blast Cells (%): 0-5.0\r\n* Rating: M2; Blast Cells (%): 5.1-25.0\r\n* Rating: M3; Blast Cells (%): > 25-50\r\n* Rating: M4; Blast Cells (%): > 50.0\r\n* The term “blast cell” includes any cell that cannot be classified as a more mature normal element, and includes “leukemic cells,” pathologic lymphocytes, and stem cells
Patients must have a diagnosis of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); patients will be registered to receive treatment in either Cohort 1 (ph-) or Cohort 2 (Ph+ or Ph-like DSMKF) based on these results; diagnostic specimens must be submitted to the site’s local Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory and results of tests (cytogenetics, FISH or PCR) must confirm Ph status prior to registration; if not already known, breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) status (p190 or p210) must be evaluated in Ph-positive patients by PCR\r\n* For Cohort 2, Ph-like testing is not required specifically for this study; however, to be registered to Cohort 2 under the Ph-like DSMKF criterion, the patient must have a known or presumed activating Ph-like signature and dasatinib-sensitive mutation or kinase fusion, such as: ABL1, ABL2, colony stimulating factor 1 receptor (CSF1R), platelet derived growth factor receptor beta (PDGFRB), platelet derived growth factor receptor alpha (PDGFRA), or fibroblast growth factor receptor (FGFR)s that was otherwise identified as part of normal standard of care; prior to registering any patients with a known or presumed activating Ph-like signature and dasatinib-sensitive mutations or kinase fusions (DSMKF) treating physicians must confirm eligibility with the study chairs via email; the study chairs must respond via email with confirmation of patient eligibility prior to patient registration
It is preferred, but not required, that corticosteroids and hydroxyurea should start only after all diagnostic samples have been obtained; however, if the patient was previously on corticosteroids and/or hydroxyurea, this is allowable provided that the patient still has measurable disease at time of the bone marrow aspirate\r\n* Corticosteroids and/or hydroxyurea, as well as any of the other therapies mentioned (with the exception of IV cyclophosphamide), may continue to be administered, at physician discretion, until 1 day prior to blinatumomab administration\r\n** IV cyclophosphamide must be discontinued at least 7 days prior to blinatumomab administration
Patients must have specimens submitted for blinatumomab immunogenicity assessment; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to LabConnect
ALL PATIENTS: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Blood urea nitrogen (BUN) =< 30 mg/dl
Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor; GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
NOTE: Central pathology review must occur between steps 1 and 2 of registration; once appropriate pathology specimens are received, central pathology review will occur within 15 days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
Prior WBRT
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621H based on the presence of an actionable mutation
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to molecular analysis for therapy choice (MATCH) to APEC1621B based on the presence of an actionable mutation
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621G based on the presence of a BRAF V600 mutation
Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:\r\n* Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed); in the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study\r\n* Consecutive elevated serum tumor markers (HCG or AFP) that are increasing; increase of an elevated lactate dehydrogenase (LDH) alone does not constitute progressive disease\r\n* Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the presence of an actionable mutation
Pre-registration: Patients must have local diagnosis of papillary craniopharyngioma and have tissue slides available for submission to central pathology review; central pathology review will include immunohistochemistry (IHC) testing for BRAF V600E mutation (VE1 clone) and beta-catenin IHC (membranous, non-nuclear pattern) if needed to confirm diagnosis of papillary craniopharyngioma
Histologically proven papillary craniopharyngioma as documented by central pathology review with positive BRAF V600E mutation by IHC
APEC1621SC: Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to molecular analysis for therapy choice (MATCH) to APEC1621A based on the presence of an actionable mutation
Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ? 1.5 × institutional ULN.
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy\r\n* Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:\r\n** Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)\r\n** Uncorrectable coagulopathy\r\n* For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:\r\n** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment\r\n** Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment\r\n* Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
Eligible for CHOP regimen
Previous exposure to pralatrexate.
Cutaneous T cell lymphomas except transformed mycosis fungoides (MF)
Proteinuria
Known history of uncontrolled sleep apnea syndrome, or sleep apnea requiring supplemental oxygen, and other conditions that could result in excessive daytime sleepiness
Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria: a) Subjects with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following: i. Age > 18 months (> 547 days) regardless of biologic features or ii. Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or iii. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features. b) Subjects with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following: i. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or ii. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status. c) Subjects with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.
Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
Ability to tolerate PBSC collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
Lactating females are not eligible unless they have agreed not to breastfeed their infants.
History of hypersensitivity to ribociclib or compounds of similar chemical or biologic composition to ribociclib or other drugs formulated with polysorbate 80; or enzalutamide; all herbal, alternative and food supplements (i.e., prostate cancer [PC]-Spes, saw palmetto, St John wort, etc.); they must be discontinued prior to treatment start; patients may continue on a daily multi-vitamin, calcium and vitamin D
Margins of the resected specimen or re-excision specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the pathologist\r\n* Notes: Additional operative procedures may be performed to obtain clear margins; focally positive margins are acceptable based on technical feasibility of additional surgery and/or the potential for benefit with further surgery based on the extent and location of the positive margin (eg, focally positive deep margin at the pectoralis fascia); also, patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection
Active collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion
total abstinence (if it is their preferred and usual lifestyle)
have a vasectomized partner with confirmed azoospermia. NOTES:
Patients with MDS must have failed to respond to, or progressed after, adequate treatment with a hypomethylating agent (HMA), or had documented intolerance of an HMA, and must have an International Prognostic Scoring System (IPSS) score ? 1.5
Patient has an extensively disseminated primary glioblastoma
Positive test for latent TB at Screening (Quantiferon test)
Ewing's family of tumors (EFTs)
Previous enrollment in the present study
For NSCLC:
One prior line of therapy which must include sorafenib or participant must have progressed or been intolerant to sorafenib for participants not eligible for transarterial chemoembolization. Participants who had sorafenib for locally advanced disease or are intolerant to sorafenib are eligible. Participants may have had clinical progression only following sorafenib or local therapy.
Have a viral load <100 international units/milliliter (IU/mL).
For hepatitis B participants, must be on a nucleoside analog reverse transcriptase inhibitor (lamivudine, telbivudine, adefovir, tenofovir, or entecavir).
Have major abnormalities documented by ECHO with Doppler:
Have septal aneurysm or other heart aneurysm.
Any aneurysm of the major vessels.
Subject must be referred for treatment with ibrutinib.\r\n* Since ibrutinib will not be supplied as part of the study, the subject’s ability to obtain ibrutinib from a commercial supplier must be confirmed prior to enrollment
Uncontrolled hypomagnesemia, hypokalemia or hypocalcemia, defined as values below the lower limit of normal (LLN) for the institution despite adequate electrolyte supplementation or management
Histologically confirmed locally advanced gastric (primary endpoint includes proximal and mid-body stomach) or esophagogastric adenocarcinoma; distal gastric (antral) adenocarcinomas are eligible for enrollment but will not be included in the primary analysis
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study; orange juice is allowed
Histological confirmation of melanoma will be required by previous biopsy or cytology.
Subject has failed or intolerant to radiotherapy.
Subject has a KPS ? 60.
Subject has an active implantable or other electromagnetic device.
Be willing to undergo percutaneous endoscopic gastrostomy (PEG) placement, if necessary
Hematological and biochemical indices within acceptable ranges at Screening.
Parts B1, B3, and C: During prior platinum therapy, requirement for dose reduction or discontinuation of carboplatin or cisplatin for toxicity or lack of tolerability
History of malignancy with confirmed activating RAS mutation at any time; Note: prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility
Patients must be willing and able to avoid consuming food and beverages containing grapefruit, star fruit or Seville oranges while on ibrutinib study therapy
Patient is non-responsive to, refractory to, or intolerant of ESAs, or ESAs are contraindicated or unavailable, or a documented serum erythropoietin level of > 500 U/L.
Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 times the upper limit of normal (ULN).
OVCA pts excluded with any of the following: non-epithelial, including malignant mixed mullerian tumors, unresolved bowel obstruction
Rare Tumors:
Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
Peripheral blast count </= 20,000/mm3 at the time of initiation of infusion on Cycle 1 Day 1
Adult (? 18 years old)
Presence of an unresectable liver mass consistent with cholangiocarcinoma, for which treatment with gemcitabine plus cisplatin is intended.
Chronic diarrhea (excess of 2-3 stools/day above normal frequency).
Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
Ability to hold their breath for > 20 seconds for 5 times
Patients whose lung tumors are being monitored with magnetic resonance (MR) imaging (MR imaging of the anchored transponders is safe but yields an image artifact around the anchored transponders)
Posterior lesions that would be > 19 cm distance from Calypso detector plate; patients may be treated in the prone position in order to meet the required minimum distance
Pathologically confirmed relapsed/ refractory DLBCL
Radio- or toxin-immunoconjugates within 10 weeks
Primary tumors and/or metastatic lesions must demonstrate HER2-neu overexpression by immunohistochemistry (IHC 3+) or amplification by in situ hybridization based on the following:\r\n* Single-probe average HER2 copy number >= 6.0 signals/cell\r\n* Dual-probe HER2/chromosome enumeration probe 17 (CEP17) ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number > 6.0 signals/cell\r\nPatients may be estrogen and/or progesterone positive (>= 1%) or negative (< 1%); hormone receptor status will be a stratification factor
Patients must have received at least two lines of HER2-directed therapy in the inoperable locally advanced and/or metastatic setting; prior therapy for inoperable locally advanced/metastatic disease should include trastuzumab plus pertuzumab as well as ado-trastuzumab; pertuzumab and ado-trastuzumab should have been previously used, unless for reasons that include, but are not limited, to the following: intolerance to pertuzumab and/or ado-trastuzumab, medical contraindication, regimen declined by patient, treating investigator discretion, or medical insurance coverage issues which prevented administration of pertuzumab or ado-trastuzumab; these reasons must be reviewed with the study chairs and documented in the medical record and care report form; patients who relapse within 12 months of completing neoadjuvant/adjuvant pertuzumab or ado-trastuzumab would be considered as having progressed on that regimen
Women and men of all races and ethnic groups are eligible for this trial
Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or gastric cardia (GC) based on biopsy material or adequate cytologic exam; tumors of the GC are defined as originating within 5 cm of the GEJ
Denosumab or zoledronic acid are allowed
Meets protocol-specified criteria for qualification and contraception
the analysis of results
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Hospitalization for an acute medical issue within 4 weeks prior to screening visit that would otherwise not be managed in an infusion center or outpatient clinic setting (i.e., a patient admitted to complete a transfusion would not be ineligible)
Tumours that are known to have genomic alterations in PTEN or PIK3CB by local test results may also be eligible. Part B - Tumour amenable to taking of paired biopsies in opinion of the investigator.Patients with TNBC or mCRPC: PTEN-deficient tumours Parts A,B or D1(mCRPC)
Serum potassium > 3.5 mmol/L Parts C2 and D2
Prospectively determined eligible PTEN alteration determined by next generation sequencing, protein deficient determined by IHC or PIK3CB mutation/amplification. Part D2
Pre-existing Grade 2 or higher chronic diarrhoea
Sensitive or narrow therapeutic range substrates of CYP2D6
Exposure to sensitive or narrow therapeutic range substrates of the drug metabolising enzymes CYP2C8, CYP2C9, CYP2C19 or the drug transporters Pgp, BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 within the appropriate wash-out period before the first dose of study treatment.
Abnormal ECHO or MUGA at baseline <55%.
The pathology from the primary surgery must be reviewed and finalized at either Dana-Farber Cancer Institute/Brigham & Women's Hospital or the pathology department at any participating institutions
Status post gross total resection with curative intent
Biopsy-proven, systemic DLBCL with a proliferation rate =< 90%, that has been confirmed by an acquired immune deficiency syndrome (AIDS) Malignancy Clinical Trial Consortium (AMC)-approved site pathologist using hematoxylin and eosin (H&E) and immunohistochemical stains; if a hard copy of the pathology report is unavailable at the time of enrollment into the screening segment, a verbal report by the pathologist confirming the diagnosis must be documented in the medical chart; a hardcopy of the pathology report must be available prior to randomization (enrollment into the Treatment Segment); Note: measurable disease is not an entry requirement
Pathology slides from tumor tissue obtained by surgical excision or core biopsy must be reviewed by the designated site pathologist, or backup pathologist, prior to study entry; confirmation of the diagnosis must be documented by the AMC-approved pathologist prior to study entry; please reference the AMC-068 Manual of Procedures (MOP) for further instructions on documenting the diagnosis; the site pathologist for non-Hodgkin lymphoma (NHL) must be approved through the AMC's external quality assurance (EQA) process
Absolute granulocytes >= 1500 cells/uL (1.5 x 10^9 L)
Participants must have a lumbar puncture with negative cerebral spinal fluid cytology within 4 weeks prior to enrollment
Participants with circumstances that will not permit completion of the study or required follow-up; for instance, if travel to and from treatment site is an issue
Patient deemed to be suitable candidate for myeloablative or reduced intensity conditioning allogeneic HSCT using PBSC or marrow as stem cell source
There is at least 1 metastatic site at one or more of the following sites: spine or non-spine bone and at maximum 5 sites can be treated on protocol
Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage are NOT eligible for participation\r\n* Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating, the vessels is acceptable; CT with contrast is strongly recommended to evaluate such lesions\r\n* Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed\r\n* Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
Histologically or cytologically proven diagnosis of advanced stage angiosarcoma that is not amenable to treatment with curative intent; specify site of origin as cutaneous vs. non-cutaneous
Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT
Abnormal serum calcium, magnesium, or potassium levels
Previous exposure to pazopanib hydrochloride or a vascular endothelial growth factor receptor (VEGFR) targeted kinase therapy, except for bevacizumab or VEGFR-Trap (Aflibercept)
Based on surgeon's assessment, patient is recommended to undergo cytoreduction surgery via laparotomy with the operative goal of this procedure to achieve optimal cytoreduction to less than 1 cm of residual disease
Gynecologic Oncology Group (GOG) performance status > 2
Refusal to accept allogeneic or autologous blood transfusion
Plan for exploratory laparoscopy prior to laparotomy for assessment of disease resectability
Surgeon has high suspicion (> 50% chance) that cytoreduction surgery will be aborted due to inability to achieve optional cytoreduction to < 1 cm residual disease
Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma; there must be pathologic or imaging confirmation of tumor progression or regrowth; the patient’s histologic diagnosis must be confirmed on central pathology review prior to registration step 2\r\n* If a patient has already had central pathology review at MD Anderson Cancer Center (MDACC) (for example, from a previous enrollment to protocol CERN08-02), the central pathology does not need to be repeated; previous pathology confirmation can be utilized for this study’s pathology eligibility testing
Active scleroderma or calcinosis cutis with features of Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome
Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
Right bundle branch block + left anterior hemiblock (bifascicular block)
Lumbar CSF must be assayed for cytology, alpha fetoprotein (AFP) and beta human chorionic gonadotrophin (HCGbeta); a quantitative serum determination of AFP and HCGbeta should be performed at the time of the lumbar CSF assay
For the diagnosis of pure germinoma, HCGbeta (serum and CSF) must be =< 100 mIU/ml, serum AFP must be =< 10 IU/l (ng/ml) and =< institutional norm and initial CSF AFP =< 2 IU/l (ng/ml) and =< institutional norm with histologically proven diagnosis of germinoma at diagnosis or subsequent relapse
For histologically unconfirmed MMGCT, serum and/or CSF tumor markers of HCGbeta > 100 mIU/ml or any elevation of above AFP > 10 IU/L (ng/ml) and/or above institutional norm in the serum and CSF AFP >= 2 IU/L (ng/ml) and/or institutional norm
Patients with no elevations of serum and/or CSF HCGbeta and AFP must have histological diagnosis of malignant GCT or germinoma
Patient must either have recurrence of CNS GCT or should be refractory to initial therapy
Ages > 50 years with hematologic malignancies treatable by related or unrelated HCT
Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by the principal investigators at the collaborating centers and at FHCRC
Waldenstrom’s macroglobulinemia: must have failed 2 courses of therapy
PARTICIPANTS FROM ST. JUDE AND COLLABORATING SITES PARTICIPATING IN THERAPEUTIC AND BIOLOGICAL OBJECTIVES:
PARTICIPANTS FROM COLLABORATING SITES PARTICIPATING IN BIOLOGICAL OBJECTIVES ONLY: Informed consent must be obtained by local principal investigator (PI) or his/her designee according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH/Good Clinical Practice and local guidelines before enrollment into study
PARTICIPANTS FROM COLLABORATING SITES PARTICIPATING IN THERAPEUTIC AND BIOLOGICAL OBJECTIVES:
PARTICIPANTS FROM COLLABORATING SITES PARTICIPATING IN BIOLOGICAL OBJECTIVES ONLY:
Hematocrit >= 25% (may be reached by transfusion)
Subjects with radiographic signs of excessive intra-cranial mass effect with associated rapid neurologic deterioration, and/or spinal block, are unsafe to undergo BBBD chemotherapy and are not eligible
Immunotherapy
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study;
If BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
Ocular melanoma.
Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.
Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies.
Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible.
A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
Need for vasopressor or ventilatory support
Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor (CAR) T cells directed against B cells within 8 weeks of Cycle 1 Day 1
Patients who are candidates for enrollment for the phase I or surgical studies must sign a screening consent and provide pre-trial tumor material for Rb1 testing unless testing is not needed due to diagnosis or the availability of prior Rb1 IHC results; the screening consent is to be obtained according to institutional guidelines
PHASE I (STRATUM 1): Patient has intact Rb1 protein confirmed either from previous results or screened tissue; all testing must be performed in a CLIA certified laboratory; DIPG patients with radiographically typical appearance will be waived from this requirement
Patient has a known hypersensitivity to ribociclib or any of its excipients as described below: \r\n* The capsules contain only the drug substance without any excipients\r\n* The film-coated tablets consist of drug substance and compendial quality colloidal silicon dioxide, crospovidone, hydroxypropylcellulose, magnesium stearate and microcrystalline cellulose; the film-coating is a mix of compendial quality iron oxides, lecithin, polyvinyl alcohol, talc, titanium dioxide, and xanthan gum\r\n* The oral solution consists of ribociclib succinate in water with an orange flavoring agent and common excipients such as preservatives, sweetener and pH modifier
Subject has a history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
Patients may not receive any non-oncology vaccine therapy during the period of NEO PV-01 or pembrolizumab administration and until at least 8 weeks after the last dose of the booster vaccine. Seasonal influenza vaccines are allowed but may not be administered between the first dose of pembrolizumab and the last booster dose of NEO-PV-01
Nursing women are excluded from this study because there is an unknown but potential risk of AEs in nursing infants secondary to treatment of the mother with pembrolizumab, personalized neoantigen peptides, and adjuvant.
Angioimmunoblastic T-cell lymphomas (AITL);
failed to achieve at least a partial response after 2 or more cycles;
progressed after an initial response
Has participated in Merck MK-3475 (pembrolizumab) clinical trials
Has known carcinomatous meningitis
Serum total bilirubin within normal range for the institution (biliary drainage is allowed for biliary obstruction) (within 14 days of treatment initiation)
Homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype) or heterozygotes for UGT1A1*28 (UGT1A11 7/6 genotype) only for the phase I part
Ocular melanoma
Documented germline mutation or somatic mutation (or homozygous deletion) in one of the DNA repair genes listed below that is deleterious or suspected to be deleterious; the mutation must be identified through a Clinical Laboratory Improvement Act (CLIA)-approved next generation sequencing (NGS) panel\r\n* Cohort 1: Germline mutation in one of the DNA repair genes listed below OR\r\n* Cohort 2: Somatic mutation or homozygous deletion in one of the DNA repair genes listed below or a somatic mutation of BRCA1 or BRCA2 (without germline BRCA 1 /2 mutation) \r\n* DNA Repair Gene List: ATM, ATR, BARD1, BRIP1 (FANCJ), CHEK2 , FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD50, RAD51C, RAD51D, plus other hormone receptor (HR)-related genes at the discretion of Dr. Tung with the key study collaborators \r\n** All deep (homozygous) deletions, frameshift mutations and truncating mutations in the genes listed above are eligible as well as missense variants in these genes that have previously been reported as pathogenic or likely pathogenic
Germline BRCA1 or BRCA2 mutation
Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
Any of the following:\r\n* Individuals/or persons who are nursing\r\n* Individual/or persons who are pregnant\r\n* Individuals/or persons of childbearing potential who are unwilling to employ adequate contraception
Glucose-6-phosphate dehydrogenase (G6PD) deficiency (i.e. below normal limits)
Archival tissue confirming the diagnosis must be reviewed by Brigham and Women's Hospital (BWH)/Dana-Farber Cancer Institute (DFCI)/Massachusetts General Hospital (MGH) pathology
Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
Assessment of HER2 status in patients with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (37) as practicable.
Patients for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without written report of ISH determined HER2 copy number, provided the investigational site confirms that archival tissue is available.
Receipt of trastuzumab or ado-trastuzumab emtansine within 4 weeks of scheduled C1D1 dosing.
Subjects who experienced immune related pneumonitis, pituitary or thyroid dysfunction, or pancreatitis while on treatment with immuno-oncology agents
For all groups:
Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
For participants in Part 2:
Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option and confirmation of the presence of AKT1, AKT2, or AKT3 mutations detected by the Memorial Sloan-Kettering (MSK)-integrated mutation profiling of actionable cancer targets (IMPACT) assay platform or other Clinical Laboratory Improvement Act (CLIA)-approved test
ER+ breast cancer patients harboring the AKT1 E17K mutation (patient population tested in MSK IRB# 14-214, study D3610C00001 part E, ClinicalTrials.gov NCT01226316)
No known activating mutations in KRAS, NRAS, HRAS and BRAF
Glycosylated hemoglobin (HbA1C) >= 8.0%
Requirement for insulin for routine diabetic management and control
Proteinuria 3+ on dipstick analysis or > 500 mg/24 hours
Sodium or potassium outside normal reference range for site
Evidence of HER2 positive metastatic breast cancer in either a primary or metastatic site, if 3+ by an immunohistochemistry (IHC) method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an in situ hybridization (ISH) method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/chromosome enumeration probe [CEP] 17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/CEP 17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; and HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell) or amplified by fluorescence in situ hybridization (FISH) > 2.0; high average copy number of HER2 (>= 6.0 signals/cell) is considered positive regardless of the HER2/CEP17 ratio
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
All Cohorts
Have BSA involvement corresponding to stages IA, IB or IIA CTCL with at least 3 distinct lesions
Histological or cytological confirmation of NSCLC; a pathology report confirming the diagnosis of NSCLC must be obtained and reviewed by the treating physician prior to registration to study
Active second cancers
Histologically proven recurrent or residual intracranial or metastatic meningioma or meningioma with extracranial spread
Grade I meningiomas will be allowed as long as they meet criteria for progression
Metastatic meningiomas (as defined by extracranial meningiomas) and meningioma with extra-cranial spread are allowed
Participants with brainstem lesions
Participants who have a diagnosis of an immunodeficiency
Paranasal sinus/nasal cavity malignancy is considered unresectable with negative margins surgery or resection would be considered excessively morbid; this could include lesions with:\r\n* Carotid involvement\r\n* Cavernous sinus invasion\r\n* Brain invasion\r\n* Orbital apex\r\n* Intraconal space\r\n* Pterygoid musculature involvement\r\n* Invasion of the clivus
Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
Clinical or radiologic suspicion of residual MCC at the time of enrollment
Legal incapacity or limited legal capacity.
ECOG of 0-1 at screen
Diagnosis of secondary MDS
MDS associated with 5q(del) abnormality
Screen serum erythropoietin level > 400 mIU/mL,
Presence of at least one measurable lesion as defined by RECIST version (v)1.1; a previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the completion of irradiation
Neutrophils >= 1.5 x 10^9/L
Failed previous HSC collections or collection attempts.
Combination/multi-agent cyto-reductive therapy
Plans to receive maintenance treatment within 100 days post-engraftment (e.g. Lenalidomide, Bortezomib, Pomalidomide, Thalidomide, Carfilzomib, etc.)
Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
Ulcerated skin lesions
Has proteinuria
Any patient who is eligible for HSCT at the time of study screening
Potassium >= lower limit of normal (LLN) range for the institution
Magnesium >= LLN
Sodium >= LLN
Phosphorus >= LLN; NOTE: Supplementation may be given before the first dose of study medication
Has diagnosis of immunodeficiency
Tumor O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction, MSPCR, or quantitative polymerase chain reaction [PCR]) are acceptable
Procurement: Any patient with biopsy proven pancreatic adenocarcinoma
Visceral crisis or lymphangitic spread\r\n* NOTE: Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
Patient has a history of clinically significant dry eye (xerophthalmia) or other corneal abnormality, or if a contact lens wearer, does not agree to abstain from contact lens use from baseline through the last TVB-2640 dose
Histological confirmation of HER2-positive advanced breast cancer; HER2+ is defined by 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
Ocular melanoma
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm)
Subject has voluntarily agreed to abide by all protocol required procedures including study related assessments, and management by the treating institution for the duration of the study and long-term follow-up.
Serum free light chain (FLC) assay: involved FLC level ?10 mg/dL and an abnormal serum FLC ratio (<0.26 or >1.65).
Subject must have documented diagnosis of either:
Subject has confirmed sufficient expression of NY-ESO-1 and/or LAGE-1a by reverse transcription polymerase chain reaction (RT-PCR) as determined by a central laboratory contracted by the Sponsor (this determination will also be made under a pre-enrollment screening ICF).
Subjects with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
Immunomodulator therapy (IMiD e.g. lenalidomide or thalidomide) -1 week
Received 2-4 prior lines of therapy, including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to lenalidomide in the last line. Refractory status to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle.
Must be able to take antithrombotic prophylaxis.
Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC-line], or central venous catheter) (Insertion only required if randomized to Arm A).
Prior exposure to pomalidomide
Known intolerance to IMiDs.
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation.
No more than grade 1 abnormalities of potassium, calcium (confirmed by ionized calcium), magnesium, and phosphorus (supplementation allowed)
A blood pressure (BP) =< 95% percentile for age, height, and gender; patients on stable doses of no more than one anti-hypertensive medication, with a baseline BP =< 95% percentile for age, height, and gender will be eligible
No evidence of dyspnea at rest
No exercise intolerance
Additional criteria may apply. MELANOMA (pembrolizumab only)
Uveal melanoma is excluded
Members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions
Patients with GBMs located in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: mesial temporal lobe, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum
Has a diagnosis of immunodeficiency
Known CD20-negative status at relapse or progression
Inadequate hematologic function (unless due to underlying lymphoma), defined as follows: Hemoglobin less than (<) 9 grams per decilitre (g/dL), absolute neutrophil count (ANC) <1.5*10^9 cells per liter (cells/L), platelet count <75*10^9 cells/L
Subjects with symptomatic bradycardia
Prior treatment with protein-bound paclitaxel allowed if it has been six months since received or progressed on protein-bound paclitaxel and plan to continue to receive protein-bound paclitaxel with MinnelideTMcapsules
Acceptable coagulation status:
PT ? 1.5 times institutional ULN
PTT ? 1.5 times institutional ULN
Participants eligible for taxane monotherapy
Subjects who have received drugs that directly or indirectly inhibit calcineurin or Nuclear Factor of activated T cells (NFAT) activity .
Patient with angina not well-controlled by medication;
Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations.
Primary surgical treatment is lumpectomy + SLNB or ALND --or-- mastectomy + ALND
Abnormal cardiac rhythm not controlled with medication; Hx of stroke within 1 year; Hx of coronary events and/or heart failure within 1 year.
Hx of drug-induced acute tubular necrosis.
ALK amplification (> 10 signals of the ALK gene);
Presence of any ALK fusion protein that arises from a chromosomal translocation.
Patient declines participation in NANT 2004-05, the NANT Biology Study
Pancreatic ductal adenocarcinoma (PDAC)
ANC > 1,500/µl (unsupported by growth factors) and
Any evidence of hematemesis, melena, hematochezia, ? grade 2 hemoptysis, or gross hematuria
Proton pump inhibitor: the concomitant use of proton-pump inhibitors (including, but not limited to, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) with palbociclib is prohibited; recommendations about the use of antacids or H2-receptor antagonists include, but not limited to: cimetidine, famotidine, nizatidine, and ranitidine; if needed, administer H2-receptor antagonists with a staggered dosing regimen (twice daily); the dosing of palbociclib should occur at least 10 hours after H2-receptor antagonist evening dose and 2 hours before the H2-receptor antagonist morning dose; local antacids: as acid lowering agents, local antacids may decrease palbociclib absorption and exposure; however, if needed, local antacids should be given at least 2 hours before or at least 2 hours after palbociclib administration
Planning to receive or have received autologous stem cell transplantation (ACST) per institutional standards as part of standard of care\r\n* Pre-ASCT participants may consent but will not be eligible to begin treatment until after ASCT, and will have to fulfill all inclusion and exclusion criteria before starting protocol\r\n* All participants must initiate day 1 of protocol therapy within 30-60 days post stem cell reinfusion; study PI can grant exception for a patient to start as late as 75 days post stem cell reinfusion with a reasonable justification for a delay (e.g. recovery from post -ASCT toxicity) and this will not be a protocol deviation, nor require an exception to be filled
Recovery from ASCT toxicity as defined as outpatient status, able to drink, eat normally, and do not need intravenous hydration prior to day 1 of therapy
Brentuximab vedotin naive OR had at least stable disease by Lugano Classification to prior brentuximab vedotin treatment
Total carmustine (BCNU) dose of > 600 mg/m^2 with prior treatments including transplant conditioning regimen
Prior diagnosis of inherited or acquired immunodeficiency
Malignancy of non-squamous histology that carries a BRAF, KRAS, NRAS or HRAS mutation(s).
Female subjects:
Subject has legal incapacity or limited legal capacity.
Documented primary diagnosis of histologic- or cytologic-confirmed adenocarcinoma of the stomach or gastroesophageal junction.
fluoropyrimidine (IV 5-FU capecitabine, or S-1),
taxanes (paclitaxel or docetaxel) or epirubicin,
irinotecan,
trastuzumab in case of HER2-positive
ramucirumab
Malignancies other than adenocarcinoma of the stomach or gastroesophageal junction (including hematologic malignancies) within 3 years.
Subjects with DLBCL, BCLu, HGBCL NOS, or HGBCL with translocations of MYC and BCL2 and/or BCL6, must have had no prior chemotherapy for lymphoma. Steroids for palliation prior to enrollment are allowed.
Total abstinence from sexual intercourse
A vasectomized partner
Total abstinence from sexual intercourse
Subjects with positive HBV core antibody or surface antigen are eligible as long as they have an undetectable HBV DNA PCR, and receive concurrent antiviral therapy with entecavir, tenofovir, or lamivudine, and continued for a minimum of 6 months after completion of therapy.
Known carcinomatous meningitis
Prior bevacizumab
Subjects with known metastases that are currently involving the lumen of the gastrointestinal tract.
There must be histologic confirmation of a diagnosis of colorectal adenocarcinoma.
Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal limits. (control by thyroid replacement therapy is acceptable.) Participants with T3, free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible
Participants in all combination therapy arms must not have a history of exposure to an immunotherapy experiencing an immune-mediated adverse event that required permanent discontinuation of the immunotherapy.
Willing to fast for 6 hours before and 2 hours after Oradoxel administration
Histological Diagnosis
KRAS Mutant CRC: Advanced KRAS mutant CRC who have progressed or are ineligible for both irinotecan and oxaliplatin based chemotherapy
KRAS Wild Type CRC: Advanced KRAS wild type CRC who have progressed or are ineligible for both irinotecan and oxaliplatin based chemotherapy and who are relapsed or refractory to at least 1 prior systemic therapy that included an anti-EGFR antibody, such as cetuximab, panitumumab or others.
History of exposure to cumulative doxorubicin dose ? 360 mg/meter squared. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/meter squared of doxorubicin
Carcinomatous meningitis, as defined by positive cytology
Uncontrolled Disseminated Intravascular Coagulation (DIC)
Wild-type TP53 status
Acceptable coagulation profile
Leukemic blast counts of >25,000/µl
Deletion of chromosome 17, or del(17p)
Willingness to avoid pregnancy or fathering children
Known deficiencies or suspected defect in the urea cycle
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject
Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
Other malignant diseases than the ones being treated in this study
Acceptable blood work
Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas
Presence of alteration in CDK pathway (amplifications in CDK4, CDK6, CCND1, CCND2, CCND3 or CCNE1 or loss of CDKN2A) using a Clinical Laboratory Improvement Act (CLIA)-certified assay
Uncontrolled electrolyte disorders that can compound the effects of QTc-prolonging drug (e.g. hypocalcemia, hypokalemia, hypomagnesemia)
COHORT C: Carcinomatous meningitis, as defined by positive cytology
Has a diagnosis of immunodeficiency
COHORT I
SBRT target size > 8 cm in maximum diameter (or > 100 cc in volume)
Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Participants with bilateral diffuse lymphangitic carcinomatosis
Subject with any prior Grade ? 3 irAE to other therapeutic proteins or immunotherapy, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-hydroxytryptamine antagonists, or corticosteroids;
Subject has clinical evidence of Disseminated Intravascular Coagulation
AGS62P1
L-Histidine base
L-Histidine HCl
?, ? -Trehalose Dihydrate
Polysorbate 20
Prior ACT infusion within 6 months of study enrollment (cohorts include ACT with tumor infiltrating lymphocytes [TIL], human leukocyte antigen [HLA]-class I T cell receptor [TCR]-engineered lymphocytes, HLA-class II TCR-engineered lymphocytes, and chimeric antigen receptor [CAR]-engineered T cells)
COHORT 1: Has a white blood cell count > 30 x 10^9/L\r\n* NOTE: Leukapheresis and hydroxyurea is permitted to meet this criterion and should be stopped >= 12 hours before starting treatment on the study
COHORT 2: Has a white blood cell count > 30 x 10^9/L\r\n* NOTE: Leukapheresis and hydroxyurea is permitted to meet this criterion and should be stopped >= 12 hours before starting treatment on the study
Men and women of all ethnic groups are eligible for this trial.
Active treatment with medications that lower the seizure threshold which cannot be held: \r\n* Aminophylline/theophylline\r\n* Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone)\r\n* Bupropion\r\n* Lithium\r\n* Pethidine\r\n* Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine)\r\n* Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
Neutrophils >= 1.5 x 10^9/L
Total lymphocyte count >= 0.5 x 10^9/L
Active herpetic skin lesions or prior complications of herpes simplex virus (HSV)-1 infection (such as herpetic keratitis, herpetic encephalitis)
Receipt of a therapeutic anticoagulant
Common variable immunodeficiency
Biopsy-proven advanced stage mantle cell lymphoma with proliferation-related Ki-67 antigen (Ki-67) > 10% in first complete remission (timeline 8 months prior to enrollment)
Participants with CD4 counts > 50/microL are eligible for this study if their viral load is < 50 copies/mL by reverse transcription polymerase chain reaction (RT-PCR) since majority of the participants have received aggressive chemotherapy that can potentially decrease the CD4 counts despite the ART therapy; timeline: within 3 weeks prior to start of trial
Participants with unexplained anemia, and/or thrombocytopenia
Participants with clear evidence of myeloproliferative disorders, or myelodysplastic disorders in the marrow
Active cytomegalovirus (CMV) retinitis, or other active CMV-related organ dysfunction
Relapse of pneumocystis carinii pneumonia within the past year before enrollment
Dementia of any kind
For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
Transfusion-dependence in subjects previously treated with an ESA (requires a minimum ESA trial of > 40,000 U/week recombinant human erythropoietin (rHuEPO) x 8 weeks or equivalent dose of darbepoetin or other erythropoietin agent), or
Serum erythropoietin level of > 500 mU/mL in subjects not previously treated with an ESA.
Female subjects must be either:
Clinically significant anemia due to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. If marrow stain for iron is not available, the transferrin saturation (iron/total iron binding capacity Fe/TIBC) must be >20% or serum ferritin must be >100 ng/dL.
Subjects who have exhibited allergic reactions to tipifarnib, or structural compounds similar to tipifarnib or to its excipients.
The subject has legal incapacity or limited legal capacity.
Patients who underwent neurosurgery (NSGY), whole brain radiation therapy (WBRT), or stereotactic radiosurgery (SRS) to a brain lesion must have a new measurable lesion; previously surgically excised lesion/tumor bed, may be used as a measurable lesion if disease has progressed since surgery (NOTE: SRS may be done to a lesion that will not be used for response evaluation and should be done > 2 weeks prior to registration; any WBRT must have occurred > 60 days ago; any NSGY procedure must have been completed > 3 weeks prior to registration and baseline imaging)
Brain metastasis must not be impending herniation or other significant vasogenic edema requiring increasing steroid doses; lesions must not have frank hemorrhage
Histopathologically confirmed diagnosis of metastatic or unresectable uveal melanoma or non-uveal melanoma harboring a GNAQ or GNA11 mutation; Note: For subjects with a diagnosis of uveal melanoma, documentation of mutation status for uveal melanoma will not be required prospectively given the high rate of GNAQ/11 mutations (> 90%) in this population
Any number of prior recurrences are allowed
Symptomatic atrial fibrillation
Patients with known inborn errors of metabolism of primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency, beta-oxidation defects, pyruvate carboxylase deficiency and porphyria
Severe sickle cell disease [Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb S?) genotype] with at least 1 of the following manifestations (a-e):
History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy);
Three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ? 2.7 m/sec.
Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory. Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or who experience a sudden, profound change in the serum hemoglobin after a RBC transfusion are not excluded.
A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
Demonstrated lack of compliance with prior medical care as determined by referring physician.
Serum creatinine ? specified maximum values based on age as described below:
Have no symptoms of cranial hypertension or convulsions within 14 days before Cycle 1 Day 1 (anti-epileptic drugs and corticoids are allowed to control any preexisting symptoms)
Currently on abiraterone and/or enzalutamide and not progressing; OR
Halabi Nomogram score <1951
Successfully pass the screening CPET by achieving: o Volitional exhaustion (RPE ? 9 using the 0-10 RPE scale) after 8 (or more) minutes, in the absence of any cardiorespiratory abnormalities.
If cardiorespiratory abnormalities are identified, please refer the patient to his managing physician for further assessment and diagnosis.
Note: To assist practitioners with delivering valid CPET assessments, patients nearing exhaustion should achieve a respiratory exchange ratio (RER) of ?1.1.
RER is not a criteria of the test. This objective measure should only be used to assist practitioners with patient management and decision-making.
The subject is fluent in the language as designated by the institution at which he would be enrolled.
Men participating in vigorous aerobic exercise for more than 60 minutes per week or resistance exercise two or more days per week
Experiences shortness of breath, chest discomfort, or palpitations when performing activities of daily living
Men who do not complete the baseline lifestyle and quality-of-life questionnaires and 3-days of diet diaries or Food Frequency Questionnaire (FFQ) (TBD) will not be eligible
Patient has had more than one recurrence or progression of their tumors.
Osteoporosis (T-score of less than -2.5 by DEXA scan)
A prospective patient for allogeneic HCT for a malignant hematologic disorder
Matched sibling, cord blood and haploidentical donors are not eligible.
Prior HCT (allograft or prior autograft)
Requirement for systemic immune suppressive medication
Waldenstrom’s macroglobulinemia or immunoglobulin (Ig)M myeloma
Diarrhea > grade 1 in the absence of antidiarrheals
Renal failure requiring hemo-or peritoneal dialysis
No concurrent treatment on another clinical trial; supportive care trials or nontreatment trials, e.g. quality of life, are allowed
Prisoners or participants who are involuntarily incarcerated
GU cancers with accessible metastases (e.g., bladder, renal)
Any solid tumors with masses that are accessible without imaging
Unresolved irAEs following prior biological therapy, except that stable and managed irAEs may be acceptable (e.g., hypothyroidism or hypopituitarism on appropriate replacement).
Grade 2 or higher peripheral ischemia [brief (< 24 hours) episode of ischemia managed non-surgically and without permanent deficit].
Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
Lack of availability for immunological and clinical follow-up assessment.
Proteinuria: dipstick ?2+
Normal thyroid and pituitary functions
Splenectomy
Known CD20-negative status at relapse or progression
Lesion size 8 mm - 3 cm
Subjects who have lesions within 2 cm of central structures, will be eligible on a case-by-case basis \r\n* Tumor within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
Pulmonary metastases found at relapse (does not have to be first relapse); no more than 3 lesions per hemi-thorax will be treated but other lesions in the lung may be present
Lesion larger than 3 cm in diameter
Neutrophils >1,000 µL
Serum potassium within normal range.
Olaparib\r\n* Patients with solid tumors that harbor DNA damage repair gene mutations as exemplified below detected by next-generation sequencing (NGS) or real-time- polymerase chain reaction (RT-PCR) in assays performed at a CLIA-certified laboratory:\r\n** Examples of DNA damage repair deficiency “BRCA-ness” (somatic mutations in tumors), but not limited to, are: breast cancer 1, early onset (BRCA 1), breast cancer 2, early onset (BRCA2)/Fanconi anemia group D1 (FANCD1), partner and localizer of BRCA2 (PALB2 or FANCN), RAD51 recombinase (RAD51), RAD52 homolog, DNA repair protein (RAD52), BRCA1 interacting protein C-terminal helicase 1 gene (FANCJ), Fanconi anemia complementation group D2 (FANCD2), 26S proteasome complex subunit DSS1 (DSS1), MRE11 homolog A, double strand break repair nuclease (MRE11), RAD50 double strand break repair protein (RAD50), nibrin (NBS1), Bloom syndrome RecQ like helicase (BLM), ATM serine/threonine kinase (ATM), ATR serine/threonine kinase (ATR), checkpoint kinase 1 (CHK1), checkpoint kinase 2 (CHK2), Fanconi anemia complementation group (FANC) A,-B,-C, -E, -F, -G,-L, M, D2
AZD5363 plus olaparib\r\n* Patients with solid tumors with PIK3CA or AKT mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway detected by NGS or RT-PCR in assays performed at a CLIA-certified laboratory:\r\n** activating mutations in PIK3CA, AKT1, AKT2, AKT3, ARID1A\r\n** other molecular aberrations leading to dysregulation of the PI3K/AKT pathway, for example phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1)\r\n** during the course of the study new information may emerge relating to molecular aberrations that dysregulate the PI3K/AKT pathway; patients whose tumors bear these aberrations can be included in the study
The AZD1775 plus olaparib and AZD2014 plus olaparib additional inclusion criteria will be added as addendums to the protocol and opened once the recommended phase II doses are available
Previous enrollment in the present study
Glycosylated hemoglobin (HbA1c) =< 7.0%
Subjects must have had histologic verification of malignancy at original diagnosis or relapse, except in subjects with optic pathway gliomas, or subjects with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (HCG)
Subjects who are currently receiving enzyme inducing anticonvulsants are not eligible
Clinical Laboratories:
ANC < 1,500/µL.
If the patient is otherwise not deemed a good study candidate by sole discretion of the principal investigator
Submission of original biopsy for review and verification by hematopathologist at local institution
Participants with prior Hepatitis B or C are eligible on the condition that participants have adequate liver function as defined by Inclusion Criterion number 16 and Exclusion Criterion number 5
Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R) like but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), and JNJ40346627 (J & J)
Retinoblastoma protein (RB) positivity as defined by RB expression (score of 0.5 or 1) with concurrent p16in4a loss (score of 0-2)
Absence of occlusive main portal vein thrombus, branch venous thrombus is allowed
Must have appropriate wash out (> 6 half-lives) of androgen receptor antagonists, 5 alpha reductase inhibitors or ketoconazole prior to the start of cycle 1; if the agent is not in the table below, the washout should be 2 weeks\r\n* Bicalutamide; approximate half-life: 6 days; washout period required: 36 days\r\n* Flutamide; approximate half-life: 6 hours; washout period required: 36 hours\r\n* Nilutamide approximate half-life: 4 days; washout period required: 24 days\r\n* Finasteride; approximate half-life: 8 hours; washout period required: 48 hours\r\n* Aminoglutethimide; approximate half-life: 15 hours; washout period required: 4 days\r\n* Ketoconazole; approximate half-life: 8 hours; washout period required: 48 hours
History of severe hypersensitivity reaction (>= grade 3) to docetaxel, polysorbate 80 containing drugs, or any of the capsule components of enzalutamide, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene
Difficulty swallowing capsules or requirement for a feeding tube.
Previous therapy with GS-1101 (CAL-101), IPI-145 or any drug that specifically inhibits PI3K or mechanistic target of rapamycin (mTOR) within last 6 months
Patients may have any of the following:\r\n* Myc-overexpression (> 40%) by immunohistochemistry (IHC)\r\n* Myc-amplification (> 4 copies), as determined by fluorescent in-situ hybridization (FISH)\r\n* MYC-rearrangement, as determined by FISH
The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:\r\n* B-cell lymphoma (BCL)-2 rearrangement by FISH\r\n* BCL-6 rearrangement by FISH\r\nNOTE: although not required, it is encouraged that MYC and BCL-2 be measured by immunohistochemistry (IHC) and clearly documented
Total bilirubin =< 1.5 x upper limit of normal (ULN); NOTE: exceptions can be granted from principal investigator (PI) for instances of Gilbert’s disease, and/or primarily indirect bilirubinemia, if due to recent transfusion and/or hemolysis
NOTE: exceptions can be granted from PI for instances of Gilbert’s disease, and/or primarily indirect bilirubinemia, if due to recent transfusion and/or hemolysis
There is no limit on the number of prior relapses but the most recent relapse must be the first relapse on a bevacizumab-containing regimen
Participants may not have received prior therapy with any other Src, platelet-derived growth factor receptors (PDGFR), or fibroblast growth factor receptors (FGFR) inhibitor; prior treatment with an anti-vascular endothelial growth factor receptor (VEGFR) or anti-vascular endothelial growth factor (VEGF) agent is also allowed but only one relapse following a bevacizumab-containing regimen is allowed
cMET amplification by FISH (GCN ? 6),
ALCL, ALK negative
Subcutaneous panniculitis-like T-cell lymphoma For enrollment into the AITL expansion cohort, subjects must have he diagnosis of AITL.
Female subjects must be either:
Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
Has adequate hematological and physiological functions.
Known immunodeficiency disorders, either primary or acquired
Hematocrit > 30%
Active mucositis
Systemic staging of the chest/abdomen (abd), pelvis is required for study entry; body fluid will be assessed based on this study
Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
Radiographic evidence of intratumor cavitation.
Able to undergo all screening assessments outlined in the protocol.
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ? 2.5 x UNL but ? 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) ? UNL but i) ? 2.5 x UNL in case of liver metastases and ii) ? 5 UNL in case of bone metastases; albumin ? 2.5 g/dl.
paclitaxel
ibuprofen or to more than one non-steroidal anti-inflammatory drug.
Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
Not responding or failed treatment on AZA or decitabine (note they are also eligible if additionally they have failed another ESA after at least 4 cycles)
Responders who cease responding
Never responded
Red Blood cell transfusion dependent (defined as ? 2 RBC units required in the 8 weeks prior to starting in the study).
Post-menopausal defined as the absence of menses for at least one year (serum FSH ?20IU/L can also be measured according to local practice), OR
If sexually active male, patient must:
Ability to take aspirin or other anticoagulation (ARM 3 only)
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
Any medical conditions that, in the Investigator’s opinion, would impose excessive risk to the patient; examples of such conditions include any pre-existing kidney disease (acute or chronic, unless renal insufficiency is felt to be secondary to MM), hypertension, active seizure disorder or pulmonary diseases that would impose excessive risk to the patient
Patient has hypersensitivity to boron, mannitol sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy including required prophylactic medications
Coagulation: PT > 4 seconds more than ULN or INR > 1.7
Radiosensitizing chemotherapy (taxol [paclitaxel], taxotere [docetaxel], cisplatin, gemcitabine [gemcitabine hydrochloride], 5-fluorouracil [fluorouracil]) given within one week of radiation treatment
Patients must have histologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective, and for which: a) there is reasonable expectation of response to the combination of carboplatin/paclitaxel OR b) breast cancer (BRCA) 1/2 germline mutation is present; results from Myriad will be acceptable; if testing for BRCA 1 and 2 germline mutations is done through another organization, a report from a genetics consult with a qualified medical professional confirming that the laboratory results show a recognized germline deleterious BRCA 1 or 2 mutation or rearrangement is required; if the latter cannot be obtained, principal investigator (PI) or study chair review of the lab results and confirmation of BRCA mutation or rearrangement will be required OR c) BRCA 1/2 somatic mutation previously identified using a Clinical Laboratory Improvement Amendments (CLIA) certified assay
Prior consent to have tumors used for unspecified future research
Willing to agree that the local medical oncologist may be informed that patient has agreed to participate in the study
All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values) must be =< grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0) at the time of randomization, subjects with endocrinopathies (e.g. hypopituitarism, hypothyroidism, hypoadrenalism) caused by immune therapies currently on adequate hormone replacement WILL be permitted, subjects with endocrinopathies (e.g. hypopituitarism, hypothyroidism, hypoadrenalism) caused by immune therapies currently on adequate hormone replacement WILL be permitted
PTT =< 1.3 x ULN
BRAFV600 mutation positive
NRAS codon 12, 13, or 61 mutation
Have initiative and means to be compliant with protocol and within geographical proximity to make required study visits as judged by Investigator
PTT > 1.3 x ULN
Planned palliative procedures for alleviation of bone pain
Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN), within 14 days before the first dose of cabozantinib
Pathologically confirmed de novo DLBCL
DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) and will be screened per the American Association of Blood Banks (AABB) (AABB guidelines and the recipients will be informed of any deviations)
DONOR: ABO compatibility (in order of priority)\r\n* Compatible or minor ABO incompatibility\r\n* Major ABO incompatibility
Creatinine less than 1.5 x UNL
Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
Clinically relevant retinal abnormalities as per the medical history or ophthalmologic findings in the pretreatment evaluation (e.g., retinitis pigmentosa or macular degeneration).
Histologically confirmed invasive lobular breast cancer, that is hormone receptor-positive and HER2-negative, measuring at least 1 centimeter (cm) radiographically or clinically, clinical stages I-III; invasive lobular histology will be diagnosed at the enrolling institution for purposes of study participation; subsequently, invasive lobular histology will be confirmed by central pathology review, but this central review will not be required prior to patient enrollment
Participants must be fully postmenopausal
HER-2 positivity
Nottingham grade 1-2. Specifically, nuclear and mitotic scores must be less than or equal to 2.
Presence of luminal B pathology
Unable to accept blood product transfusions
Subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criterion #4;
Subjects with gastric mucosa-associated lymphoid tissue (MALT) lymphoma must be Helicobacter pylori (HP)-negative
Requiring mechanical ventilation
Vasopressor requirement
Tumor tissue, from either initial diagnosis or subsequent surgery, on formalin fixed paraffin embedded (FFPE) slides (n = 12) must be available and submitted to the Pathology Laboratory at Children’s Medical Center-Dallas for correlative biological studies (including phosphorylated S6 235/236, phosphorylated S6 240/244, phosphorylated 4EBP1, phosphorylated PRAS40 (pT246), phosphorylated P70S6K, and PTEN expression); Note: central review of these slides is required, but may be completed concurrently with patient registration; completion of central review is not required prior to starting therapy
BRAF mutation-positive (V600 E or K) melanoma for Parts 1, 2 and 3, or for Parts 1, 2, 4 and 5 only BRAF mutation-negative (wild type) melanoma with documented progression of >=1 measurable lesion after prior therapy (if prior therapy was received). The inclusion criterion does not apply to participants with solid tumors in Parts 4 and 5 (dose confirmation only).
Prior radiotherapy to the target area.
Proteinuria greater than 2 grams/24 hours.
Conditions which can result in impaired absorption, distribution, metabolism or excretion of the study treatment.
Gleason sum of 7, 8, 9, or 10 at the time of prostatectomy
Prior immunotherapy including sipuleucel-T
For Part E (LY2835219 + exemestane + everolimus): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus.
Recurrent or chronic pancreatitis
Surgery achieves either no gross residual disease (R0) or optimal cytoreductive status defined as no single lesion measuring more than 5.0 mm in its greatest diameter
Intraoperative frozen section suggesting hepatobiliary, pancreatic, adrenal, or urinary tract cancer
Patients much have a negative purified protein derivative (PPD) skin test and a negative Quantiferon assay or a tuberculosis (TB) T-spot test; indeterminate results, due to lack of response to the mitogen control reflecting their immunocompromised state, will be permitted
Diagnosis of extranodal NK/T lymphoma, per WHO classification, 4th ed., which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining.
Hemophagocytic lymphohistiocytosis.
Absolute lymphocyte count (ALC) <400/µL.
Previously untreated Ph negative precursor B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain; patients who have untreated B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain, but Ph status is unknown, may also enroll
Mature B-cell (Burkitt's) ALL
Other serious or life-threatening conditions deemed unacceptable by the principal investigator
The patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained, in accordance with institutional policies approved by the U.S. Department of Health and Human Services
Man or woman >= 18 years old.
Is willing to undergo tumor genotyping for TP53 mutation, insertion, or deletion at screening. Confirmation of TP53 nonmutant status is encouraged, but not required prior to DS-3032b dosing.
Is willing to provide additional archived samples for comprehensive genomic and/or proteomic analyses if the subject has a partial response/complete response to DS-3032b treatment.
Diagnosis of amyloidosis
Life-threatening illness or organ system dysfunction compromising safety evaluation
Requirement for hemodialysis or peritoneal dialysis
Prior vismodegib or other antagonists of the hedgehog (Hh) pathway
Molecular confirmation of a RET translocation is required to begin protocol therapy; methods of acceptable molecular confirmation include RET fluorescent in situ hybridization (FISH) and next-generation sequencing performed in a Clinical Laboratory Improvement Amendment (CLIA) certified lab
Patients must have a histologically confirmed CD20+ lymphoproliferative disease that is related to an immunosuppressed state (e.g., post-transplant lymphoproliferative disorder [PTLD], diffuse large B-cell lymphoma [DLBCL] of the elderly, iatrogenic immunodeficiency-associated lymphoproliferative disorder [LPD]) and for which rituximab monotherapy would be considered to be appropriate frontline therapy
NOTE: patients who do not meet the above criteria because of disease involvement of the organ in question, or because of acute systemic illness due to lymphoma, may enroll with permission of the study principal investigator (PI) and approval from the Data Monitoring Committee; this flexibility be allowed due to the heterogeneity of the patient population, the wide range of complications seen in the initial presentation of EBV-related malignancy, and the frequent difficulty encountered in attempting to clearly document that organ dysfunction is the result of an underlying lymphoproliferative disorder
In addition, patients with abnormal renal function may be included if the abnormal function is due to allograft dysfunction resulting from diagnosis of PTLD, or from reduction/cessation of immunosuppression aimed at treatment of PTLD
Pregnancy or active nursing of an infant is not permitted
Treatment with a somatostatin analog (e.g., octreotide acetate) is required for all participants; octreotide naive patients may initiate this during the screening period or at start of study
No unhealed wounds, ulcers or bone fractures
>= 3 weeks from protocol tissue procurement since treatment (surgery, chemo-, radiation-, hormone- therapy, check point blockade [e.g., anti-CTLA-4, PD-1, PDL-1]); (windows are in relation to the date of the protocol tissue procurement)
Patients previously treated outside of the University of Wisconsin (UW) must have their pathology slides sent to the UW for review and confirmation\r\n* NOTE: a copy of the pathology report is sufficient for registration
Patients will be included if they have a National Comprehensive Cancer Network score for fatigue over 3 (NCCN > 3) as determined by the standard fatigue scale of 0-10 unless otherwise approved by the principle investigator or principal investigator's (PI’s) designee
Participants with an Inventory of Depressive Symptomatology (IDS) score > 32 or IDS #18 score 2 >= will be referred to Dr. Andrew Miller
Participants with uncontrolled or chronic pain, a score greater than 4 on the standard pain scale, will be excluded unless otherwise approved by the principal investigator or PI’s designee
Adverse event requiring discontinuation of vemurafenib in the antecedent protocol
PIK3CA WILD TYPE AND MUTANT COHORT (closed 03/17/2016): Patients who were pre-registered to National Cancer Institute (NCI) 9170 trial (Phase II Trial of Neoadjuvant MK-2206 in Combination with either Anastrozole if Postmenopausal or Anastrozole and Goserelin if Premenopausal in Women with Clinical Stage 2 or 3 PIK3CA Mutant Estrogen Receptor Positive and HER2 Negative Invasive Breast Cancer), started anastrozole (or anastrozole plus goserelin if premenopausal) =< 6 weeks, and were found negative for PIK3CA hotspot mutations are eligible to be screened for the wild type cohort; in institutions without NCI 9170 open, or after completion of enrollment to NCI 9170 in institutions where it is open, patients will be pre-registered to this trial and those with PIK3CA mutations will be enrolled to the PIK3CA mutant cohort
PIK3CA WILD TYPE COHORT (closed 03/17/2016): tumor PIK3CA mutation present\r\n* Note that if a patient did not have sufficient research tissue for PIK3CA sequencing at pre-registration or if PIK3CA sequencing result is delayed, she could be registered and enrolled on the PD991 trial without assigning to a particular cohort at the time of enrollment; PIK3CA sequencing will be performed in the future on tumors collected at subsequent time points to assign the treatment cohort or when the PIK3CA sequencing data is available
PIK3CA WILD TYPE COHORT (closed 03/17/2016): ECOG performance status of 0, 1 or 2
PIK3CA WILD TYPE COHORT (closed 03/17/2016): If premenopausal, patient must be willing to comply with pregnancy requirements
PIK3CA WILD TYPE COHORT (closed 03/17/2016): Platelets >= 100,000/mcL
ENDOCRINE RESISTANT COHORT: Pre- or post-menopausal women are eligible; if premenopausal, patient must be willing to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian suppression during the study
PIK3CA MUTANT AND WILD TYPE COHORT (closed 03/17/2016): Evidence of inflammatory cancer (clinical presentation of skin erythema involving more than one third of the breast or pathological evidence of dermal lymphatic involvement)
Patient with C-kit (CD117) positive tumour detected immuno-histochemically
Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
Patient previously treated with a dose of imatinib > 400mg
Patient intolerant to imatinib
Male subjects must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant
Male subjects must agree not to donate semen or sperm while taking pomalidomide and/or carfilzomib until at least 28 days after the last pomalidomide/carfilzomib dose
Subjects with known or suspected amyloidosis of any organ
Significant or recent gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, or complete blood count [CBC] grade >= 2 diarrhea of any etiology)
Baseline (pre-treatment) electrocardiogram (EKG) with any of the following changes consistent with cardiac ischemia:\r\n*Significant ST depression (ST depression of >= 2 mm, measured from isoelectric line to the ST segment at a point 60 msec from the end of the QRS complex)\r\n* Significant ST elevation (> 1mm in limb lead or 2 mm in precordial lead measured at a point 0.04 sec [1 mm] after the J-point [the end of the QRS complex] and compared to baseline [line drawn from P start to T end])\r\n* Investigators are encouraged to consult with cardiologists locally and with the study chair should any questions arise
Pts may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
Male pts cannot donate semen or sperm while taking pomalidomide and for 28 days after completing the study.
All pts must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
Pts with known sensitivity to any immunomodulatory drugs (IMiDs)
Known allergies to carfilzomib or Captisol
Waldenström's macroglobulinemia
Pts with primary systemic amyloidosis
Other\r\n* Diffuse metastatic spread confined to one organ system is ineligible; examples of this include leptomeningeal spread in the CNS and peritoneal carcinomatosis. \r\n* Metastatic disease sites must be treatable with stereotactic radiosurgery (at discretion of treating physician); patients with oligometastatic sites not amenable to SRS treatment, either through size or locations, are ineligible for this trial
Oligometastatic disease sites not eligible based on concern for toxicity: \r\n* Trachea involvement (direct invasion, tumors close to or abutting trachea are eligible)\r\n* Heart (direct invasion or involvement, pericardial lymph nodes can be treated)
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Other \r\n* Lung cancer with pleural effusion (wet IIIB) are not eligible \r\n* Recurrent cancers are not eligible \r\n* Diffuse metastatic spread confined to one organ system is ineligible; examples of this include leptomeningeal spread in the CNS and peritoneal carcinomatosis
Oligometastatic disease sites not eligible: \r\n* Trachea involvement (direct invasion, tumors close to or abutting trachea are eligible)\r\n* Heart (direct invasion or involvement, pericardial lymph nodes can be treated)
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Pathologic diagnosis must be based on pathology or pathology review by Department of Pathology at Massachusetts General Hospital (MGH) or another Dana-Farber/Harvard Cancer Center (DF/HCC) institution and must be finalized within two weeks of the radiation start date
Participants who have had radiotherapy to the site to be treated
Patients known to have germ-line adenomatous polyposis coli (APC) mutations or clinical manifestations of Familial Adenomatous Polyposis(FAP)/Gardner's syndrome can be included
Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material;Gleason score must be in the range of 2-6. > 6 cores are strongly recommended.
Clinical stages T1a-T2a N0 M0 (AJCC Criteria 7th Ed.). Staging must be done by treating investigator.
Six or more café-au-lait spots (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in postpubertal subjects)
Freckling in the axilla and/or inguinal region
Plexiform neurofibroma
Two or more Lisch nodules
A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
A first-degree relative with NF1
Antibiotics: clarithromycin, erythromycin, troleandomycin
Anti-HIV agents: delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir
Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day), voriconazole
Antidepressants: nefazodone, fluvoxamine
Calcium channel blockers: verapamil, diltiazem
Miscellaneous: amiodarone
In addition, grapefruit, grapefruit juice, seville oranges and star fruit should be avoided, as they inhibits CYP3A4
Severely impaired lung function
If requires pheresis to collect blood, prothrombin time (PT) < 1.5 upper limit normal
If requires pheresis to collect blood, partial thromboplastin time (kaolin) (PTTK) < 1.5 upper limit normal
Available autologous transduced peripheral blood T-cells with >= 15% expression of CAR-Kappa determined by flow-cytometry
No evidence of local recurrence or distant metastases
AST (SGOT) >2x ULN
Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
Participants in the control arm from Study BO21976/TDM4450g whose disease progression has occurred during the transition interval between the parent study and this extension study may initiate trastuzumab emtansine treatment at the time of enrollment into study TDM4529g (NCT00781612)
AEs leading to single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment discontinuation in the parent study
Ongoing SAEs from the parent study
History of hypersensitivity with previous trastuzumab emtansine or any agent used with trastuzumab emtansine in the parent study, precluding further dosing
Patients with an autoimmune disorder of the central or peripheral nervous system will be eligible; this will include:\r\n* Primary Central Nervous System (CNS) vasculitis\t\r\n* Rasmussen’s encephalitis\r\n* Autoimmune peripheral neuropathy (anti-Hu [Anna-1], anti-GM1 [GD1b], anti-MAG, anti-ganglioside, anti-sulfatide)\r\n* Autoimmune cerebellar degeneration\r\n* Gait Ataxia with Late age Onset Polyneuropathy (GALOP)\r\n* Stiff Person Syndrome\r\n* Chronic Inflammatory Demyelinating Polyneuropathy\r\n* Myasthenia Gravis\r\n* Lambert-Eaton myasthenic syndrome\r\n* Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) / tropical spastic paraparesis (TSP)\r\n* Opsoclonus / myoclonus (anti-Ri)\r\n* Neuromyelitis optica\t\r\n* Multiple sclerosis (only patients with relapsing/remitting multiple sclerosis [MS] will be included)\r\n* Other central or peripheral nervous system autoimmune diseases as approved by study neurologists and the Fred Hutchinson Cancer Research Center (FHCRC) faculty at Patient Care Conference (PCC)
Pregnancy or expressed plans to become pregnant within 1 year of the procedure
Stages II, III, or IV (Ann Arbor Staging)
Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
Receiving erythroid stimulating agents (erythropoietin [EPO]: Procrit, Aranesp)
Primary immunodeficiency disorder or other nonmalignant inherited disease (except Fanconi anemia) treatable by allogeneic HCT
Fanconi anemia
Granulocytes > 1500/mm^3
No prior exposure to immunotherapy agents
Recursive partitioning analysis (RPA) class III patients (expected to be treated less than 2 years from first course of therapy and have a tracheostomy or percutaneous endoscopic gastrostomy [PEG] tube at presentation)
Melanoma (excluding uveal melanoma);
Gastric or gastroesophageal junction adenocarcinoma
Have previously been enrolled in this study or any other study investigating SM-88 or who have previously received any component of SM-88 in a clinical trial.
Subjects exhibiting idiosyncratic reactions to psoralen compounds.
Subjects with a history of the light sensitive diseases for which methoxsalen would be contraindicated. Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism.
Subjects treated, or anticipated to be treated, with delavirdine (due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors caused by phenytoin).
Subjects with prior organ transplant or being treated, or anticipated to be treated, with cyclosporine (because long-term administration of the combination of cyclosporine and sirolimus is associated with deterioration of renal function).
The effects of prexasertib and LY3300054 on the developing human fetus are unknown. For this reason, pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with prexasertib and LY3300054, breastfeeding women are also excluded.
Other acute leukemias that are of ambiguous lineage or of other types
Negative antiviral serology:
Negative human T-lymphotropic virus (HTLV)-1 and 2 antibodies.
Two appropriate CB units identified for the subject.
The contrast-enhancing intraparenchymal brain metastases(s) must be well circumscribed and must have a maximum diameter of =< 3.0 cm in any direction on the enhanced scan
Participants must be willing to undergo a research biopsy at baseline and at cycle 2 day 1 if extracranial metastases are safely accessible. Participants for whom biopsies cannot be safely performed must be willing to submit an archival primary and/or metastatic specimen. The biopsies may be waived with prior principal investigator (PI) approval for the first 6 participants enrolled to the safety run in phase
CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
Known leptomeningeal or brainstem metastases. The presence of leptomeningeal enhancement alone, without associated clinical manifestations and/or positive CSF cytology, will not be constituted as known leptomeningeal metastases
For enrollment to the phase I portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via Next Generation [NextGen] sequencing using the Dana Farber Cancer Institute [DFCI]/Brigham and Women's Hospital [BWH] OncoPanel or any Clinical Laboratory Improvement Act [CLIA]-certified method) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
For enrollment to the phase II portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) and have had progression of disease on prior BRAF and MEK inhibitor therapy
Pregnant women are excluded from this study because MCS110, dabrafenib and trametinib are anti-cancer agents with the potential for teratogenic or abortifacient effects. Pregnancy status will be verified at various points in the trial and a serum pregnancy test will be required. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MCS110, dabrafenib or trametinib, breastfeeding should be discontinued if the mother is treated with MCS110, dabrafenib or trametinib
Require continued treatment with a medication that is a sensitive CYP2C9 substrate with a narrow therapeutic index.
Are unable to take no food or liquids other than water for 2 hours before and 2 hours after each dose of AG-270.
Scheduled for pancreaticoduodenectomy
Significant cognitive impairment or documented psychologic impairment
Post randomization exclusion will occur if the patient is found to have unresectable disease at laparotomy and therefore will not have the potential for the same post-operative complications
Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway
PHASE II: Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway
ALL PHASES:
At least 1 measurable lesion that can be reproducibly measured in 2 dimensions
Inclusion of women, minorities, and other underrepresented populations: this protocol is open to males and females of all races
Presence of metastatic disease that would be amenable to the required biopsies; ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ; if not possible, then biopsy of the lesions in different organs will be permitted
Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ? 2.0 or average HER2 copy number ? 6.0 signals/cells)
Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:\r\n* Treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable\r\n* Participants who have had prior whole- brain radiation therapy and/or SRS and then whose lesions have subsequently progressed are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS \r\n* Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control\r\n* Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria
Visceral crisis or impending visceral crisis at time of screening
CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
Known leptomeningeal or brainstem metastases (defined as positive CSF cytology and/or unequivocal radiological evidence of clinically significant leptomeningeal involvement; CSF sampling is not required in the absence of suggestive symptoms to exclude leptomeningeal involvement)
Known intolerance to trastuzumab or pertuzumab or atezolizumab
Patient must have progressed on their most recent line of therapy. Progression must have been demonstrated by radiological or clinical assessment.
Proteinuria < 1 g/day
Cohorts 1 to 3: Have platinum-resistant disease and have documented test results assessing alterations in the BRCA1 and BRCA2 genes prior to receiving study treatment.
For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma
During the study, and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) and men must agree not to donate sperm for the purposes of assisted reproduction
Exhibits clinical signs of meningeal involvement of MM
The subject is capable of understanding and complying with protocol requirements.
Patients with tumors lying close to an airway, major blood vessel or spinal cord that, in the opinion of the investigator, could cause occlusion or compression in the case of swelling, or erosion into a major vessel in the case of necrosis.
Has testing for a BRAF mutation prior to study entry
Lesion ? 5cm in size
Mandatory biopsy is required during screening
Diagnosis:
Participants who cannot receive gadolinium
Participants with inadequate mental capacity to complete quality of life questionnaires
Histology other than adenocarcinoma
Prior exposure to isatuximab or participation in clinical studies with isatuximab.
Is receiving an monoamine oxidase-inhibitors (MAOI) or any drug which has significant MAOI activity (e.g., meperidine, linezolid, methylene blue) within the 21 days before screening, or has a history of Serotonin Syndrome after receiving serotonergic drugs.
Evidence of electrolyte imbalance
Previous enrollment in the present study
Mucinous or tubal histology or other good prognosis histology
Must consent to provide biomarker analyses as described in the protocol.
Dose Escalation (Segment 1): 0 - 1
Dose Expansion (Segment 2): 0 - 2
Subjects with advanced solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit).
Other locoregional therapy [e.g., radiofrequency ablation (RFA), TACE (transarterial chemoembolization), TARE (transarterial radioembolization), DEB-TACE (drug eluting bead transarterial chemoembolization)]: 6 weeks
Subjects must be willing to avoid extensive sun exposure, phototherapy, and use of a tanning salon during trial participation.
Neutrophils ?1,500 ?L.
Serum potassium within normal range.
Any human papillomavirus (HPV) status or smoking history is permitted; oropharyngeal cancer patients are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV polymerase chain reaction (PCR) or in situ hybridization (ISH) testing
Suitable for a new tumour biopsy.
Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured.
Patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation (germline or somatic)
Logistical or psychological hindrance to participation in clinical research
Histological diagnosis of nonsquamous NSCLC.
Are untreated.
Participation in the DES component of the study.
TNBC is defined as:
Human papillomavirus-negative HNSCC
Any solid malignancy known to be MSI high/MMR deficient per local test results, including but not limited to: CRC, stomach adenocarcinoma, esophageal adenocarcinoma and endometrial cancer
Has a diagnosis of immunodeficiency
For enrollment to arm 1: participants must have a confirmed CCND1, 2, or 3 high-level amplification, CCND1 mutation, or a CCND1 splice variant expected to lead to nuclear retention of cyclin D1 protein, via Dana-Farber Cancer Institute (DFCI)/Brigham and Women's Hospital (BWH) OncoPanel or any Clinical Laboratory Improvement Act (CLIA)-certified method
For enrollment to arm 2: participants must have a confirmed CDK4 or CDK6 high-level amplification, identified via DFCI/BWH OncoPanel or any CLIA-certified method
Participants receiving an enzyme-inducing antiepileptic drug (EIAED) who cannot be transferred to a non-EIAED (e.g., levetiracetam, lacosamide, lamotrigine, etc.) prior to the initiation of protocol therapy
Has a ROS1 translocation
Have documentation of V600-activating BRAF mutation status or consent to BRAF V600 mutation testing during the screening period.
Has Ocular Melanoma
Females with a histologically proven CAH/EIN or grade I endometrial carcinoma (EC) for which surgery is planned; the pathologic report from the referring facility will be used to determine pathologic eligibility; this report must be within 45 days of their baseline (pre-surgical) clinic visit
Women with severe bone density issues/osteoporosis (defined as any medical treatment for osteoporosis, and/or a T-score of -2.5 or lower, and/or history of fracture of the hip or spine)
Be between the ages of ?18 and ?65 years
Have other life-threatening illness
Subjects receiving monoamine oxidase (MAO) inhibitors within 21 days of study enrollment (epacadostat increases serotonin levels, theoretically increasing the risk of serotonin syndrome, although this has not been reported in any ongoing clinical studies to date)
Subject is considered an appropriate candidate (per Investigator assessment) for induction therapy with 6 cycles of R-CHOP-21 immunochemotherapy.
Agree to ongoing pregnancy testing during the course of the study as outlined in the PPRMP.
All subjects must:
Agree not to share IP with another person
Be counseled about pregnancy precautions and risks of fetal exposure and agree to requirements of the Pregnancy Prevention and Risk Management Plan (PPRMP)
Complete left bundle branch or bifascicular block.
Troponin-T value > 0.4 ng/mL or B-type natriuretic protein (BNP) > 300 pg/mL by central laboratory assessment Subjects with baseline troponin-T > ULN or BNP > 100 pg/mL are eligible but must have a cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy.
Nodal status - positive (FNA or core biopsy of the node[s] is cytologically or histologically suspicious or positive; Imaging is suspicious or abnormal but FNA or core biopsy was not performed.)
LVEF assessment must be performed within 42 days prior to randomization. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional preferences.) The LVEF must be ? 55% regardless of the cardiac imaging facility's lower limit of normal.
Excisional biopsy or lumpectomy performed prior to study entry.
Symptomatic peripheral ischemia.
All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible; endoscopy reports or subsequent gastrointestinal (GI) clinic note should clearly state both the T and N stage
Deemed a suitable candidate for esophagectomy by the treating surgeon as documented in a pre-operative assessment visit per standard practice at each participating institution
All patients have to agree to participate in the correlative study of sample collection for immune correlative assays in order to participate in the main study; however, if the sample cannot be obtained due to feasibility issues, the patient will be allowed to continue on treatment
Metastatic colorectal cancer (mCRC) categorized as microsatellite stable (MSS) by polymerase chain reaction (PCR) per local assay at any time prior to Screening or by the central laboratory.
were unable to tolerate the prior first-line regimen
Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L], calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Pathologically documented diagnosis of colorectal adenocarcinoma.
Normal coagulation profile
Negative antiviral serology
Acceptable coagulation status, as specified below:
Known clinically important respiratory impairment
Any CT imaging findings indicating radiation or drug-induced lung disorders at the time of screening
Only females are eligible. Menopausal status: i. Postmenopausal defined by:
Potassium, sodium, calcium (corrected for serum albumin), magnesium, and phosphorus within normal limits for the institution;
Documented cardiomyopathy;
Medications that have a narrow therapeutic window and are predominantly metabolized through CYP2C8, CYP2C9, CYP2C19, or CYP3A4;
CD19 expression is required at any time since diagnosis; if patient has received anti-CD19 targeted therapy (i.e. blinatumomab), then CD19 expression must be subsequently demonstrated. CD19 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or >= 90% by flow cytometry; the choice of whether to use flow\r\ncytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject; in general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples
Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy will be eligible if < 5% of circulating levels of CD3+ cells express the previous CAR by flow cytometry
NOTE: the first subject in the first dose cohort must be >= 18 years of age if an adult has not been treated at that dose cohort on the companion Stanford protocol “Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults with Recurrent or Refractory B Cell Malignancies” and undergone safety evaluation at day 28 without evidence of dose limiting toxicity (DLT)
Recurrent or refractory ALL limited to isolated testicular
Patients with any anginal chest pain; defined by a known diagnosis of angina; or defined by chest pressure, squeezing, radiating pain to arms, shoulders, or neck from the chest; with or without exertion
Scheduled to receive a continuous course of fractionated, conventional external beam with a cumulative radiation dose between 55 and 72 Gy at each site
Current mucositis
Planned to receive Erbitux™ (Cetuximab) or similar targeted therapy between Baseline and 6 weeks post-RT
Tumors of the lips, sinuses, salivary glands, nasopharynx, hypopharynx, or larynx
Patients must have a diagnosis of biopsy-proven diagnosis of AL amyloidosis according to the following standard criteria:\r\n* Histochemical diagnosis of AL amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence and immunohistochemistry\r\n* If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary\r\n* Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non amyloid forming [uninvolved] free light chain [FLC]) ? 50 mg/L)\r\n* Systemic amyloid organ involvement including renal, cardiac, gastrointestinal (GI) and/or nervous system involvement as well as soft tissue disease
Untreated biopsy proven AL amyloidosis
N-terminal pro b-type natriuretic peptide (NT Pro-BNP) > 8500 pcg/mL
Dialysis dependent renal failure
Subject has known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification\r\n* Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study
Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia (Kyle et al, 2003) or have high risk disease with an serum IgM level of 6,000 mg or higher (Gustine et al, 2016)
Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required
Prior exposure to ibrutinib or ulocuplumab
Healthy women age 35 - 75 years with either heterogeneously dense (C) or extremely dense (D), breast tissue on 2D mammography, based on American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS©) fifth edition classification) in either breast within 3 months prior to randomization. Mammogram with BI-RADS final assessment category 1 or 2 (negative or benign findings).
Pregnant women are excluded from this study because the effects of 4-OHT gel on the developing human fetus at the recommended dose and route are unknown.
Women who have had a prior mastectomy (unilateral or bilateral), segmental mastectomy, reduction mammoplasty or breast augmentation including implants.
Women with an abnormal mammogram (BI-RADS final assessment category 3-probably benign, 4-suspicious, or 5-malignant findings). Women with BI-RADS 0 assessment (needs additional imaging evaluation) that are subsequently found to have negative (BI-RADS 1) or benign findings (BI-RADS 2), are NOT excluded.
Women with only synthetic 2D mammograms generated from 3D (tomosynthesis) are excluded as breast density measurements are not yet validated for synthetic mammograms. Women with combination 2D+3D mammograms are not excluded.
Any remission after chimeric antigen receptor (CAR)-T cell therapy
Subjects 1 and 2 (in cohort 1) will be >= 12 years’ old
Non-cooperative behavior or non-compliance of the patient and/or of his/her family
Cardiopulmonary dysfunction
Thrombosis of the main portal vein
Clinicopathological diagnosis of Waldenstrom macroglobulinemia, and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia
Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required
Hemosiderosis/hemochromatosis
Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology
total abstinence (if it is their preferred and usual lifestyle)
do not have a vasectomized partner with confirmed azoospermia
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: AST (SGOT)/ALT (SGPT) =< 5.0 X ULN if hepatic metastases are present
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Creatinine =< 1.5 X the institutional ULN OR
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of neuromuscular disorders that are associated with elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
EXPANDED ACCESS COHORT: Participants must be currently enrolled to DFCI protocol number 13-506 or discontinued from protocol 13-506 solely because the study agents were no longer available via protocol 13-506
EXPANDED ACCESS COHORT: History of neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
ANC ? 1000/µL
Subjects currently being treated with a CYP 2C9, CYP 2C8, CYP 2C19, CYP 2D6, and P-gp substrate with a narrow therapeutic index.
Pregnant or lactating as the treatments used in this study includes drugs that are FDA Pregnancy Category D.
Acute leukemias of ambiguous lineage
AML that transformed from previously treated myelodysplastic syndromes
Prior history of temozolomide chemotherapy provided concurrent to external beam radiotherapy and after as per current standard of care; however, temozolomide would not be required to have been provided concomitantly or after radiation if the patient had unmethylated MGMT promoter or if the patient initially was diagnosed with a low grade glioma; at least 8 weeks must have passed from the last dose of temozolomide and first dose of cyclophosphamide and/or rQNestin34.5v.2
Subjects with any recurrence (first, second, third, etc recurrence) will be able to be enrolled
Main portal vein vascular invasion; for the dose escalation, segmental portal vein is allowed
Prior embolization and/or ablation; for the dose escalation, prior embolization and ablation is allowed as long as the patient has progressed with a new RECIST measurable lesion
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Subjects must be refractory to or intolerant of existing cancer therapy(ies) known to provide clinical benefit.
Presence of deep vein thrombosis based on screening lower extremity Doppler ultrasonography.
previously treated with abiraterone, enzalutamide alone or in combination AND must have demonstrated evidence of objective progression as per PCWG3 criteria
KPS of ? 70 or ECOG of 0 to 1
more than one sequential second generation AR-directed therapy
Cohort 2: Prior adverse reaction(s) to carboplatin
>= 1% of CD30-positivity by immunohistochemistry confirmed by hematopathology review at the participating institution
Brentuximab vedotin
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
For enrollment to the phase I portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via next generation [NextGen] sequencing using the Dana-Farber Cancer Institute [DFCI]/Brigham and Women's Hospital [BWH] OncoPanel or any Clinical Laboratory Improvement Act [CLIA]-certified method) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
Hepatopulmonary shunting < 20% as documented via hepatic artery perfusion study
Subjects with chronic infection by hepatitis C virus (HCV) who are untreated or who failed previous therapies for HCV are allowed on study; in addition, subjects with successful HCV treatment (defined as sustained virologic response [SVR] 12 or SVR 24) are allowed as long as 4 weeks have passed between completion of HCV therapy and start of study drug
Untreated active HBV
Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
Local radiation therapy (RT) is allowed as needed to manage symptoms appropriately, as long as there remains a measurable lesion in the CNS
Whole-brain RT may be used, without a pre-defined washout period, prior to commencement of study therapy if the lesion that has been radiated is not the sole measurable lesion, or the patient is eligible based on positive CSF cytology
Diagnostic biopsy reveals perineural invasion (PNI) and/or lymphovascular invasion (LVI)
Trismus or compromised airway
Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability
Patients must weigh ? 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
History of orthotopic liver transplantation, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting. Prior Whipple procedure is permitted provided the anatomy is still compatible for perfusion with the Melphalan/HDS system.
Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.
Neutrophils < 1,500 cells/µL.
Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability
Lack of availability for follow up assessments
The investigator’s belief that the subject is medically unfit to receive pembrolizumab and or unsuitable for any other reason
INCLUSION - PROCUREMENT: If pheresis required to collect blood:\r\n* Aspartate aminotransferase (AST) < 1.5 × upper limit normal
EXCLUSION - PROCUREMENT: Clinically significant viral infection or uncontrolled viral reactivation of Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus (Adv), BK-virus, or human herpesvirus 6 (HHV-6)
Prior isotope therapy with strontium-89, samarium or RAD223
All herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St. John's wort, etc.) must be discontinued before registration; subjects may continue on a daily multi-vitamin, calcium and vitamin D
All hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) must be discontinued before registration; no washout period will be required for any of these agents
Initiation of bisphosphonate/denosumab therapy during the study; subjects on stable doses of bisphosphonates or the tumor necrosis factor receptor superfamily member 11a, subfamily L (RANK-L) inhibitor, denosumab, which have been started no less than 4 weeks prior to registration, may continue on this medication
Participants who cannot receive gadolinium
Histologic or cytologic diagnosis of a WDNET, Ki67 =< 30%, unresectable, of foregut origin (thymic, bronchopulmonary, gastric, duodenal, and pancreatic) confirmed by the enrolling institution\r\n* Note: If patients have a functional NET, they are permitted to continue on a somatostatin analog for hormonal symptom control
Any previous exposure to docetaxel
Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors).
Neutrophils ?1000/?L (?1 x 10^9/L)
Additional criteria for cohort D (anti-PD1 combo) will be supplied in an appendix at a later date.
Additional criteria for cohort D (anti-PD1 combo) will be supplied in an appendix at a later date.
Participants with evidence of pneumonitis on scans at screening will be excluded
Prior exposure to CWP232291.
Subjects with carcinomatous meningitis
known P gp substrates with a narrow therapeutic index
Spinal Instability Neoplastic score >= 7 unless lesion reviewed by a neurosurgical service and considered stable
Participants with bone lesions requiring surgical fixation to provide mechanical stability are ineligible; participants with previously fixed lesions are allowed
No evidence of PR prolongation or atrioventricular (AV) block on baseline electrocardiogram (ECG)
Esophagogastrectomies will be performed via a laparotomy and a right thoracotomy with en-bloc removal of perigastric, celiac, periesophageal and subcarinal lymph nodes; esophagogastric reconstruction will be performed above the level of the azygo-caval junction using an end-to-end (EEA) stapling device
Esophageal tumors that are located in the mid esophagus or higher i.e. not involving distal esophagus or gastroesophageal (GE) junction
Tumors whose proximal end are higher that the level of the carina
Tumors extend 5 cm or more into the stomach
Willing to remain abstinent from consuming alcohol.
Treatment with the following medications are contraindicated with DSF: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertraline, tindazole, tizanidine, atazanavir.
At Massachusetts General Hospital (MGH), samples will be tested using a multiplex polymerase chain reaction (PCR) technology called anchored multiplex PCR (AMP) for single nucleotide variant (SNV) and insertion/deletion (indel) detection in genomic DNA using next generation sequencing (NGS); briefly, genomic DNA was isolated from a formalin-fixed paraffin embedded tumor specimen is sheared with the Covaris M220 instrument, followed by end-repair, adenylation, and ligation with an adapter; a sequencing library targeting hotspots and exons in 39 genes (including BRAF, exons 11 and 15) is generated using two hemi-nested PCR reactions; Illumina MiSeq 2 x 147 base paired-end sequencing results are aligned to the hg19 human genome reference using BWA-MEM; MuTect and a laboratory-developed insertion/deletion analysis algorithm are used for SNV and indel variant detection, respectively; this assay has been validated to detect SNV and indel variants at 5% allelic frequency or higher in target regions with sufficient read coverage; this test was developed, and its performance characteristics were determined by the MGH Center for integrated diagnostics
Men or women ? 18 years old at the time of signing the ICF
MK-1454 (cut/subcut lesions) and MK-1454+pembro (cut/subcut lesions) Arms:
Has ?1 distant, discrete non-injected lesion which is amenable to biopsy.
All Arms:
Pre- or post-menopausal women are allowed; if pre- or peri-menopausal, concurrent ovarian suppression for pre- or peri-menopausal women is required
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Cumulative volume of all tumors ? 15 cc
Able to operate the NovoTTF-100M device independently or with the help of a caregiver
Known allergies to medical adhesives or hydrogel
Diagnosed with pathologically (histologically) proven invasive mammary carcinoma (ductal, lobular or other) of the breast who have undergone either mastectomy or lumpectomy with any type of axillary surgery or axillary sampling
For patients who have undergone mastectomy, any type of mastectomy and any type of reconstruction (including no reconstruction) are allowed; metallic components of some tissue expanders may complicate delivery of proton therapy; any concerns should be discussed with the Breast Committee Study Chairs prior to registration
Dermatomyositis with a creatine phosphokinase (CPK) level above normal or with an active skin rash or scleroderma
Adequate Blood Pressure Control defined as a blood pressure (BP) <= the 95th percentile for age, height, and gender measured, subjects on stable doses of no more than one anti-hypertensive medication, with a baseline BP <= 95th percentile for age, height and gender, will be eligible.
Diagnosis of VTE <= 30 days prior to study enrollment for which potential benefits of anticoagulation therapy to prevent recurrence of VTE are felt by the treating physician to exceed the potential harms
Any anticoagulation drug/strategy may be used to treat the index VTE; protocol treatment will begin <= 30days after the index VTE diagnosis date
Therapy with any azole antifungals (e.g., itraconazole, ketaconazole, voriconazole) at the time of enrollment
A blood pressure (BP) =< the 95th percentile for age, height, and gender, and not receiving medication for treatment of hypertension; please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
MDS classified as follows:
Progression (according to 2006 IWG criteria) at any time after initiation of AZA or DAC treatment or Failure to achieve complete or partial response or hematological improvement (HI) (according to 2006 IWG) after at least six 4-week cycles of AZA or either four 4-week or four 6-week cycles of DAC administered or Relapse after initial complete or partial response or HI (according to 2006 IWG criteria)
Off all treatments for MDS (including AZA and DAC) for ? 4 weeks before randomization; growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated
Willing to adhere to protocol prohibitions and restrictions
Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)
intra-uterine devices (IUDs),
vasectomized partner
sexual abstinence in accordance with an individual's lifestyle
For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0
For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0
Malignancies other than UC within 5 years prior to Cycle 1, Day 1
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating BRAF V600 mutations a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrolment) Vismodegib
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating hedgehog pathway relevant mutation (activating mutation of smoothened [SMO] or loss-of-function mutation of protein patched homolog-1 [PTCH-1]) a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment)
Molecular testing results from CLIA-certified laboratories (using tissue) demonstrating programmed death-ligand 1 (PD-L1) copy number gain/amplification, deficiency in mismatch repair enzymes (dMMR), high levels of microsatellite instability (MSI-H) or elevated tumor mutational burden (TMB >=10 mutations/ MB).
Eligible for another actively accruing Roche/Genentech-sponsored interventional clinical trial Study-Drug Specific Exclusion Criteria: Trastuzumab plus Pertuzumab
Cancers with exon 20 mutations
LVEF below institutional lower level of normal (LLN) or below 50%, whichever is lower
ALK-positive NSCLC, neuroblastoma, and childhood tumors
Participants with symptomatic bradycardia
Calcium >= LLN
Magnesium >= LLN
Potassium >= LLN
A cluster of differentiation (CD)4+ lymphocyte count > 50/mcL will be required within 2 weeks of study participation
Participating participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry; as study-specific (antiretroviral-based) strata fill, however, only participants who are receiving the therapies eligible for the remaining open strata will be accrued
Depending on the stage of the protocol, pathway activation based on p-S6 will need to be done in real time to assess if patient is eligible
Additional graft selection criteria specified in section 2.5
Prior allogeneic HCT.
Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib
Prior radical prostatectomy
Serum potassium ? 3.5 mmol/L. Supplementation and re-screening is allowed.
Prior bilateral orchiectomy
Potassium above the institutional lower limit of normal (supplementation to meet this is allowed)
Magnesium above the institutional lower limit of normal (supplementation to meet this is allowed)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\r\n* There will be no exclusion of patients with known visual impairment or symptoms, including by not limited to peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; patients will have a baseline ophthalmologic exam to serve as a point of comparison and further exams as needed should visual symptoms develop; no pretreatment eye exam findings or ocular symptoms have been associated with an increased risk of ocular toxicity seen with AT13387
Neuronal tumors \r\n* Ganglioglioma (excluding tumors with anaplastic astrocytic components) \r\n* Infantile desmoplastic ganglioglioma
The study is open to all participants regardless of gender or ethnicity; efforts will be made to extend the accrual to a representative population; if differences in outcome that correlate to gender, racial, or ethnic identity are noted, accrual may be expanded or additional studies may be performed to investigate those differences more fully
Prior allogeneic HSCT
Patient with active Hepatitis B or C determined by serology and/or NAAT.
Radioactive iodine (RAI)-refractory disease defined as 1 or more of the following:\r\n* Patients who have received greater than 600 mCi of radioactive iodine in their lifetime OR\r\n* RAI-avid metastatic lesion which remained stable in size or progressed despite RAI treatment within 9 months of RAI treatment OR\r\n* 10% or more increase in serum thyroglobulin (on thyroid-stimulating hormone [TSH]-suppression) within 9 months of RAI treatment OR\r\n* Index metastatic lesion non-RAI avid on a diagnostic RAI scan OR\r\n* Presence of fluorodeoxyglucose (FDG) avid metastatic lesions on positron emission tomography (PET)/CT scan (standardized uptake values [SUV]max > 5 of any single lesion)
Specific body surface area (BSA) criteria depending on enrolling dose level: no restrictions for dose level 0, BSA >= 0.75 required for dose levels -1 and -2, BSA > 0.90 required for dose levels -3 and -4
Negative result of BRAFV600E and BRAF Ins T screening test
Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and recommended by the Investigator.
Patients requiring biliary stent placement must have biliary stent placed > 7 days prior to screening.
Patient must consent to provision of a sample of blood in order that the specific correlative marker assays (Correlative Studies) may be conducted.
Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.
Patient has a > 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except Ampulla of Vater cancers)
Neuroendocrine Tumors (well- and moderately-differentiated) of the lung, appendix, small intestine, colon, rectum, or pancreas
Mesothelioma
Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
OR
Has known glioblastoma multiforme of the brainstem
Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH)
Testing for LVEF is not required for pre-registration, but patient must not have a recent LVEF < LLN or have symptoms of congestive heart failure
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASHINGTON UNIVERSITY [WASH U] GENOMICS AND PATHOLOGY SERVICES [GPS] LABORATORY): Tumor tissue tested positive for HER2 mutation; mutations outside the list will be assessed on a case-by-case basis by the study team to determine eligibility\r\n* Note: HER2 mutations listed and detected by Guardant360 are also eligible
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
American Joint Committee on Cancer (AJCC) 7th edition clinical stages T1c to T2c
PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)
TSS of ?10 on the MPN-SAF TSS 2.0 or patients with a single symptom score of ?5 or two symptoms of ?3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats
Peripheral blast count of <10%
Able to understand and willing to complete symptom assessments using a patient reported outcomes instrument
Previously treated with pacritinib
Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
For enrollment into the China extension cohort, residence in the People's Republic of China Disease-specific Inclusion Criteria:
A valid PTEN IHC result (testingcentral laboratory tested with results directly sent to IxRS) (e.g., participants with an \invalid\ or \failed\ PTEN IHC result are not permitted to enroll)
Participant consents to allow access to diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic that is being developed in parallel with gilteritinib.
Female participants must either:
postmenopausal (defined as at least 1 year without menses) prior to screening or
For United Kingdom sites:
Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
For United Kingdom sites:
Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
Established IUD or IUS
Male is sterile due to a bilateral orchiectomy
Serum potassium and magnesium greater than the institutional LLN.
Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency
Active or chronic corneal disorder, including but not limited to the following: Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
Required used of folate-containing supplements (e.g. folate deficiency)
Single-probe average HER2 copy number < 4.0 signals/cell
Dual-probe HER2/CEP17 ratio < 2 with an average HER2 copy number < 4.0 signals/cell.
Are postmenopausal for at least 1 year before the screening visit, OR
Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
Histological or cytological confirmation diagnosis of NSCLC.
For the dose expansion paired biopsy cohort:
History of hypersensitivity to any active or inactive ingredient of HS-10296 or to a drug with a similar chemical structure or class to HS-10296.
Non-leukocyte leukocyte-depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Is participating in another therapeutic clinical trial
Able to operate the NovoTTF-100L device independently or with the help of a caregiver
Known allergies to medical adhesives or hydrogel
Admitted to an institution by administrative or court order
Richter’s transformation confirmed by biopsy
Logistical or psychological hindrance to participation in clinical research
Current use of metformin, or strong antioxidants (extracts from grape seed, milk thistle; pine bark, green tea, saw palmetto; resveratrol; flavonoids; catechins; ellagic acid), large quantities of red grapes, white button mushrooms, red wine
HSIL cytology with no invasive features identified on colposcopy or the baseline biopsy
Compliant on combined anti-retrovirals (cART) if HIV infected
No risk factors for microinvasive disease (no colposcopic features of microinvasion, adequate colposcopy and negative endocervical curettage)
Invasive features on colposcopy and the biopsy specimen
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
Normal coagulation panel.
Negative antiviral serology.
FAZ053 in combination with PDR001: NSCLC/TNBC / Selected indication(s) in dose expansion group Q6W dosing regimen
History or current status of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) that needed to be treated by systemic therapy, such as immuno-suppressants and hypoimmunity (e.g., myelodysplatic disorders, marrow failures, acquired immune deficiency syndrome [AIDS], transplant immunosuppression)
Any condition that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
Participants with known addiction to any drugs
Participants enrolling into the NTRK cohort must have an NTRK1, 2, or 3 rearrangement as confirmed by targeted NextGen sequencing using the DFCI/BWH OncoPanel or another CLIA-certified method
Lack of availability for follow up assessments
The investigator’s belief that the subject is medically unfit to receive nivolumab, and/or ipilimumab or unsuitable for any other reason
Confirmed diagnosis of SAA, either from initial diagnosis or follow-up assessments, defined as:
Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA.
Participant has taken any of the following medications within the past 3 months:\r\n* A thiazolidinedione (e.g. pioglitazone [Actos] or rosiglitazone [Avandia]),\r\n* A biguanide (e.g. metformin [Glucophage, Glumetza, Fortamet, Riomet] or proguanil [Paludrine])\r\n* A combination drug containing one of the agents above (brand names include: ACTOplus Met, Avandamet, Avandaryl, Duetact, Glucovance, Invokamet, Janumet, Jentadueto, Komboglyze, Metaglip, PrandiMet, Synjardy, Xigudo)
Participant is currently taking a cationic drug or multidrug and toxin extrusion [MATE] inhibitor (e.g. amiloride [Midamor]; cimetidine [Tagamet]; digoxin [Lanoxin, Digitek, Digox]; dolutegravir [Tivicay]; morphine [Roxanol, Duramorph, Kadian, MS Contin]; procainamide [Pronestyl, Procanbid]; quinidine [Quinidex, Cardioquin, Quin-G, Quinora]; quinine [Qualaquin, Quinamm, Quiphile]; ranitidine [Zantac, Deprizine, Gabitidine]; ranolazine [Ranexa]; triamterene [Dyrenium)] trimethoprim [Proloprim, Trimpex, Primsol]; vancomycin [Vancocin, Vancoled]; or vandetanib [Calpresa])
Participant has > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 limb edema (5 - 10% inter-limb discrepancy in volume or circumference at point of greatest visible difference; swelling or obscuration of anatomic architecture on close inspection)
Participant is an active alcoholic or consumes excessive amounts of alcohol per the following definitions:\r\n* Female: More than 3 drinks on any day or a total of more than seven drinks in a week\r\n* Male: More than 4 drinks on any day or a total of more than 14 drinks in a week\r\n** 1 drink = \r\n*** Beer: 12 oz. (1 standard size can or bottle)\r\n*** Wine: 5 oz. (one standard glass)\r\n*** Spirits: 6 oz. (one mixed drink or one 1.5 fluid oz. shot)
PROCUREMENT INCLUSION: Diagnosis of relapsed/refractory HL or NHL
TREATMENT INCLUSION: Available autologous T cells with ? 15% expression of CD30CAR determined by flow-cytometry
No evidence of hypercalcemia, renal failure, anemia, and bone lesions (CRAB) criteria or new criteria of active MM which including the following:\r\n* Increased calcium levels (corrected serum calcium > 0.25 mmol/dL above the upper limit of normal or > .275 mmol/dL) related to MM\r\n* Renal insufficiency (attributable to MM)\r\n* Anemia (hemoglobin [Hb] 2 g/dL below the lower limit of normal or < 10 g/dL) related to MM\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* Bone marrow plasma cells > 60%\r\n* Serum involved/uninvolved free light chain (FLC) ratio >= 100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice\r\n* MRI with two or more focal lesion that is at least 5 mm or greater in size\r\n** Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible
Known amyloid involvement
Previous treatment with ixazomib, or participation in a study with ixazomib whether treated with ixazomib or not
Abnormal blood results
Coexisting ophthalmic disease likely to require slit-lamp examination within the next 90 days
Acute or chronic medical or psychological illnesses that prevent endoscopy procedures
Pregnant or intend to become pregnant, breastfeeding or intend to breastfeed during the study
Mantle cell lymphoma Any histologies not specifically mentioned must be discussed with medical monitor.For subjects enrolled in the phase 3 portion of study, pathologic samples will be submitted for central confirmation of disease histology.
Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
Prior HDT with autologous HSCT
Prior allogeneic HSCT
Known sensitivity to immunoglobulins or any of the components to be administered during dosing.
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal metastatic disease; or intracranial hemorrhage Additional Exclusion Criteria:
PRE-REGISTRATION (OPTIONAL)
Ability to complete questionnaire(s) by themselves or with assistance
If there are 3 or more attempts by the surgeon to clear margins, patient is not eligible for study
ANC ?1.5 x 10?/L
Anthracyclines within 90 days before first ZW25 dosing or lifetime load exceeding 300 mg/m² adriamycin or equivalent
Trastuzumab, pertuzumab, lapatinib, or T?DM1 within 3 weeks before first ZW25 dosing
Presence of other life-threatening illness
Have never used tamoxifen, raloxifene, or other antiestrogen compounds
Participant who has started or increased dosage of lipid-lowering agents in the last 30 days of enrollment; or are taking fibric acid (fenofibrate, gemfibrozil) lipid lowering agents.
Progression on a prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan for unresectable metastatic colorectal adenocarcinoma
For biopsy cohort, participants must be bevacizumab naive or received the last bevacizumab treatment at least 12 months prior to Cycle 1 Day 1 and according to the investigator's judgment the planned biopsies would not expose participants to substantially increased risk of complications
Participants with known microsatellite (MSI)-high status
Proteinuria value > 1.0 g at screening
Is currently receiving tazemetostat as either monotherapy or in combination with other approved drug(s) or investigational agent(s) on an Epizyme-sponsored clinical trial or any other clinical trial being conducted with tazemetostat that is not sponsored by Epizyme (including but not limited to, Investigator initiated trials). For subjects on combination therapy, the other therapeutic(s) must have been completed or will be provided by a source other than Epizyme
For French subjects only: Is either affiliated with or a beneficiary of a social security category.
Practice true abstinence or
Have a male partner who is vasectomized.
Be vasectomized, or
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study.
Presence of a hip prosthesis
Participants must have one of the following (confirmed via targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another Clinical Laboratory Improvement Act [CLIA]-certified method):\r\n* For the replicative stress cohort: MYC amplification, CCNE1 amplification, Rb loss, FBXW7 mutation, or another genomic abnormality indicative of replicative stress as agreed upon with the principal investigator -OR-\r\n* For the HR deficiency cohort: genomic or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, the Fanconi anemia pathway genes, or another genomic or somatic mutation in a known HR gene as agreed upon with the principal investigator.\r\n* For enrollment to the CCNE1 cohort: CCNE1 amplification of 6-fold or greater. Patients with borderline amplification levels may be considered following approval from the overall principal investigator.
Pregnant or breastfeeding females; the potential effects of prexasertib use during pregnancy and breastfeeding are not known and prexasertib has the potential for teratogenic or abortifacient effects.
Metastases detected below the tentorium or beyond the cranial vault, including tumors with evidence of leptomeningeal metastases as previously indicated;
Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
Have acceptable coagulation parameters defined as:
Active cardiomyopathy
Baseline labs as within standard of care (complete blood count [CBC], comprehensive metabolic panel [CMP], lactate dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], etc) are required within 14 days of enrollment
Part B2: Have advanced/metastatic cancer carrying activating mitogen-activated protein kinase (MAPK) pathway alteration
Part B4: Have metastatic melanoma carrying NRAS mutation
Part D: Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion)
Have serious preexisting medical conditions.
Have prior malignancies. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low, as judged by the Lilly clinical research physician, are eligible for this study.
Unresectable HCC, defined by imaging criteria or cytohistologic assessment; TACE as a preferred method of treatment is determined by a multidisciplinary Brigham and Women’s Hospital (BWH)/Dana Farber Cancer Institute (DFCI) Liver Tumor Board
Evidence of hepatic decompensation including esophageal or gastric variceal bleeding or hepatic encephalopathy
Color Doppler ultrasonography showing portal vein tumor thrombosis with complete main portal vein obstruction without cavernous transformation; or obstructive jaundice
Patients with active implanted medical device, a skull defect (such as, missing bone with no replacement), a shunt or bullet fragments; examples of active electronic devices include deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts
Patients with known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
Patient capable of undergoing anesthesia
Patient selected to undergo Whipple procedure or distal pancreatectomy
Gemcitabine + nb-paclitaxel
FOLFIRINOX
Neoadjuvant Chemordiation was administered as IMRT or 3DCRT wPreoperative External beam dose (NCCN)
50.4 Gy (1.8 Gy per fraction) with concurrent gemcitabine, capecitabine, or infusional 5-fluorouracil
An IRE candidate (IRE is Percutaneous irreversible electroporation)
Recurrent or previously resected tumors
Oxygen dependence of > 2 L/min continuously throughout the day at baseline
Have persistent active cGVHD manifestations, as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD, after at least 2 months of steroid therapy.
Platelet count ? 50 × 109/L (without transfusion or thrombopoietin or thrombopoietin analogues within 2 weeks of study entry)
A vasectomized partner
Regular and excessive use of alcohol within the 6 months prior to study entry defined as alcohol intake > 14 drinks per week in a man or > 7 drinks per week in a woman. Approximately 10 g of alcohol equals one \drink\ unit. One unit equals 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine.
Previous therapy with Bruton's tyrosine kinase (BTK) inhibition
Female subjects must be:
The subject has legal incapacity or limited legal capacity.
UGT1A1*28 homozygote or heterozygote
Must meet criteria for high risk disease\r\n* Patients with International Neuroblastoma Staging System (INSS) stage 4 disease are eligible with the following\r\n** MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features\r\n** Age >18 months (> 547 days) regardless of biologic features\r\n** Age 12-18 months (365-547 days) with any of the following unfavorable biologic features (unfavorable pathology and/or deoxyribonucleic acid [DNA] index =1) or any biologic feature that is indeterminate/unsatisfactory/unknown
Ambulatory with an ECOG 0-1
Meet protocol-specified lab requirements
Malignant bowel obstruction
Acute or chronic skin and/or microvascular disorders
Edema or lymphedema in the lower limbs > grade 2
Ability to complete questionnaire (s) by themselves or with assistance
Able to complete all mandatory tests
Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136
Active systemic lupus or scleroderma
Boosts to the chest wall after mastectomy; nodal boosts are allowed
DLBCL, regardless of cell of origin or underlying molecular genetics
PMBCL
Gr3b-FL
TH-FL
Biopsy-confirmed CD20+ expression of the underlying malignancy by immunohistochemical staining or flow cytometry between the most recent dose of an anti-CD20 monoclonal antibody (mAb) and study enrollment
ANC > 1000/µL
Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
Patient is a candidate for salvage resection
Hypersensitivity to any of the inactive ingredients (histidine, sucrose, polysorbate 80) or to other humanized monoclonal antibodies (mAbs)
Must have received at least 1 cycle of induction therapy for front-line AML including cytarabine continuous infusion + anthracycline +/- cladribine or etoposide for 1 or 2 cycles, high dose cytarabine with or without fludarabine, cladribine or clofarabine, >= 4 cycles of azacitidine/decitabine or the equivalent experimental therapy (the latter as confirmed by the principal investigator [PI])
The patient has confirmed relapsed or refractory MM
Known intolerance to immunomodulatory drugs (IMiDs)
Absolute lymphocyte count (ALC) >500/µL
Primary refractory HL or DLBCL
Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension; multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 10 cm as long as the dose constraints to normal tissue can be met
Prior radiofrequency ablation (RFA) to index lesion
Extrahepatic metastases
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the study sponsor
Adequate labs
Acceptable lab testing results
Allow biopsies
MET exon 14 skipping alteration or MET amplification (MET:CEP7 ratio >= 1.8) by molecular testing (local testing is accepted for eligibility; all patients will have confirmation at Massachusetts General Hospital [MGH] but this result is not necessary for eligibility; local molecular pathology result will suffice); this testing can be from any archival or fresh sample
AZD4635 in a different cohort in this study.
Vitiligo or alopecia.
Enrollment into another therapeutic clinical trial.
Prior exposure to either ipilimumab or combined checkpoint blockade
Prisoners or subjects who are involuntarily incarcerated
Absolute neutrophil count ? 1.5 x 10?/Liters (L) (1500/cubic millimeters)
Hemoglobin ?9 grams per deciliter or ?5.6 millimoles per liter
Lactate dehydrogenase (LDH) =< 1.5 x ULN
Have baseline anti-vaccinia antibody titers < 10
Be receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study
Carcinomatous meningitis
Documented MAPK pathway alteration
Has an active infection requiring systemic antibiotic therapy at time of enrollment\r\n* Treatment with antibiotic prophylaxis for indwelling biliary stent(s) or peri-procedural antibiotics for uncomplicated biliary stent exchanges is allowed and not an exclusion
Participants who have had prior exposure to ibrutinib
Positive cytology
If the standard biopsy cores are positive, they must be from the same location in the prostate as MR lesion was biopsied and proven to be cancerous. (Left / Right, Base, Mid Gland, Apex).
The presence of 3 or more MR Visible lesions positive on biopsy.
Acute urinary tract infection.
Altered mental status preventing consent or answering questions during conduct of the trial will be excluded for safety purposes.
Other medical or surgical conditions, especially involving the cardiac, respiratory, renal or hepatic organ systems that would either be unsafe for the patient, would limit study participation, or that would impede the determination of causality of any adverse events experienced during the conduct of this study.
ANC ? 1,000/?L
Involved in other experimental protocols (except with permission of the other study PI)
High grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements or DLBCL, NOS per the 2016 revision of the WHO classification of lymphoid neoplasms (Swerdlow et al, 2016).
Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
Patient must have biopsy-confirmed diagnosis of Langerhans cell histiocytosis
The patient is ?18 years old.
prior IMiD exposure
acceptable lab values prior to randomization
refractory to bortezomib
The patient is at least 18 years old.
The patient has serum electrolytes (including calcium, magnesium, phosphorous, sodium and potassium) within normal limits (supplementation to maintain normal electrolytes is allowed).
The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids.
Participants may receive either a myeloablative or a non-myeloablative (reduced-intensity) conditioning regimen
Age >= 4 years old and toilet-trained; participants must be able to deposit stool samples directly into stool collection containers
Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitor, short-course methotrexate, steroids, mycophenolate mofetil, or sirolimus
Participants undergoing active therapy for immune-mediated or infectious colitis upon admission for allogeneic HSCT
Clinical evidence of extra-capsular extension on scans.
Adequate labs
Appropriate staging imaging.
ANC < 1,500/µL
The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (parts A and B), and COWA; the neurocognitive assessments will be uploaded into the National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, and Gynecologic Oncology Group (NRG) Oncology RAVE system for evaluation by Dr. Wefel; once the upload is complete, within 3 business days, a notification will be sent to the site to proceed to Step 2 registration; at minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible
Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall. as determined by central assessment by the Neurocognitive Co-Chair, Dr. Wefel
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
Prior exposure to ixazomib; however, prior bortezomib exposure is allowed
Have confirmed human papillomavirus-associated lesions based on in-situ hybridization testing and/or polymerase chain reaction which may be performed on a newly obtained biopsy or archived sample
Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
BSA (m2) of <0.5
Subjects diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, or Ph+ ALL
Known CD20-negative status at relapse or progression
Subjects who consume more than 3 alcoholic beverages per day
Mesothelioma.
Gastroenteropancreatic neuroendocrine tumors (GEPNET).
Pancreatic adenocarcinoma.
Creatine phosphokinase (CPK) ? 2.5 × ULN.
Concomitant diseases/conditions:
Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart).
Documented MAPK alteration
DONOR: Related donors for recipients who have monogenetic mutations must be unaffected; for recipients with de novo mutations, testing of related donors is largely not required, but is recommended in all cases and is required when the donor is the child of the recipient; mutation testing needs to be performed by a CLIA-certified lab, if such testing is available; for donors who carry one mutated allele of a PID which is inherited in either an autosomal recessive or X-linked fashion, the donor must have no discernable symptomatology or penetrance of the mutation suggesting that they are affected carriers; this should be verified through disease-appropriate quantitative and functional assays to assess the function of the potential donor’s immune system (e.g. whole blood EBV DNA quantitative polymerase chain reaction [qPCR], natural-killer group 2, member D [NKG2D] activity, T, B, and natural killer cells [TBNK] panel, and quantitative immunoglobulin levels for a female carrier of the magnesium transporter 1 [MAGT1] mutation that causes X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia [XMEN]); furthermore, the X-chromosome inactivation pattern should be assessed for female carriers of X-linked diseases if they are considered as potential donors to confirm favorable and complete lyonization of hematopoietic cells; for PIDs inherited in an autosomal dominant fashion, donors who have one mutated allele for the recipient’s disease will be considered ineligible to donate, regardless of the donor’s phenotype; additional blood tests may be required to assess for quantitative and/or qualitative defects in the donor’s immune system, particularly in cases where PID mutation testing is not available or the PID mutation is not identified\r\n* A NIAID protocol (07-I-0033, Detection and Characterization of Infections and Infection Susceptibility, PI: Steve Holland) is already in place and will handle all the genetic/genomic analysis for recipients and potential donors on this protocol, including the management of results, genetic counseling, and education
Pathologic bradycardia or heart block
Any open wound
ARM 1 - AP
ARM 2 - A: ANC: >= 1500/mcL
If a patient fully meets criteria for Arm 1, but has profound hearing loss and the physician feels that the patient should not receive cisplatin, the patient will be eligible for Arm 2
History or current status of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) that needed to be treated by systemic therapy, such as immuno-suppressants and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, acquired immune deficiency syndrome [AIDS], transplant immunosuppression)
Any condition that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
Participants with known addiction to any drugs
Ability to understand and willingness to sign a written informed consent that is consistent with International Council for Harmonisation to organize applications to regulatory authorities for registration of pharmaceuticals for human use-good clinical practice (ICH-GCP) guidelines
Meningeal carcinomatosis
Molecular testing in a CLIA-certified laboratory must have demonstrated a deletion involving the CDKN2A locus or a mutation within the locus that can be deemed from best available evidence to be likely to cause inactivation of a gene within or protein encoded by CDKN2A; sequencing or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) methods are acceptable; the investigators will consider analyses performed according to similar standards as applied by Foundation Medicine (likely to be the most common source of molecular diagnostic data for patients in this trial)
Two oncologists disagree on prognosis or resectability
Patients must have histologically or cytologically confirmed LCH, ECD or HS; confirmation of outside pathology at Brigham and Women’s Hospital (BWH) will be performed but is not mandatory prior to study enrollment
18+ yrs (US), 21+ yrs (Singapore)
Normal urinalysis
Pts w/ osteopenia (T-score of -1 to -2.5 at L/R total hip, L/R femoral neck or lumbar spine [L1-L4]) eligible
Current or anti-cancer therapy w/in 4 wks pre-study or w/Grade ?1 side effects not resolved w/in 4 wks pre-study
Osteoporosis (T-score of <?2.5 at L/R total hip, L/R femoral neck, or lumbar spine [L1-L4] by DEXA scan)
Symptomatic vertebral fragility fractures or fragility fracture of hip, pelvis, wrist, or other location (fragility fracture - any fracture w/out trauma or as a result of a fall from ?standing height)
Moderate (25%-40% decrease vertebral ht.) or severe (>40% decrease vertebral ht.) morphometric vertebral fractures
?-CTX serum level >1000 pg/mL (morning after ?10hrs fasting)
Thiazolidinedione peroxisome proliferator-activated receptor gamma agonist (e.g. Actos® [pioglitazone] and Avandia® [rosiglitazone]) w/in 4 wks prior to study drug
PO or IV glucocorticoid for ?4 wks at daily dose eq. to ?7.5 mg of PO prednisone w/in 12 wks prior to study drug dosing
Gastric bypass
All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within the 30 days prior to receiving the first dose of AMG 330
For subjects in expansion cohort only: Ingestion of any food or drink containing grapefruit or Seville oranges, or St. John´s wort, within 7 days prior to receiving the first dose of AMG 330
Low- or high-grade non-nodular, previously untreated (\treatment naïve\) dysplastic BE, confirmed by histopathological analysis. If nodular BE or Intramuscosal Cancer (ImCA) is identified during patient screening, this may be treated with Endoscopic Mucosal Resection (EMR) ?6 weeks prior to treatment under this protocol. If previous EMR was performed, follow-up endoscopy must be negative for nodular BE. Patients with ImCA must be at low risk for recurrence, confirmed by EMR pathology results negative for positive margin, poorly differentiated carcinoma, and lymphovascular invasion.
BE length ?6cm excluding visible BE islands, and Prague Classification C ?0 / M ?1
Operable per institution's standards
Non-dysplastic or indefinite for dysplasia BE, confirmed by histopathological analysis
Esophageal stenosis/stricture preventing advancement of a therapeutic endoscope (patients may have the stenosis/stricture dilated and then be treated with CryoBalloon ablation under this protocol at a subsequent procedure ?2 weeks later)
Symptomatic untreated strictures
Any endoscopically-visualized abnormalities such as ulcers, masses or nodules. Neoplastic nodules must first be treated with EMR ?6 weeks prior to planned treatment under this protocol.
History of esophageal cancer more extensive than T1a or not meeting criteria for low risk of recurrence (confirmed by EMR pathology results negative for positive margin, poorly differentiated carcinoma, and lymphovascular invasion)
Large (>4cm) hiatal hernia
Prior distal esophagectomy
Any clinical or histological suspicion of esophageal adenocarcinoma invading into the submucosa by endoscopic mucosal resection (EMR), or confirmed T1a cancer with positive deep margin by EMR
Patients must have histologically confirmed adenocarcinoma of the prostate without previous therapy for PC\r\n* Treatment-naive AND\r\n* Undergoing RP as initial, locally definitive therapy for PC AND\r\n* Eligible for RP in a 3 month timeframe AND\r\n* Consentable for RP
Subject’s biopsy specimen reveals neuroendocrine or small cell features
Subject has prior use of any anti-cancer treatment or product, such as PC-SPES (or any other PC-x product: PC-HOPE, PC-CARE, PC-PLUS, etc)
Active atopic dermatitis or skin condition that disrupts the epidermis
Splenectomy
Subject, or subject’s close household contacts (defined as those who share housing or have close physical contact) have any of the following conditions during the screening and/or treatment periods:\r\n* Active or a history of atopic dermatitis, eczema or other eczematoid skin disorders that disrupt the epidermis\r\n* Other acute, chronic or exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves\r\n* Pregnant or nursing\r\n* Immunodeficient or immunosuppressed (by disease or therapy), including human immunodeficiency virus (HIV) infection
Subject’s close household contacts include children less than the age of three
Subject has participated in any previous study involving PROSTVAC, Sipuleucel-T or ipilimumab, regardless of whether the subject received PROSTVAC, Sipuleucel-T or ipilimumab
Both men and women and members of all races and ethnic groups will be included
High-Grade Neuroendocrine Carcinoma (HGNEC), any organ of origin, including a pathology of neuroendocrine features, in patients previously been treated with chemotherapy Although neuroendocrine tumors may be classified differently based on organ of origin, in the context of this protocol they are defined as high grade on the basis of either
Aggressive clinical behavior requiring previous treatment with chemotherapy even if histologic features such as the Ki67 index or mitotic rate corresponds with low or intermediate grade.
Histological, molecular or cytological confirmation of: Part A:
MDS:
Prior exposure to Astellas ASP2215.
myelodysplasia
Matched related HSCT
Mismatched related HSCT
SBRT or hypofractionated IMRT target size > 10 cm in maximum diameter (or greater than 100 cc in volume)
Renal failure requiring hemo- or peritoneal dialysis
Prior abiraterone and enzalutamide are permitted, but not required
The presence of lymphadenopathy greater than 3 cm in the short-axis diameter
Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
Renal failure requiring hemo-or peritoneal dialysis
For diseases other than Waldenstrom's macroglobulinemia (WM), presence of radiographically measurable presence of ? 1 lesion that measures ? 2.0 cm in the longest dimension (LD) and ? 1.0 cm in the longest perpendicular dimension (LPD)
Willingness and ability to comply with protocol-specified Pneumocystis jirovecii pneumonia (PJP) prophylaxis
Previous exposure to 5-AC (azacitidine) or decitabine
Active cases (within the past 12 months) of depressive disorder, manic episodes, and/or anxiety requiring active treatment with a selective serotonin reuptake inhibitor (SSRI); patients being treated with an SSRI for non-psychiatric indications (such as hot flashes) are allowed and should go through the appropriate washout
Actively receiving chemo-immunotherapy
For subjects with NMIBC, failure or intolerance of prior BCG therapy; failure is defined as evidence of TCC on cystoscopic examination and biopsy or cystoscopic examination and urine cytology at least 6 weeks from completion of last BCG or intravesical treatment
Subjects with NMIBC must be suitable for and willing to undergo a radical cystectomy at the completion of study therapy
Subjects with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder are not allowed
Part 2: HNSCC, with confirmed p53 mutations
Part 2: Ovarian or HNSCC, with confirmed p53 mutations
Angina pectoris,
Part 2:
The presence of or imminent occurrence of airway obstruction, unless tracheostomy in place.
Persistent toxicity from recent therapy that has not sufficiently resolved in the judgment of the study physician.
Must have select advanced cancers with specific genetic profiles
Concomitant second malignancies
Patients must have positive genetic testing for NF1 in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or a diagnosis of NF1 based on clinical National Institutes of Health (NIH) consensus criteria of at least one other diagnostic criterion in addition to the presence of a PN; NF1 mutation analysis will be performed on germline deoxyribonucleic acid (DNA) as described by Messiaen & Wimmer; histologic confirmation of tumor is not necessary in the presence of consistent clinical and imaging findings, but should be considered if malignant transformation of a PN is clinically suspected; additional criteria are as follows:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Patients must have at least one measurable PN, defined as a lesion of at least 3 cm measured in one dimension; patients who underwent surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable as per criteria above; measurability and suitability for volumetric MRI analysis of the target PN must be confirmed with the National Cancer Institute (NCI) Pediatric Oncology Branch (POB) prior to enrolling a patient; the target PN will be defined as the clinically most relevant PN, which has to be amenable to volumetric MRI analysis; PN will be classified as “typical PN” or “nodular PN” versus \solitary nodular PN\ prior to enrollment
The PN must be inoperable, defined as a PN that cannot be surgically completely removed without risk for substantial morbidity due to: encasement of or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN either causes morbidity or it is growing and has the potential to cause morbidity such as (but not limited to): head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, and lesions of the extremity that cause limb hypertrophy or loss of function or pain; PN growth will be defined as a >= 20% increase in PN volume within approximately 3 years prior to enrollment on this trial
Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
Supplementation with vitamin E greater than 100% of the daily recommended dose
Known ophthalmologic conditions, such as:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Subjects requiring vasopressor or mechanical ventilation.
The subject has tested positive for the Clostridium difficile toxin within 7 days of study entry.
Renal failure requiring hemo-or peritoneal dialysis
For patients with invasive breast cancer sentinel node biopsy (SLNB) must be performed; if SLNB performed prior to BCS and precision breast IORT, pathology report must confirm no evidence of nodal disease; SLNC may also be performed concurrently with BCS; if this is the case the pathology will not be available prior to IORT
Histologically or cytologically proven diagnosis of NSCLC or SCLC; in cases where the histology and cytopathology results are consistent with a carcinoma but immunohistochemistry stains are indeterminate and unable to support the lungs as the most likely site of origin, the diagnosis of NSCLC or SCLC may be established in conjunction with the radiographic and clinical picture
Monocular vision or has media opacities or any other condition that precludes monitoring of the retina or the fundus, or has a history of ophthalmology exam with retina or cornea abnormalities
Hematological values:
diagnosis of HGG, DIPG, low grade astrocytoma, medulloblastoma/PNET, ependymoma, neuroblastoma, RMS and tumours with ErbB deregulation
Study participants will be women who have gone through a bi-lateral oophorectomy procedure
Willingness to provide all biologic specimens as required by the protocol
If liposomal doxorubicin hydrochloride (DOXIL) is selected as the investigator’s choice chemotherapy:\r\n* Lifetime exposure to doxorubicin =< 240 mg/m^2 (or equivalent biologic dose if prior exposure to a different anthracycline)
Must have anti-measles immunity as demonstrated by serum immunoglobulin (Ig)G anti-measles antibody levels of >= 1.1 EU/ml as determined by BioPlex Measles IgG multiplex flow immunoassay
Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of the ovary
Resistant to all of the following: DOXIL, gemcitabine hydrochloride (GEM), topotecan hydrochloride (TOPA), and weekly paclitaxel (TAXOL); (NOTE: resistance is defined as either 1) less than a complete response to any chemotherapy regimen containing the agent in question [consider weekly TAXOL as a separate agent from every-three-week TAXOL], 2) serum CA-125 >= 2 x ULN within 180 days of last dose of chemotherapy containing the agent in question, confirmed by a second CA-125 [the second CA-125 does not have to be within 180 days of chemotherapy], or 3) CT or PET/CT evidence of cancer recurrence/progression within 180 days of last dose of chemotherapy containing the agent in question; [for example, if a patient previously received carboplatin and GEM, had a complete response, and had initial evidence of relapse > 180 days after the last dose of GEM, that patient would not be considered resistant to GEM])
On anticoagulation and unable to discontinue temporarily
Subject in whom the anatomic application site is equal to or less than 47cm²; and
Subject in whom the bleeding flux from the identified lesion is > 0.000040[g/(cm²•s)] and ?0.013[g/(cm²•s)].
Subject with known sensitivity to starch or starch-derived materials;
Subject with poor blood glucose control as per glycosylated hemoglobin > 9%.
Subject undergoing a cardiac procedure in which there is no aortic anastomosis or aortotomy suture line to evaluate using the bleeding severity scale (i.e., not for treatment at the distal coronary artery bypass graft anastomosis);
All races and ethnic groups are eligible for this study
INCLUSION CRITERIA FOR STRATUM C: Diagnosis of hypermutated brain tumors\r\nPatients with brain tumors and increased tumor mutation burden as determined by\r\n* Confirmed diagnosis of CMMRD syndrome by Clinical Laboratory Improvement Act (CLIA)-certified germline gene sequencing OR\r\n* Confirmation of high mutation burden by whole genome/exome sequencing performed in a CLIA-certified laboratory and/or the use of Foundation One next generation sequence panel or another CLIA approved targeted sequencing lab with publicly available correlations between number of mutations found in the panel and mutations per megabase and/or genome; for protocol purposes a high mutation burden will be defined as at least 100 non-synonymous coding-region mutations by whole exome/genome sequencing (well above two standard deviations of the number of median similar mutations described in pediatric CNS cancers) AND/OR a high tumor mutation burden (TMB) or intermediate TMB based on the reporting parameters of the panel; TMB parameters provided for the Foundation One reports are high tumor mutation burden is >= 20 mutations per megabase or intermediate TMB is between 6 to 19 mutations per megabase\r\n* Confirmed diagnosis of Lynch syndrome by CLIA-certified germline gene sequencing; patients with Lynch syndrome will not be accounted for in primary objective unless their tumors are determined to have the minimum number of mutations described above but they will still be eligible for this study\r\n* Low-grade tumors in patients with CMMRD or Lynch syndrome do not have to reach the threshold of 100 mutations for study inclusion
Inclusion of participants with confirmed positive serology of at least one auto-antibody panel (anti-nuclear antibody, anti-double stranded DNA, cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic antibody) at screening should be discussed between Sponsor and investigators, and if judged clinically relevant could be referred to a specialist (Rheumatologist) to exclude an underlying auto-immune disease
Baseline QTc interval > 470 milliseconds (ms), baseline resting bradycardia <45 beats per minute (bpm), or baseline resting tachycardia >100 bpm
Histologically or cytologically confirmed diagnosis of metastatic NSCLC according to the 7th edition of the AJCC Cancer Staging Manual. In addition, the NSCLC must harbor an ALK rearrangement, as assessed using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above is not locally available, a test to confirm ALK rearrangement must be performed by a Novartis designated central laboratory. Patients must wait for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib
At least one extracranial measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
Patient is receiving unstable or increasing doses of corticosteroids.
Subjects less than 18 years old are being excluded in this study as melanoma is extremely uncommon in this age group and insufficient data are available in adults using dendritic cell therapy to assess potential risk in subjects less than 18 years old. Participation of women and minorities is encouraged, although it is recognized that melanoma is much more common in the Caucasian population
Study subjects with known chronic infection with HIV, hepatitis B or C, since these infections may interfere with the evaluation of vaccine-induced immune responses. Infectious disease testing will be performed whenever a study subject exhibits clinical signs of infection or to confirm a history of infection. Testing will also be performed for all study subjects undergoing leukapheresis, as required by the blood bank for autologous blood products (standard donor transmissible disease testing)
Study subjects previously treated with one of the peptides used in this trial, melanoma protein vaccine, melanoma whole cell vaccines, or with Montanide are not eligible
Lack of availability of study subject for immunological and clinical follow up assessments
Study subjects < 18 years of age who cannot undergo the leukapheresis procedure, do not meet the disease staging and/or the size criteria for frequent blood donations
CLL ARMS (ARM A and ARM C) FOR COMBINATION THERAPY INCLUDING IDELALISIB ARM:
Is chronically taking a sensitive CYP3A substrate or a CYP3A substrate with a narrow therapeutic index and cannot be switched to an alternative agent at least 7 days prior to study initiation that in the opinion of investigator/treating physicians precludes utilization of idelalisib
Meet standard criteria for RIT:\r\n* < 25% marrow involvement with FL\r\n* No evidence of myelodysplasia
Willing to travel to a radioimmunotherapy site for Zevalin, if necessary
Follicular grades IIIA or IIIB are not eligible
Current treatment with therapeutic doses of Coumadin-derivative anticoagulants (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed)
CD22 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry; the choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patent; in general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
Patients who have undergone a gross total resection for recurrence will be eligible, and MLA will be directed at treating a peritumoral margin of 0.5-1 cm surrounding the resection cavity to disrupt the blood brain barrier (BBB) and potentially increase access of MK-3475 to the peritumoral infiltrating glioma cells
Presence of brainstem lesions or lesions that are less than 5 mm from the hypophysis or cranial nerves
Histologically or cytologically confirmed stage III or IV HNSCC oral cavity, hypopharynx, oropharynx, larynx (excluding p16 or human papillomavirus [HPV]-positive oropharynx primaries and sinonasal primaries)
Patients with a history of a metabolic disorder including documented defect in urea metabolism (including documented history of gout), carnitine deficiency (primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency), fatty acid metabolism, beta-oxidation defects, pyruvate carboxylase deficiency, mitochondrial function, porphyria, or treatment refractory nephrolithiasis
Active bowel obstruction, ileus, or active or remote pancreatitis
Conditions that may increase the risk of the diet or significantly reduce compliance (i.e. cognitive impairment, frank dementia, etc)
Patient inability to complete baseline screening 3-day diet record
Principal Inclusion criteria:\n\n          -  Aged at least 18\n\n          -  The presence of a solid malignant tumour that is not considered appropriate for\n             further standard treatment\n\n          -  Module 1 and 2 Part B study expansions, and Module 3: patients must have a tumour at\n             least 1 cm in size that can be measured using a CT or MRI scan\n\n          -  Module 1 Part B Study expansion: second line lung adenocarcinoma with ATM deficient\n             tumours.\n\n          -  Module 2 Part B All - No previous treatment with PARP inhibitor.\n\n          -  Module 2 Part B1 Study expansion: advanced gastric adenocarcinoma (including GEJ)\n             patients with ATM deficient tumours\n\n          -  Module 2 Part B2 Study expansion: advanced gastric adenocarcinoma (including GEJ)\n             patients with ATM proficient tumours\n\n          -  Module2 Part B3 Study expansion: Second or thrid line HER2 negative breast cancer\n\n          -  Module 2 Part B4 Study expansion: Second or third line triple negative breast cancer\n             (TNBC) Module 3: advanced recurrent or metastatic non-small cell lung cancer, or head\n             and neck squamous cell carcinoma\n\n        Principal exclusion criteria\n\n          -  A diagnosis of ataxia telangiectasia\n\n          -  Prior exposure to an ATR inhibitor\n\n          -  Bad reaction to AZD6738\n\n          -  Module 1: Contra-indicated for treatment with carboplatin\n\n          -  Module 2: Contra-indicated for treatment with olaparib\n\n          -  Module 3: Contra-indicated for treatment with MEDI4736
Platelets >= 100,000/mm^3 transfusion independent (no platelet transfusion one week prior to enrollment)
Subjects who are homozygous for the UGT1A1*28 allele
Clinical and phenotypic verification of B cell CLL and measurable disease; immunophenotyping of the leukemic cells (blood or marrow) must demonstrate a monoclonal (or light chain positive) with immunophenotype consistent with B cell population (e.g., co-expressing cluster of differentiation [CD]19 and CD5)
Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia
Unrelated donors donating outside of the United States of America (USA)
Stratum I
Stratum II
Stratum III
Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as
PLT <20 x109/L (20,000/?L) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
Total protein <55 g/L or substitution dependency
Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)
Stratum IV
AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
Stratum V
All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
Stratum I
LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
Stratum II
Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
Stratum III
Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
Stratum IV
Stratum VI
Potassium (K) should be within the range of >= 3.6 mEq/L
Blood urea nitrogen (BUN): 10-20 MG/DL
Gamma-glutamyl transpeptidase (GGT): 0-45 U/L
Subjects being treated with a monoamine oxidase inhibitor (MAOI), or drug which has significant MAOI activity (e.g., meperidine, linezolid, methylene blue) within 3 weeks prior to screening
Use of UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, and ketoconazole
Lack of availability of a patient for immunological and clinical follow-up assessment
Acceptable hematologic status (without growth factor support or transfusion dependency):
Elevated Troponin 1 levels at screening or known to have persistently elevated brain natriuretic peptide (BNP).
Serious arrhythmia,
Presence of aneurisms of the ascending aorta or aortic stress.
Major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's discretion.
Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4 (CYP)3A4.
Drugs which are exclusively or primarily eliminated by UDP glucuronyltransferase 1A1 (UGT)1A1.
Drugs which are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window; or which are strong inhibitors of drug transporter MDR1.
Subjects treated with pemetrexed (pemetrexed disodium) previously will be eligible only if 8 weeks have elapsed between the last dose of pemetrexed and the date of surgery
Patients with porphyria or hypersensitivity to porphyrin or porphyrin-like compounds
Patients must have measurable contrast-enhancing supratentorial tumor (>= 0.2 cc [current resolution of MRSI is 0.108 cc]) in a region amenable to MRSI
Bilirubin =< 2 x UNL
Both men and women, and members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions
Patients taking any of the following category I drugs that are generally accepted to have a risk of causing Torsades de Pointes =< 7 days prior to registration (for cohort 2a and 2b [belinostat cohort] only)\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, sotalol, ibutilide, dofetilide\r\n* Erythromycin, clarithromycin\r\n* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Ongoing need for pharmacological immunosuppression, including steroids
Meets clinical diagnostic criteria for NF2 or genetically conformed NF2
At least one volumetrically measurable and >= 1 cc NF2-related VS (histological confirmation not required)
Both men and women of all races and ethnic groups are eligible for this study
Previous treatment with an agent that blocks adrenal androgen synthesis (e.g. abiraterone acetate, TAK-700, TOK-001, ketoconazole) or second generation androgen receptor (AR) antagonists (e.g., BMS 641988, ARN-509,TOK-001)
Structurally unstable bone lesions suggesting impending fracture
Medical contraindications to stopping aspirin, Coumadin or other anticoagulants prior to image-guided tumor biopsies; follow institutional guidelines when determining drugs to avoid and length of washout
International Prognostic Index must be documented:\r\n* ECOG performance status >= 2 (1 point)\r\n* Age >= 60 (1 point)\r\n* >= 2 extranodal sites (1 point)\r\n* Lactate dehydrogenase (LDH) > upper limit of normal (1 point)\r\n* Ann Arbor stage III or IV (1 point)
Patients who are reported to be of direct Asian-Pacific (China, Japan, Taiwan, Singapore, Republic of Korea, and Thailand) ancestry
Disease confined to locoregional site and can be encompassed in a stereotactic body radiosurgery “portal”
Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A) OR any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B)
Unable to be treated with a muscle blockade agent (e.g. pancuronium bromide, atricurium, cisatricurium, etc.)
Have Q-T intervals greater than 550 ms unless treated with an Accysync model 72 synchronization system controlling the NanoKnife system’s output pulses
Receive non-conventional fractionation schedules, such as stereotactic radiation (5 fractions or less) or received higher than 54 gray (Gy) delivered conventionally
Planned treatment with the LR-IUD for CAH or grade 1 EC by primary physician
PHASE I: If post allogeneic HCT: Confirmed CD19+ leukemia recurrence defined as >= 0.01% disease by Seattle Children’s Hospital (SCH) or University of Washington (UW) Pathology Department following allogeneic HCT
PHASE I: For the post allo-HCT cohort, chimerism analysis must demonstrate > 95% either donor or recipient in peripheral blood CD3 cells, must be done within 1 month of enrollment (no mixed chimerism are eligible)
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Subject has tolerated prior dose of modified \r\nT cell infusion without experiencing a dose limiting toxicity OR if patient did have a dose limiting toxicity (DLT), they have fully recovered back to baseline
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Subject has evidence of persistence of leukemic cells OR has CD19+ B cell recovery detected within 1 year of initial T cell infusion
Previous immunization against CT7, MAGE-A3, other cancer-testis antigens, or WT1
Willing to sign a durable power of attorney
Subjects must be co-enrolled in 03-C-0277
Markedly decreased visual acuity if attributed to other causes than GBM.
Patients must have had histologic verification of an extracranial germ cell tumor that is not a pure teratoma (mature or immature), pure germinoma, or pure seminoma
INCLUSION - PROCUREMENT: Either previously infected with varicella zoster virus (VZV; chicken pox) or previously vaccinated with VZV vaccine
INCLUSION - TREATMENT: Available autologous transduced cytotoxic T lymphocytes with ? 20% expression of GD2 CAR and killing of GD2-positive targets ? 20% in cytotoxicity assay
In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, are eligible if they • have relapsed and/or refractory disease, OR are>=65 years of age and not candidates for or have refused standard chemotherapy. Subjects with multiple myeloma are eligible if they have progressed despite therapy with an alkylating agent, proteasome inhibitor, and immunomodulatory agent, either as individual regimens or in combination. Subjects with NHL are eligible if they have received at least two prior lines of systemic therapy, including at least one line of immunochemotherapy with an anti-CD20 antibody (if their tumor expresses CD20). In Part 2, the NHL cohort will separately enrol subjects with double- and triple hit lymphoma, so that a minimum of 10 subjects with this subset of disease will be enrolled. To be eligible for this sub-cohort, tumor sample from the subject must demonstrate rearrangement and/or overexpression of MYC and either BCL2 and/or BCL6 genes. Evaluation of double- or triple-hit status may be performed via appropriate local testing, and the determination of double- or triple-hit diagnosis will be at the discretion of the investigator and GSK Medical Monitor.
Subject must be stable enough to be expected to complete dosing through the DLT observation period as assessed by the investigator.
Ability to comply with dietary and tobacco/alcohol abstinence requirements.
Cumulative anthracycline exposure greater than 450mg/m^2 doxorubicin equivalents prior to enrollment
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Known sensitivity to conductive hydrogels
COHORT B: biopsy proven light chain amyloidosis with organ involvement requiring therapy
Previously untreated
Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma only
HEALTHY VOLUNTEER BLOOD DONORS
Subjects must either have a CA 19-9 value > the institutional upper limit of normal (ULN) on two separate checks at least 2 weeks apart OR have had an R1 resection margin OR N1 nodal disease regardless of CA 19-9 level
Recipient of a myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant (HSCT):\r\n* Conditioning regimen to be prescribed at investigator’s discretion, but will be prospectively defined as myeloablative or non-myeloablative
Cirrhosis
Prior exposure to panitumumab in any setting
Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab
Patient must complete all required tests in section 4.
Post exploratory thoracotomy must be done > 3 weeks prior to study registration or patient did not have post exploratory thoracotomy.
Prior radiotherapy to thoracic area.
Gleason score =< 6 (neither architectural pattern =< 3)
Vitamin D3 supplementation at > 2,000 IU daily
Primary hyperparathyroidism (serum calcium [Ca] > 10.5 mg/dL and parathyroid hormone (PTH) > 72 pg/ml)
Lithium medication
Breast size exceeding the technical limitation of daily set-up reproducibility. This may be center-specific and will be assessed at the discretion of the treating center.
Women with post-surgical temporary breast expanders will require individual assessment. Depending on the manufacturing product and other treatment planning-specific details the patient may be eligible or may be deemed ineligible, as determined by treating investigator.
Collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
Presence of either an FGFR3 mutation or FGFR3 over-expression within bladder tumor tissue. FGFR3 mutations in exons 7, 10, and 15 will be assessed by polymerase chain reaction (PCR)-single strand conformation polymorphism (PCR-SSCP) sequencing analysis utilizing the CertNDx® molecular grading assay performed in the Clinical Laboratory Improvement Amendments (CLIA)-certified Predictive Biosciences™ laboratories; FGFR3 over-expression will be assessed by standard immunohistochemistry (IHC) analysis performed within the Indiana University Simon Cancer Center Immunohistochemistry (IHC) Core Lab
Documented BCG-refractory disease defined as failure to achieve a tumor free state after at least 2 prior induction courses of intravesical BCG therapy; NOTE: For patients with residual non-invasive tumors (i.e. Ta, T1, Tis) after an initial 6-week induction course of intravesical BCG therapy, a second induction course of intravesical BCG therapy is required; patients with persistent non-invasive tumors (i.e. Ta, T1, Tis) despite an initial 6-week and second induction intravesical BCG therapy course are considered BCG-refractory and, therefore, eligible for study; patients with non-invasive tumor recurrences (i.e. Ta, T1, Tis) after only an initial 6-week induction course of intravesical BCG therapy are considered BCG-resistant and not eligible for study until persistent non-invasive tumor (i.e. Ta, T1, Tis) is demonstrated after a second induction course of intravesical BCG therapy has been administered; there is no maximum limit on the number of prior BCG therapy courses; in addition, there is no maximum limit on the number of prior non-BCG intravesical therapy courses (i.e. gemcitabine, valrubicin, interferon, mitomycin C, etc.)
Medically unfit to undergo cystectomy or electively choosing to forego cystectomy
PART I: Naive to trastuzumab (Herceptin), pertuzumab (Perjeta) and lapatinib (Tykerb), ado-trastuzumab emtansine (Kadcyla) or other HER2-directed therapies
PART I: Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery
PART II: Baseline LVEF by 2D echocardiogram >= 55%
PART II: ANC >= 1000 cells/mm^3
PART II: ALC >= 500 cells/mm^3
PART II: Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery
Pregnant women are excluded from this study because AdHER DC vaccine may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AdHER DC vaccine, breastfeeding should be discontinued if the mother is treated with AdHER DC vaccine
Symptomatic neurologic disease compromising instrumental activities of daily living or requiring medication
Leukemia participants aged 1 to 5 years with induction failure and favorable cytogenetics (i.e., ETV6-RUNX1 or hyperdiploidy defined as deoxyribonucleic acid [DNA] index >= 1.16 or modal chromosome number >= 51)
Patient must not have any active infection or concurrent illness obscuring toxicity or dangerously altering drug metabolism
Part B6 only: Participants must have squamous NSCLC; documented evidence of an activating molecular aberration of the PI3K/mTOR pathway
Have serious preexisting medical conditions
ANC >/= 800/mm3, Cohort 8 (PTCL): ANC >/= 1000/mm3
QTcF (Fridericia Correction Formula) > 480 on 2 out of 3 EKG’s (if first EKG is =< 480, no need to repeat, if first electrocardiogram [EKG] is > 480 repeat twice for a total of 3 EKG’s)
COHORT B, GROUP 5: MESOTHELIOMA: Patients must have histologically or cytologically proven diagnosis of malignant mesothelioma; both pleural and peritoneal mesothelioma are allowed
Methylation CHFR gene promoter in archival tissue biopsy\r\n* A patient will be considered to have CHFR methylation if he/she has a methylation specific band on methylation-specific PCR (MSP) for the CHFR gene or lack of expression by IHCs; MSP primers are publicly reported and developed at Oncomethylome in a Clinical Laboratory Improvement Amendments (CLIA) laboratory; patients who test positive for MSI at any of the 5 loci will be considered MSI+ as per standard convention or who have absent expression of mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), or PMS2 postmeiotic segregation increased 2 (PMS2) by IHC\r\n* Results from another institution’s CLIA-certified MSI/IHC will be considered for eligibility\r\n* Patients with microsatellite instability and a family history supportive for a possible diagnosis of hereditary nonpolyposis colorectal cancer will be referred to a genetics counselor for further evaluation and recommendations
Patients’ melanoma must be positive for both tyrosinase and human leukocyte antigen (HLA)-A2 per Loyola University Medical Center pathologic review from fine needle aspiration (FNA)/core/excisional biopsy of lesion
Special classes of subjects such as fetuses, pregnant women, children, prisoners, institutionalized individuals, or others who are likely to be vulnerable
Metastatic or unresectable measurable cancers that express mesothelin; as in other protocols conducted by Dr. Hassan in the National Cancer Institute (NCI), epithelial mesotheliomas and pancreatic cancers do not need to be assessed for mesothelin expression since all of these tumors have been shown to express mesothelin; other metastatic or unresectable cancers must be shown to expresses mesothelin as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) or immunohistochemistry on tumor tissue; bi-phasic mesotheliomas must express mesothelin on greater than 50% of the cells in the epithelial component; diagnosis will be confirmed by the Laboratory of Pathology, NCI
Willing to sign a durable power of attorney
Subject’s must be co-enrolled in protocol 03-C-0277
Involved/un-involved light chain ratio must be < 100
In addition to having SMM, patients must also be classified as “high-risk SMM” per Mayo Clinic or Spanish Programa Espanol de Tratamientos en Hematologia (PETHEMA) criteria; NOTE:\r\n* Criteria set forward by Rajkumar, Landgren, Mateos may also be used to define high risk disease, namely clonal bone marrow plasma cells >= 10% and any one or more of the following:\r\n** Serum M protein >= 30 g/L\r\n** IgA SMM\r\n** Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes\r\n** Serum involved/uninvolved FLC ratio >= 8 (but < 100)\r\n** Progressive increase in M protein level (evolving type of SMM; increase in serum M protein by >= 25% on 2 successive evaluations within a 6-month period)\r\n** Clonal bone marrow plasma cells (BMPCs) 50%-60%\r\n** Abnormal PC immunophenotype (>= 95% of BMPCs are clonal) and reduction of >= 1 uninvolved immunoglobulin isotypes\r\n** t(4;14) or del(17p) or 1q gain\r\n** Increased circulating plasma cells (PCs)\r\n** MRI with diffuse abnormalities or 1 focal lesion\r\n** PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction
An artificial implant that cannot be easily removed (e.g., heart valves, prosthetic hips or knees, or other devices), which could allow a nidus of infection.
Known cardiac valvular disease (e.g. bicuspid aortic valve) or arterial aneurysm(s) that may allow a nidus of infection.
Currently using antibiotics and/or anti fungal agent (however, topical antibiotics are permitted).
5-FC
5-FU
Appropriate contraception in both genders
Proteinuria dipstick > 3+ or >= 2 gm/24 hours
Granulocytes ? 1,500/ml
Clinical stages T1-T2c N0 M0 as staged by the treating investigator. (AJCC Criteria 7th Ed.- appendix III).
Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material; Gleason score must be in the range of 2-7. > 6 cores are strongly recommended.
Scheduled for induction BCG intravesical therapy
Willing and able to give blood sample
Willing and able to fill out a pill diary to ensure compliance
Unwillingness to undergo RPFNA
Hypokalemia or hypomagnesemia if it cannot be corrected
Up to 4 lesions may be included; for a single lesion the sum of three orthogonal diameters can be no more than 20 cm; for multiple lesions, no lesion can have a sum of orthogonal diameters greater than 15 cm
Both peripheral and central tumors are accepted for this trial
Both men and women and members of all races and ethnic groups are eligible for this trial
CD4 lymphocyte count or other T lymphocyte subset count will not be used to determine eligibility
Prior immune therapy (e.g. related vaccinia and fowlpox vaccines or antigen-specific peptides) is allowed
EXPANSION COHORTS ONLY
CD19 and/or CD22 must be expressed on at least 50% of the lymphoblasts
Human anti-mouse antibody (HAMA) levels of > 100 ug/ml or human ricin antibodies (HARA) > 100 ug/ml HARA after cycle 1
Neutrophils >= 1500
Must be willing to have an Ommaya reservoir placed and a candidate for an Ommaya reservoir placement
Concurrent external beam radiation is not allowed with the exception of palliative radiotherapy to a localized region for pain control (i.e. vertebral disease, pelvis, etc) which IS allowed while on the study protocol \r\n* NOTE: patients may need a CSF flow study at the discretion of the treating principal investigator; if a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment
Subjects with neurofibromatosis type 1 (NF1) are also eligible
No evidence of dyspnea at rest
No exercise intolerance
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Diagnosis of advanced RCC associated with HLRCC (cohort 1) or sporadic/non-HLRCC papillary RCC (cohort 2)
Subjects must have relapsed after at least one prior purine analogue-containing regimen (fludarabine, cladribine or pentostatin), OR at least two non-purine analogue containing regimens
Neurotropism is identified pathologically by the presence of melanoma cells around nerve sheaths (perineural invasion) or within nerves (intraneural invasion).
Occasionally, the tumour itself may form neuroid structures (termed 'neural transformation'; this is also regarded as neurotropism)
\normal\-looking nerves that appear to be \entrapped\ within the tumour should not be regarded as neurotropism
Available for follow up
Albinism
Participation in other clinical trials with the same primary endpoint
Pathologically confirmed malignancy for which high-dose rate brachytherapy is appropriate as a component of their therapeutic regimen
Any patient or tumor/anatomical factors that may prevent brachytherapy apparatus from being properly and safely inserted and positioned and from radiation therapy being administered per American Brachytherapy Society (ABS) guidelines
Evidence of HCL by flow cytometry, reviewed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for CD19, CD22, CD20, and CD11c
BMBx consistent with HCL, reviewed by Laboratory of Pathology, NCI; BMBx may be negative in HCLv in patients with increasing peripheral blood HCLv cells and spleen size
Symptomatic splenomegaly
DONOR: HLA-matched sibling cord blood exclusions: Any cord blood units without full maternal testing and negative results for hepatitis A, B, C, HIV, and HTLV-1 viruses; any additional available virology results on the unit itself will be reviewed but are not mandated, complete or always available; cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
DONOR: Unrelated Umbilical Cord Blood: The UCB unit with the least HLA disparity (with the patient) will be selected first (i.e., selection priority is 6/6 match > 5/6 match> 4/6 match); additional UCB units then may be selected to achieve the required cell dose; if a second unit is required, this unit will be the unit that most closely HLA matches the patient and meets minimum size criteria outlined below of at least 1.5 x 10^7 TNC/kg (ie a smaller more closely matched unit will be selected over a larger less well matched unit as long as minimum criteria are met)
DONOR: Unrelated Umbilical Cord Blood: Any cord blood units without full maternal testing and negative results for hepatitis A, B, C, HIV, and HTLV-1 viruses; any additional available virology results on the unit itself will be reviewed but are not mandated, complete or always available; cord blood units are presumed to be CMV negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
Prior myeloablative transplant containing full dose TBI (greater than 8 Gray [Gy])
Potassium within normal range (supplementation is allowed)
Calcium within normal range (supplementation is allowed)
Magnesium within normal range (supplementation is allowed)
No presence of left bundle branch blocks (LBBB)
No currently active diarrhea that may affect the ability to absorb ZD6474
No other active cancers
Patients must be treated with a standard accepted chemotherapy regimen for rhabdomyosarcoma (for example, according to Intergroup Rhabdomyosarcoma Study [IRS]-IV, IRS-V, or future IRS study)
If tissue diagnosis is not feasible for any reason, such as undue risk to the patient to acquire tissue diagnosis, the following will be accepted as confirmed AR-PCNSL diagnosis:\r\n* Positive brain fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) and\r\n* EBV detected in the cerebrospinal fluid (CSF) using polymerase chain reaction (PCR)
Ability to understand and willing to provide informed consent\r\n* If patient unable to understand informed consent, a previously designated durable power of attorney for healthcare or an individual with legal authority may substitute in this capacity\r\n* Assignment of a durable power of attorney for healthcare if not already done
Current symptom of keratitis or retinopathy at >= grade 2
Known history of allergy or intolerance which, in the opinion of the investigator, was an unacceptable adverse reaction attributed by the investigator to any prior anti-neoplastic therapy specifically targeting vascular endothelial growth factor or the VEGF receptor – i.e. pazopanib (Votrient), bevacizumab (Avastin), sorafenib (Nexavar), sunitinib (Sutent), axitinib (Inlyta), etc.
Non-healing wounds on any part of the body.
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.
Has an immediate need for external beam radiotherapy
AUTOLOGOUS APHERESIS: Known primary immunodeficiency
TREATMENT WITH SJCAR19: Available SJCAR19 product with >= 15% expression of the CD19-chimeric antigen receptor (CAR), and killing of CD19+ targets >= 20% in an in vitro cytotoxicity assay
TREATMENT WITH SJCAR19: Agreement to participate in long-term follow-up on protocol NCT00695279
Pathologic stages T2-T3b, N0-Nx-N1, M0-1 as staged by the pathology report (American Joint Committee on Cancer [AJCC] criteria 8th edition [Ed.])
Members of all races and ethnic groups are eligible for this trial
Creatine kinase (CPK) =< 1.5 x ULN.
Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive study drugs) is permitted. If re-enrolled, the subject must be re-consented. Only the screening procedures performed outside of protocol-specified timing must be repeated.
Uncontrolled asthma (defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: Daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function [peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1)] without administration of a bronchodilator that is < 80% predicted or personal best [if known]).
Prisoners or subjects who are involuntarily incarcerated.
Untreated symptomatic hydrocephalus determined by treating physician.
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however, they must still undergo pregnancy testing
Treatment directed against the melanoma (eg, chemotherapy, targeted agents, biotherapy, limb perfusion) that is administered after a prior complete resection other than adjuvant radiation after neurosurgical resection and IFN for resected melanoma
Able to take aspirin (81 or 325 mg) daily or for thromboprophylaxis with lenalidomide.
Active or chronic corneal disorder, including but not limited to the following: Sjogren’s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, acquired monocular vision, and any preexisting active conjunctival disease
Required used of folate-containing supplements (e.g. folate deficiency)
Low risk T1 tumors that fulfill all of the following - size < 4 cm, lack of lymphovascular invasion and well differentiated histology, are excluded.
At time of registration and within 4 weeks prior to initiating on-protocol treatment: Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L\r\n* May be waived on a case-by-case basis for patient populations recognized to have normal baseline values below this level.
All races and ethnicities are eligible and no upper limit of age is specified
Measurable metastatic gastrointestinal epithelial cancer with at least one lesion that is resectable for TIL generation, plus one other lesion that can be measured.
Blood sample submitted for additional testing within 7 days of TIL harvest per national blood banking standards (e.g., anti-human T-cell lymphotropic [HTLV]-I/II virus, anti-T. cruzi, West Nile virus nucleic acid testing [NAT], anti-cytomegalovirus [CMV], rapid plasma reagin [RPR]), for purposes of proper handling and storage.
Willing to sign a durable power of attorney.
BM with increased fibrosis (reticulin stain > 1/3).
Seropositivity for HTLV-1.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Carcinomatous meningitis
Experienced an immune-related adverse event (irAE) that led to permanent discontinuation of prior immunotherapy
Lymphocyte count >= 0.5 × 10^9/L.
Have a target lesion/s deemed suitable by the treating physicians for stereotactic body radiation therapy (SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) 1-3 non overlapping sites in the H&N region OR  b) metastatic lesions outside the head and neck (H&N) region in the lung or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with SBRT; if the site/s of SBRT were previously radiated to > 50Gy, there should be > 6 month time interval between the last dose of radiation and the start of SBRT
Have the ability to tolerate required SBRT-related procedures (eg: lie flat and hold position for treatment) as determined by the treating physician
Should be performed within 10 days of treatment initiation: serum bilirubin ? 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Has a target lesion/s for SBRT that demonstrate any of the following:\r\n* located within 2 cm of the proximal bronchial tree\r\n* > 5 cm (> 50 cc) in greatest dimension
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
Prisoners or subjects who are involuntarily incarcerated
Peripheral blood blast count =< 30,000 at time of eligibility assessment (within 7 days of start of therapy); blast counts that increase beyond 30,000 after a patient is deemed eligible will not disqualify the patient
ALL patient refractory to their first induction only or their first relapse, will be excluded; they must be refractory to at least one salvage therapy, or relapse after first salvage, to be eligible
Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
Diagnosis of MDS according to WHO 2016 criteria
Pathologically confirmed diagnosis of IDH2-mutant acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML)\r\n* IDH2 mutations will include any IDH2 R140 or R172 alterations\r\n* Eligibility and enrollment will be based on local IDH2 mutational testing performed at any center. The presence of an IDH2 mutation at the time of initial diagnosis or any other time thereafter is necessary and sufficient. The presence of an IDH2 mutation at time of enrollment is not necessary for the purposes of eligibility
Adequate peripheral nervous system (PNS) function defined as:\r\n* PNS toxicity < grade 2
Cumulative anthracyclines must not exceed 450 mg/m^2 doxorubicin equivalents following completion of treatment on protocol; therefore for patients receiving one course on protocol cumulative anthracyclines must be less than or equal to 400 mg/m^2 doxorubicin equivalents at the time of enrollment
Prior treatments with TAK-700/Orteronel, abiraterone, ketoconazole, or enzalutamide
Subjects with delayed healing of wounds, ulcers, and/or bone fractures
Subject has 1 first-degree relative (FDR; defined as parents, offspring or siblings) with T1D AND A1C value > 6.5% or
Subject has 2+FDR with T1D
No prior stereotactic radiosurgery (SRS) to the lesions which will be treated on protocol.
NY-ESO-1 positive by immunohistochemistry (IHC) utilizing commercially available NY-ESO-1 antibodies
Must be willing and able to undergo three research PET scans
Active or recent herpes simplex virus (HSV) infection or cytomegalovirus (CMV) based on symptoms with positive swab culture and/or positive Immunoglobulin M (IgM) screening, which would complicate the post-conditioning period
Documented malabsorptive syndromes including enteropathies, gastroenteritis (acute or chronic) or diarrhea (acute or chronic)
TARGET POPULATION
Symptomatic multiple myeloma (MM) having progressed on >= 2 prior therapies including proteasome inhibitor (i.e. bortezomib, carfilzomib ixazomib), immunomodulatory drug (i.e., thalidomide, lenalidomide, pomalidomide), and daratumumab or other CD38 targeting monoclonal antibody. Subjects who are refractory to proteasome inhibitors or ONC201 are eligible. Subjects must not be candidates for treatment regimens known to provide clinical benefit to be eligible for this study
Corrected serum calcium >= 14 mg/dl within 2 weeks of enrollment (despite appropriate measure such a short course of steroids, bisphosphonates, hydration, and calcitonin)
Kyphoplasty or vertebroplasty within 1 week of enrollment
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
Be eligible and reasonably fit to undergo potentially curative resection
Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula
Inoperable on the basis of co-existent medical problems
Prior prophylactic cranial irradiation (PCI) is allowed
Ability to operate the NovoTTF-200A device independently or with caregiver aid
Previous clinical trial enrollment is allowed
History of prior whole brain radiotherapy (WBRT) other than prophylactic cranial radiation. Prophylactic cranial radiation with a maximum dose of 25 Gy delivered as 10 fractions is allowed. WBRT in excess of 25 Gy (anything over 25 Gy) is not allowed
Known allergies to medical adhesives or hydrogel
Philadelphia chromosome (Ph)-positive ALL
Agreement to be contacted by phone or e-mail for health status evaluation for up to 3 years
One previously unirradiated lesion amenable to 8 Gy x 3 radiotherapy based on dosimetric organ tolerance AND another unirradiated measurable lesion (per irRECIST) outside of the radiation field.
Immunotherapy-naive.
Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded
Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
Known intolerance to the required dose and schedule of steroid therapy as determined by the investigator
Transaminases < 3 x normal at the time of transplant.
Subjects must be co-enrolled in protocol 03-C-0277
Non-secretory MM or known amyloid light-chain (AL) amyloidosis
Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
A skull defect (such as, missing bone with no replacement)
Known hypersensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
Previous liver-directed treatments including chemoembolization, radiosphere, hepatic arterial perfusion, or drug-eluting beads
Occlusion of the main portal vein, or inadequate collateral flow around an occluded portal vein as determined by angiography
Significant arteriovenous shunt identified on angiography of the hepatic artery
Daily smoker using 10 or more cigarettes per day
Answer > 0 on suicidality question of Patient Health Questionnaire (PHQ-9) Depression Scale
Diagnosis of bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD) and or adult attention deficit hyperactivity disorder (ADHD)
Generalized Anxiety Disorder (GAD)-7 scale of 15 or higher
Expired breath carbon monoxide < 10
Abnormal electrocardiogram (EKG) (study physician discretion)
Abnormal complete blood count, comprehensive metabolic panel, urine, hemoglobin (Hgb) A1c (study physician discretion)
Positive urine toxicology-5 screen (methamphetamine, cocaine, opiates, benzodiazepines, tetrahydrocannabinol [THC])
Subjects with concomitant second malignancies
IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the principal investigator (PI).
Participants must not have ocular melanoma
Total serum calcium (corrected for serum albumin) or ionized calcium >= lower limit of normal (LLN)
Serum potassium >= LLN
Serum sodium >= LLN
Tolerate a 15 g ascorbate infusion (screening dose)
G6PD (glucose-6-phosphate dehydrogenase) deficiency
Actively receiving insulin or requiring fingerstick glucose monitoring at time of ascorbate infusion (unless an exception is granted by the investigational new drug [IND] sponsor, medical monitor, and the principal investigator [PI])
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Adequate renal function, as indicated by modified Cockcroft-Gault equation (estimated creatinine clearance [eCCR] with the use of ideal body mass [IBM] instead of mass)
Richter's transformation confirmed by biopsy
Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction < 50%
Outpatients with MPE undergoing IPC placement
Sufficient mental capacity to provide informed consent and answer Short-Form Six-Dimension health index (SF-6D) and Borg score questions
Significant proteinuria at baseline (> 500 mg/ 24 h, or > 2+ on spot analysis)
Known human papillomavirus (HPV) status
Subjects receiving monoamine oxidase (MAO)-inhibitors (MAOI) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
INCLUSION - ENROLLMENT: Her-2 3+ or fluorescence in situ hybridization (FISH) ratio of 2.2 or higher, background gene expression with normal copy number
Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is acceptable.
Patients requiring ventilator support or oxygen supplementation exceeding 40% fraction of inspired oxygen (FiO2) within 14 days of enrollment.
Poorly controlled depressive symptoms, defined as a baseline score of 10 or higher on the Patient Health Questionnaire (PHQ)-9 screening tool
Baseline serum B-type natriuretic peptide (BNP) above the age-adjusted upper limit of normal
Willingness and ability to undergo mandatory whole blood sample collections at baseline
Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc.) within the past year
Morbidities or concurrent major illness (for example, bowel obstruction or a second active malignancy) that, in the opinion of the treating healthcare provider, would make participation in the trial problematic
Creatine kinase measurement (CPK) 250 mg/dL
Mitral and/or tricuspid valvopathy or valvular prosthesis; angina; severe arterial hypertension; chronic and/or paroxysmal atrial fibrillation; previous myocardial infarction
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
Histopathologically confirmed, well-­differentiated metastatic NETs
Able to lie within the PET scanner for at least 70 minutes while undergoing scanning
Patients experiencing more than 12 watery bowel movements per day associated with volume contraction, dehydration, or hypotension, or showing evidence of enteric infection are excluded
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP subjects must still undergo pregnancy testing as described in these sections.
More than two recurrences of GBM.
Lymphocyte count >= 0.5 x 10^9/L
Concurrent treatment with non-permitted drugs including herbal remedies with immunostimulating properties (for example, mistletoe extract) or known to potentially interfere with major organ function (for example, hypericin)
Serum uric acid =< 8 mg/dL (with or without medication control)
Subjects aged 16-70 may be enrolled into the osteosarcoma cohort.
Subjects 40 years of age and older must also have a negative stress cardiac test (i.e. EKG stress test, stress thallium, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia). Stress test may be required of subjects less than 40 years of age if warranted by family history or risk factors by the treating investigator.
Somatic alteration in one of the following DDR genes as determined by genomic sequencing performed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory. Somatic alterations will include nonsense, frameshift, splice-site or missense mutations or homozygous deletions. Subjects with alterations in DDR genes not included in the list below will be considered on a case by case basis after discussion with the Principal Investigator(s). Subjects with germline alterations in DDR genes will be considered on a case by case basis and will be reviewed by the principal investigator(s). At least 6 subjects will have BRCA or ATM alterations.\r\n* Nucleotide excision repair: ERCC2, ERCC3, ERCC4, ERCC5, ERCC6\r\n* Homologous recombination: BRCA1, BRCA2, RAD50, RAD51, RAD51B, RAD51C, RAD52, RAD54L, NBN, MRE11A, RAD51D, CTIP\r\n* DNA Sensor: ATM, ATR, MDC1, ATRX, CHEK1, CHEK2\r\n* Fanconi anemia pathway: PALB2, BRIP1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, BLM\r\n* Base excision repair: XRCC2, XRCC3, XRCC4, XRCC5, XRCC6\r\n* Other: MUTYH, RECQL4, POLQ, POLE, WRN
CD19 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 90% by flow cytometry; the choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient; in general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples; CD22+ B cell malignancy is required and CD22 expression levels will be documented when available, but a specific level of expression is not an eligibility requirement; it may be documented as positive or negative
Requires therapy for symptomatic CLL in the opinion of the treating physician as defined by:\r\n* Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)\r\n* Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly\r\n* Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy\r\n* Constitutional symptoms, which include any of the following:\r\n** Unintentional weight loss of 10% or more within 6 months\r\n** Significant fatigue limiting activity\r\n** Fevers >= 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection\r\n** Night sweats > 1 month without evidence of infection
Active Richter’s transformation
Lesion that is amenable to palliative radiotherapy
Lesion that is technically feasible to irradiation and accessible for direct intratumoral injection
Elective procedure (colectomy, gynecological, or thoracic) where at least one vessel is planned to be transected by the ENSEAL X1 device per its instructions for use;
Philadelphia-positive (Ph+) ALL
If clinical or histologic diagnosis of cirrhosis and/or clinical or radiographic evidence esophageal or gastric varices, must have had esophagogastroduodenoscopy (EGD) surveillance and adequate endoscopic therapy according to institutional standards
Central or necrotic lung metastases
Imperative indication for nephron sparing surgery \r\n* Baseline chronic kidney disease (CKD) (stage 3, glomerular filtration rate [GFR]  < 60 ml/min/1.73m^2), or anatomically or functional solitary kidney (defined by renal scintigraphy of contralateral renal unit with < 15% function) or bilateral synchronous disease); and \r\n* Radius Exophytic/endophytic properties, Nearness of the tumor to the collecting system or sinus, Anterior/posterior, and Location relative to polar lines (RENAL) score >= 10 or proximity to renal hilum (defined as  < 2 mm away from at least 2 renal hilar vessels-the main artery/vein or first order branches); and\r\n* Radical nephrectomy would lead to severe CKD (stage 4, GFR < 45 ml/min/1.73m^2)
Simple or intermediate renal mass on imaging (R.E.N.A.L score =< 9)
HTN with need for 2 or more anti-hypertensives to control it at baseline (because there isn’t room to\tadd more antihypertensives if axitinib causes increased blood pressure [BP])
Congestive heart failure (CHF) since axitinib can cause CHF
Baseline abnormal thyroid function tests
Capable of understanding and complying with protocol requirements.
LDH < 2 times ULN for each institution.
Requires continuous anti-coagulation or anti-platelet therapy that cannot be safely interrupted to allow for IT injection and/or history of coagulopathy.
Received systemic glucocorticoids within 28 days prior to the first dose of enzalutamide and/or CORT125281, or requirement for chronic or frequently used systemic glucocorticoids for medical conditions (e.g., rheumatoid arthritis, immunosuppression after organ transplantation)
Taken drugs known to interact with Rapamune such as cyclosporine, diltiazem, erythromycin, ketoconazole (and other antifungals), nicardipine (and other calcium channel blockers), rifampin, verapamil within 14 days prior to enrollment
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken. (Note: apalutamide does not have to be taken on an empty stomach)
For cohorts B1 and B2 only, biopsy confirmation of metastases (if safe and feasible at treating center)
Prior exposure to ketoconazole (systemic), abiraterone acetate, enzalutamide or other agents targeting the androgen receptor (AR) signaling pathway
Lymphocyte count >= 0.5 x 10^9/L (in absence of blood transfusion).
Cohort A and C only: Intolerance or serious adverse immune related adverse events (irAEs) that were symptomatic or required or continues to require ongoing immunosuppression to previous immune checkpoint therapy.
Cohort B only: prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
Recipient of CAR-T cell therapy outside of this protocol.
DIAGNOSIS:
Other acute leukemias: leukemias of ambiguous lineage or of other types e.g. blastic plasmacytoid dendritic cell neoplasm with less than 5% blasts. Persistent/relapsed disease with cytogenetic, flow cytometric or molecular aberrations in >= 5% of cells are eligible.
Age-adjusted hematopoietic cell transplantation-comorbidity index (aaHCT-CI) less than or equal to 7.
Seropositivity for human T-lymphotropic virus type 1 (HTLV-1).
Grade >= 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis
Participants with recurrent, progressive, or refractory brain tumors
STRATUM A: Participants with recurrent, progressive, or refractory non-WNT non-SHH (NWNS) medulloblastoma or ependymoma as confirmed through central pathology review
STRATUM A: Participants with subependymoma or myxopapillary ependymoma
STRATUM A: Female participants who are breastfeeding a child
STRATUM A: Participants with a pathogenic somatic or known germline retinoblastoma (RB1) gene mutation
STRATUM B: Female participants who are breastfeeding a child
STRATUM B: Participants with a pathogenic somatic or known germline retinoblastoma (RB1) gene mutation
STRATUM C: Female participants who are breastfeeding a child
STRATUM C: Participants with a pathogenic somatic or known germline retinoblastoma (RB1) gene mutation
Currently or previously being on hydroxyurea
Uncontrolled hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalemia, hyperkalemia, hypomagnesemia or hypermagnesemia
Participants who are WOCBP who are continuously not heterosexually active are exempted from contraceptive requirements but still must undergo pregnancy testing
Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy; investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly
Participants must not be prisoners or be involuntarily incarcerated
Glycosylated hemoglobin (HbA1c) < 7.0%.
Prior ipsilateral thoracotomy (the likely presence of adhesions will limit ability to perform a precise block guided by thoracoscopy). Note: previous VATS or robotic surgery is permissible.
Redo ipsilateral thoracotomy
History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.
Previous participation in a liposome bupivacaine study.
Have a diagnosis of a tumor with evidence of genomic instability on Clinical Laboratory Improvement Amendments (CLIA) certified genomic testing, inclusive of mutations in POLE, POLD1 for arm 1 and in BRCA1 and BRCA2 for arm 2; in arm 2, enrollment of breast and ovarian histologies will be limited to a total of 10 patients
Tumors harboring non-hotspot POLE or POLD1 mutations that show clear evidence of microsatellite instability (MSI) will be excluded
Known microsatellite stable (MSS) status by either immunohistochemistry (IHC) or polymerase chain reaction (PCR). Known or evaluable BRAF and KRAS status.
Off all mycosis fungoides (MF)-directed therapy at the time of enrollment, with the exception of ruxolitinib
COHORT I ONLY: Patients are candidates for enrollment in cohort 1 if they have an indication for ruxolitinib based on splenomegaly or symptoms and are either on ruxolitinib already or going to start therapy with ruxolitinib
COHORT I ONLY: Patients that are on ruxolitinib may enroll in study as long as they are willing to remain on ruxolitinib during the study and have not lost response to ruxolitinib defined as an increase in > 5 cm in spleen size from nadir. There is no minimum or maximum time requirement for time on ruxolitinib
COHORT I ONLY: Participants must have splenomegaly (defined by ultrasound or computed tomography [CT] scan of the abdomen) or symptoms (demonstrated by the presence of 1 symptom score > 5 or 2 symptom scores > 3) related to myelofibrosis as measured by the myeloproliferative neoplasm symptom assessment form MPN-SAF and platelets > 25/uL and hemoglobin > 7/dL
COHORT II ONLY: Participants are ineligible for ruxolitinib – do not have splenomegaly or symptoms of myelofibrosis as defined by the MPN-SAF. Or participants failed ruxolitinib as defined by loss of response to therapy and no allergy to ruxolitinib in the past
Patients with vulvar cancer originating from differentiated vulvar intraepithelial neoplasia (d-VIN), as opposed to vulvar intraepithelial neoplasia of usual type, are excluded; vulvar squamous cell carcinoma originating from differentiated VIN (d-VIN) is HPV negative; however, rare cases of HPV positive d-VIN can occur; patients are not excluded if their tumor has tested positive for HPV or there is no documentation of prior VIN type
Patients >= age 50 must have an comorbidity score (hematopoietic cell transplant-comorbidity index [HCT-CI]) =< 4 (Sorror). The principal investigator is the final arbiter for comorbidity;
Performance status >= 70% (Karnofsky); patients > 50 years should have adequate cognitive function; any concerns regarding cognitive function should be addressed by a geriatrician/neurologist;
Bilirubin =< 5X UNL;
Evidence of portal hypertension with varices, ascites, or hepatic encephalopathy;
Noncompliance - inability or unwillingness to comply with medical recommendations regarding therapy or follow-up, including smoking tobacco. Smoking cessation is a standard teaching practice prior to admission for all patients undergoing stem cell transplant. Any patient who refuses to stop smoking prior to transplant will not be eligible for this study.
Adequate coagulation profile.
Ongoing Grade >1 proliferative or nonproliferative retinopathy.
Asymptomatic adenovirus viremia defined as no symptoms of adenovirus disease and EITHER two positive and quantifiable quantitative polymerase chain reaction (qPCR) tests taken one week apart or one single measurement with >= 1000 copies.
Unable to undergo general, spinal or local anesthesia
Prior transurethral prostatic resection (TURP)
Confirmation of diagnosis
Nasopharyngeal primary site, if WHO type III (non-keratinizing and EBV-positive as established at the local site)
Active infection requiring systemic antibiotics or antifungals within 7 days prior to first dose of study drug; exception: tetracycline family antibiotics (tetracycline, doxycycline, minocycline) administered for the management of cetuximab-related rash may be continued per the investigator’s judgment
Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
Serologic status and/or polymerase chain reaction (PCR) testing reflecting active hepatitis B or C infection
The patient will receive thoracic stereotactic body radiotherapy at MD Anderson.
The patient has a contra-indication for using a CPAP device.
The patient is uncooperative.
The patient has reduced consciousness.
The patient has sustained trauma or burns to the face.
A response of at least 4 on a 10 point scale (with 0 = not tired at all and 10 = extremely tired) to the question “how tired did you feel in the past week?”
Sedentary activity pattern (< 90 minutes per week of moderate-to-vigorous intensity sports activity) within the past year
Physically able to exercise and physician consent to start an exercise program
Obstructive renal failure that is not relieved with stents or nephrostomy tube/s
Patient is a candidate for radical cystectomy as a potentially curative option
Patients with inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome)
Willing to undergo mandatory biopsy at screening and on treatment. Part A only: the first 3 subjects in each cohort are exempt from this requirement.
Previous enrolment in the present study.
Port-a-cath placement: no waiting is required
Haemoglobin <90 g/L
Hepatic intra-arterial embolization or peptide receptor radionuclide therapy (PRRT) within 4-8 weeks; cryoablation, radiofrequency ablation or trans-arterial chemoembolization of hepatic metastases within ? 4 weeks of study enrollment
Subjects with carcinomatous meningitis
Adequate coagulation profile:
Negative viral serology:
Known histological transformation to an aggressive lymphoma (ie, Richter transformation). Note: Biopsy documentation of the absence or presence of transformation is not required.
Have at least 1 resectable lesion to generate TIL
Potassium and magnesium within normal range
Necrotic tumors or tumors close to large blood vessels that may impose an increased bleeding risk when treated with anti-VEGF agents.
Clinical signs of or documented leptomeningeal carcinomatosis. Features such as headache, nuchal rigidity, and photophobia may indicate meningeal involvement.
Current participation in any other interventional clinical study (except survival follow up).
Active or recent thrombolic events
SGPT (ALT) ? 110 U/L and
Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
Subject currently receiving abiraterone and prednisone for CRPC.
Rapidly progressive symptoms of mCRPC.
Arrhythmias requiring class Ia and III antiarrhythmics and/or grade >= 2 bradycardia
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Patient and urologist must agree that patient is suitable for prostatectomy
Serum potassium >= 3.5 mmol/L
Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing potential causes of death (such as but not limited to, unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension)
Prior elotuzumab
Signed and dated written informed consent prior to admission to the study in accordance with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (GCP) guidelines and to the local legislation
Ability to take pills by mouth
History of hypersensitivity of osimertinib (or active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib)
Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV; patients must be at least 3 months from the last dose of BV
Subject must have been as fully resected as possible per the physician's judgment.
Subjects must be deemed unfit for RC due to comorbid conditions with a risk of mortality.
Subject must refuse or not be eligible for radiotherapy.
Subjects must be willing to undergo a cystoscopy.
Subjects must be willing to undergo a biopsy for assessment of clinical response.
Other active malignancies.
Presence of any bladder or urethral anatomic feature that in the opinion of the Investigator may prevent the safe placement, indwelling use, or removal of TAR-200.
Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy tube is allowed).
Evidence of bladder perforation during diagnostic cystoscopy.
Bladder post-void residual volume (PVR) of >750 mL.
Difficulty providing blood samples.
Hepatic metastases present which are amenable to biopsy
Hematocrit >= 27%
Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration
Is aged ?20 years old in Japan or ?18 years old in other countries
At least 1 lesion accessible for biopsy
Lack of a complete response after receiving ibrutinib for > 1 year OR presence of known ibrutinib resistance mutation
Lesion to be resected is more than 5 cm
Not a radiosurgical candidate per radiation oncologist’s discretion
Lesions of any surface span as long as =< 1 cm in maximal height measured from the skin surface for which local control is desired are eligible; a single patient may have multiple eligible lesions that are individually enrolled for the study.
Patients who are receiving or are planned to start topical chemotherapeutics, retinoids or imiquimod to other lesions that are not planned for enrollment are eligible; however, the lesion being considered for enrollment should not be under active therapy with these topical agents immediately prior to enrollment.\r\n* Use of topical chemotherapeutics, retinoids or imiquimod on the lesion that is a candidate for enrollment must be halted at least 24 hours prior to enrollment in the study.
Lesions with a height > 1 cm measured from the skin surface are not eligible for this protocol.
Have locally confirmed MSS or pMMR CRC; MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a PCR-based assay; pMMR is defined as presence of protein expression of 4 MMR enzymes (MLH1, MSH2, MSH6 and PMS2) by immunohistochemistry
Lymphocytes* ? 500/mm³ (? 0.5 x 10^9/L)
(* = without ongoing growth factor or transfusion support)
Hx or condition related to thrombosis, embolism or vascular occlusion/ischemia, including but not limited to: TIA, stroke, MI, stent placement, valve replacement and/or repair
Currently with an active acute infection, or suspected infection, a single oral temperature of ? 101° F or a temperature of ? 100.4°F sustained over a 1 h period in past 24 h. Subjects on prophylactic antibiotics are not excluded from study
Coagulopathy or receiving anticoagulants that result in PT or aPTT values greater than 1.3 X upper limit of normal or elevated D-dimer of decreased fibrinogen
Receipt of tranexamic acid or other antifibrinolytics within 48 hrs prior to infusion
Subjects may receive radiotherapy for symptomatic metastases prior to enrollment provided that there is at least one other non-irradiated lesion amenable to LCT at the time of enrollment. When feasible, stereotactic body radiation therapy (SBRT) or other hypofractionated techniques are strongly encouraged.
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution.
Prisoners or subjects who are involuntarily incarcerated.
Corneal or retinal abnormality likely to increase the risk of eye toxicity
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
Bilirubin =< 1.5 x IULN
Bilirubin 1.5-2 x IULN
ALT and AST 2.5-5 x IULN
Diagnosis of cutaneous, paranasal sinus, salivary, or nasopharynx SCC, or diagnosis of neck nodes with unknown primary
Diagnosis of P16/HPV-ISH positive OPSCC
Research participants with new symptoms of CHF, cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications must have a cardiac consultation, creatinine phosphokinase (CPK), and troponin testing at pre -study and as clinically indicated
Research participants with any other active malignancies
If the research participants has new symptoms of CHF, cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications they already had a cardiac consultation, creatinine phosphokinase (CPK), and troponin testing at pre study deeming them fit for study participation
Research participants must not require more than 2 mg TID of dexamethasone during CAR T cell therapy
Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) regimen followed by standard of care local therapy as determined by their treating physician
Current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
Previous enrollment in the present study
The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening)
Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
Prior olaratumab therapy must have included at least 2 full cycles of olaratumab/doxorubicin (that is, a minimum of 4 doses of olaratumab).
Participants, who completed at least 2 cycles of combination olaratumab/doxorubicin therapy then discontinued doxorubicin due to toxicity or maximum dosing and proceeded to olaratumab monotherapy, are eligible.
Patient with known dihydropyrimidine dehydrogenase (DPD) deficiency
Subjects must have a minimum of three (3) evaluable, discrete lesions.
Subjects must be willing to refrain from sunbathing for the duration of the study.
History of sun hypersensitivity and photosensitive dermatoses including porphyria, systemic lupus erythematosus, Sjögren's syndrome, xeroderma pigmentosum, polymorphous light eruptions or radiation therapy within 30 days of enrolling.
Unhealed sunburn.
Subjects receiving systemic steroids, nitrogen mustard, psoralen UVA radiation therapy (PUVA), narrow band UVB light therapy (NB-UVB) or carmustine (BCNU) or other systemic therapies for CTCL within 3 weeks of enrollment.
NSCLC Expansion Cohort: Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
Dose Escalation, Renal insufficiency, NSCLC and CPI-Treated Expansion Cohorts: For subjects with urothelial cancer and NSCLC: Subjects must submit a tumor tissue for Nectin-4 expression. Enrollment for these subjects is not dependent on the immunohistochemistry using the H-Score (IHC H-Score).
Known sensitivity to any of the ingredients of the investigational product enfortumab vedotin (ASG-22CE)
Has ocular conditions such as:
Monocularity
Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder
Cord blood product manufactured by the NCBP (at least one, if the graft contains more than one units)
Willingness and ability of patients to report selected study outcomes (e.g., GHS and HRQoL) using an electronic device or paper backup questionnaires.
Ocular melanoma
Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and Immunomodulatory Drugs
Proteinuria >3.5 gm/24 hr
Has residual thrombus post nephrectomy in the vena renalis or vena cava.
Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
Combo C :Existing periorbital edema.
Ascites requiring non-pharmacologic intervention or escalation in pharmacologic intervention to maintain symptom control, within 6 months prior to the first scheduled dose
Main portal vein thrombosis (Vp4) as documented on imaging
Prior diagnosis of Langerhans cell histiocytosis (strata A and B) or LCH-related disorder (stratum C) established by standard diagnostic criteria and confirmed histologically
Drugs with known renal toxicity (e.g. vancomycin, amphotericin B, acyclovir, cyclosporin, methotrexate, tacrolimus) should be avoided to the extent possible during the 5 days of clofarabine treatment in each cycle or, if required, administered cautiously and with close monitoring
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621I based on the presence of an actionable mutation\r\n* Positive Rb expression by immunohistochemistry is required for study enrollment
Female participants must be either postmenopausal defined as:
Chimeric Antigen Receptor (CAR)-T cell therapy.
Current participation in another research or observational study.
Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.
Chronic or acute GI disorders resulting in diarrhea of any severity grade.
Cirrhosis.
Biomarker-positive for deoxyribonucleic acid (DNA)-repair anomalies
Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who have had a partial/subtotal hysterectomy are eligible to participate in the study
Candidates for ADT and docetaxel. Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization
Women 18 years of age or older, who are either: Postmenopausal or Pre/perimenopausal women with medically-induced menopause by treatment with agents to induce chemical menopause.
Letrozole combination cohort (L): metastatic breast cancer (MBC) with progression who are candidates for a letrozole-containing regimen, with palbociclib.
Fulvestrant combination cohort (F): MBC with progression who are candidates for a fulvestrant containing regimen, with palbociclib.
Patients with advanced/metastatic disease who have symptomatic visceral spread, and who have life threatening complications needing immediate therapy, such as massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver replacement with tumor.
Serum creatinine is based on age/gender
Hematopoietic growth factors
Biologic (anti-neoplastic agent)
Recurrent or secondary GBM
Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction [MSPCR] or quantitative polymerase chain reaction [PCR]) are acceptable
Patients must have no evidence of significant mass effect, no midline shift, and no uncontrolled clinical signs of mass effect
Recurrent or secondary GBM
Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.
Multifocal, recurrent or metastatic Glioblastoma (GBM) or gliomatosis cerebri (For the sub-study, the subject can have multifocal GBM and gliomatosis cerebri but can't have recurrent or metastatic GBM)
Evidence of complete or partial bowel obstruction
Hemoglobin A1C (HbA1C) < 7.0%
Patients who have a neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
HSIL comprising 2 or more lesions, or anal HSIL in at least 2 octants, or anal HSIL that has recurred or is persistent after prior ablative treatment\r\nNote: HSIL should be in the anal canal at either the squamocolumnar junction or distal anus on HRA at screening or randomization; the extent of HSIL should be based on available biopsy results and visual appearance
Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to randomization for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to randomization
Condyloma occupying more than 50% of the circumference of the anal canal or that obscures a satisfactory exam
Hypertension:\r\n* Patients, 3-17 years of age must have a blood pressure that is =< 95th percentile for age, height and gender at the time of registration\r\n** The normal blood pressure by height, age and gender tables can be accessed in the Generic Forms section of the Pediatric Brain Tumor Consortium (PBTC) members’ webpage\r\n* Patients who are >= 18 years of age must have a blood pressure that is < 140/90 mm of Hg at the time of registration\r\n* Note: if a blood pressure (BP) reading prior to registration is above the 95th percentile for age, height and gender it must be rechecked and documented to be =< the 95th percentile for age, height and gender prior to patient registration
Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local laboratory result
(Arm A only): Subject must be hypomethylating agent naive (i.e. prior azacitidine, decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as lenalidomide is allowed
Severe cardiopulmonary disease precluding the use of the minimally invasive technique as deemed by Internal Medicine Preoperative Assessment, Consultant and Treatment (IMPACT)
Inability to tolerate prolonged trendelenburg position as deemed by anesthesiology
Phosphorus WNL
Calcium WNL
Magnesium WNL
Symptomatic or rapid visceral progression
Malignancies other than TNBC within 5 years prior to randomisation)
Presence of an abnormal ECG
Histological confirmation of adrenocortical carcinoma (ACC) based on either: i). Weiss Score of >= 3 in patients who had earlier surgical resection OR ii). biopsy results compatible with ACC in the context of clinical setting highly suggestive of ACC (adrenal mass > 4 cm invading surrounding organs or associated with distant metastases).
For mitotane treated patients, mitotane should have been stopped at least 28 days prior to study enrollment AND to have mitotane serum level of < 2 mg/L.
Infratentorial tumors
Diffuse leptomeningeal gliomatosis
Diagnosis of neuroblastoma as defined per International Neuroblastoma Response Criteria
Evidence of neuroblastoma outside osteomedullary sites (any neuroblastoma outside osteomedullary sites must have been removed prior to trial entry)
Up to 4 metastatic lesions: \r\n* Must have at least 1 bone lesion AND each non-visceral lesion should be less than 5 cm\r\n* Visceral lesions will be limited to one lung lesion (< 2 cm); no liver lesions allowed
Two lesions can be in close proximity (i.e. within 5 cm of each other) if they meet radiation SBRT normal tissue toxicity requirements
Prior radium Ra 223 dichloride
Orchiectomy
Metastases that in the judgment of investigator-radiologist are not amenable to SBRT
Serum potassium >= 3.5 mmol/L
Tumor specimen obtained prior to treatment initiation by interventional radiology guided biopsy will be interrogated per immunohistochemistry (IHC) and features should be as follows for a patient to be eligible \r\n* Overexpression of androgen receptor (AR)-C terminal and AR-N terminal and PTEN with lack of ARV7 expression along with and ki67 =<10%\r\n* No RB loss or p53 mutation and \r\n* No expression of neuroendocrine markers CD56 and chromogranin (all markers assessed by standardized IHC protocols)
Structurally unstable bone lesions suggesting impending fracture
Prior use of ketoconazloe, enzalutamide, abiraterone or apalutamide or participation in a previous clinical trial of ketoconazloe,enzalutamide, abiraterone or apalutamide
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
Histologically confirmed HR+/HER2- (according to American Society of Clinical Oncology/College of American Pathologists guidelines) invasive carcinoma of the breast
Biopsy-amenable residual disease in the breast measuring >= 1 cm in at least one dimension on ultrasound cm in at least one dimension on ultrasound
Able to complete the quality of recovery (QoR) 15 questionnaire.
Troponin-I =< ULN
Creatine kinase (CK)-MB =< ULN
Brain natriuretic peptide (BNP) =< ULN
AML associated with inv(16); t(16;16); t(8;21) or t(15;17)
Previously untreated MDS with isolated del5q (for which lenalidomide is approved an approved therapy) and chronic myelomonocytic leukemia (CMML) with rearrangements of the PDGF receptor (for which imatinib is approved therapy), unless they have previously failed these approaches
Subjects who have hypersensitivity to decitabine, CDX-1401, poly-ICLC or nivolumab
Herbal supplements that have been shown to modulate testosterone or androgen signaling (e.g. Saw Palmetto) are not allowed while on study
Newly diagnosed oligodendroglioma (oligo) (low grade oligo, low grade mixed oligoastrocytoma, anaplastic oligo, anaplastic mixed oligo) by histology and or molecular classification
Historical pathological tissue evidence of high risk oligo (low grade oligo, low grade mixed oligoastrocytoma, anaplastic oligo, anaplastic mixed oligo) by histology and or molecular classification
1p and 19q deletion status known
IDH 1 & 2 mutations status known
MGMT status known
Complete or partial response to salvage chemotherapy by International Working Group (IWG) criteria
Participants must have a genomic (DNA and/or ribonucleic acid [RNA]) alteration (mutation, fusion, and/or amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, FGF1, FGF3, FGFR1 or FGFR3, as identified by tumor (formalin-fixed, paraffin-embedded [FFPE] or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing; sequencing will be performed through the University of Michigan MI-ONCOSEQ study (Clinical Laboratory Improvement Act [CLIA]-certified), or other (non-university [U] of Michigan) CLIA-certified tumor DNA or RNA sequencing
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Confirmed diagnosis of primary cold agglutinin disease (CAgD) based on the following criteria: a) Chronic hemolysis, b) Polyspecific direct antiglobulin test (DAT) positive, c) Monospecific DAT strongly positive for C3d, d) Cold agglutinin titer >= 64 at 4 degree Celsius, and e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+, and, f) No overt malignant disease
Bilirubin level above the normal reference range
Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening
Negative inked histologic margins from lumpectomy, with the exception of a focus of positive margin at the pectoralis fascia
Active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
Significant post lumpectomy complications requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation or nodal evaluation is acceptable
Gamma-glutamyltransferase =< 2.5 x ULN
Phosphate =< 1.1 x ULN
History of hypersensitivity to any of the excipients in the Debio 1347 formulation (lactose hydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, and magnesium stearate)
History and or current evidence of ectopic mineralization/calcification including but not limited to the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification
Corneal disease, such as bullous or band keratopathy, corneal desquamation, keratitis, corneal ulcer, or keratoconjunctivitis
Pregnant or lactating woman (any woman of childbearing potential who has menstruated within the year prior to enrolment will undergo pregnancy testing within 72 hours prior to receiving the first dose of study medication)
Participants with biopsy-proven adenocarcinoma of the pancreas that is determined to be potentially or borderline resectable by National Comprehensive Cancer Network (NCCN) criteria
Partial thromboplastin time (PTT) WNL+/- 15 % unless on active anticoagulation (suggested to be drawn peripherally to prevent port drawn elevation due to routine heparin flush of ports) obtained ? 14 days prior to randomization
Symptomatic evidence of gastric outlet obstruction
Currently enrolled in a clinical study.
Have a serious concomitant systemic disorder.
All patients with oropharyngeal SCCHN must be tested for HPV (by p16 and/or HPV in situ hybridization [ISH] or polymerase chain reaction [PCR])
Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with reduced intensity conditioning (RIC) have the significant potential for teratogenic or abortifacient effects
Consent to receive FMT administered endoscopically (colonoscopically) and undergo necessary bowel preparation pre-procedure\r\n* Understand infectious risks associated with FMT administration; although FMT infusate has been screened for bacteria, viruses, fungi and parasites there is a risk of transmission of known and unknown infectious organisms contained in the donor stool; post-FMT bacteremia (e.g. E. coli), sepsis and fatal events may rarely occur\r\n* Understand non-infectious risks associated with FMT administration\r\n** Possible allergy and/or anaphylaxis to antigens in donor stool\r\n** Theoretical risk of developing disease possibly related to donor gut microbiota including but not limited to: obesity, metabolic syndrome, cardiovascular disease, autoimmune conditions, allergic/atopic disorders, neurologic disorders, psychiatric conditions and malignancy\r\n* Understand risks associated with colonoscopy including risk of infection transmission, colonic perforation, aspiration pneumonia, and death\r\n* Understand that data regarding the long-term safety risk of FMT are lacking
Presence of absolute contra-indications to FMT administration\r\n* Toxic megacolon\r\n* Severe dietary allergies (e.g. shellfish, nuts, seafood)\r\n* Inflammatory bowel disease\r\n* Anatomic contra-indications to colonoscopy
Cytologic or biopsy confirmed adenocarcinoma of the pancreatic head, body or tail
Locally advanced, unresectable pancreatic cancer as determined by a pancreaticobiliary surgeon as part of a multidisciplinary discussion at MDACC, including triphasic CT demonstrating tumor abutment of the superior mesenteric artery (SMA) or celiac axis, superior mesenteric vein (SMV) or portal vein (PV) involvement which is not resectable without vascular reconstruction.
Patient must have metal stent in place if duodenal stent is required. If patient has plastic stent, this must be replaced prior to radiation.
Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to <= 5mm.
Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure.
Patient is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a Novartis or former GSK sponsored study which has fulfilled the requirements for the primary objective.
Patient's indication is commercially available and reimbursed in the local country.
Patient has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication.
Patient currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study.
No clinical or radiographic evidence of malignant regional adenopathy
Patients with either diffuse (> 1 quadrant or > 5 cm) suspicious microcalcifications on mammogram or diffuse non-mass-like enhancement on MRI
AdV DNA plasma viremia of ? 1,000 copies/mL and rising, defined as two consecutive results ? 1,000 copies/mL from the designated central virology laboratory, with the second result being greater than the first.
Patient must receive the following medical regimen as part of standard of care immunoprophylaxis for GvHD in either study arm at doses and regimen determined by local institutional guidelines, physician preference, and patient need: MTX or MMF + calcineurin inhibitor (CSA or TAC) +/- ATG (ATG use is limited to 30% of patients).
Patient is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.
Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, ALA dehydratase deficient porphyria)
Elevated urinary or plasma PBG or ALA values within the past year,
No more than 3 lesions may be treated; the maximum sum of the diameter(s) of the lesion(s) must be =< 6 cm
Completion of the OPN-305-106 study
Principal Investigator adjudicated efficacy response defined as either transfusion independence\, \stable disease\, \minor HI-E response\ or \major HI-E response\ and in the opinion of the Principal Investigator the patient may benefit from continued treatment with OPN-305 monotherapy or combination treatment with azacitidine.
Withdrawal from the OPN-305-106 study prior to the final EOT visit
Participants must not have carcinomatous meningitis
Patient must be able to pass radiation evaluation (i.e.: able to receive 200 cGy)
An irradiated lesion is considered evaluable only if it has shown enlargement since the completion of last radiation
Lack of available therapist/clinic,
Lack of insurance coverage or funding to support cost of care.
Uncontrolled hyperthyroidism or parathyroidism (for which endocrinologist recommends against neck compression).
Increased intracranial pressure or other contraindications to internal or external jugular venous compression.
Acute facial infection (e.g., facial or parotid gland abscess).
Any condition in which increased venous and lymphatic return is undesirable.
Demonstrate adequate organ function as defined in protocol, AND normal (WNL of local lab range) serum correct calcium, and phosphorus levels.
Subjects with central nervous system (CNS) involvement are eligible provided that they are asymptomatic and in the opinion of the study principal investigator (PI) have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion; subjects that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization
Absolute blood lymphocyte (ALC) >= 100 cells/ul\r\n* If subject has an apheresis product or T cells available for manufacturing of T cell product, there is no minimum ALC requirement
Subjects must be able to tolerate apheresis procedure, including placement of temporary apheresis line if required
Cytologic or histologic proof of adenocarcinoma of the stomach or gastroesophageal junction.
Subjects with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacity.
Moderate or severe symptomatic metastatic disease; subjects who meet either of the following criteria must be excluded:\r\n* A requirement for treatment with opioid analgesics for any reason within 28 days prior to registration\r\n* Average weekly pain score of 4 or more as reported on the 10-point Visual Analog Scale (VAS) on the Registration Pain Log
Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to registration
Blood counts are not required to be normal prior to enrollment on trial
Gamma-glutamyl transpeptidase (GGT) must be =< 2.5 x institutional upper limit of normal (grade 1 or less per CTCAE 4)
No evidence of dyspnea at rest and no exercise intolerance
History of clinical hypersensitivity to the designated combination immunotherapy, GM-CSF, Interferon-alpha-2b (Merck), yeast, beef, or to any components used in the preparation of the experimental vaccine.
BUN >30 in conjunction with a creatinine >2.
Proteinuria >1+ on urinalysis or >1 gm/24hr.
Pathologic confirmation of eligible histology
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Minimum of 3 radiographically apparent lesions such that there is:\r\n* Minimum of one lesion in areas that have not been previously irradiated that is considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria AND\r\n* Minimum of two lesions in areas that have not been previously irradiated that are determined by interventional radiology to be of a size and in a location that a single probe could ablate at least 75% of the lesion; Note: Hepatic lesions measuring =< 3 cm may be treated, as determined by interventional radiology; Note: Brain metastases are not acceptable as lesions defining measurable disease, nor are they candidate lesions for cryoablation
Presence of a candidate treatment lesion (subcutaneous, nodal, or visceral) accessible and safe for radiotherapy and serial intralesional injections as specified by the protocol
Known contraindications to radiotherapy including but not limited to radiation sensitivity syndromes such as xeroderma pigmentosum and ataxia telangiectasia mutated
T1 to T2a tumors OR T3 tumors smaller than 7 cm invading the mediastinal or pericardial pleura are also eligible for this protocol as long as normal tissue dose constraints can be met
No previous HIPEC
Be willing to participate in the collection of blood and tissue for banking and future correlative studies.
Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.
Solid tumors with one or more of the following DNA repair defects:\r\n* BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD54L (validated from archival tumor tissue or germ line testing from any Clinical Laboratory Improvement Act [CLIA] approved lab); this testing should occur prior to study consent or enrollment
Mandatory biopsy on study entry, if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
Myelodysplastic features on peripheral blood smear
Patients must meet the Thomas Jefferson University Hospital (TJUH) bone marrow transplant (BMT) standard of procedure (SOP) guidelines for “Patient Criteria for Autologous HSCT”
Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and within 14 days prior to course 3 day 1 (C3D1); participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) may submit an archived specimen\r\n* Note: After the first 6 participants undergo biopsy on cabozantinib, we will review their adverse event profiles to ensure no more than a 20% rate of grade 3 or higher bleeding or wound healing complications occur; if more than 2 patients (> 20%) have safety concerns, we will reassess the safety of collecting the research biopsies; full review of all grade (including grade 1 and 2) may also prompt changes and will be reviewed by the study team; Exelixis may be consulted if necessary
SAFETY LEAD-IN COHORT
BIOCHEMICAL RECURRENCE COHORT
Previous serious adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
Subjects in custody and or residing in a nursing home or rehabilitation facility;
Condition requiring medication with potential photosensitizing effects (tetracyclines, quinolones, sulphonamides, phenothiazines, sulfonylurea hypoglycaemic agents, thiazide diuretics, griseofulvin, and amiodarone) if these treatments could not be stopped at least 10 days before and for 3 days after the VTP procedure or replaced by treatments without photosensitizing properties;
Diagnosis of BOS by one of the following criteria\r\n* Transbronchial or surgical lung biopsy demonstrating the obliterative bronchiolitis lesion\r\n* Volumetric computed tomography (CT) scan with lung density analysis with ? 28% air trapping\r\n* National Institutes of Health (NIH)-based PFT criteria for the diagnosis of BOS: FEV1/FVC < 0.7 and FEV1 < 75% \r\n* Evidence of clinical improvement after treatment for BOS initiated
No features supporting an alternative diagnosis by transbronchial biopsy, bronchoalveolar lavage (BAL), surgical lung biopsy, culture and non-culture based data, if performed
There are no gender or race-ethnicity-based restrictions
The following medications may significantly increase the level of pirfenidone and should not be taken concurrently including: fluvoxamine, ciprofloxacin > 500 mg twice daily, systemically administered aminolevulinic acid, vemurafenib and enoxacin, any other strong inhibitors of P450 isozymes CYP1A2, CYP2C9, 2C19, 2D6, and 2E1 should be avoided
Prior exposure to agents targeting IL-6 or the IL-6 receptor
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
Serum potassium ? 3.5 mmol/L
Prior immunotherapy including sipuleucel-T
Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
Have a baseline glycated hemoglobin (HbA1c) ? 6.4
Subjects must have at least one bi-dimensionally measurable lesion; one of the measurements must be >= 1.5 cm in one dimension
Women are eligible to participate if: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
Prisoners or subjects who are involuntarily incarcerated.
Symptoms of urogenital atrophy including dyspareunia or vaginal dryness
Vaginal stenosis which would not allow vaginal probe to be placed (based on physician exam)
Significant mental or emotional problems that would interfere with study participation (as assessed by the National Comprehensive Cancer Network [NCCN] Distress Thermometer); any value higher than 7 will trigger further intervention, but ultimately enrollment into the clinical trial will be determined by the enrolling physician
Have pathologically confirmed DLBCL on biopsy
Men with > 5 bony metastases
Men with new or progressing lymphadenopathy clearly consistent with prostate metastasis on imaging or proven by pathologic biopsy at any time three months or later following their initial definitive therapy
Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
Men who will receive radical prostatectomy to the primary site
Fecal incontinence
Metastatic melanoma or epithelial cancer with at least one lesion that is resectable or in selected cases, available peripheral blood mononuclear cells (PBMCs)
Subjects must be co-enrolled on protocol 03-C-0277
Patients with active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) are ineligible
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec are ineligible
Any prior chemoradiotherapy is allowed
Active infection requiring treatment or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
Patients must have severe SCD defined as 1 or more of the following:\r\n* Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours\r\n* History of >= 2 episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea)\r\n* History of >= 3 severe pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea)\r\n* Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving >= 8 transfusions per year for >= 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)\r\n* An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity >= 2.7 m/sec in adult patients
Previous HCT
Able to complete questionnaires by themselves or with assistance
Subject is participating in any other therapeutic clinical study (observational or registry trials are allowed)
Infection requiring intravenous antibiotics that was completed < 1 week of study enrollment (day 1) with the exemption of prophylactic antibiotics for long line insertion or biopsy
Tumors with known IDH1 (isocitrate dehydrogenase 1) or known IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing
Active tuberculosis or bacille Calmette-Guerin (BCG) infection
Post-menopausal or undergoing ovarian suppression
Urinary N-telopeptide level above 40 nM bone collagen equivalent (BCE)/mM creatinine measured at ARUP
Any atrophic macular condition including intermediate or advanced age-related macular degeneration
Use within 28 days of registration of calcitonin, recombinant parathyroid hormone-related peptides, mithramycin, radium, strontium ranelate, or gallium nitrate
Patient agrees to have 10 week follow-up visit at a participating Johns Hopkins facility
Patient agrees to allow access to or provide clinical, imaging, and laboratory follow-up information for until time of death or data analysis, whether or not obtained from Johns Hopkins providers
Subjects must have disease that can be safely biopsied (for RP2D biopsy expansion cohort only), and agree to undergo a pretreatment and on-treatment biopsy.
Subjects who enroll in the triple-negative breast cancer (TNBC) dose expansion cohort should adhere to the American Society for Clinical Pathology (ASCP)/College of American Pathologists (CAP) guidelines for the definition of TNBC.
Lactic acid levels > 2 mmol/L and/or serum pH < 7.35 at screening.
Bi-lineage or bi-phenotypic leukemias
Prior therapy with a compound of the same mechanism as PF-05082566 (immunomodulation of 4-1BB)
Subjects must be followed at the Cleveland clinic for AS
Subjects must be willing to adhere to the dietary modification outlined in the protocol.
Subjects not followed by the Cleveland clinic.
Subjects unable to adhere to the dietary modification outlined in the protocol.
Presence of current angina;
Morphological or cytological features of myelodysplasia and/or post-chemotherapy aplasia on BM assessment;
Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart);
Prior irradiation to > 30% of BM reserves (including total body irradiation), regardless of the washout period;
Rapidly progressive relapse requiring urgent chemotherapy as determined by treating physician
Glycosylated hemoglobin (HbA1c) =< 7.9 %
Willingness to travel to the CTSC at WCMC weekly
History of nephrolithiasis or nephrolithiasis including that incidentally discovered during computed tomography (CT) screening
Known selenium deficiency
Vegetarian or vegan eating habits
Gum chewing habit
Diagnosis of primary systemic AL amyloidosis of tissue as determined by: a. Congo red staining of tissue showing apple green birefringence AND b. Clonal plasma cell disorder as determined by: i. Immunohistochemistry, in situ hybridization (ISH) or flow cytometry demonstrating kappa or lambda light chain restriction on bone marrow biopsy AND/OR ii. Monoclonal protein on serum or urine electrophoresis/immunofixation OR abnormal free light chain ratio
Non-AL amyloidosis
Clinically overt myeloma a.) Lytic bone lesions or biopsy proven plasmacytoma b.) Hypercalcemia (corrected for albumin) > 11 mg/dL unexplained by other causes
Have a histological diagnosis of advanced STS (by local pathology review), for which treatment with doxorubicin, ifosfamide and mesna is deemed appropriate by the investigator.
Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
Have previously completed or withdrawn from any study investigating olaratumab.
Have received prior treatment with olaratumab, doxorubicin, or ifosfamide, or have participated in other trials investigating olaratumab.
Have known urinary outflow obstruction, or inflammation of the urinary bladder (cystitis).
Have a resting heart rate of >100 beats per minute (bpm).
EGFRvIII, the target antigen, must be identified on tumor tissue by immunohistochemistry (IHC) or polymerase chain reaction (PCR), i.e. EGFRvIII positive via pathology report
Bevacizumab naive
Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (time to maximum concentration [Tmax] > 99.5 degrees Fahrenheit [F], 37.5 degrees Celsius [C])
Histological confirmation of mycosis fungoides as confirmed by the Mayo Clinic Arizona Dermatopathology Department
Ability to complete questionnaire(s) by themselves or with assistance
Photosensitivity disorder, including but not limited to porphyria, or concomitant photosensitizing drugs that place the patient at an elevated risk of developing severe side effects to PDT or RT
Any underlying condition which prevents the patient from being able to undergo the required number of sessions of PDT or RT and required follow up
Pathology review at Monroe Dunaway (MD) Anderson (Note: if patient’s prostate biopsy was not read at MD Anderson, it must be reviewed at the study site to confirm eligibility).
Patient is suitable for prostatectomy.
Serum potassium >= 3.5 mmol/L.
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken.
Patients who have had > 1 LHRH agonist or antagonist depot injection or received depot injection > 30 days before study entry.
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.
Patients receiving medications known to lower the seizure threshold are ineligible unless discontinued or substituted at least 4 weeks prior to study entry. These include: 1) aminophylline/theophylline; 2) atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone); 3) bupropion; 4) lithium; 5) pethidine; 6) phenothiazine antipsychotics (e.g., prochlorperazine (compazine), chlorpromazine, mesoridazine, thioridazine); 7) tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).
Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 170 or diastolic pressures above 110 despite anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes. (for example doctor’s visit related stress i.e. \white coat syndrome\.
Allergies, hypersensitivity, or intolerance to prednisone, LHRH analog or excipients of prednisone LHRH analog, abiraterone acetate and apalutamide.
Previous investigational antiandrogens (e.g., apalutamide, enzalutamide, BMS-641988).
Anti-androgens (steroidal or non-steroidal) such as cyproterone acetate, flutamide, nilutamide, bicalutamide, etc. other than assigned study drug unless given for =< 4 weeks.
Estrogens, progestational agents such as megestrol, medroxyprogesterone, diethylstilbestrol (DES), cyproterone, spironolactone > 50 mg/kg, etc. unless discontinued at least two weeks prior to randomization.
Androgens such as testosterone, dehydroepiandrosterone (DHEA), etc. unless discontinued at least two weeks prior to randomization.
Have a CAR T cell product likely to meet release criteria based on available in-process testing, as reviewed and acknowledged by the individual(s) listed on the protocol’s delegation of authority log who are authorized to make this determination
Patient must have < 1.0 cm midline shift pre-operatively
Patients who have tumors for which the Gd-enhancing mass appears to be covered =< 90% using 2 catheters and assuming a 3.0 cm diameter based on pre-operative planning are unlikely to have adequate LITT and thus ineligible for the study
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Previous enrollment in the present study
There must be evidence of progression on or after last treatment regimen received. NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP must still undergo pregnancy testing as described in these sections.
A pathologically confirmed (histology or cytology) malignant neoplasm with at least one target lesion that is confirmed by conventional imaging and is determined to express somatostatin receptors by 68Ga-DOTATOC (TATE) PET within 6 months prior to treatment with 90Y-DOTATOC
Completion of Norfolk Quality of Life Questionnaire
Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) or 131I-MIBG therapy for this malignancy
Any subject for whom, in the opinion of their physician, a 12-hour discontinuation of somatostatin analogue therapy represents a health risk; also subjects who have received sandostatin long-acting release (LAR) in the past 28 days or long-acting lanreotide within the past 8 weeks are excluded; subjects may be maintained on short acting octreotide during the time from last injection of long-acting somatostatin analogue until 12 hours (hrs) prior to injection of study drug; known antibodies to octreotide, lanreotide, or DOTATOC or history of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTATOC
Subject weighs more than 450 pounds
For Dose-Escalation Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy molecularly confirmed using Cobas assay or a comparable Food and Drug Administration (FDA)-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy or not previously received BRAF targeted therapy, and for which standard curative or palliative measures do not exist or are no longer effective.\r\n* If test at Clinical Laboratory Improvement Act (CLIA)-certified lab used a non-FDA approved method, information about the assay must be provided to the overall principal investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF detection kit and Cobas 4800 BRAF V600 mutation test).
For Dose-Expansion Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy.\r\n* If test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided to the overall principal investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF detection kit and Cobas 4800 BRAF V600 mutation test).
Potassium > 3 and < 5.5 mmol/L.
Candidate for potentially curative antibiotic therapy for gastric mucosa-associated lymphoid tissue (MALT); (gastric MALT lymphoma patients with stage I/II helicobacter [H.] pylori positive lymphoma must fail therapy with H.-pylori directed therapy before being considered for this study)
Alpha 1,3 galactose IgE (“alpha gal”) < 0.35 IU/ml or “negative” within 10 days prior to “on study” status
Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers. Calculation of TRM score:
Comorbidities.
>= 1 osseous and/or extra-osseous lesion that can be radiated
Solitary plasmacytoma
Has a diagnosis of immunodeficiency
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Lack of contraindications to systemic immunotherapy (see list of exclusions below)
Persons who are incarcerated or otherwise under compulsory detention by an authority are not eligible
Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of enrollment
GFR ?45 mL/min/1.73 m2 calculated by CKD-EPI
Ongoing hospitalization prior to Screening
Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes)
Have documented radiographic progression to or documented intolerance of first line systemic chemotherapy which included either gemcitabine or fluorouracil (5-FU) based regimen (including capecitabine)
Has received prior immunotherapy including anti–PD-1, anti–PD-L1, or anti–PD-L2 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma consistent with ATLL\r\n* Included subtypes will be: acute, lymphomatous, and chronic unfavorable; chronic unfavorable is defined as the chronic variant with at least one of the following: lactate dehydrogenase (LDH) > upper limit of normal (ULN), blood urea nitrogen (BUN) > ULN, albumin < lower limit of normal (LLN)\r\n* Positive HTLV-1 antibody testing with confirmatory testing via western blot, enzyme-linked immunosorbent assay (ELISA), or molecular testing (polymerase chain reaction [PCR])
Prior treatment: Previously untreated or has received a maximum of one cycle of any combination chemotherapy (e.g. cyclophosphamide/hydroxydaunorubicin/oncovin/prednisone [CHOP], cyclophosphamide/hydroxydaunorubicin/oncovin/etoposide/prednisone, [CHOEP], dose-adjusted etoposide/vincristine/doxorubicin/cyclophosphamide/prednisone [DA-EPOCH], cyclophosphamide/oncovin/doxorubicin/methotrexate-ifosfamide/VePesid/AraC [CODOX-M/IVAC], hyper cyclophosphamide/dexamethasone/doxorubicin/vincristine [CVAD]) within 4 weeks of study entry; additionally, a patient may have taken antiretroviral therapy (e.g. zidovudine [AZT] and/or interferon [IFN]) at any time prior to study enrollment
Previous exposure to brentuximab vedotin (BV)
Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this clinical study protocol, so long as they consent to that part.
Previous enrollment or randomization in the present study.
Prisoners or subjects who are involuntarily incarcerated.
Inclusion Criteria (All questions must be answered \YES\ in order for the subject to be\n        considered for the study):\n\n          1. Is the subject a male or female between18 and 75 years of age inclusive who is able to\n             provide informed consent?\n\n          2. Does the subject have histologically-confirmed diagnosis of CD20-positive DLBCL based\n             on the WHO classification? The diagnosis must be confirmed at the enrolling site.\n             Subjects with history of indolent lymphoma or follicular Grade 3 lymphoma are not\n             eligible.\n\n          3. Does the subject have an ECOG score of 0, 1 or 2?\n\n          4. Does the subject have an IPI score of at least 3?\n\n          5. Does the subject have an estimated life expectancy of at least 12 weeks?\n\n          6. Does the subject have adequate organ function as follows:\n\n               1. Hepatic: total bilirubin ?1.5 times upper limit of normal (ULN); alanine\n                  transaminase (ALT) and aspartate transaminase (AST) ?1.5 times ULN (<5 times ULN\n                  if liver involvement)\n\n               2. Renal: estimated GFR of >50 ml/min by Cockcroft- Gault equation\n\n               3. Bone marrow: platelets ?75 x 109/L, absolute neutrophil count (ANC) ?1.5 x 109/L,\n                  hemoglobin ?10 g/dL, unless there is bone marrow involvement\n\n          7. If the subject is a male or female with reproductive potential, is he/she willing to\n             use an approved contraceptive method (for example, intrauterine device [IUD], birth\n             control pills, or barrier device) during and for 3 months after discontinuation of\n             study treatment? Women of childbearing potential must have a negative serum pregnancy\n             test within 7 days prior to start of treatment.\n\n          8. Does the subject have a left ventricular ejection fraction ?50% by echocardiography or\n             nuclear medicine multi-gated scan?\n\n          9. Is the subject able to swallow tablets?\n\n         10. Does the subject have adequate transportation to allow for required follow-up visits?\n\n         11. Does the subject agree to have blood stored for possible future biomarker analysis?\n\n        Exclusion Criteria (All must be answered \NO\ in order for the subject to be considered for\n        the study):\n\n          1. Has the subject received treatment with an investigational drug within the last 30\n             days?\n\n          2. Is the subject receiving, or has the subject received, any other radiation or systemic\n             anticancer treatment for lymphoma?\n\n          3. Is the subject pregnant or breastfeeding?\n\n          4. Does the subject have known central nervous system (CNS) involvement?\n\n          5. Does the subject have any significant concomitant disorder, including active\n             bacterial, fungal, or viral infection, incompatible with participation in the study?\n\n          6. Does the subject have a second primary malignancy (except adequately treated\n             non-melanoma skin cancer)? Patients who have had another malignancy in the past, but\n             have been disease-free for more than 5 years, are eligible.\n\n          7. Is the subject unable to discontinue use of a concomitant medication that is a strong\n             inducer or inhibitor of CYP3A4? (See Appendix A).\n\n          8. Does the subject have a family history of long QT syndrome, or a QTc interval >450\n             (males) or 470 (females) at screening, a history of arrhythmias or a history of\n             unexplained syncope?\n\n          9. Must the subject take any medication that can prolong the QT/QTc interval? (See\n             Appendix C)\n\n         10. Does the subject have a history of severe allergic or anaphylactic reaction to\n             monoclonal antibody therapy?\n\n         11. Does the subject have a confirmed diagnosis of progressive multifocal\n             leukoencephalopathy?\n\n         12. Does the subject have a history of grade 2 or higher peripheral neuropathy?\n\n         13. Does the subject have any of the following cardiac disorders: uncontrolled\n             hypertension, unstable angina, myocardial infarction within 8 weeks of Day1, NYHA\n             Grade 2 or higher congestive heart failure, ventricular arrhythmia requiring\n             medication within 1 year of Day 1, NYHA Grade 2 or higher peripheral vascular disease?\n\n         14. Has the subject received a live vaccine within 28 days of study Day 1?\n\n         15. Is the subject HIV positive?\n\n         16. Does the subject have evidence of chronic hepatitis C infection as indicated by\n             antibody to HCV with positive HCV-RNA?\n\n         17. Does the subject have evidence of chronic hepatitis B infection as indicated by\n             either:\n\n               1. HBsAg+ or\n\n               2. HBcAb+ with HBV-DNA+
Tolerated previous transrectal ultrasound guided biopsy procedure under local anesthetic\r\n* Uncomplicated previous transrectal ultrasound (TRUS) biopsy procedure (i.e., no prior hospitalization due to sepsis, prostatic abscess or severe hemorrhage following TRUS prostate biopsy)
For the Western safety cohort only: willingness to undergo serial skin tissue biopsies.
Western Safety Cohort Only: Participants with Japanese heredity.
Patients with evidence of significant arterial insufficiency or microangiopathy in any organ due to any reason, which could lead to distal extremity hypoxia, as evidenced by any gangrenous change in distal limbs or requiring resection for this reason.
Arterial anatomy which would preclude selective transarterial chemoembolization
Patients must be a candidate for intralesional therapy\r\n* At least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion >= 10 mm in longest diameter OR\r\n* Multiple injectable melanoma lesions which in aggregate have a longest diameter of >= 10 mm\r\n* Must have no known bleeding diathesis or coagulopathy that would make intratumoral injection unsafe
Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the Food and Drug Administration (FDA): Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course); please note exception above for persistent T1 disease; there is no upper limit on the amount of prior BCG a subject may have received
Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis
Subjects must have histologically or cytologically confirmed EBV-positive LPD or an EBV-positive NHL confirmed by the Laboratory of Pathology, National Cancer Institute (NCI)\r\n* Cohort 1: EBV-positive B-cell LPD; subjects may be previously untreated or relapsed from prior therapy\r\n** Lymphomatoid granulomatosis (LYG), grades I-II\r\n** Chronic active EBV disease (CAEBV)\r\n** EBV-positive post-transplantation lymphoproliferative disorder (PTLD); NOTE: PTLD after solid organ transplantation is excluded; patients who, at the discretion of the investigator, need urgent therapy with standard agents will not be eligible\r\n* Cohort 2: EBV-positive B-cell NHL subjects must have relapsed from previous treatment with an anthracycline and rituximab-based regimen or be considered not eligible for the same\r\n** Lymphomatoid granulomatosis (LYG), grade III\r\n** EBV-positive immunodeficiency-associated diffuse large B-cell lymphoma (DLBCL)\r\n** EBV-positive DLBCL
Subjects with second malignancies requiring active systemic therapy are excluded; subjects with second malignancies not requiring active systemic therapy or pre-malignant conditions such as monoclonal B-cell lymphocytosis (MBL) or monoclonal gammopathy of undetermined significance (MGUS) may be eligible
Any form of primary immunodeficiency.
Subjects with histologically- or cytologically-documented incurable human papillomavirus (HPV)-positive OPSCC. HPV-16 serotype will be assessed by Cervista assay.
Subject entering the study will need to consent for mandatory biopsy at study entrance and as an optional procedure prior to C3 for biomarker evaluation. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient.
Subjects with carcinomatous meningitis.
Prisoners or subjects who are involuntarily incarcerated.
Subject (when applicable, parental/legal representative) must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted.
No evidence of dyspnea at rest
Females of Childbearing Potential (FCBP) and male subjects who have reached puberty (and when applicable, with parental/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.
All male and female subjects must follow all requirements defined in the pomalidomide Pregnancy Prevention Program.
Male subjects must, as appropriate to age and the discretion of the study physician:
Subject has first degree family member with a known hereditary coagulopathy.
Is currently receiving and able to discontinue erlotinib, gefinitib, or afatinib.
Superficial bladder tumors (Ta, Tis, T1) OR
Biochemical recurrence within one year of completion of radiotherapy
Active lupus or active scleroderma
Prior prostatectomy
Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
Biopsy-proven histochemical diagnosis of amyloid light-chain (AL) amyloidosis based on tissue specimens with Congo red staining or other histologic stain; thioflavin T or S, or crystal violet; tandem mass spec or immunohistochemistry (IHC) confirmation of immunoglobulin-derived amyloidosis is encouraged; cases in which histochemical confirmation is lacking need to be discussed with one of the Multiple Myeloma Research Foundation (MMRF) protocol chair/co-chairs
Measurable hematologic disease as defined by:\r\n* Serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non-amyloid forming [uninvolved] free light chain [FLC]) >= 50 mg/L)
Objective measurable (cardiac, renal or liver) organ amyloid involvement defined as follows (amyloid involvement of at least 1 required):\r\n* Mean wall thickness > 12 mm on echocardiogram, with no other cardiac cause or an elevated N-terminal pro b-type natriuretic peptide (NT-ProBNP) (> 332 ng/L) in the absence of renal failure or atrial fibrillation\r\n* Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day in a 24-hour urine collection\r\n* Total liver span > 15 cm in the absence of heart failure or alkaline phosphatase > 1.5 times institutional upper limit of normal (ULN)\r\n* NOTE: Amyloid involvement of other organ systems is allowed, but not required
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis; exception: patients with amyloid heavy (AH) or mixed AL/AH type amyloidosis are potentially eligible
Cardiac stage 2 or 3 with N-terminal prohormone (NT-pro)-B-type natriuretic peptide (BNP) > 8500 ng/L
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
Known intolerance to steroid therapy (defined as being unable to tolerate at least 20 mg dex/week)
Documented evidence of active acromegaly
Biochemically controlled
Conventional or stereotactic pituitary radiotherapy any time in the past
Symptomatic cholelithiasis
Dopamine agonists, within 12 weeks
At least 1 lesion accessible for biopsy in addition to the target lesion
Participants with carcinomatous meningitis
Candidate for OsteoCool RF ablation per the labeled indication applicable in their respective country/region
Metastatic lesions targeted for treatment must be located in the thoracic and/or lumbar vertebral body(ies), periacetabulum, iliac crest, and/or sacrum OR benign bone tumors (Europe and Canada only) - no restrictions on location of lesion
Report worst pain score ?4/10 at the target treatment site within the past 24 hours
Planned treatment site(s) accompanied by objective evidence of secondary radiculopathy or neurologic compromise
Subjects in concurrent studies can only be enrolled with permission from Medtronic. Please contact Medtronic's study manager to determine if the subject can be enrolled in both studies.
Ages > 50 years with hematologic malignancies treatable by unrelated hematopoietic cell transplant (HCT)
Ages =< 50 years with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by the principal investigators at the collaborating centers and at FHCRC
Aggressive nonHodgkin lymphomas (NHL) and other histologies such as diffuse large B cell NHL– not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT
Waldenstrom’s macroglobulinemia – must have failed 2 courses of therapy
Have either:
Had previous exposure to Betafectin® or Imprime PGG
Total abstinence (if it is their preferred and usual lifestyle)
Do not have a vasectomized partner with confirmed azoospermia.
Subjects with central nervous system (CNS) involvement are eligible provided that they are asymptomatic and in the opinion of the study principal investigator (PI) have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion; subjects that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization
Absolute blood lymphocyte (ALC) >= 100 cells/ul\r\n* If subject has an apheresis product or T cells available for manufacturing of T cell product, there is no minimum ALC requirement
Subjects must be able to tolerate apheresis procedure, including placement of temporary apheresis line if required
Planned radiation treatments at Mayo Clinic Rochester
More than one prior course of radiotherapy or prior prescription doses exceeding 60 Gy to target volumes
Unable to undergo an 18F-DOPA-PET scan (e.g., Parkinson’s disease, taking anti dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists)\r\n* Note: Other potentially interfering drugs: amoxapine, amphetamine, benztropine, buproprion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline); if a patient is on any of these drugs, list which ones on the On-Study form
Female subject must either:
Be of non-childbearing potential: Clearly premenarchal or documented surgically sterile
Subject and subject's parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment.
Known cirrhosis or chronic hepatic failure
Subject previously dosed with isavuconazonium sulfate.
NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commercially available NY-ESO-1 antibodies
Must be willing and able to undergo three research PET scans
Active or recent herpes simplex virus (HSV) infection or cytomegalovirus (CMV) based on symptoms with positive swab culture and/or positive IgM screening
Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to nab-paclitaxel or anti-PD1/PDL1 or human albumin
Sodium >= 130 mEq/L
Breast implant on the side of the body that will receive HIFU application
Active keratitis or current corneal disorder.
CD19 expression is required at any time since diagnosis; if patient has received anti-CD19 targeted therapy (i.e. blinatumomab or CD19-CAR T cells), then CD19 expression must be subsequently demonstrated; CD19 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or >= 90% by flow cytometry; the choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject; in general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples
Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy will be eligible if < 5% of circulating levels of CD3+ cells express the previous CAR by flow cytometry
Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy, and willingness to undergo biopsy before and after treatment
Willingness to undergo research biopsy
Known mutation in KRAS at position G12, G13, or Q61
Must have average worst pain score within specific range on the NPRS from assessment.
Must be willing and capable of understanding and cooperating with the requirements of the study.
Ability to discriminate intensity of thermal stimuli using QST.
Subjects able to complete the study duration.
Subjects with leptomeningeal metastases in lumbar area.
Evidence of brain pathology or increase intracranial pressure.
Presence of an IT shunt.
Has evidence or a coagulopathy or hemostasis problem.
Subjects with additional loci of pain above the mid-thoracic level or other pain disorder due to non-cancer etiology.
Subjects who have not completely recovered from any toxicities from previous treatments.
Prior exposure to decitabine or azacitidine will be an exclusion criterion for the use of decitabine or azacitidine alone
Male subjects will be considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition)
Presence of a candidate treatment lesion (subcutaneous or nodal lesions are preferable but visceral lesions will be considered) accessible and safe for radiotherapy and serial intralesional injections
Systolic >= 80
Patient has ever had confirmed extravesical urothelial disease (upper tract and urethral including prostatic urethral)
No retropharyngeal nor level IV (or lower) lymphadenopathy (i.e. nodes in level I-III only).
Mini-mental status exam (MMSE) >= 24
Prior WBRT
MMSE < 24
Participants with local conditions or systemic illnesses that would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc
For biopsy identified patients: be willing to undergo repeat biopsy of a target lesion before treatment and after radiation; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the principal investigator
Patients with histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required (presence of arterial hypervascularity with venous washout). For subjects without cirrhosis, histological confirmation is mandatory. The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing
Any patient who cannot be compliant with the appointments required in this protocol must not be enrolled in this study
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that will not undergo SRT and that is amenable to monitoring\r\n* Note: All brain metastases will receive SRT; therefore, a patient with brain metastases that will be treated with SRT must also have extracranial disease that will not undergo SRT and that is amenable to monitoring
DOSE ESCALATION COHORT: Prior receipt of docetaxel is permitted
PHARMACODYNAMIC EXPANSION COHORT: Prior receipt of docetaxel is not permitted
PHARMACODYNAMIC EXPANSION COHORT: Consent to allow mandatory paired (pre- and on- treatment) fresh tissue biopsies if deemed safe to do so for quantitation of Akt pathway signaling proteins
Absolute lymphocyte count (ALC) >= 0.8 x 10^9/L.
Clinical =< 2.0 cm unifocal lesion
No clinical or pathologic evidence of nodal involvement
Amenable to regular follow-up (according to research policies) for at least 5 years
Within 7 days (+ 3 day window) of enrollment: Serum bilirubin =< 1.5 x the institutional ULN, or =< 3 x ULN if confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology)
Positive screening EBV antibody titer on screening test
RAPID EXPANSION PROTOCOL (REP) ELIGIBILITY: Clinical performance status equivalent to ECOG 0-1 at the last calendar clinical visit
Fiber optic exam with laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure) within 8 weeks prior to registration
Claustrophobia
At least one RAI-avid lesion identified on the most recent radioiodine scan (a diagnostic, post-therapy, or post-ablation scan) prior to study registration; (both RAI-sensitive and RAI-refractory patients are eligible if at least one tumor with RAI avidity of any degree can be identified within these parameters)
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); (this will not apply to subjects with confirmed Gilbert's syndrome [persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology], who will be allowed only in consultation with their physician)
Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
Agrees to the placement of an intraperitoneal port before the start of chemotherapy and remains in place through day 28 or longer
Active smoker
Histologically or cytologically confirmed HER2-positive (3+ by IHC or amplified by FISH) according to ASCO/CAP guidelines\r\n* Note: A HER2 result of 2+ by ICH is equivocal and requires a reflex test (same specimen using the alternative test) or new test (new specimen, if available, using same or alternative test)
Overweight or obese
Priority for members of a minority group
Individuals reporting < 3 days/week of mild or moderate activity
Willing to consent and accept randomization
Willing to provide an email address to register their Amazon Echo speaker at their home
Planning to relocate within the next 4-5 weeks
Mental condition that prevents patient from performing the study activities and requirements
Have at least one non-contiguous lesions that is distinct from the radiation candidate lesion that is able to be evaluated radiographically or clinically
Radiation therapy (XRT) >= 2 weeks for local palliative XRT; >= 6 months must have elapsed after XRT involving > 50% of the craniospinal axis or > 50% of the pelvis
Note: transfusions are permitted to meet these platelet and hemoglobin criteria if the reason for the cytopenias are judged to be secondary to marrow involvement with tumor per principal investigator (PI) or PI designee
No evidence of dyspnea at rest, and
Any other ongoing serious medical problem unrelated to cancer or its treatment that is not covered by the detailed exclusion criteria and which is expected to interfere with the anti-tumor effect of infused EA-NK cells or the action of hu14.18-IL2 or to significantly increase the severity of the toxicities experienced from this immunotherapy regimen
Enrollment in any other treatment studies that would interfere with the endpoints of this study from screening up to 28 days after the last immunotherapy (EA-NK cells or last infusion of hu14.18-IL2) in the opinion of the PI or PI designee is not permitted
Patients PRE-identified as having either a germline deleterious mutation or tumor expression of a deleterious mutation) as determined by next-generation DNA sequencing only, in at least one gene involved in DNA damage repair through homologous recombination including but not limited to: ARID1A, ATM, ATRX, MRE11A, NBN, PTEN, RAD50/51/51B, BARD1, BLM, BRCA1, BRCA2, BRIP1, FANCA/C/D2/E/F/G/L, PALB2, WRN, CHEK2, CHEK1, BAP1, FAM175A, SLX4, MLL2 or XRCC\r\n* Patients with somatic mutations will be PRE-identified as having a homologous recombination mutation based on next-generation sequencing (NGS) done in a Clinical Laboratory Improvement Act (CLIA) certified, College of American Pathologists (CAP) tested and bioinformatics-validated testing lab PRIOR to enrollment in this current protocol; the testing may have been done at any time prior to enrollment; HOWEVER, if any patient has had NGS testing more than 3 months prior to enrollment, or if there has been intervening therapy, then a repeat NGS test must be done and the deleterious somatic mutation must be re-identified for inclusion\r\n** The determination of a deleterious mutation must be supported in the documentation included in the testing, and should include clinical, or pre-clinical literature to support the finding that a specific mutation results in impaired function of the gene, and thus impaired DNA repair through homologous recombination; variants of unknown significance will not be eligible\r\n* Patients with germline deleterious mutations may have been identified at any time point prior to inclusion in the protocol and do NOT need to have this genetic testing repeated regardless of time frame and intervening therapy
Patient is capable of swallowing pills whole
Acute GvHD prophylaxis with methotrexate and tacrolimus
Subjects who participated in a clinical trial of acute GvHD prophylaxis in which chronic GvHD was a secondary end point
Currently on therapy for active chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); prophylactic therapy is allowed
Richter transformation.
Medical conditions, per the investigator’s judgment, that predispose the patient to untoward medical risk in the event of volume loading (e.g. intravenous [IV] fluid bolus infusion), tachycardia, or hypotension during or following treatment with Pexa-Vec
Histologically-proven (preferably confirmed by National Institute of Health [NIH] pathology review if initial pathology was done outside of NIH, but not mandatory), surgically inoperable, PHEO/PGL patients
PHEO/PGL that is associated with the SDHx mutations or is not associated with any known susceptibility genetic mutations for PHEO/PGL (a.k.a. “apparent sporadic”), based on documented genetic testing results obtained prior to study enrollment; PHEO/PGL that is associated with non-SDHx mutations such as VHL, NF1, and RET will not be eligible for this study
Patient is or will be enrolled on protocol 00-CH-0093, Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma
Ability and willingness to obtain all required scans per study schedule
Must have outside endocrinologist/medical oncologist who can follow the patient after receiving peptide receptor radionuclide therapy (PRRT) at the NIH
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
Patients with histological and/or cytological evidence of BPDCN in the peripheral blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is either previously untreated or is persistent/recurrent following prior treatment for BPDCN. Eligibility criteria for UCART123 administration
Must have at least one intrahepatic lesion amenable to SBRT
Prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) allowed, however, patient must have separate intrahepatic lesion amenable to SBRT and biopsy
History of hypersensitivity to alectinib or any of its excipients; in addition, subjects who are unable to tolerate the 600 mg twice daily BID dose of alectinib will not be permitted to enroll unless doses of alectinib below the entry level are being investigated (e.g. dose level -1 and -2) and they have previously tolerated alectinib monotherapy at the dose being investigated
Current diagnosis of symptomatic bradycardia
Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
Any of the following:\r\n* Pregnant persons\r\n* Nursing persons\r\n* Persons of childbearing potential who are unwilling to employ adequate contraception
Have at least one metastatic lesion amendable for biopsy (core, punch, or fine needle aspiration [FNA])
Patients who have previously been treated with another agent targeting the MUC20/c-Met axis, including either monoclonal antibodies to MUC20 or c-Met, or small molecule inhibitors of c-Met
Subjects who have carfilzomib-related posterior reversible encephalopathy syndrome (PRES) and thrombotic microangiopathy (TMA) should not be challenged with carfilzomib
Clinically, subject is a candidate for cytoreductive nephrectomy
Active and inactive vaccinations within 4 weeks of the first dose of avelumab and while on trial is prohibited
Consented for genome sequencing and dbGAP-based data sharing
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered
Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Documentation of CD20+ status
Patients must have an indication for therapy per standard modified Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria including:\r\n* Symptoms attributable to lymphoma, threatened end-organ function, cytopenia secondary to lymphoma, bulky disease (defined as: single mass > 7 cm in diameter, or 3 or more masses > 3 cm in diameter), splenomegaly, and steady progression over at least 6 months
Willing to undergo craniotomy and resection of their glioblastoma at Mayo Clinic
Signs or symptoms of life-threatening raised intracranial pressure: as defined by the treating neurosurgeon, including severe headache, nausea, decreasing level of consciousness, precluding 4-7 day delay in scheduling neurosurgery
Vulvar HSIL must be HPV-16+ by a polymerase chain reaction (PCR), ribonucleic acid (RNA), or in situ hybridization test from a CLIA certified laboratory
Have been treated on any Merck-sponsored pembrolizumab-containing gastric cancer pivotal trial will require prior authorization by Merck in order to enroll in this study
Pathologically confirmed adenocarcinoma of the esophagus, GEJ or stomach.
Presence of one or more cutaneous lesions (measuring at least 1 cm x 1 cm in size; if only one lesion is present it should be up to the investigator discretion to determine eligibility)
Confirmation of G12V mutated KRAS, NRAS or HRAS by the Laboratory of Pathology of the National Cancer Institute (NCI)
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Absolute neutrophils > 1,500/µL
Serum lactate dehydrogenase (LDH) levels < 1.5 × ULN
AML Blast cell expressing CD123 by flow cytometry performed as per standard practice
Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the Memorial Sloan-Kettering [MSK] Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have human anti-human antibody (HAHA) antibody titer =< 1300 enzyme-linked immunosorbent assay (Elisa) units/ml; human anti-mouse antibody positivity is allowed
Total volume of lesions =< 30 cm^3
Maximum volume of largest lesion =< 5 cm^3\r\n* This volume limit would be equivalent to a largest diameter of about 2.1 cm, assuming a perfect sphere
Not a candidate for or eligible for but refused Gamma Knife radiosurgery
Urine protein (dipstick): negative or trace; in case of trace, a urinalysis has to be performed in the local laboratory and have to confirm that such abnormality is not to be considered clinically significant, according to the investigator's judgement
Patient has sufficient stored T cell product to manufacture appropriate doses of T-APCs
COHORT A
Prior to lymphodepletion on protocol PLAT-02, total CD19 antigen load in the bone marrow is <15% of cells analyzed by flow cytometry (CD19 antigen load includes both CD19+ leukemia cells and non-malignant B cells)
Has sufficient CD19 CAR T cell product (1x10^6 CAR T cells/kg) meeting release criteria for infusion
COHORT B
COHORT C
Following CAR T cell infusion on PLAT-02, patient initially achieved BCA and has now lost BCA in the bone marrow or peripheral blood, before 6 months; BCA is defined as < 1% CD19+ cells by lymphocyte subset testing, as measured by flow cytometry\r\n* If patient has disease relapse in this setting, disease must remain CD19+
Has sufficient CD19 CAR T cell product (1x10^6 CAR T cells/kg) meeting release criteria for re-infusion
LDH ?2.5 times the ULN.
Known lactose intolerance.
Immunosuppression, of any kind
Active on-going immunologic or autoimmune disease including but not limited to systemic or cutaneous lupus erythematosus, cutaneous psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, sicca syndrome, polymyalgia rheumatica, polyarteritis nodosa, granulomatous polyangiitis, microscopic polyangiitis, polyarteritis nodosa, temporal arteritis, giant cell arteritis, dermatomyositis, Kawasaki disease
Pre-treatment biopsy must establish the diagnosis AND have enough remaining tissues to satisfy the mandatory research studies
Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
AT SCREENING: Serum chemistries, renal and liver panels within institutional normal limits or meets the requirements for radical prostatectomy.
Currently enrolled in another interventional study.
Patients with known contraindications to radiotherapy including inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia telangiectasia, Nijmegen breakage syndrome)
Serum sodium >= LLN
Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pomalidomide+dexamethasone (pom+dex) arm (e.g., Risk Evaluation and Mitigation Strategies [REMS], pregnancy prevention programs).
Have one of the following confirmed histologically, cytologically, or through biochemical testing:\r\n* Wild-type GIST (GIST without KIT or PDGFRA mutation);\r\n* PHEO/PGL with a germline mutation in SDHA, SDHB, SDHC, or SDHD;\r\n* Renal cell cancer associated with HLRCC\r\n* Testing will be performed in Clinical Laboratory Improvement Act (CLIA) certified labs using genetic tests for KIT/PDGFRA and testing panels developed for patients with PHEO/PGL; results from outside labs will be accepted; pathologic diagnosis will be reviewed and verified at the Clinical Center
1-3 sites of recurrence (< 60 cc per site, total volume < 100 cc)
Previous enrollment in the present study
Patient is confirmed to have actively symptomatic pneumonitis
Must have a Functional Performance Status of less than or equal to 2 on the ECOG scale (Appendix VII).
Must have reached legal age to consent.
Recognized immunodeficiency condition including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have acquired, hereditary, or congenital immunodeficiencies, including HIV infection or have been splenectomized.
Has a diagnosis of congenital immunodeficiency
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Subjects who fail to meet the above criteria
Men taking propranolol on a daily for any reason are excluded
No prior exposure to colony stimulating factor 1 receptor (CSF1R) antagonists such as but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), JNJ40346627 (Johnson & Johnson), including both anti-CSF1R and small molecule inhibitors and prostaglandin E2 receptor 4 (EP4) antagonists
Active hydronephrosis
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Participants with interstitial pneumonia or extensive and symptomatic fibrosis of the lungs
Exclude if patient has cirrhosis or is currently being actively treated for hepatitis C
Subjects taking drugs that interact with OATP1B3 (an anion transporter), MRP2 (a multidrug resistant protein), and/or P-glycoprotein (P-Gp)
Subjects with bowel obstruction
DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel (testing of de novo or archiaval tumor tissue (via central laboratory) or prior historical testing (with Sponsor approval) using the Foundation Medicine, FoundationOne® NGS gene panel test.
Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
Diagnosis of MDS (Myelodysplastic syndromes).
Haemoglobin >= 9.0 g/dL
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
All races and ethnic groups are eligible for this trial
Residual side effects from chemotherapy or radiation, which have not gotten better except for nerve pain or tingling or hair loss.
Patients must have histologically or cytologically confirmed metastatic/recurrent adenoid cystic carcinoma (ACC) or non-adenoid cystic carcinomas (non-ACC) of major or minor salivary glands
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Primary site other than oropharynx
Subjects must not be a known carrier of BRCA1 or BRCA2 gene mutation
Subjects must not be pregnant or unwilling to undergo pregnancy screening
Previous esophageal dilatation is permitted, provided the patient has developed recurrent dysphagia since that procedure
T4 tumors with involvement of any adjacent structure, including the trachea, aorta or pleura
Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium[Ca] > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab\r\n* Subjects who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible\r\n* Subjects who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while in the study
Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
On-going gross hematuria associated with clots
Patients with history of (h/o) pneumocystis pneumonia (PCP) or positive cytomegalovirus (CMV) viremia confirmed twice at least 1 day apart at screening
Previous chest radiotherapy
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only upon treating physician, principal investigators (PI) or co-PIs approval
Richter transformation
FOR ALL PHASES (Ib AND II):
FOR ALL PHASES (Ib AND II): Current therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer; subjects must have discontinued therapies for at least 28 days prior to first baseline biopsy
FOR ALL PHASES (Ib AND II): Participants receiving anticoagulation therapy are not allowed
FOR ALL PHASES (Ib AND II): Chronic oxygen therapy
Known contraindications to radiotherapy
Prior thoracic irradiation
Medical contraindications to thoracic irradiation
Hydronephrosis or biliary obstruction
Childs B or C cirrhosis
Evidence of severe portal hypertension by history, endoscopy, or radiologic studies\r\n* Note: Any diagnosis of portal hypertension or clinical stigmata of such including but not limited to gastric or esophageal varices, umbilical vein varices or telangiectasias
Patients must have bone marrow and peripheral blood studies available for confirmation of diagnosis of AML; CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 [Flt-3] status) will be obtained as per standard practice.
PRE-REGISTRATION
HER2 status confirmed positive by means of immunohistochemistry (IHC) or in situ hybridization (ISH) according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 guidelines; it is considered positive if scored as 3+ by an IHC method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an ISH method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/chromosome enumeration probe (CEP)17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell)
Active substance abuse or psychiatric disorders; in case, the patient falls under the lower spectrum of psychiatric disorders and is able to function well under medication, the patient could be accrued at the discretion of the physician
For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (adriamycin-bleomycin-vinblastine-dacarbazine [ABVD]) or an alternative non-cross resistant regimen (e.g. mustargen-oncovin-procarbazine-prednisone [MOPP])
Eligible for any higher priority transplant protocols
No prior cystectomy
Prior cystectomy
Known or suspected high-frequency microsatellite instability (MSI-H) CRC
Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Subject previously treated with blinatumomab.
Prisoners or subjects who are involuntarily incarcerated
Drugs with a predisposition to hepatoxicity should be used with caution
Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes; a second post-treatment biopsy will be offered but will not be mandated
Availability of and patient acceptance of curative therapy
Any of the following:\r\n* Pregnant persons or persons of reproductive ability who are unwilling to use effective contraception\r\n* Nursing persons
Performance status >=70% (Karnofsky); patients > 50 years should have adequate cognitive function; any concerns regarding cognitive function should be addressed by a geriatrician/neurologist
If previously exposed to irradiation, the combined prior and anticipated exposure for Cycle 1 is not expected to exceed organ exposure limits outlined in Table 2
MVT-5873 and MVT-2163 administered as part of a different protocol
Tumour sites amenable to repeated biopsies.
Willingness to undergo paired tumour biopsies during the trial.
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). (This will not apply to subjects with confirmed Gilbert’s syndrome [persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology], who will be allowed only in consultation with their physician)
Previously enrolled in the present study
Must be functionally and technically fit for partial laryngectomy. Subsite study candidates will be evaluated by enrolling physician. The assessment checklist will be submitted at time of enrollment and evaluated by Dr. Gross or Dr. Phan.
creatinine phosphokinase isozymes CPK-MB and CPK-MM ? ULN;
Patients requiring treatment with one or more medications known to interact adversely with digoxin, namely thiazide and/or loop diuretics, quinidine, ritonavir, amiodarone, cyclosporine, itraconazole, propafenone, spironolactone, verapamil
Patients eligible for intensive induction chemotherapy and “medically unfit” based on a treatment related mortality (TRM) score >= 13.1\r\n* TRM score= a scoring model which predicts early death following intensive induction chemotherapy in newly diagnosed AML; \r\n** Model looks at ECOG performance status (PS), age, platelet count, albumin, second (2nd) AML, white blood cells (WBC), percentage (%) peripheral blasts, creatinine\r\n** Score above 13.1 associated with 31%+ chance of death after induction
Serum free light chain (FLC) > 100 mg/L of involved FLC
Patients with tumors > 7 cm or tumors involving the main bronchus or associated vessels or tumors that invade any critical structures (such as esophagus, brachial plexus, heart, mediastinal major vessels) are not suitable for SABR
Must have either a clinical diagnosis of NF1 or a germline NF1 mutation, or in patients without the NF1 syndrome, demonstrate an NF1 mutation in the GIST verified in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; in patients without the NF1 syndrome, confirmation of the NF1 mutation in the GIST is required for enrollment
For a clinical diagnosis of NF1 patients must have at least two of the diagnostic criteria for NF1 listed below:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* A neurofibroma or plexiform neurofibroma\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
At least 4 weeks must have elapsed since any surgeries, with evidence of good wound healing
Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
Ophthalmological conditions as follows:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion\r\n* Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)\r\n* Evidence of optic glioma, malignant glioma, malignant peripheral nerve sheath tumor,\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility
No supplementation with vitamin E is permitted because the selumetinib capsules contain vitamin E
Able to walk and jog on a treadmill, in the opinion of the treating physician
Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline defined as at least one of the following:\r\n* Achieving a plateau in oxygen consumption concurrent with an increase in power output;\r\n* Respiratory exchange ratio >= 1.1 (RER);\r\n* Volitional exhaustion with a rating of perceived exertion >= 17 (RPE)
For the sixteen patients who elect to participate in the optional technology portion involving electronic step counts and blood pressure monitoring, the patient must have a Bluetooth-enabled smart phone, which is compatible with the wireless health monitors
HPV testing must be compliant with the following criteria:\r\n* p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al)\r\n* p16 IHC positivity is to be validated using an HPV polymerase chain reaction (PCR) during the induction phase; this is essential as HPV genotype influences treatment arm allocation, with non-HPV16 HPV strains being considered high risk
Unidentifiable primary site
Prisoners or subjects who are involuntarily incarcerated
(For Cohort A) Archived tissue available pre-screening to confirm FR alpha+ breast cancer. (For Cohort B) ·Confirmed FRalpha+ breast cancer defined as high FRalpha expression: >= 75% of cells having >= 1+ expression, or moderate FRalpha expression: 25%-74% of cells with >= 1+ expression
Active or chronic corneal disorder, including but not limited to the following: Sjogren’s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
Required used of folate-containing supplements (e.g. folate deficiency)
Screening evaluation appropriate for leukapheresis and T-cell collection
Internal review of histology
Successful collection of T cells for huJCAR014 manufacturing
CRITERIA FOR LYMPHODEPLETING CHEMOTHERAPY AND huJCAR014 TREATMENT: Presence of active acute or chronic GVHD
Persistent >= grade 2 diarrhea regardless of etiology
Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication; however, corticosteroid can be dropped after confirming of no asthma like reaction to paclitaxel after 3 doses
Malignancies resulting in cutaneous metastasis originating from: breast, lung, head and neck, pancreatic, urinary bladder, prostate, testicular, ovarian, uterine, cervical, gastric, adrenal, thyroid, parathyroid cancers, or other solid tumors which previously responded to taxane treatment;
ANC ? 1,500/µl
Open or ulcerated wound(s) extending through the dermis within the treatment area;
mCRC with prior progression on standard multi-agent combination chemotherapy and regorafenib as a standard approved monotherapy; progression on prior regorafenib is required for inclusion in this clinical study; prior regimens may include fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX) -/+ bevacizumab, folinic acid-fluorouracil-irinotecan (FOLFIRI) -/+ bevacizumab or -/+ cetuximab (if KRAS wild-type) or panitumumab (if KRAS wild-type); other prior regimens may include 5-FU or capecitabine -/+ bevacizumab, irinotecan -/+ cetuximab or panitumumab, FOLFIRI -/+ ziv-aflibercept or ramucirumab
Renal failure requiring hemo-or peritoneal dialysis
Previous failure of iodine-131 (131I) therapy or not candidates to receive 131I as assessed by treating physician
Life expectance of >= 12 weeks
Ability and availability to complete all prescribed biopsies (prior to the first evofosfamide dose and between day 15 of Cycle 2 and day 8 of Cycle 3)
Have identified a backup cells source in case of engraftment failure. The source can be autologous, related or unrelated.
Patients with uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
Subjects with UGT1A1*28 polymorphisms.
Frequent vomiting.
Previous enrollment in this study, followed by withdrawal for any reason.
For patients in the relapse or refractory cohort, any other therapy not being a hypomethylating agent after hypomethylating agents (HMA) failure or more than 4 months since completion of last cycle of hypomethylating agent. Please note that hypomethylating agent may include second generation compounds such as SGI-110, oral decitabine or oral azacitidine and will also include combinations with investigational agents
Philadelphia chromosome (Ph)+ ALL
Willing to comply with protocol therapy and required safety monitoring (self-report, pulse oximetry, remote spirometry, labs)
Must have had a nephrectomy (radical or partial) and must provide the cell block from the nephrectomy
Additional prior systemic treatments not allowed
Subradiographic and/or cytopathologic evidence of peritoneal carcinomatosis found at staging laparoscopy\r\n* Documentation of cytopathologic diagnosis of malignant peritoneal cytology in the absence of disseminated peritoneal disease must be obtained; if cytologic analysis reveals atypical cells of undetermined significance, a repeat lavage with cytopathologic analysis will be performed and must demonstrate evidence of malignancy\r\n* Limited peritoneal involvement (=< P1 or peritoneal cancer index [PCI] < 10) found at staging laparoscopy or on final pathology that is deemed completely resectable is permitted
Physiologically able to undergo HIPEC and gastrectomy
Disseminated extra-peritoneal or solid organ metastases\r\n* Includes carcinomatosis associated with clinically or radiographically evident ascites (greater than 500 cc)\r\n* Excludes greater omentum and ovarian metastases
Harboring a mutation in the BRAF oncogene or the KRAS or the NRAS oncogene
Primary amyloidosis (AL) or myeloma complicated by amyloidosis
Nonsecretory multiple myeloma based upon standard M-component criteria (i.e., measurable serum/urine M-component) unless the baseline serum free light chain level is elevated; patients with plasmacytomas with biopsy proven known mutations may be included as long as they have evaluable disease by imaging
Metastatic or unresectable AR+ triple-negative breast cancer (TNBC); AR positivity assessed centrally and defined as immunohistochemical (IHC) staining of >0% of tumor nuclei.
No prior therapy with AR antagonists including but not limited to bicalutamide, enzalutamide, abiraterone and orteronel.
Documented evidence of an ALK rearrangement (by fluorescence in situ hybridization [FISH], immunohistochemistry [IHC], or next generation sequencing [NGS]), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
Histologic or cytologic diagnosis of NSCLC who have received previous intrathoracic radiation therapy with definitive intent and have a tumor recurrence in or near the prior irradiation fields; re-biopsy of the recurrence is not required and is left to the discretion of the treating physician, although every effort should be made to confirm recurrence pathologically
Clinical target volume (CTV) size must be < 250 cc, no more than 74 Gy of prior radiation in 2 Gy fractions previously administered
The primary lesion must be accessible for endoscopic biopsy and injection as evaluated by a gastroenterologist at New York-Presbyterian (NYP)-Columbia; further, the patient must be deemed able to tolerate repeated endoscopy procedures by an anesthesiologist and/or gastroenterologist at NYP-Columbia
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) or requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use
Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
Untreated symptomatic hydrocephalus determined by treating physician
Serious concomitant systemic disorder.
Currently enrolled in another clinical trial.
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Previous enrollment in the present study
Drugs that potently inhibit or induce CYP3A4 should be administered with caution
Trametinib may be an inhibitor of CYP2C8 in vivo; caution should be exercised when dosing trametinib concurrently with medications with narrow therapeutic windows that are substrates of CYP2C8
Must be fit enough to receive next-line chemotherapy (either gemcitabine, docetaxel, or pemetrexed [non-squamous only]) according to the discretion of the treating physician
Patient has salivary gland primary
For part 1, subject will have ? 1 and ? 5 tumors (prior to TURBT), none of which exceeds 3.0 cm in diameter; for part 2, patient will have ? 2 and ? 5 tumors (prior to TURBT), none of which exceeds 3.0 cm in diameter (resection loop ~1 cm).
Subject is surgical candidate for TURBT as part of normal NMIBC treatment plan. For part 1, successful completion of TURBT procedure. For part 2, successful completion of TURBT procedure with one marker lesion left intact; the marker lesion should be > 0.5 cm and < 2.0 cm in diameter.
Able to retain bladder instillations for up to 120 minutes (± 15 minutes).
Has had any previous exposure to paclitaxel or docetaxel in the last 5 years.
An indwelling ureteral stent.
Has an active diagnosis of interstitial cystitis.
Acute leukemias of ambiguous lineage
ANC ? 1.5 x 109/L
Thrombotic or embolic events;
Acute or subacute intestinal occlusion;
Willing to receive an mpMRI
Prior prostatectomy
Known sensitivity to any of the study medication components
Children are excluded from this study, but will be eligible for future pediatric trials
Legal incapacity or limited legal capacity
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Center for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men
Evidence of distant metastases as determined by the central reading committee
More than one primary lesion
In the opinion of the investigator, EUS directed implantation posing undue subject risk e.g. previous EUS-FNA was considered technically too difficult to perform, or imaging demonstrates multiple collateral vessels surrounding or adjacent to the target tumor
Evidence of radiographic invasion into stomach, duodenum or peritoneum (if not certain confirmation must be obtained prior to enrolment)
All primary cutaneous T-cell lymphomas
Recent (within the past year) or active suicidal ideation or behavior
Patients must have a serum creatinine less than or equal to 2.0 mg/dL and total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of a biliary stent or percutaneous transhepatic drainage is acceptable; once biliary drainage has been established, institution of protocol therapy may proceed when the total bilirubin falls to 4.0 mg/dL or lower)
Absence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, sever brain injuries, dementia, or psychosis
Patients must have minimal or no disease related-symptoms (minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly scheduled narcotics)
Willing to travel to the National Institutes of Health (NIH) for follow-up visits
Subject re-enrollment: this study permits the re-enrollment of a subject that has discontinued the study as a screen failure (ie, subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however, they must still undergo pregnancy testing as described in this section
Prisoners or subjects who are involuntarily incarcerated
Subjects must have at least 1 injectable cutaneous, subcutaneous soft tissue or nodal lesion >= 10 mm in longest diameter; of note, bone lesions are not eligible for injection unless there is a soft tissue component that is amenable to injection; injectable lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment
Active herpetic skin lesions or prior complications of herpetic infection
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for human herpesvirus 1 (HSV-1) induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
Unless considered to be due to leukemic organ involvement.
Female participants must be either postmenopausal defined as:
Participant had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1 translocation.
Circulating blast count > 30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed)
Synchronous primaries outside of the oropharynx and larynx
BUN >30 and a creatinine >2.
Proteinuria >1+ on urinalysis or >1 gm/24hr.
Agrees to take measures to avoid becoming pregnant during the study and
Patients who require anticoagulation, systemic steroids, statin therapy or beta-blocker therapy. The beta-blocker might compromise use of epinephrine for the rare possibility of anaphylaxis. Hypertension controlled by other agents does not disqualify, provided other criteria are met.
Ability to take pills by mouth
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject
Only for subjects enrolled in Arm 3 - Neratinib and trametinib: all skin rash (dermatitis acneiform, erythema, xeroderma, eczema) should be at grade 1 when starting trametinib treatment.
Only for subjects enrolled in Arm 3 - Neratinib and trametinib: history of retinal disorder, dry eye syndrome, or blurry vision need to be evaluated by ophthalmology prior to starting treatment.
Only for subjects enrolled in Arm 3 - Neratinib and trametinib: albumin less than 3 Gm/dL.
Neutrophils < 1,500/mm^3
Prisoners or subjects who are involuntarily incarcerated
Has a pathologic diagnosis of invasive esophageal, gastroesophageal or gastric adenocarcinoma
Plan for neoadjuvant chemoradiation
Has a diagnosis of scleroderma
The presence of a TP53 mutation should be determined by Genoptix (or institutional preferred equivalent assay) for all patients; detection of a TP53 mutation at the time of initial diagnosis is sufficient for enrollment; detection of a TP53 mutation in either the peripheral blood or bone marrow is adequate for enrollment
Inability to tolerate first-line treatment with sorafenib (e.g., unacceptable toxicity), tumor progression on sorafenib, patient preference to stop sorafenib and for alternative therapy/trial, or patient preference to forgo sorafenib for alternative therapy/trial
Poorly controlled or refractory (grade 3-4) hepatic encephalopathy
Must be able to swallow ribociclib (LEE-011) tablet/capsule
Borderline or low-malignant potential histology
Presence of active neurological disorder(s).
Diagnosis of choroidal melanoma
Histologically confirmed diagnosis of initial or recurrent anal or vulvar high-grade squamous intraepithelial lesion diagnosed on or after 1/1/2014; study pathologist will use p16 staining as needed to rule out low-grade squamous intraepithelial lesion (LSIL) disease
No clinical evidence of HSIL on screening examination; if HSIL is suspected, a biopsy will be done to exclude HSIL; patients whose screening visit reveals HSIL on biopsy, may be re-screened one time, >= 2 months after therapy
Willingness to sign medical records release form and tissue release form
Prior HPV vaccination
Currently participating in an interventional research study related to HPV, except the Anal Cancer HSIL Outcomes Research (ANCHOR) study (NCT02135419)
Metastatic colorectal cancer with mismatch repair deficiency (MMR-D or microsatellite instability [MSI]-high)
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Acute leukemias of ambiguous lineage
In general good health as determined by the medical provider
Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry; the patient’s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH); if unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression; the sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment
Seronegative for human T-cell lymphotropic virus type 1 (HTLV-1)
At time of protocol enrollment, the patient should be negative for cytomegalovirus (CMV) by antibody testing or by PCR; in case of disagreement between these 2 CMV tests, the tests will be repeated and department (Dept.) of Laboratory Medicine consulted
Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
For enrichment stage of trial only (if necessary): Confirmation of a suspected/known deleterious mutation in a gene of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D or other DNA repair genes) via Clinical Laboratory Improvement Act (CLIA) certified testing
Previous enrolment in the present study
Richter’s transformation confirmed by biopsy
Unable to understand the purpose and risks of the study
Somatostatin receptor (SSTR) positive sites as demonstrated by either SSTR2 positivity (2+ or 3+ intensity and greater than 10% tumor cell occupying the receptors) or a nuclear medicine scan utilizing 111In-DTPA-phe3-octreotide (Octreosca) or 68Ga-DOTA-tyr3-octreotide within 12 months prior to anticipated cycle 1 day 1 (C1D1) demonstrating SSTR positive tumor sites
Prior peptide-receptor radiotherapy (PRRT)
Subjects for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk
Proteinuria, grade 2 (i.e., >= 2+ proteinuria)
Cabazitaxel: AST =< 1.5 x ULN
No evidence of clinical progression, in the form of increased lesions on cross-sectional imaging, or new cancer-attributable symptoms or worsening of existing symptoms
Received more than 10 cycles of docetaxel (for docetaxel cohort only) or 6 of cabazitaxel (for cabazitaxel cohort only)
Positive serum anti-poliovirus titer >= 1:8 prior to biopsy
A history of neurological complications due to past poliovirus (PV) infection would imply previous virus replication in the central nervous system (CNS); based on animal studies, previous exposure to poliovirus administered intracerebrally can reduce subsequent virus replication in the CNS
Patients with a diagnosis of agammaglobulinemia, that is:\r\n* Undetectable anti-tetanus toxoid immunoglobulin G (IgG)\r\n* Known history of agammaglobulinemia
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Renal failure requiring hemo-or peritoneal dialysis
AST and ALT>5xULN
Urinary tract obstruction or marked hydronephrosis
Monitored anesthesia care (i.e., regional anesthesia alone without plans for general anesthesia)
Poor health literacy
Documented CD20+ FL.
Did not discontinue because of tolerability concerns.
Not a candidate for curative treatments (i.e., resection, transplantation)
Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 60 days of signing the ICF
Patient must have at least 3 measurable lesions that are >= 1.5 cm in one dimension; one of the lesions must be >= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by interventional radiology and principal investigator (PI) (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
Ability to complete questionnaire(s) by themselves or with assistance
Biopsy proven T2 malignant melanoma
Unable to tolerate general anesthesia
Melanoma located on face or digits
Modified KPS of < 80%
> 5 comorbidity points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI)
Anti-thymocyte globulin (ATG) within 8 weeks of HSCT admission
Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan
Evidence of wound dehiscence
Clearance of 99mTc mercaptoacetyltriglycine (MAG3) within 1.5 x ULN and no evidence of obstruction on the scan
Subjects must have received, were ineligible to receive, or refused at least one cytotoxic chemotherapy and enzalutamide or abiraterone or both enzalutamide and abiraterone
Subject is currently on renal dialysis
Prior exposure to elotuzumab or pomalidomide
Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis
All patients must have no more than 3 contiguous vertebral body levels treated at a single site, and no more than 3 discontiguous vertebral body levels treated
All patients must have received prior conventional external-beam radiation therapy (cEBRT) to the site of interest to no more than a critical neural tissue dose equivalent dose (EQD)2/2 of 42 Gy in a single session or 50 Gy cumulative over multiple sessions and cauda equina dose EQD2/2 of 50 Gy in a single session or 60 Gy cumulative over multiple session
All races and ethnic groups are eligible for this trial
Prior history of radiation at the site of interest resulting in a critical neural tissue dose of EQD2/2 of > 42 Gy in a single session
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
Previous enrollment or randomization in the present study.
Unresolved partial or complete small or large bowel obstruction.
Non-English speakers will be excluded from participating in the patient-reported outcomes component of the study.
Prisoners or subjects who are involuntarily incarcerated
Soft tissue disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; (Note: the appearance of one or more new non-osseous lesions is also considered progression); clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes) and at least 10 mm in diameter as assessed using calipers (e.g., skin nodules)\r\n* Per Prostate Cancer Working Group 2 (PCWG2): Visceral (lung, liver adrenal) or extranodal lesions need to be >= 10 mm in one dimension, using spiral CT; however, lymph nodes need to be >= 20 mm in at least one dimension to be considered new
No structurally unstable bone lesions suggesting impending fracture
A score of 0-1 on Brief Pain Inventory (BPI)-Short Form (SF) question 3 (worst pain in last 24 hours) will be considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic
PRE-SCREENING: Mesothelin positive
Renal failure requiring peritoneal dialysis or hemodialysis
In the opinion of the treating investigator, patients must be an unsuitable candidate for a pediatric-inspired regimen, reasons for which may include (but not be limited to) older age (i.e., >= 40 years), practical/logistical barriers to or toxicity concerns from administration of a pediatric-inspired regimen, or Ph+ disease
Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT.
Previous enrolment in the present study
Men who are expecting to father children within the research period
Have received radiation therapy with concurrent temozolomide; total radiation dosage can range from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over 6 weeks, or the equivalent in a hypofractionated protocol (for example, 4000cGy in 15 fractions or 2500cGy in 5 fractions); patients who are MGMT negative do not need to have received temozolomide
Specific mutations:
International Prognostic Index (IPI) score of 2-5
Demyelinating form of Charcot-Marie-Tooth disease
Prior radiotherapy to the mediastinal/pericardial region
Positive results for the human T-lymphotrophic 1 virus (HTLV-1)
CD4 count >= 100 in the dose-finding cohort; once the dose-finding cohort is complete and if safety is established, participants with any CD4 count, including CD4 count < 100, will be allowed in the dose-escalation phase
Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance
serum free light chain greater than or equal to (>=) 5.0 milligram/deciliter (mg/dL) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 5 mg/ dL
One or more organs impacted by AL amyloidosis according to consensus guidelines
NT-ProBNP > 8500 nanogram per liter (ng/L)
For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=2730 IU/mL to less than or equal to (<=) 273000 IU/mL in whole blood or >=910 IU/mL to <=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator.
Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation.
Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] coinfection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
Have previously completed, discontinued, or have been withdrawn from this study.
Patients must be positive for the RARA super-enhancer associated biomarker or RARA pathway associated biomarker at the time of study screening.
Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
Bilateral breast cancers are allowed if the treating clinician has determined the patient should be treated as ER+ and HER2- negative
Diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis
Palpable splenomegaly of 5 to 10 cm below left subcostal margin on physical exam AND active symptoms of MF at the screening visit as demonstrated by presence of 1 symptom score ? 5 or 2 symptom scores ? 3 using the Screening Symptom Form
Unwillingness to be transfused with blood components
Subjects with peripheral blood blast count of > 10% at the screening or baseline hematology assessments
Subjects who are not willing to receive red blood cell (RBC) transfusions to treat low hemoglobin levels
Previously obtained tumor sample exhibits a hypermutator phenotype; for the purposes of this trial, a hypermutator phenotype is defined as tumors harboring >= 30 mutations (non-synonymous somatic point or indel mutations) detected by the Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or comparable next generation sequencing performed in a Clinical Laboratory Improvement Act (CLIA) environment; contingent to approval by the MSK principal investigator, patients with less than 30 mutations may be eligible if they display a mutation in a mismatch repair gene or other mutations in genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MutL homolog (MLH)1, MutS protein homolog (MSH)2, MSH6, PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS)2, polymerase (deoxyribonucleic acid [DNA] directed), epsilon-1 (POLE), polymerase (DNA directed), delta 1, catalytic subunit (POLD) as determined by validated methods, or if microsatellite instability is present, as identified by polymerase chain reaction (PCR) or other validated methods\r\n* Note: the MSK-IMPACT (Integrated Mutation Profiling for Actionable Cancer Targets) assay is a next generation genomic profiling performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in a CLIA-certified Molecular Diagnostic Service laboratory; IMPACT provides full exon coverage of 410 cancer related genes and can detect base substitutions, small indels, copy number alterations and selected gene re-rearrangements; in some cases, additional assays such as Sanger sequencing or fluorescence in situ hybridization (FISH) may be required to confirm specific results detected on IMPACT; patients at MSK will have this assay to determine eligibility; use of other validated next-generation sequencing techniques for eligibility may be considered, provided they are performed in a CLIA-certified laboratory and are approved by the MSK principal investigator
Relapsed or refractory B-cell NHL, including
Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosofamide, bendamustine) within 2 weeks of leukapheresis.
Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to leukapheresis.
Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
Adequate renal and hepatic function (creatinine ? 2.0 x IULN, bilirubin ? 1.5 IULN, AST and ALT ? 3.0 x IULN or 5 x IULN if known liver metastases).
Complete or partial response by International Working Group (IWG) Working Group or International Conference on Malignant Lymphoma (ICML) criteria to maximum of one salvage line of chemotherapy without pre-HDT/ASCT salvage radiotherapy
Salvage therapy that includes involved field radiotherapy
Pure seminoma after orchiectomy presenting with isolated retroperitoneal lymphadenopathy OR stage I pure seminoma with isolated retroperitoneal relapse; relapse should be within 3 years
Biopsy is not required, though if biopsy of the retroperitoneal node(s) was obtained, pathology must be consistent with pure seminoma
Serum alpha-fetoprotein (AFP) not greater than 1.5 times the upper limit of the local laboratory assay within 14 days of RPLND
Serum lactate dehydrogenase (LDH) not greater than 1.5 times the upper limit of the local laboratory assay within 14 days of RPLND
Corrected calcium at or below ULN
All participants who are prescribed lenalidomide or pomalidomide must be counseled at a minimum of every 21-28 days about pregnancy precautions and risks of fetal exposure (Cohorts B, C, E, F)
ANC >/=1500 cells/mcL (Cohort C)
Evidence of progressive MM compared to pretransplant evaluation (Cohort C)
All subjects must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the National Institutes of Health (NIH) consensus conference criteria; in addition to a plexiform neurofibroma, one or more of the following diagnostic criteria for NF1 must be present:\r\n* Six or more Cafe Au Lait spots (>= 0.5 centimeter [cm] in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the spheroid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
For subjects enrolled for “major deformity” or a “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be contacted to review patient eligibility prior to enrollment
Dental braces or prosthesis that interferes with volumetric analysis of the neurofibroma(s)
Inclusion Criteria:\n\n        Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting\n        the following criteria:\n\n        Phase 1 Expansion\n\n          1. Patient has failed all standard therapies or standard therapy does not exist or is not\n             tolerated.\n\n          2. Patient has specific FGF/FGFR aberrations\n\n               -  Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other\n                  FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or\n                  amplifications\n\n               -  Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic\n                  oligodendroglioma) with FGFR gene fusions or activating mutations.\n\n               -  Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations\n\n               -  All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (? 10\n                  copies), FGFR gene fusions, or FGFR activating mutations\n\n        Phase 2\n\n          1. Patient has histologically or cytologically confirmed, locally advanced, metastatic,\n             unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by\n             the Sponsor's designated central laboratory\n\n          2. Patient has been treated with and failed at least one prior systemic gemcitabine and\n             platinum-based chemotherapy for the advanced disease\n\n          3. Must have documentation of radiographic progression of disease on prior systemic\n             therapy\n\n          4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid\n             Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO\n             criteria (2010) for brain tumors.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n\n          6. Adequate organ function\n\n        Exclusion Criteria:\n\n        A patient will be excluded from this study if any of the following criteria are met:\n\n          1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus\n             homeostasis.\n\n          2. History and/or current evidence of clinically significant ectopic\n             mineralization/calcification.\n\n          3. History and/or current evidence of clinically significant retinal disorder confirmed\n             by retinal examination.\n\n          4. A serious illness or medical condition(s)
Documented HER2 mutation.
Significant renal pathology defined as:\r\n* Estimated creatinine clearance (CrCl) < 40 mL/min (using Cockcroft-Gault formula based on actual body weight) and serum creatinine > 2.0 mg/dL; OR\r\n* Active, untreated SSc renal crisis at the time of enrollment; presence of nephrotic range proteinuria (defined as >= 3.5 gms/24 hours, or protein:creatinine ratio >= 3.5), active urinary sediment, urinary RBCs > 25 per HPF, or red cell casts require further investigation by a nephrologist to rule out glomerulonephritis, overlap syndromes, or other causes of renal disease in all subjects; subjects with glomerulonephritis or overlap syndromes will be excluded
Hematocrit < 27%
Presence of other comorbid illnesses with an estimated median life expectancy < 5 years
Must have MS/MMR result available at time of registration; MS/MMR status is to be determined per local practice (i.e. immunohistochemistry [IHC], polymerase chain reaction [PCR], or other methods)
Histologic diagnosis of GIST
At least 1 measurable lesion according to modified RECIST Version 1.1 (non?nodal lesions must be ?1.0 cm in the long axis or ?double the slide thickness in the long axis) within 21 days prior to the first dose of study drug.
malabsorption syndromes
Clinical signs or symptoms of GI obstruction or requirement of routine parenteral nutrition or tube feedings
Prior exposure to enzalutamide, androgen receptor antagonist ARN-509 (ARN-509) or other investigational AR-directed therapy in the setting of mCRPC
Pathologically confirmed MCL, with documentation of monoclonal CD20+ B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy
Has a diagnosis of immunodeficiency
Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc)
Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery
Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of REGN2810, or associated with immune-mediated adverse events that were ? grade 1 within 90 days prior to the first dose of REGN2810, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures.
Part A: Relapsed or refractory extracranial solid tumors and (Phase 1b expansion) relapsed or refractory extracranial solid tumors with molecular alterations, non-gene fusions;
Part B: Relapsed or refractory primary CNS tumors with molecular alterations, including gene fusions, documented by a CLIA-approved lab prior to enrollment;
Part C: Relapsed or refractory neuroblastoma;
Part D: Relapsed or refractory non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1, or ALK gene fusions documented by a CLIA-approved lab prior to enrollment;
Patient's cancer must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available
Non-clear subjects must be ENPP3 positive, defined as IHC H-score ?15
Hematopoietic function as follows:
No clinical symptoms of hypothyroidism
Female subject must either:
post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F
requirement for intravenous alimentation;
Has ocular conditions such as:
Monocularity
Visual acuity of 20/70 or worse in both eyes
Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections
Papilledema or other active optic nerve disorder
Has known sensitivity to any of the ingredients of:
Inlyta® (axitinib) and/or,
1% prednisolone acetate ophthalmic suspension and any other corticosteroids.
Prior pemetrexed is allowed except Arm A dose level 4 (cisplatin 75 mg/m^2)
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
If a patient declines to participate in genetics research, there will be no penalty or loss of benefit to the patient; a patient who declines genetics research participation will not be excluded from any other aspect of the main study
FOR AML ONLY: Absence of uncompensated disseminated intravascular coagulation (DIC- as diagnosed by standard International Society on Thrombosis and Hemostasis [ISTH] criteria)
Availability of and patient acceptance of curative therapy
AML ONLY: Current disseminated intravascular coagulopathy (DIC)
TCL ONLY: Any mass >= 5 cm
Lack of availability of a patient for immunological and clinical follow up assessment
DLCO =< 60%
CELL PROCUREMENT: CD19 positivity of lymphoblasts confirmed by flow cytometry or immunohistochemistry (IHC) per institutional standards
CELL PROCUREMENT: Bilirubin =< 1.5 x upper limit of normal (ULN), unless attributed to Gilbert’s syndrome, obtained within 72 hrs prior to procurement
CELL PROCUREMENT: Aspartate aminotransferase (AST) =< 3.0 x ULN, obtained within 72 hrs prior to procurement
CELL PROCUREMENT: Alanine aminotransferase (ALT) =< 3.0 x ULN, obtained within 72 hrs prior to procurement
CELL PROCUREMENT: Subjects with relapsed fulminant CD19+ ALL that is rapidly progressing who cannot safely delay definitive treatment for their ALL by at least 4 weeks in the opinion of the investigator
CELL PROCUREMENT: Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use if the milk is collected while the mother is being treated on study)
LYMPHODEPLETION: Subjects must have autologous transduced activated T-cells that meet the certificate of analysis (CofA) acceptance criteria
LYMPHODEPLETION: Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use if the milk is collected while the mother is being treated on study)
iC9-CAR19 CELL INFUSION: Corticosteroid use is contraindicated following iC9-CAR19 infusion unless medically necessary e.g., to treat CRS)
iC9-CAR19 CELL INFUSION: Severe systemic uncontrolled disease or toxicities that develop after lymphodepletion may prompt exclusion from cell infusion at the discretion of the investigator
Willing and able to receive adequate prophylaxis and/or therapy for thromboembolic events
Ability to complete study-related (QoL, pill diary) questionnaire(s) by themselves or with assistance
Non-secretory MM or known amyloid light-chain (AL) amyloidosis
Approval for hydroxychloroquine treatment by an eye doctor, based on a screening eye exam; examples of disqualifying baseline conditions include macular degeneration and other retinal disease such as cataracts that would interfere with required funduscopic examinations, or severe baseline visual impairment, retinopathy or visual field changes, or having only one functional eye; all patients must undergo a screening eye exam prior to enrollment
Prior treatment with everolimus is allowed, if the patient was able to tolerate 10 mg daily everolimus with acceptable side effects, and if everolimus was not given in combination with fosbretabulin; a 1 week washout period will be required if patient was previously on everolimus
Prior brentuximab vedotin is allowed in the dose-finding portion of the study (dose-finding cohort); in the expansion cohort, patients cannot be refractory to BV (defined as developing progressive disease while on treatment or progressed within 3 months of finished last dose of brentuximab vedotin)
To be performed within 10 business days prior to day 1: Cardiac function (12 lead-electrocardiogram [ECG] versus [vs] non 12 led ECG) shows no underlying arrhythmia or heart blocks (for VRP only)
Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model
Concomitant illness associated with a likely survival of < 1 year
Score greater than 7 on the Insomnia Severity Index and meet the criteria for insomnia disorder as defined by the Diagnostic and Statistical Manual of Mental disorders, 5th Edition (DSM-5) as assessed by the insomnia interview schedule
As per self report, heavy drinker (regularly having more than 14 alcoholic beverages per week)
As per self report, engaging in night shift work
As per self report significant needle phobia as to prevent participation in acupuncture
As per self report, currently engaged in ongoing acupuncture
Measurable disease per modified severity weighted assessment tool (mSWAT) and/or Sezary count
Lenalidomide, thalidomide or other immunomodulatory drugs (IMiDs)
Renal failure requiring hemodialysis or peritoneal dialysis
Phase II portion of the study - histologically or flow cytometry confirmed diagnosis of BCLL/SLL according to NCI-WG 1996 guidelines; patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
Corrected calcium WNL
Magnesium WNL
Ability to complete questionnaire(s) by themselves or with assistance
Prior prostatectomy
History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
Active malignant relapse
Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable, any histology is acceptable)
Have unresectable malignant mesothelioma (any histology)
Positive CD30+ immunohistochemical expression
Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become\r\nincarcerated during the study
Normal preoperative coagulation blood test (prothrombin time)
Patients judged by their urologist or preoperative evaluation center (PEC) center to be unsafe to forgo pharmacologic prophylaxis or systemic anticoagulation postoperatively (whether or not they are on systematic anticoagulation for indications other than VTE)
Epidural analgesia
Complete portal vein thrombosis on CT scans
Failure to satisfy minimum criteria of lung shunting (> 20%) or presence of extrahepatic gastrointestinal activity on microaggregated albumin (MAA) scan or angiogram that preclude SIR-Spheres
Known ER, PgR and HER2 statuses.
T1 with T ?1.5cm, T2 or T3 by at least one radiographic or clinical measurement
M0
Any T0, Tis, T1 < 1.5 cm, T4; or N2-3; or M1 BC.
Bilateral invasive BC.
Haemoglobin ?9 g/dL
Neutrophils ?1.5 x 10^9/L
A concomitant medical condition requiring receipt of a therapeutic anticoagulant that in the opinion of the treating physician cannot safely allow for therapeutic injection of ONCOS-102 and tumor biopsies. Local clinical practice can be followed with regard to holding a therapeutic anticoagulant during invasive procedures such as biopsies.
Grade 3 or higher colitis attributable to PD1 blockade; note that colitis attributable to ipilimumab is not excluded
Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive avelumab) is permitted; if re-enrolled, the subject must be re-consented; only the screening procedures performed outside of protocol-specified timing must be repeated
Uncontrolled asthma (defined as having 3 or more of the following features of partially controlled asthma within 28 days prior to starting study treatment: daytime symptoms more than twice per week, any limitation of activities, any nocturnal symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known lung function [peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1)] without administration of a bronchodilator that is < 80% predicted or personal best [if known])
Prisoners or subjects who are involuntarily incarcerated
DONOR: HLA-haploidentical first-degree relatives of the patient, including biological parents, siblings, or children, or half-siblings
IMMUNE RECONSTITUTION STUDY ONLY: Decline to participate in the main trial, or main trial closed to accrual due to safety review
IMMUNE RECONSTITUTION STUDY ONLY: Received haploidentical BMT with the current standard of two days of PT-CY (and no PT-BEN)
IMMUNE RECONSTITUTION STUDY ONLY: Be willing and able to provide written consent/assent for the immune reconstitution portion of the trial only
IMMUNE RECONSTITUTION STUDY ONLY: Between 8 and 60 years old
Co-morbidities precluding patient's ability to tolerate BMT
Active infection at time of hospital admission of haploidentical (Haplo) BMT
Any NSAIDs or omega-3 free fatty acid supplementation within the last 14 days
COHORT 2: Subjects in the post-operative setting (cohort 2) are not required to have measurable disease and response rate will not be assessed in cohort 2
EXPANSION COHORT
Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Subjects must be considered appropriate candidates for high dose (HD) IL-2 by one of the treating investigators listed on the protocol; HD IL-2 candidacy evaluation is per institutional guidelines at each site and should include a dobutamine stress echocardiogram or equivalent; subjects with a positive stress test for cardiac ischemia would be excluded from this trial
Autoimmune diseases such as rheumatoid arthritis are NOT allowed; vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed
Neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Prior radiation doses equivalent to, or greater than, 8000 cGy to the target lesions at 200 cGy fractions at any timepoint
Target lesions greater than 10 cm
Myeloproliferative neoplasms/myelofibrosis
Natural Killer cell malignancies
Voluntary written consent (adult; legally authorized representative on behalf of cognitively impaired adult; or parent/guardian with presentation of the minor information sheet, if appropriate)
CML in blast crisis
Glycosylated hemoglobin (HbA1c) =< 7.0%
Has a diagnosis of immunodeficiency
Positive serum anti-poliovirus titer prior to biopsy
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Patient is capable of swallowing pills whole
Demonstrated willingness and ability to record daily caloric intake either on paper or in online program
Daily caloric consumption < 1000 calories
Prisoners or subjects who are involuntarily incarcerated
Histological confirmation of cholangiocarcinoma
Has known serious neuropsychiatric condition
Subjects must not be or have an immediate family member (spouse, parent, legal guardian, sibling or child) who is an investigational site sponsor or staff directly involved with the trial, unless IRB approval is granted previously
Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX vaccine
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature)
Inoperable on the basis of co-existent medical problems
Patient has history of clinically significant dry eye (xerophthalmia) or other corneal abnormality or, if a contact lens wearer, does not agree to abstain from contact lens use from day 0 through the last study drug dose
secondary to MDS treated at least by hypomethylating agent or
LDH < 2 x ULN
Serum CK/CPK ?2.5 x ULN.
Unlikely to cooperate in the study.
Known active or chronic pancreatitis
Breast size B cup or larger, to allow for IORT procedure
Patients must have a diagnosis of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase by having met all of the following criteria at the time of their initial diagnosis\r\n* Cytogenetic confirmation of Philadelphia chromosome or variants of the t(9;22) translocations; patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome\r\n* Peripheral blood or bone marrow blast count < 10%\r\n* Peripheral blood basophil count < 20%\r\n* Platelet count >= 100,000 x 10^9/L\r\n* If the peripheral blood counts are unavailable from the time of their original diagnosis, but there is no evidence of accelerated or blast-phase disease from prior clinical or other medical records, then they will be allowed to participate
Patients must have an ongoing complete cytogenetic response (CCyR) on a TKI (imatinib, dasatinib, nilotinib, or bosutinib), defined as follows:\r\n* 0% Ph+ cells in metaphase, in the bone marrow and/or a negative peripheral blood fluorescence in situ hybridization (FISH) analysis for BCR-ABL1 gene fusion
Patients must be in a major molecular remission (MMR) on a TKI (imatinib, dasatinib, nilotinib, or bosutinib) for a minimum of 1 year leading up to enrollment; major molecular remission is defined as BCR-ABL1 transcripts =< 0.1% by quantitative real time polymerase chain reaction (QPCR) (International Scale [IS]) or >= 3-log reduction in BCR-ABL1 messenger ribonucleic acid (mRNA) from the standardized baseline, if QPCR (IS) is not available\r\n* MMR must be documented on at least 2 occasions, at least 3 months apart, in the 6 to 12 months leading up to enrollment
Patients in complete molecular remission (CMR) on a TKI (imatinib, dasatinib, nilotinib, or bosutinib); CMR is defined as no detectable BCR-ABL1 mRNA by QPCR (IS) using as assay with a sensitivity >= 4.5 logs below the standardized baseline
Atypical BCR-ABL1 mRNA transcripts that cannot be monitored with QPCR
Patients with previously documented BCR-ABL Kinase Domain mutations that confer resistance to nilotinib; this includes, but is not limited to, the T315I mutation
Have documented testing for human epidermal growth factor receptor 2 (HER2-neu) overexpressing, and for those with tumors overexpressing HER2-neu, have documented progression on Trastuzumab-containing therapy
History of developing any condition during prior treatment with ramucirumab for which ramucirumab must be permanently discontinued according to the ramucirumab label.
Blood urea nitrogen (BUN) =< 30 mg/dl
Post-operative complications including significant neurological decline or hemorrhage that causes a drop in Karnofsky performance status (KPS) to less than 60 or renders the patient not suitable for chemoradiation as determined by their treating physician
Geriatric assessment score of >= 2
Known or suspected amyloidosis
Subjects not able to tolerate elotuzumab, lenalidomide, carfilzomib, or dexamethasone
Prior cerebrovascular accident (CVA) with persistent neurological deficit
Diarrhea > grade 1 in the absence of antidiarrheals
Pulmonary function test is required, within 3 months of start; the treating physician will assess suitability by usual clinical criteria used for IL-2 treatment generally consistent with the Proleukin prescribing information; there is no specific minimum result specified by the protocol
Relapsed within 1 year of first response
Patients undergoing an extrapleural pneumonectomy (EPP); lung sparing surgeries, such as pleurectomy/decortication, are acceptable
Has carcinomatous meningitis as determined by positive cerebrospinal fluid (CSF) cytology
Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression; pre- or peri- menopausal subjects must have a negative urine pregnancy test confirmed at screening
Willing to donate blood for research at 4 time points
Willing to undergo core biopsies for research at study entry and at ~4 weeks
Prior treatment with an anti-androgen (abiraterone, apalutamide [ARN-509], bicalutamide, enzalutamide, AR antagonist ODM-201 [ODM-201], TAK-448, TAK-683, orteronel [TAK-700], seviteronel [VT-464])
Systemic estrogens or androgens within 14 days before initiating therapy; vaginal estrogens are allowed if necessary for patient comfort
Not on full dose anticoagulants
Troponin-I, creatine kinase muscle and brain (CK-MB), B-type natriuretic peptide (BNP) =< ULN
If patient is pre- or peri- menopausal, then will need to have concurrent ovarian suppression; patients may have already gotten the loading dose of ovarian suppression; pre- or peri-menopausal subjects must have a negative urine pregnancy test confirmed at screening
Willing to donate blood for research at 4 time points
Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464)
Systemic estrogens or androgens within 14 days before initiating therapy; vaginal estrogens are allowed if necessary for patient comfort
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Dependency on IV hydration or total parenteral nutrition (TPN)
Previous enrolment in this trial
Haemoglobin <90 g/L (<9 g/dL)
Ejection fraction (EF) <55% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram [ECHO], multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
PART I: Patients with Waldenstrom’s macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom’s Macroglobulinemia (IWWM)
PART IB: Patients with Waldenstrom’s macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom’s Macroglobulinemia (IWWM)
Has evidence of immune- mediated hepatitis, nephritis, or thyroiditis
Has evidence of colitis
Must be deemed medically fit for SBRT by the treating physician
Past history of external beam radiotherapy within the projected treatment field of any of the disease sites to be treated by MRI-guided, online adaptive SBRT
Serum potassium >= 3.5 mmol/L
Clinical stage T4 (invasion into rectum or ureters) significantly increases the morbidity of the surgery\r\n* Patients with rectal or ureteral invasion will be considered to have unresectable disease
Troponin-I, creatine kinase MB (CK-MB), B-type natiuretic peptide (BNP) =< ULN
Planned goal TSH suppression 0.1-0.5 mU/L for at least 18 weeks postoperatively
Planned postoperative TSH goal different than 0.1-0.5 mU/L
Neutrophil count >= 1.5 x 10^9/l at cycle 1 day 1 of docetaxel cisplatin and 5-FU (TPF)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase must be within the range allowing for eligibility at cycle 1 day 1 of TPF:\r\n* Alkaline (Alk) Phosphate (PHOS) =< upper limit of normal (ULN); AST or ALT =< ULN: Eligible\r\n* ALK PHOS =< ULN; AST or ALT > 1x but =< 1.5x: Eligible\r\n* ALK PHOS =< ULN; AST or ALT > 1.5x but =< 5x: Eligible\r\n* ALK PHOS =< ULN; AST or ALT > 5x ULN: Ineligible\r\n\r\n* ALK PHOS > 1x but =< 2.5x; AST or ALT >1x but =< 2.5x; AST or ALT =< ULN: Eligible\r\n* ALK PHOS > 1x but =< 2.5x; AST or ALT > 1x but =< 1.5x: Eligible\r\n* ALK PHOS > 1x but =< 2.5x; AST or ALT > 1.5x but =< 5x: Ineligible\r\n* ALK PHOS > 1x but =< 2.5x; AST or ALT > 5x ULN: Ineligible\r\n\r\n* ALK PHOS > 2.5x but =< 5x; AST or ALT =< ULN: Eligible \r\n* ALK PHOS > 2.5x but =< 5x; AST or ALT > 1x but =< 1.5x: Ineligible\r\n* ALK PHOS > 2.5x but =< 5x; AST or ALT > 1.5x but =< 5x: Ineligible\r\n* ALK PHOS > 2.5x but =< 5x; AST or ALT > 5x ULN: Ineligible\r\n\r\n* ALK PHOS > 5 ULN; AST or ALT =< ULN: Ineligible\r\n* ALK PHOS > 5 ULN; AST or ALT > 1x but =< 1.5x: Ineligible\r\n* ALK PHOS > 5 ULN; AST or ALT > 1.5x but =< 5x: Ineligible\r\n* ALK PHOS > 5 ULN; AST or ALT > 5x ULN: Ineligible
Female sex
Clinical or pathologic evidence for distant metastases
Currently using lenalidomide or hypomethylating agents (HMA)
Microcytosis on screening blood cell count (CBC) (mean corpuscular volume [MCV] < 81 fL)
Blood urea nitrogen (BUN) =< 1.5 times institutional normal
DOSE EXPANSION COHORT:
Postmenopausal status is defined either by: I). Prior bilateral oophorectomy OR ii). Age ? 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range. Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure menopausal status.
Premenopausal status is defined as either: I). Patient had last menstrual period within the last 12 months, OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
Perimenopausal status is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as \Premenopausal\
Resting heart rate ? 50 bpm
Subjects with ALT > 5 x ULN at day 1 are not eligible for enrollment
Subjects with clinically apparent ascites or encephalopathy, or untreated varices are not eligible for enrollment
Documented progression or intolerance to sorafenib as demonstrated by:\r\n* Radiographic (by modified [m]RECIST) or symptomatic progression on/after sorafenib\r\n* Intolerance to sorafenib consisting of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater during drug-related adverse event which persisted in spite of comprehensive supportive therapy according to institutional standards AND persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily)
Underlying psychiatric disorder requiring pharmacological intervention or a Hospital Anxiety and Depression Scale (HADS) score of 8 or more
A history of Common Toxicity Criteria (CTC) grade 3 bleeding esophageal or gastric varices within the past 2 months; prior variceal bleed is permitted if patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months; patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened (using either esophagogastroduodenoscopy [EGD] or capsule endoscopy) for esophageal varices, unless such screening has been performed in the past two years from study entry and the patient is receiving medical treatment for prophylaxis of variceal bleeding, such as non-selective beta blockade; if varices are identified that require intervention (banding), patient will not be eligible until varices are adequately treated; patients presenting with gastric varices will not be eligible for the study
Have a serious concomitant systemic disorder.
Prior diagnosis of thrombosis or known hypercoagulable state
Any malabsorption problem
Granulocytes >= 1,500/mcL
LEAD IN COHORT
NEOADJUVANT COHORT
Prior splenectomy
The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact):\r\n* Persons with active or a history of eczema or other eczematoid skin disorders\r\n* Those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves\r\n* Pregnant or nursing women; children under 3 years of age
Patient must be able to swallow tablet or have existing gastrostomy feeding tube to enable administration of tablet
Part 1 (Dose Escalation): Diagnosis of B-cell DLBCL, FL, MCL, or HL, as documented by medical records.
For subjects with DLBCL, FL, MCL, HL, or CLL/SLL: presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ?1 lesion that measures ?2.0 cm in the longest dimension [LD] and ?1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT]).
In subjects requiring biliary decompression, biliary stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed
Has received prior immunotherapy including anti–PD-1, anti–PD-L1, or anti–PD-L2 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
Adequate baseline organ function defined by: International Normalization Ratio (INR) and activated partial thromboplastin time (aPTT) <=1.3xupper limit of normal (ULN); platelet count (PLT) >=10,000 (transfusions permitted to bring PLT to >10,000); total bilirubin <=1.5xULN (Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35% or subject has a diagnosis of Gilbert's syndrome); Alanine transaminase (ALT) <=2.5xULN; creatinine <=1.5xULN OR calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or measured from 24 hour urine >=50 milliliters (mL)/minute (min); and Ejection fraction >=lower limit of normal (LLN) by Echocardiogram (ECHO) or multigated acquisition scan (MUGA)
Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower
Subjects must have at least one site of disease that is accessible for intratumoral injection of SD-101 (diameter >= 10 mm), percutaneously
Two or more cancers not resectable through a single lumpectomy incision
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Previously treated with ixazomib (excluding comparator or placebo participants not on current treatment with ixazomib) in a Millennium-sponsored study. Participants will be eligible to enter the rollover study when:
The parent study is closed or planned to be closed; and
PB or BM basophils ?20%
Prior exposure to BP1001
Radical prostatectomy has been scheduled at Johns Hopkins Hospital
The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to study entry
Subjects must have a CTA scan confirming the PE diagnosis and with at least one measurable index lesion in a segmental or larger pulmonary artery prior to randomization;
Subjects with PE lesions only in the sub-segmental or smaller arteries;
Subjects who within 48 hours of randomization have used an anti-Factor IIa agent such as dabigatran or an anti-FXa agent such as rivaroxaban, apixaban, or edoxaban;
NSCLC with evidence of a centrally cavitating lesion
Ability to complete questionnaire(s) by themselves or with assistance
Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model
May have previously received monotherapy with demethylating agents for MDS or AML or treatment with a mitoxantrone- or cladribine-based regimen for MDS or AML, including G-CLAM, but not demethylating agent as priming for or in combination with chemotherapy
Concomitant illness associated with a likely survival of < 1 year
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor-investigator staff directly involved with this trial, unless prospective Institutional Review Board [IRB] approval (by chair or designee) is given allowing exception to this criterion for a specific subject
Transaminases < 3 x normal at the time of transplant
No known infection with HIV. Due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown.
Creatinine ? 3.0 xULN
Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR
Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR
Clinical or pathologic evidence for distant metastases
Inadequate renal function, defined as calculated or estimated creatinine clearance < 60 mL/min unless lymphoma, KSHV-MCD, or KSHV-associated inflammatory cytokines syndrome (KICS)-related
Platelets < 75,000/mm^3 unless lymphoma, KSHV-MCD, or KICS-related
History of hypersensitivity reactions attributed to thalidomide, lenalidomide, or pomalidomide, including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, or pomalidomide
Indeterminate or negative HER2 status
Have documented objective radiographic progression after stopping treatment with first-line therapy; Note: the same image acquisition and processing parameters should be used throughout the study for a given subject
Tumor sample confirmed as KRAS or NRAS [codons 12 and 13 (exon 2), 59 and 61 (exon 3), and 117 and 146 (exon 4)] or BRAF [codon 600 (exon 15)] mutation positive
Clinical evidence of bowel obstruction at the time of study entry
If elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed; if drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolled
Radiographic evidence of cavitary or necrotic tumors
Maximum projected treatment length 15 cm and width 5 cm, which are the dimensions of the largest available CivaSheet
Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Patient is receiving any azole.
Mental incompetence or criminal incarceration
Must have stage 2, 3 or 4 disease, with either high tumor burden by GELF criteria and/or FLIPI 3-5 (for FL)\r\n* To meet GELF criteria, patient must have at least one criterion:\r\n** Nodal or extranodal mass > 7 cm (document here the largest/longest single nodal or extranodal mass diameter)\r\n** At least 3 nodal masses: each > 3.0 cm in longest dimension\r\n** Systemic symptoms due to lymphoma or B symptoms\r\n** Splenomegaly with spleen > 16 cm by computed tomography (CT) scan\r\n** Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)\r\n** Leukemic presentation (> 5.0 x 10^9/L malignant circulating follicular cells)\r\n** Cytopenias (absolute neutrophil count < 1.0 X 10^9/L, hemoglobin < 10 gm/dL, and/or platelets < 100 x 10^9/L) AND/OR\r\n* To meet FLIPI criteria for FL, patient must have a score of 3, 4, or 5 (one point each for below criterion):\r\n** Age > 60 years\r\n** Ann Arbor stage III-IV\r\n** Hemoglobin level < 12 mg/dL\r\n** >= 5 nodal areas\r\n** Serum lactate dehydrogenase (LDH) level above normal\r\n* FLIPI2; each patient should be assessed for the presence or absence of the following 5 adverse prognostic factors:\r\n** Age (> 60 years versus [vs.] 60 years or less)\r\n** Hemoglobin level (< 120 g/L vs. 120 g/L or higher)\r\n** Beta2-microglobulin (above normal vs. normal or below)\r\n** Largest involved lymph node (> 6 cm vs. 6cm or lower)\r\n** Bone marrow (involved by histology vs. not involved)
Lesion size >= 3 cm in maximum dimension or >= 1 cm and deemed a poor candidate for other ablative approaches
Contraindications to general anesthesia
The Hepatobiliary Multidisciplinary Committee (HDMC) must approve of this intervention
The Hepatobiliary Multidisciplinary Committee (HDMC) disapproves of this intervention
Insurance will not cover the procedure
Patient is currently participating in an Immunocore-sponsored study of IMCgp100 and is actively receiving IMCgp100. Patient must have fulfilled all required assessments in the parent study (unless the study is being terminated)
Patient has been permanently discontinued from any IMCgp100 study or from IMCgp100 treatment in the parent study due to unequivocal progressive disease, unacceptable toxicity, non-compliance to study procedures, withdrawal of consent, or any other reason
Patient must have a graded prognostic assessment (GPA) score 0.5 or greater
Largest lesion =< 4 cm diameter
Metastases within 2 mm of the optic apparatus
Histologically confirmed residual ovarian cancer at time of second-look surgery; patients with cytological evidence of malignant cells in washings obtained as part of the second look procedure are eligible even if biopsies are negative
History of gastrointestinal or urinary fistulae, non-healed or chronic wound, or other conditions that, in the investigator’s view, would contraindicate or significantly increase the risks of bevacizumab therapy
Lactate levels > 2 mmol/L and or and serum pH < 7.35 at screening
Untreated active major depression
Bipolar disorder
Glaucoma
CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351I mutation)
Persons with an infection that is not responding to antimicrobial therapy
Histological confirmation of GIST
Mutational testing of patient samples for KIT and platelet-derived growth factor receptor (PDGFR) mutations; (this will not hold up starting therapy, but will be done for all patients lacking up front mutational testing)
This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
Prisoners or subjects who are involuntarily incarcerated; (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
No active or co-existing malignancy with life expectancy less than 12 months, sources for the determination of clinical significance by the treating physician will be included in the subject’s medical record
Philadelphia chromosome (Ph)-positive ALL
Acceptable coagulation status: INR ?2.0 x ULN and PTT ?2.0 x ULN.
Any condition contraindicating leukapheresis.
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men; patients who feel they cannot comply with this recommendation are not eligible
Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement
Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to =< 5 mm
Accessible tumors for sequential biopsies
Acute or chronic skin disorders that would interfere with subcutaneous injection of the vaccine or subsequent assessment of potential skin reactions
Allergies to any vaccine, that after discussion with Immunovaccine, are serious enough to warrant exclusion from this study
Not adhering to pregnancy prevention recommendations
Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
Allergic or unable to tolerate TMZ for any reason; any patient that successfully completed at least 5 weeks of Temodar during standard of care XRT/TMZ and whose blood counts meet the eligibility requirements within 4 weeks post XRT/TMZ is eligible
PHASE II: Patients must have received and progressed on fluoropyrimidine or fluoropyrimidine based therapy; receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting unless either of these agents are otherwise contraindicated in the opinion of the treating physician in which case a fluoropyrimidine only may be used; prior regorafenib or TAS-102 therapy is not required
Willing to limit daily alcohol intake to the following: one 12-oz glass of beer, one 6-oz glass of wine, or one 1.5-oz portion of 80-proof alcohol
Central ER determination on pre-registration biopsy completed
Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in situ hybridization [ISH] or a polymerase chain reaction [PCR]-based test)
Concomitant treatment with the following drugs that may interact with S-1: Sorivudine, brivudine, uracil, eniluracil, folinate/folinic acid, Cimetidine, dipyridamole, and nitroimidazoles, including metronidazole and misonidazoleMethotrexate, Clozapine,Allopurinol,Phenytoin,Flucytosine, a fluorinated pyrimidine antifungal agent,Coumarin-derivative anticoagulant
Common variable immunodeficiency
Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing)
Serum potassium < 3.5 mmol/L
History of asthma that is nonsteroidal anti-inflammatory drug (NSAID)-induced or with asthma that is classified as ‘mild-persistent’ or worse (based on symptoms occurring more than 2 days per week)
Medically fit to undergo cystectomy
Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis
Neutrophils >= 1.5 x 10^9 /L
Prior taxanes for CRPC
Prior enzalutamide, abiraterone or ketoconazole
Patients must have a documented germline neurofibromatosis 1 (NF1) mutation in a Clinical Laboratory Improvement Act (CLIA) certified laboratory or a diagnosis of NF1 based on clinical National Institutes of Health (NIH) consensus criteria; in addition to substantial cutaneous neurofibroma burden, at least one of the criteria below have to be present:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
No supplementation with vitamin E is permitted
Known ophthalmologic conditions, such as:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR)\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility \r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Histologically proven malignant pleural mesothelioma MPM that is considered resectable according to the following criteria:\r\n* Confined to one pleural space\r\n* No chest wall invasion\r\n* No transdiaphragmatic involvement\r\n* No invasion of mediastinal structures
The ability to take folic acid, vitamin B12, and dexamethasone according to protocol
Presence of third space fluid which cannot be controlled by drainage
Tumor must be mismatch repair (MMR) proficient as determined by microsatellite instability or immunohistochemistry for MMR proteins\r\n* Microsatellite instability testing must be microsatellite instability (MSI)-stable or MSI-low\r\n* Or immunohistochemistry (IHC) for MMR proteins must demonstrate intact MMR proteins
Patient must be a candidate for SBRT to at least one intrahepatic lesion; there is no limit on the number of intrahepatic lesions the patient may have
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study, is excluded
Previous allo-HSCT of any kind
Prior exposure to a short interspersed element (SINE) compound
Active hepatitis B or C determined by serology and/or nucleic acid testing (NAT)
History of oxalate nephrolithiasis or urine oxalate >60 mg/dL
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; Note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Simultaneous participation in other therapeutic clinical trials will not be allowed
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Diagnosis of immunodeficiency
Patient desires and is medically fit to undergo prostatectomy
Documentation of HPV tested by polymerase chain reaction (PCR)
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of American [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
No prior known history of retinal neovascularization, macular edema or macular degeneration; patients without such a history are required to have a baseline ophthalmologic exam as part of screening, and must not have evidence of retinal neovascularization, macular edema or macular degeneration on the screening exam in order to be eligible
Candidate for TSEB based on investigator determination
Previous TSEB therapy with total dose > 20 Gy
Demyelinating form of Charcot-Marie-Tooth syndrome
Known cirrhosis
Known (histology/cytology proven) or evidenced by radiology of recurrent and/or metastatic SCCHN not suited for local therapy
Subjects must have at least 1 lesion that is measurable by irRECIST\r\n* A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per irRECIST, and has clearly progressed\r\n* Subjects undergoing fresh tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator or if no other lesion suitable for biopsy, then an irRECIST target lesion used for biopsy must be >= 2 cm in longest diameter
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
History of or current relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
FOR PARTICIPANTS WHO WILL BE RECEIVING NAB-PACLITAXEL (ALL ARMS EXCEPT ARM B1 SINGLE AGENT LEAD-IN)
FOR PARTICIPANTS WHO WILL NOT RECEIVE NAB-PACLITAXEL (ARM B1 SINGLE AGENT LEAD-IN ONLY)
FOR ALL ARMS OF THE PROTOCOL
Normal serum lactate dehydrogenase (LDH)
No mass ?7 cm.
Less than 3 nodal sites, each with diameter >3 cm
Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one of more of the following criteria:\r\n* Patient has persistent or recurrent high-grade Ta/carcinoma in situ (CIS)/ urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses); patient has high grade T1 urothelial carcinoma after induction BCG (>= 5 doses) only or after induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses)\r\n* Patient is disease-free at completion of BCG (i.e., complete response) but then experiences a high-grade recurrence before or at the 6 month follow-up cystoscopy\r\n* Recurrence after treatment with at least 3 doses of a BCG refractory agent (for example, though not limited to, gemcitabine, docetaxel, valrubicin or an interferon adenovirus)
Active ALL in the central nervous system (CNS), as defined by >= 5 leukocytes per microL with identifiable blast cells in the cerebrospinal fluid (CSF), and/or the presence of cranial-nerve palsies
Evidence of cerebrospinal fluid (CSF) dissemination (positive CSF cytology for malignancy or MRI findings with CSF dissemination)
ARDS characterized by hypoxemia and bilateral radiographic opacities not fully explained by cardiac failure or fluid overload as judged by the treating physician using all available data; moderate ARDS includes patients with malignancies with the previous presentation and a partial pressure arterial oxygen and fraction of inspired oxygen (P/F) ratio =< 200 or oximetric saturation to the fraction of inspired oxygen (S/F) ratio of =< 214; the duration of the hypoxemia criterion and the radiograph criterion must be within 10 days of the time of enrollment
ARM B ONLY
Brain lesion(s) greater than 5 cm in diameter
Lesion(s) involving the brainstem, optic chiasm or optic nerve(s)
Patients willing to be treated with frame-based gamma knife SRS at MD Anderson main campus or MD Anderson at the Woodlands
Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence occurs remote from the treated site
Patients on an enzyme-inducing anti-convulsant who cannot be switched to a non-enzyme-inducing anti-convulsant with a 2 week wash-out period from time of drug discontinuation until day 1 of study treatment
Craniopharyngioma diagnosed by histology, cytology or neuroimaging or intra-operative assessment
Refractory or recurrent retinoblastoma with vitreous seeding meeting eligibility criteria by ultrasonic biomicroscopy performed during examination under anesthesia (EUA) by an ophthalmologist: \r\n* At least three consecutive clock hours of disease-free, attached peripheral retina through which the intraocular injection may be administered\r\n* Absence of invasion in anterior and posterior chamber\r\n* Absence of anterior hyaloid detachment\r\n* Absence of retinal detachment at the entry site\r\n* Absence of tumor at the entry site
Participants must not have an invasive infection at time of protocol entry
Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
Patients who have a history of a small or large bowel obstruction within 2 weeks of screening or who have and active partial small bowel obstruction or percutaneous endoscopic gastrostomy (PEG)-tube
met the screening criteria for CI through a positive response to at least 1 of 2 scaled questions from the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) i.e. Please rate on a scale from 0 to 10, the difficulty level you have in concentrating on things, like reading a newspaper or watching television? \0\ means no difficulty and \10\ means very difficult. Please rate on a scale from 0 to 10, the difficulty level you have in remembering things. \0\ means no difficulty and \10\ means very difficult, will be included.
Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon
Deemed medically inoperable per urology evaluation
Circulating blast count > 30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed)
Presence of donor specific antibodies (DSA) with mean fluorescence intensity (MFI) of > 2000 as assessed by the single antigen bead assay, < 6 weeks prior to starting transplant conditioning
Diagnosis of Philadelphia chromosome positive (Ph+) (by cytogenetics or FISH) or BCR-ABL+ (by polymerase chain reaction [PCR]) CML in CP (cohort 1), AP (cohort 2) or BP (cohort 2)
Histologic or cytologic diagnosis of adenocarcinoma of the pancreas
Short removable metal stents rather than plastic stents are strongly encouraged but not required for palliation of initial obstructive jaundice
Eligible for LDAC therapy, based on Investigator assessment
Prior exposure to BP1001
Histologically confirmed adenocarcinoma of the pancreas or ampulla of Vater; at least the majority of the histopathologic specimen must be identified as adenocarcinoma as opposed to another histologic subtype; in patients with a diagnosis of recurrent disease (based on radiographic progression and/or rising CA19-9 levels) and a history of a biopsy-proven adenocarcinoma of the pancreas or the ampulla of Vater, repeat biopsy of the recurrence site is not required for participation of the trial
Pancreatic or periampullary tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning
Achieving partial response (PR) or very good partial response (VGPR) with systemic chemotherapy
Subjects must have had histologic verification of neuroblastoma at original diagnosis or relapse
PART 1 EXCLUSION CRITERIA: Potential subjects and/or parents/guardians who, in the opinion of the investigative team, are likely to be non-compliant with study schedules or procedures
PART 2 GROUP 1 EXCLUSION CRITERIA: Subjects who are currently receiving treatment with agents that are known to cause QTc prolongation in humans; agents causing a strong signal will be prohibited
PART 2 GROUP 1 EXCLUSION CRITERIA: Potential subjects and/or parents/guardians who, in the opinion of the investigative team, are likely to be non-compliant with study schedules or procedures
PART 2 GROUP 2A EXCLUSION CRITERIA: Subjects who are currently receiving treatment with agents that are known to cause QTc prolongation in humans; agents causing a strong signal will be prohibited
PART 2 GROUP 2A EXCLUSION CRITERIA: Potential subjects and/or parents/guardians who, in the opinion of the investigative team, are likely to be non-compliant with study schedules or procedures
PART 2 GROUP 3 EXCLUSION CRITERIA: Subjects who are currently receiving treatment with agents that are known to cause QTc prolongation in humans; agents causing a strong signal will be prohibited
PART 2 GROUP 3 EXCLUSION CRITERIA: Potential subjects and/or parents/guardians who, in the opinion of the investigative team, are likely to be non-compliant with study schedules or procedures
Subjects must be aged between >= 18 years and =< 64 for AML and > 40 and =< 64 for ALL
Potassium > lower limit of normal (LLN) or correctable with supplements prior to first dose of study medication
Magnesium > LLN or correctable with supplements prior to first dose of study medication
Total calcium (corrected for serum albumin) >= LLN or correctable with supplements prior to first dose of study medication
Patients should not be prescribed concomitant medications that may contribute to prolonged QTc without consultation with the chemotherapy pharmacist; additional ECGs should be done at the investigator’s discretion to ensure the subject’s safety; drugs that are generally accepted to increase the risk of Torsades de Pointes, include (but not limited to):\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, ibutilide, dofetilide, sotalol\r\n* Erythromycin, clarithromycin\r\n* Chlorpromazine, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Nasopharyngeal primary site
Significant electrolyte imbalance prior to enrollment (note that patients may be supplemented to achieve acceptable electrolyte values):\r\n* Hypomagnesemia < 1.2 mg/dL or 0.5 mmol/L\r\n* Hypokalemia < 3.0 mmol/L
NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies
Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, supratentorial ependymoma, or mixed glioma are NOT eligible for either Stratum
Willing to sign a durable power of attorney
Elevated expression above of WT1 in pre-treatment bone marrow or peripheral blood by either of two methods:\r\n* Increased expression of WT1 determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood; \r\n* Demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by a Fred Hutchinson/Seattle Cancer Care Alliance pathologist
ELIGIBILITY FOR APHERESIS/BLOOD COLLECTION:\r\n* Human leukocyte antigen (HLA)-A*02:01 expression\r\n* Elevated expression above of WT1 in bone marrow or peripheral blood: increased expression of WT1 will be determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood; or when available, demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by Fred Hutchinson/Seattle Cancer Care Alliance hematopathology
Unable to generate antigen-specific WT1-specific CD8+ T cells for infusions; however, if a lower than planned number of cells is available, the patient will have the option to receive the generated WT1-specific T cells
The expression of WT1 in the patient’s peripheral blood and/or bone marrow will be determined; if WT1 expression in the patient specimen is within the normal physiologic range or is not detected, the patient will be ineligible for treatment with WT1-specific T cells (and will not be included in the observation cohort)
Medical or psychological conditions that, according to the PI, would make the patient unsuitable candidate for cell therapy
Serum potassium >= 3.5 mmol/L
Be capable of swallowing study agents whole as a tablet
Clinical and microbiologic relapse of C. difficile associated diarrhea after at least one course of adequate antibiotic therapy or refractory disease that does not respond to treatment\r\n* At least 10 days of vancomycin at least 125 mg four times daily (QID), or metronidazole 500 mg three times daily (TID)\r\n* C. difficile associated diarrhea is defined as:\r\n** >= 3 loose or watery stools per day for at least 2 consecutive days or >= 8 loose stools in 48 hours and\r\n** Positive Clostridium difficile polymerase chain reaction (PCR)
Serious cardiopulmonary comorbidities
Active fistula
Ileus
Gastroparesis
mCRPC EXPANSION COHORT: Platelets >= 100,000/mcL without growth factor support
Have previously received or are ineligible for treatment with blinatumomab; ineligibility will include (but not be limited to) cluster of differentiation 19 (CD19)-negative disease, denial of insurance coverage, physician discretion, and/or patient refusal
Eligible for:\r\n* Cohort A: Robot-assisted radical cystectomy (RARC) as per the attending urologist\r\n* Cohort B: Robot-assisted radical Nephrectomy (RARN)/robot-assisted partial nephrectomy (RAPN) as per the attending urologist\r\n* Cohort C: RAPN as per the attending urologist
No evidence of gross hematuria
No evidence of hydronephrosis
Blood urea nitrogen (BUN) < 30 mg/dL
Serum phosphate levels that are within normal limits (2.4 - 4.1 milligrams per deciliter mg/dL) at baseline.
Subject meets the reproductive criteria as follows:
Absence of proteinuria
Considered to be suitable intensive (cytotoxic) induction candidates
Patients at Washington University must be enrolled in HRPO# 201011766 (“Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases”); this is not a requirement for secondary sites; however, secondary sites must provide informed consent forms that document that permission for whole genome, whole exome, and/or genome wide sequencing, and data sharing among institutions, was obtained; because the study will also be sequencing non-diseased (normal) tissue, the informed consent forms must explicitly ask if patients wish to be informed, (or in the case of their death, their next-of-kin) if a deleterious mutation is identified in their non-diseased tissue, as this may be heritable
Willing to comply with the treatment assignment:\r\n* Intent to proceed with high-dose cytarabine (HiDAC) consolidation for LAM VAF < 2.5%\r\n* Intent to proceed with either HiDAC consolidation or allogeneic stem cell transplantation, at the discretion of the treating physician, for LAM >= 2.5%
Caregiver capable of providing post-HCT care
Caregiver capable of providing post-HCT care, who will be present once induction therapy with filgrastim, cladribine, cytarabine, mitoxantrone hydrochloride (GCLAM) begins
Prior allogeneic HCT
DLCOc < 40% or FEV1 < 50%
Direct bilirubin or ALT > 2 x upper limit of normal, unless these abnormalities are thought to be related to Gilbert’s disease or leukemic infiltration of hepatic parenchyma
Known or ordered molecular testing for MSI, BRAF, and KRAS status
In their treating physician’s opinion is a good candidate for BCG therapy
Not be on agents known to alter rapamycin metabolism significantly
On agents known to alter rapamycin metabolism significantly
Individuals who are not a good candidate for BCG in their treating physician’s opinion
Pathologic confirmation of the diagnosis either at original diagnosis or recurrence
Known non-synonymous mutation in the following genes: Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK; genomic sample preferably from relapse, but may be from other stage of treatment if relapse sample is not reasonably obtainable; genetic analysis for determination of eligibility occurs as part of routine care and is not being performed specifically for the purposes of this study
Platelets >= 75,000/mcl (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts)
Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL)
CD19 negative B-cell leukaemia
Burkitt cell or mixed lineage acute leukaemia
STUDY-SPECIFIC EXCLUSIONS:
Lung metastases will be unresectable due to anatomic location, distribution, or patients’ comorbidities, as determined by review of imaging by a faculty member in the Department of Thoracic & Cardiovascular Surgery
Patient refusal to participate in randomization
At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma (Cheson Criteria); the site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions
Platelets (plt) >= 50 K/cu mm; for subjects with plt < 50 K/cu mm due to significant marrow involvement by MCL, plt must be > 25 K/cu mm
Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy.
Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments; for example, atrial fibrillation, bundle branch blocks, or as approved by the sponsors).
Current dependency on total parenteral nutrition or IV fluid hydration.
Previous enrolment in the present study
Diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera (post-PV) myelofibrosis (MF) or post-essential thrombocythemia (post-ET) MF based on the World Health Organization (WHO) criteria or the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria, which must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to screening; measurement of janus kinase 2 (JAK2) V617F allele burden in BM samples, if not done within 6 months prior to screening, must be provided with the screening BM biopsy/aspirate report (patients are eligible regardless of JAK2 mutation status)
Willing to adhere to the prohibitions and restrictions specified in this protocol (Notation: the subject's willingness to adhere to prohibitions and restrictions must be clearly communicated in the on-study note)
Hyponatremia (defined as serum sodium level < 130 mEq/L)
Adequate oral intake and nutritional status without current or likely need for enteral or parenteral feeding during chemoradiation or the preoperative period
Inadequate caloric or fluid intake whereby there is a current or likely future need for enteral or parenteral feeding during chemoradiation or the preoperative period
Prior fistula within thorax, including bronchoalveolar or esophageal
The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer
Known loss of complete cytogenetic response (CCyR) by marrow cytogenetic or blood fluorescence in situ hybridization (FISH) for breakpoint cluster region (BCR)- v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1)
Gross (visible) hematuria
Treatment-related mortality (TRM) score =< 13.1 as calculated with simplified model
Concomitant illness associated with a likely survival of < 1 year
Previous receipt of azacitidine, decitabine, anthracyclines, cytarabine, or other nucleoside analogues for treatment of AML or MPN/MDS other than as noted for cytarabine
A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure
Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (myeloablative regimen 1, reduced intensity regimen 3)
Serum glutamate pyruvate transaminase (SGPT)/bilirubin < to 2.0 x normal (myeloablative regimen 1), reduced intensity regimen 3; SGPT/bilirubin < to 4.0 x normal (nonmyeloablative regimen 2)
Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
Written informed consent and any locally-required authorization (e.g., Health Information Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
For participation in the patient-reported outcomes and qualitative interviews, subjects must be fluent in English
Previous enrollment in the present study
RESEARCH SAMPLE COLLECTION: Considered for high-dose melphalan followed by autologous hematopoietic cell transplantation and undergoing pre-HCT workup
Received high-dose melphalan (>= 140 mg/m^2) followed by autologous HCT based on the institutional guidelines and within +45 and +180 after autologous HCT at the time of panobinostat maintenance initiation
Prior allogeneic HCT
UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
Natural killer cell malignancies
Myeloproliferative neoplasms/myelofibrosis
Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
CML in blast crisis
Willing and qualified for active surveillance at Johns Hopkins or the University of Washington
Serum potassium >= 3.5 mmol/L
The use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
The subject has been diagnosed and treated at an external facility, and the resulting tissue specimen is of insufficient quality such that it precludes clinical sequencing or any other necessary study procedure, and the subject is unwilling to undergo an additional biopsy procedure
The subject is a prisoner
> 18 years old
non-hilar tumors
invasive mediastinal staging requirement will be based on current American College of Chest Physicians (ACCP) lung cancer staging criteria and will be performed by any of the following tests, in appropriate patients, alone or in combination based on study site preference in accordance with ACCP guidelines - mediastinoscopy, mediastinotomy, VATS, endobronchial ultrasound, endoscopic ultrasound.
Metabolic: glycosylated hemoglobin (HbA1c) < 7.0%
Patients having prior therapy with Laser Induced Thermal Therapy (LITT) is allowed, but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence
Need for urgent palliative intervention (e.g., impending herniation)
Neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Eligible for and planning to receive standard fractionated RT with concurrent TMZ
Willing to remain abstinent from consuming alcohol while on DSF
The vertebral body site to be treated must be located from the second to the twelfth thoracic vertebrae (T2-T12)
No more than 3 contiguous or discontiguous vertebral levels involved with metastasis in the spine to be irradiated in a single session or 3 sessions
Lesions located outside of the spinal segments of T2 to T12
Histologic evidence of muscularis propria invasion
Patients with hydronephrosis that has not been addressed with a documented assessment (i.e. normal GFR, no intervention necessary) or an intervention such as placement of a stent or nephrostomy tube
Expression of one (1) or more of the following TAPAs: SP17, AKAP4, Ropporin, PTTG1 and Span-xb, by either reverse transcriptase polymerase chain reaction (RT-PCR) and/or immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood.
Unable to receive TKI for insurance reasons (uninsurable)
Refuse or unable to perform telephone or video conferences with research coordinator
Transfusion independent (no red blood cell or platelet transfusions in the preceding 2 weeks of screening)
Has favorable risk AML as defined by the presence of isolated t(8;21) or inv(16) or t(16;16)(p13.1;q22) on a standard karyotype or mutated NPM1 with concurrent wild-type FLT3 on molecular testing
Disease amenable to maximal surgical debulking via extended pleurectomy/decortication as determined by a surgeon specializing in mesothelioma
FGFR genetic alterations (specifically FGFR1-3 mutation, amplification, or translocation) via deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) based assay; prescreening has to be completed prior to enrollment on this study; commercial or local testing is typically expected, but samples can also be sent to the University (Univ.) of Chicago for testing\r\n* The following genetic aberrations will be screened for:\r\n** FGFR1 amplification, FGFR1 somatic mutations, FGFR1 translocations\r\n** FGFR2 somatic mutations, FGFR2 translocations, FGFR2 amplification\r\n** FGFR3 somatic mutations, FGFR3 translocations, FGFR3 amplification\r\n*Other genetic FGF/FGFR pathway aberrations may be acceptable should such genetic changes be observed to emerge and require approval per the lead investigator for enrollment (e.g. fibroblast growth factor (FGF) amplification); should one genetic aberration be overrepresented in one or both of the arms the lead investigator (Dr. Seiwert) may decide to restrict enrollment of such patients; a notification/memo will be sent out to all investigators should such a restriction on enrollment be implemented (see inclusion criteria); for example, if more than 5 pts with FGFR1 amplification are enrolled further enrollment of FGFR1 amplified patiens will be put on hold, or if FGFR translocations are under-represented enrollment may be focused on this aberration
Consent to undergo a fresh biopsy in case of benefit from therapy and subsequent progression
HPV status in oropharyngeal carcinomas; while HPV status (e.g. via p16) does not have to be known prior to consenting, the HPV status (e.g. using p16 immunohistochemistry [IHC]) needs to be established prior to start of therapy
History and/or current evidence of tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification
Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, confirmed by ophthalmologic examination
Study medication cannot be administered through gastric (G)-tube, unless additional information from the manufacturer becomes available in the future
Prior allogeneic HCT
Screening evaluation appropriate for leukapheresis and T-cell collection
Successful collection of T cells for JCAR014 manufacturing
Internal review of histology
Any form of active primary or secondary immunodeficiency
Diagnosis of ductal adenocarcinoma of the pancreas (PDAC).
Serum magnesium >= ILLN
Patients must agree to tissue collection for correlative studies (including participation in PA13-0291 and PA13-0247 for MD Anderson participants) at the specified timepoints
Prisoners or subjects who are involuntarily incarcerated
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Previous enrollment or randomization in the present study
Pathologically confirmed MPNST, with or without underlying diagnosis of neurofibromatosis type 1 (diagnostic criteria for neurofibromatosis type 1)
Patient may have more than one site of recurrent or metastatic disease but only one lesion that is >= 1 cm in size will be injected (if in the lung, the lesion must be >= 2 cm and adjacent to the pleura in the lung)
Cluster of differentiation (CD)4 count >= 200/uL or >= 15% of peripheral blood lymphocytes
Ability to complete questionnaire(s) by themselves or with assistance
Requiring blood product support
Current exposure to household contacts =< 15 months old or household contact with known immunodeficiency; NOTE: patient must avoid contact during documented viral shedding; participants with continuous viral shedding will be given recommendations for restricted activities to avoid contact with immunocompromised persons
Multidisciplinary evaluation of the patient must be performed with a consensus recommendation for reirradiation
Patient may not receive concurrent chemotherapy with reirradiation, other than temozolomide or bevacizumab given at the discretion of the treating neuro-oncologist
Dose-volume histogram data and cross-sectional imaging from previous radiation must be obtained; electronic dosimetry records in Digital Imaging and Communications in Medicine (DICOM) format from previous radiation are strongly preferred
Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
Requires left chest wall post-mastectomy radiation with or without bolus
Patient must be able to maintain a 30 second breath hold
Conventional chest wall radiation delivery dose of 50.4 Gy/ 28 fractions with or without a boost (boost will not be evaluated for endpoints)
The ability to take folic acid, vitamin B12, and dexamethasone according to protocol
Be a medically appropriate candidate for radical cystectomy as determined by an attending urologist and be planning to receive cystectomy
Consents to whole blood collection prior to initiating therapy, on cycle 2 day 1, and at cystectomy for support of correlative research studies
PRIOR TO CELL PROCUREMENT: Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal
PRIOR TO LYMPHODEPLETION: Patients on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites
PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: AST ? 3 times ULN
PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Available autologous T cells with ? 15% expression of CD30CAR determined by flow-cytometry required prior to treatment with ATLCAR.CD30 cells
Abnormal T cells must be CD52+ as assessed by flow cytometry or immunohistochemistry
Androgen receptor will be quantified using a Clinical Laboratory Improvement Act (CLIA)-compliant assay for AR on a biopsy specimen obtained prior to the start of treatment; AR-positivity is defined as >= 10% of nuclear staining
Relapsed, recurrent, or refractory malignancy; all solid tumor diagnoses will be eligible\r\n* Pathologic confirmation of the diagnosis either at original diagnosis or recurrence\r\n* Known non-synonymous mutation in the following genes: EGFR, ERBB2, or JAK2V617F (JAK2); genomic sample preferably from relapse, but may be from other stage of treatment if relapse sample is not reasonably obtainable; genetic analysis for determination of eligibility occurs as part of routine care and is not being performed specifically for the purposes of this study
Ductal carcinoma in situ (DCIS) or invasive epithelial (ductal, medullary, papillary, mucinous [colloid], or tubular histologies)
Patients with collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or active skin rash, systemic lupus erythematosus, or scleroderma
Cohort 2: Persistence or reappearance of minimal residual disease by flow cytometry or cytogenetic or molecular testing while being in morphological remission after allogeneic stem cell transplantation
Patients for whom a plan meeting institutional quality criteria cannot be designed for SBRT treatment via the MRI-guided teletherapy unit, but for whom an SBRT plan meeting institutional quality criteria can be designed for a conventional linear accelerator
Known mania-associated psychiatric disorder
Using drugs known to lower or increase levels of DHEA
Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal disease (estimated glomerular filtration rate (eGFR) <30ml/min), hepatic (Alanine transaminase (ALT) 2.5 times upper limit of normal (>2.5xULN), bilirubin > 2x ULN), hematological (absolute neutrophil count (ANC) <1.0 x 109/L, platelet count <75x109/L or requires regular platelet transfusions to maintain a platelet count ? 75 x 109/L , hemoglobin <9g/dL), endocrine (glycated Haemoglobin (HbA1c)>7% or random glucose >200mg/dL), pulmonary (Forced Expiratory Volume in 1 second (FEV1) <70% of predicted value), cardiac (New York Heart Association (NYHA)) class III/IV, or neurological disease
Has chronic, active colitis
Medication related exclusions
The subject has previously participated in this study.
Patient must have been evaluated by a University of California Los Angeles (UCLA) thoracic surgeon, and deemed medically and technically suitable for a pleurectomy/decortication procedure
FEV1 < 30% (based on absolute percent predicted using United States of America [USA]-ITS-NIH equation) on pulmonary function testing
Known dihydropyrimidine dehydrogenase deficiency
Previous exposure to toll-like receptor (TLR) agonist therapy
Patient population (histological or cytologically confirmed diagnosis):\r\n* Untreated elderly (> 60 years) AML if in the intermediate and poor-risk cytogenetic group and not candidates (as judged by treating doctor of medicine [MD]) for or willing to undergo standard induction therapy (i.e. elderly unfavorable cytogenetic AML) or any untreated AML age > 65 years\r\n** Note: previous therapy with a hypomethylating agent (HMA) for a diagnosis of MDS is allowed\r\n* Relapsed or refractory AML (>= 18 years)\r\n* Any MDS (>= 18 years) having failed or been intolerant to prior hypomethylating agent (HMA) treatment\r\n** Failure is defined as any disease progression while on HMA, relapse after HMA treatment or no response after 4 cycles of 5-Azacitidine or decitabine\r\n** Patients with isolated 5q-/5q- syndrome must have failed, not tolerated, or lenalidomide in addition to having failed or been intolerant to HMA treatment\r\n*** Note: patients with chronic myelomonocytic leukemia (CMML) and MDS/myeloproliferative neoplasms (MPN) overlap are allowed if meeting other study eligibility criteria\r\n*** Note: for all patient groups, therapy as part of a plan as a bridge to transplant is allowed
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study; NOTE: orange juice is allowed
Documented platelet refractoriness
Active infection requiring treatment or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
Skull defect such as missing bone or bullet fragments.
CMV seropositive
Has been treated previously with bevacizumab
CMV seronegative
Myeloproliferative syndromes
Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)
Group II: KS (no prior therapy required):\r\n*Concurrent KSHV-associated multicentric Castleman disease (MCD)\r\n*KSHV Inflammatory Cytokine Syndrome (KICS), including those also meeting clinical criteria for KS immune reconstitution syndrome (KS IRIS)
Measurable disease by the criteria proposed by the acquired immunodeficiency syndrome (AIDS) Clinical Trials Group Oncology Committee (for KS)
Negative human anti-murine antibody (HAMA) test.
Haemoglobin ?9 g/dL;
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
intravaginal
transdermal
Progestogen-only hormonal contraception associated with inhibition of ovulation
injectable
implantable
Vasectomised partner
psychiatric conditions e.g. patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the study
Evidence of > 7 tumors present in the bladder
History and/or current evidence of tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification
Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis, etc
Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and/or keratoconjunctivitis, confirmed by ophthalmologic examination
Calculated (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or measured creatinine clearance < 75% lower limit of normal (LLN)
Signs of wound-healing problems or infection at the craniotomy/biopsy site.
Monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom’s macroglobulinemia, or asymptomatic (smoldering) myeloma
Acute renal failure due solely to readily reversible causes such as hypercalcemia, hyperuricemia, dehydration, hyperviscosity, or acute tubular necrosis from nephrotoxic drugs
Prior cerebrovascular event with persistent neurologic deficit
Kyphoplasty or vertebroplasty within 1 week prior to event 1
Nonsteroidal antiinflammatory drug (NSAIDs), IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2 weeks of event 1
Prisoners or subjects who are involuntarily incarcerated
Subjects must express HLA-A2 phenotype as assessed serologically.
Albuminemia > 25g/L
Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study).
Karnofsky score of 60% or better (“requires occasional assistance, but is able to care for most of his/her needs”)
New or active infection as determined by fever, unexplained pulmonary infiltrate or sinusitis on radiographic assessment; infections diagnosed within 4 weeks of registration must be determined to be controlled or resolving prior to treatment
Vulnerable population groups, i.e., prisoners, those lacking consent capacity, non-English speaking, illiterate, pregnant females
DONOR: Donors must meet the selection criteria prior to the start of the recipient’s pre-transplant conditioning regimen as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened according to the American Association of Blood Banks (AABB) guidelines and University of Wisconsin Bone Marrow Transplant (UW BMT) program Standard Operating Procedure (SOP)
DONOR: Vulnerable population groups, i.e., prisoners, those lacking consent capacity, non-English speaking, illiterate, pregnant females
Total granulocytes of 1,000 per mcL or more
Patients must have a positive screening Epstein-Barr virus (EBV) antibody titer on screening test as this is required to protect against EBV infection during the time of lymphodepletion
Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics
For cohorts 1, 2 and 3 only: Patient's tumor must be positive by histological or molecular assay for NY-ESO-1, according to the screening algorithm; historical results may be used\r\n* For cohort 4, NY-ESO-1 results will be noted but NY-ESO-1 positivity is not required for eligibility
Must be willing and able to accept the leukapheresis procedure
Lack of availability of a patient for immunological and clinical follow-up assessment
Histologically confirmed histiocytic disorder or histologic findings compatible with a histiocytic disorder in the context of confirmatory radiologic findings
Willing to travel to the National Institutes of Health (NIH) for follow-up visits
Previous serious adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
At least one measurable GBM lesion that meets the following criteria:\r\n* Contrast enhancing and clearly defined, bi-dimensionally measurable margins, and\r\n* At least two perpendicular diameters measuring >= 10 mm and no diameters measuring >= 35 mm\r\n* (Note: MRI measurements will not include surgical cavity, cyst, or necrotic area)
Subject is a prisoner
Must be willing to be treated with SBRT only at Johns Hopkins Hospital
Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine or CRS-207 (e.g., glycerol)
Serum sodium, potassium, magnesium and calcium within normal limits for the institution (supplements may be given to correct values)
Requirement for anticoagulation treatment that increases INR or aPTT above the normal range (low dose DVT or line prophylaxis is allowed).
The maximum diameter of any lesion must be less than 4.0 cm
Ability to swallow pills, or liquid formulation and for patient or parent/legal guardian to keep an accurate medication record
Any patient with metastatic esophageal cancer that is deemed a candidate for brachytherapy for local control or treatment of dysphagia as determined by treating physician
Either enrolled in Human Research Protection Office (HRPO)# 201107221 (“Tissue and blood acquisition for genomic analysis and collection of health information for patients with gastrointestinal cancers”), which facilitates the collection of specimens for correlative studies, or consenting to collection of blood and tissue as part of this protocol for research testing
Successful test expansion -cells
No contraindications for leukapheresis
RECIPIENTS
RECIPIENTS:
Histopathologically confirmed diagnosis of previously untreated DLBCL of the non-GCB DLBCL subtype
Able to take aspirin (81 mg) daily or alternative therapy as prophylactic anticoagulation
Patients with severe bradycardia (heart rate < 40 beats per minute [bpm], hypotension, light-headedness, syncope)
Women and men of all races and ethnic groups are eligible for this trial
Gynecologic Oncology Group (GOG) performance status =< 2
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
Non-WM must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification.
HbA1c > 8.5% at Screening
Confirmed PDGFRA amplification in the tumor tissue at the time of diagnosis or time of recurrence. Central confirmation of PDGFRA amplification will be performed by FISH in CLIA certified lab (ProPath). Signal quantitation will be used to generate a PDGFRA/centromere 4 ratio. PDGFRA to Centromere 4 ratios will be interpreted as follows: 1.8 to 2.2, borderline for amplification; 2.2 to 5.0, low-level amplification; and greater than 5.0 or clustered signals that are too numerous to count would be considered highly amplified. Tumor samples with PDGFRA to Centromere 4 ratios of 2.2 or higher will be considered amplified and therefore eligible for this trial. For patients with local CLIA testing demonstrating PDGFRA amplification by Next Generation Sequencing (Foundation Medicine, CMS400), central testing will not be required.
KPS ? 60
Unresectable adenocarcinoma of the breast involving chest wall, regional nodes, or distant site
Breast cancer determined to be HER2-negative per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guidelines\r\n* Note: Eligibility should be based on the HER2 status reported at the time of the most recent biopsy or resection
Ability to take folic acid, vitamin B12, and dexamethasone according to the protocol instructions
Known or presumed intolerance of pemetrexed or sorafenib
Known or suspected malabsorption condition or obstruction
Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation
All participants >= 18 years of age must be willing to sign a durable power of attorney
Four weeks must have elapsed from the time of any antibody therapy that could affect an anti-cancer immune response at the time the patient receives the preparative regimen to allow antibody levels to decline
Subjects must be co-enrolled in protocol 03-C-0277
The subject must be deemed appropriate for neoadjuvant endocrine therapy by the referring medical oncologist
Uridine diphosphate (UDP) glycosyltransferase 1 family, polypeptide A1 (UGT1A1) *28 homozygous patients
Patients who have neuromuscular disorders that are associated with elevated creatinine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Any prior to exposure to ruxolitinib
Inclusion Criteria:\n\n        Subject must have had a diagnosis of primary or secondary warm antibody AIHA.\n\n        - Must have failed at least 1 prior treatment regimen for AIHA.\n\n        Exclusion Criteria:\n\n          -  Subject with cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or\n             paroxysmal cold hemoglobinuria.\n\n          -  Subject with a platelet count of < 30,000/?L.\n\n          -  Subject has AIHA secondary to autoimmune disease, including systemic lupus\n             erythematosis (SLE), or lymphoid malignancy and the underlying disease is not stable\n             or is not well-controlled on current therapy.\n\n          -  Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood\n             pressure ? 130 mmHg, or diastolic blood pressure ? 80 mmHg.
Diagnosis of colorectal carcinoma with intrahepatic metastases; limited extrahepatic metastasis is allowed as long as the overall metastatic burden is hepatic dominant
Prisoners or subjects who are involuntarily incarcerated
Gastrointestinal condition which could impair absorption of BVD-523 or inability to ingest BVD-523
Willing to stop current supplemental vitamin D (multivitamin with vitamin D component is acceptable)
Willing to travel to a Legacy Health/Oregon Health & Science University (OHSU) facility if necessary
Investigator does not believe study participation, for any reason, is in the best interest of the patient
Of any ethnic or racial group
Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease; diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria as is standard of care at University of California, San Francisco (UCSF)
At risk for hepatic or renal failure\r\n* Serum creatinine > 1.5 mg/dl\r\n* Serum bilirubin > 1.3 mg/ml\r\n* Albumin < 2.0 g/dL\r\n* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper normal limit\r\n* Any history of hepatic encephalopathy\r\n* Cirrhosis or portal hypertension\r\n* Clinically evident ascites (trace ascites on imaging is acceptable)
Contraindications to angiography and selective visceral catheterization\r\n* Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device)\r\n* Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically
Evidence of potential delivery of\r\n* Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration? or\r\n* Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments
Evidence of any detectable technetium Tc-99m albumin aggregated (Tc99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow
Any prior arterial liver-directed therapy, including transarterial chemoembolization (TACE), arterial embolization (TAE), and 90Y radioembolization
Any intervention for, or compromise of the ampulla of Vater
known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
Detectable circulating tumor cells (CTCs) with detectable AR?V7 splice?variant by reverse transcriptase (RT)?polymerase chain reaction (PCR)
SECOND COHORT: The most recent therapy must be enzalutamide and enzalutamide will be continued for study duration despite progressive disease; the minimum required dose of enzalutamide at enrolment should be no less than 80 mg once daily
Biopsy confirming metastatic breast cancer and retinoblastoma protein (Rb) positivity by immunohistochemistry prior to enrolling on this protocol is required; biopsy must be obtained immediately before study enrollment; no intervening treatments are allowed
Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
Patients must have clear and documented evidence of biallelic inactivation BRCA1, BRCA2 or ATM by sequencing, for example University of Washington (UW)-Oncoplex, SU2C, or Foundation One testing and/or patients with clearly deleterious mutations of other genes involved in homologous DNA repair (e.g., partner and localizer of BRCA2 [PALB2], BRCA1-interacting protein 1 [BRIP1], etc.) by sequencing via UW-Oncoplex, SU2C, or Foundation One testing may be included at the investigator’s discretion
The preoperative Memorial Sloan-Kettering (MSK) nomogram estimates the patient’s likelihood of freedom from metastatic recurrence within the first 12 years following radical or partial nephrectomy to be =< 80%
Scheduled to undergo nephrectomy as part of treatment plan, per assessment through an MSK urologic surgeon listed as investigator on this trial
Availability of a frozen biopsy core prior to cycle 1, day 1
Investigator determination that the patient is an appropriate candidate for reduced intensity allogeneic SCT with the standard Massey Cancer Center (MCC)-Virginia Commonwealth University Health System (VCUHS) Bone Marrow Transplant (BMT) Program regimen employed in this trial
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Surgically resectable malignant pleural mesothelioma (MPM) with no disease extension beyond the ipsilateral hemithorax
Receipt of drugs with laxative properties and herbal or natural remedies for constipation within 90 days of receiving MEDI4736 or MEDI + tremelimumab
No tissue is obtainable at thoracoscopy
Significant immunodeficiency making the patient unlikely to benefit from pembrolizumab therapy including a diagnosis of acquired immunodeficiency syndrome (AIDS), active hepatitis B or hepatitis C, or organ transplant requiring immunosuppressive therapy
Documentation of CD22 expression on malignant cells at relapse
No contraindications for leukapheresis
CAPMATINIB EXCLUSION CRITERIA: Previously identified allergy or hypersensitivity to components of capmatinib formulation (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes)
ENTRECTINIB EXCLUSION CRITERIA: History of other previous cancer that would interfere with the determination of safety or efficacy of entrectinib in melanoma
Pre-treatment swallowing evaluation by speech and swallowing therapist, to included a modified barium swallow showing no significant impairment with swallowing oral medications
Recommendation to undergo concurrent CRT, as determined by the treating physician, with a curative goal
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 14 days prior to the dose of study medication, throughout the study, and until 2 weeks after the last dose of AZD1775 due to potential cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) interaction with the study medication; orange juice is allowed
Confirmation of MCC by internal pathology review of initial or subsequent biopsy or other pathologic material
At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocytes [TIL] or lymphokine-activated killer [LAK] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other systemic agents that target Merkel cell carcinoma
Legal incapacity or limited legal capacity
Subjects must not be receiving growth factors, except for erythropoietin
Subjects taking fluconazole, voriconazole, itraconazole, posaconazole, and ketoconazole within 72 hours of study drug starting are not eligible; reinstitution of fluconazole, voriconazole, itraconazole, posaconazole, ketoconazole and diltiazem is permissible 72 hours after the last dose of sirolimus
Subjects with bacteremia must have documented negative blood cultures prior to study entry
Any other condition or circumstance that could interfere with adherence to the study’s procedures or requirements, or otherwise compromise the study’s objectives such as history of, or any evidence of active, non-infectious pneumonitis
Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects)
Subjects with a malignancy that contains a non-synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening
Patient has previously participated in the Toca 5 trial (Tg 511-15-01).
Patient must have previously undergone standard chemoradiation- 59.4 Gy (1.8 Gy/fraction) or 60 Gy (2.0 Gy/fraction) with concurrent and adjuvant Temodar (temozolomide)
Patient must be able to have gold fiducial markers placed in the prostate or, if patient already has fiducial markers placed, they must be in accordance with the protocol specifications
Willingness to fill out IPSS, SHIM, and EPIC quality of life forms
IPSS (American Urological Association [AUA]) score =< 15
Implanted hardware which limits treatment planning or delivery (determined by the investigator)
Inability to have gold fiducial markers placed in the prostate, or fiducial markers already placed, that are not in accordance with the protocol
Not willing to fill out IPSS, SHIM, and EPIC quality of life questionnaires
Ability to take medication orally
Hypokalemia
Anticipated lifespan greater than 12 weeks
Ocular primary tumors.
Tumors lying in mucosal regions or close to an airway, major blood vessel or spinal cord.
Subjects previously treated with CVA21.
Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
2.
For Part 2 and Part 3 of the study, participants that are eligible to undergo first time HD-ASCT.
For Part 2 and Part 3 of the study, participants with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification.
The subject must have at least 1 measurable target lesion >= 10mm in longest dimension that is in an anatomic location treatable by MR-HIFU. Note that for this study, lesions in bone WILL be considered measurable provided they meet the other criteria by Response Evaluation Criteria in Solid Tumors (RECIST) and are confirmed to be metabolically active on baseline studies by either metaiodobenzylguanidine (MIBG) uptake (for neuroblastomas) or positron emission tomography (PET) avidity. Target lesions should be located so that they can be adequately heated by a hyperthermia treatment cell with a diameter of up to 58 mm, centered at a depth of 35 to 80 mm from the skin. There should be no staples, implants, extensive scarring, or other highly ultrasound absorbing or reflecting tissue in the expected beam path. For the first 5 patients enrolled on this study only, the lesion must be located in the extremities or pelvis to be considered treatable by MR-HIFU.
Cumulative lifetime anthracycline dose of =< 450mg/m^2
A male of child-bearing potential is any male (regardless of sexual orientation, having undergone a vasectomy, or remaining celibate by choice) who meets the following criteria:\r\n* Has attained Tanner stage III or greater sexual development
Simultaneous participation in other therapeutic clinical trials will be allowed
Hypercalcemia
Agree to follow protocol required evaluations
At least 18 years old;
Clinically significant abnormal serum potassium (regardless of potassium agent supplementation); serum calcium (ionic or binding to albumin post-adjusted) or serum magnesium (regardless of magnesium agent supplementation);
History or presence of digestive tract diseases, including active gastric/duodenal ulcer or ulcerative colitis, or active hemorrhage of an unresected gastrointestinal tumor, or an evaluation by investigators of having any other condition that could possibly result in gastrointestinal tract hemorrhage or perforation;
Participants with prior documented antecedent hematological disorder (AHD)
Participants with extramedullary AML with no evidence of systemic involvement
Phototherapy (PUVA): 4 weeks
Biopsy confirmed CD8+ CTCL histology
For women on estrogen based contraceptives, family history of venous thromboembolism (VTE) and/or risk factors predisposing for VTE and other medical conditions known to be associated with VTE.
Symptomatic ischemia, unstable angina pectoris
Any condition contraindicating fulvestrant administration:
Non-Ductal Pathology: Lobular or Colloid type presence
Subjects scheduled to undergo nipple sparing mastectomy
Poor nutritional state (as determined by clinician)
Allergies to Lidocaine or Novocain
Allergies to imaging dyes
Patients with definite liver metastasis > 1 cm or signs of visceral crisis or impending visceral crisis at the clinical discretion of the treating physician
Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work) or 2 (ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours)
Undetectable haptoglobin or evidence of glucose-6-phophate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, hemoglobinopathy, hereditary spherocytosis, thalassemia or other disorder associated with hemolysis
Scheduled to undergo robotic radical prostatectomy
At least 2 anatomically distinct lesions accessible for biopsy.
symptomatic ischemia
Infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to C1D1.
Classified as having insufficient tumor shrinkage by imaging (< 80% shrinkage after 4 cycles of anthracycline-based chemotherapy based upon diagnostic imaging)
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
Localized EAC and its baseline clinical stage determined as: T2-T3N0 or T1-3N positive (+); imaging studies suspicious for metastases must be followed with a negative biopsy before a patient can enter the study
Must be considered medically fit for operation as determined by multidisciplinary evaluation
Tracheo-esophageal (TE) fistula or direct invasion into the tracheo-bronchial mucosa; a bronchoscopy (biopsy and cytology should be performed) is required to exclude TE fistula or tracheo-bronchial involvement in patients with a tumor located at < 26 cm from the incisors
Prior mediastinal irradiation (for any reason)
Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation
Bevacizumab-naive – no prior exposure to bevacizumab
Active infection requiring treatment or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
Neurological and functional examination within 24 hours prior to registration by the treating physician
Spine instability as determined by Spinal Instability Neoplastic Score (SINS) score > 12
Bony retropulsion causing neurologic abnormality
Molecular confirmation of an anaplastic lymphoma kinase (ALK) rearrangement using ALK fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) or next-generation sequencing (NGS); for ALK FISH, rearrangements must be detected in > 15% of tumor cells; if an ALK rearrangement has been detected by IHC or NGS, archival tissue must be available to confirm ALK positivity by FISH
Tumor infiltrating into large vessels or infiltrating into the proximal tracheobronchial network, visible on medical imaging; the investigator or radiologist must rule out tumors that conjoin, surround or extend into the immediate area of a large vessel (e.g.: pulmonary artery, superior vena cava)
History of hypersensitivity to any of the additives in the alectinib drug formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulfate [SLS], magnesium stearate)
Patient must have cholangiocarcinoma, gallbladder cancer or adenocarcinoma on liver biopsy with clinical features consistent with biliary primary/cholangiocarcinoma
Histological grade I, II, or III according to the modified Bloom Richardson scale
Resectable/operable or potentially resectable/operable breast cancer as determined by the treating surgical oncologist
Children are excluded from this study
Pre- or perimenopausal status or menopausal status that cannot be accurately assessed (e.g. equivocal measurements of estradiol and FSH)
Target lesion that has been previously irradiated
Evidence of distant metastases on any staging or imaging modality
Phase Ia part: advanced solid tumors or metastases including lymphoma localized in the head and neck region or thorax with an indication for fractionated palliative RT (Arm A); or treatment-naïve SCCHN eligible for fractionated curatively intended RT with concurrent cisplatin (Arm B)
Phase Ib part: treatment-naïve Stage III A/B NSCLC not eligible for surgical resection or concurrent chemoradiation (Arm A expansion cohort) or treatment-naïve SCCHN eligible for fractionated curatively intended RT with concurrent cisplatin (Arm B expansion cohort)
Poor vital organ functions defined as:
If the planned radiation field includes any part of the esophagus and the subject has symptoms of ongoing esophagitis, the subject is not eligible, unless an esophageal endoscopy rules out the presence of esophagitis
The target lesion must measure at least 15 mm in at least one dimension, and no more than 4 cm in any dimension
The additional lesions will each be treated with stereotactic radiosurgery
Moribund status or status epilepticus
Supratentorial mass effect with greater than 5 mm of midline shift or hydrocephalus
Platelets >= 50 x10^9 (SI units 10^9/L)
Histologically or cytologically confirmed diagnosis of lung adenocarcinoma that demonstrates ALK rearrangement as detected by the approved fluorescence in situ hybridization (FISH) test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana immunohistochemistry (IHC) test; evidence of rearrangement by gene sequencing tests such as FoundationOne or Caris will also be seen as evidence of ALK abnormality and meeting eligibility requirement
Co-administration of aprepitant and fosaprepitant during this study is prohibited
Core needle biopsy or surgical specimen that confirms ICC; patients must be determined to be unresectable by a multidisciplinary team that includes a hepatobiliary surgeon
Platelet (PLT) >= 100 K/CUMM
Pre-certification for the 90Y TARE should be performed prior to enrollment on this study
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
An EKG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Have biopsiable disease; if biopsy is attempted and unsuccessful (the patient undergoes an invasive procedure), the patient may still be treated
Self-identify as African American/Black, Hispanic (any race), or White non-Hispanic
Smoke at least 5 cigarettes/day or carbon monoxide (CO) reading of at least 8 ppm
Contraindications for transdermal nicotine patch therapy (TNP)
Cognitive or mental health impairment that inhibits group treatment
Unable to attend sessions
Does not self-identify as African American, Hispanic, or White (non-Hispanic)
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Cohort 6: Pre-treated patients with either cMET GCN ? 10 without cMET mutations or cMET mutations regardless of cMET GCN
Abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants (that cannot be safely held for biopsy) that would preclude tumor and skin biopsies\r\n* For fulvestrant: ongoing anticoagulation that would preclude an IM injection\r\n* For tamoxifen: documented hypercoagulable state not receiving anticoagulation
Young patient age between 12 – 15 could be included in only 6 centers (Bordeaux, Lyon, Villejuif, Lille, Marseille and Paris)
Serum calcium >= LLN
Serum magnesium >= LLN
Serum potassium >= LLN
In accordance with French Regulatory Authorities: Patients with French Social Security in compliance with the French law relating to biomedical research (Huriet Law 88-1138 and related decrees)
Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious
gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, \Variants of uncertain clinical significance\ or \Variant of unknown significance\ or \Variant, favour polymorphism\ or \benign polymorphism\ etc.)
Patients with documentation of well differentiated liposarcoma only (of the well differentiated/dedifferentiated liposarcoma family) are specifically excluded, owing to its characteristically slow growth. If high grade areas are suspected (dedifferentiation), but not proved by pathology analysis (e.g. after primary resection of a well-differentiated liposarcoma), a biopsy must be performed to demonstrate the high-grade dedifferentiated disease
Confirmed diagnosis of invasive BCC
Group 2: consent to undergo research biopsies
Any acute or chronic psychiatric problems
Glycosylated hemoglobin (HbA1c) < 7.0%
If medical history of the following, case should be reviewed by the Medical Monitor: prior biliary tract disorders (as based on Hepatobiliary SOC high level terms of: obstructive bile duct disorders, hepatic vascular disorders, structural and other bile duct disorders) or portal hypertension and/or hepatic vascular disorders
Total mastectomy
Multicentric cancers requiring double lumpectomy
AR (+), defined as >= 1% nuclear staining by IHC testing, the assessment of AR expression may have been performed any time in the past and is not limited to participation in Step 1
Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole and butylated hydroxytoluene
Known severe hypersensitivity reactions to monoclonal antibodies (Grade ?3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma Global Initiative for Asthma 2011)
Receiving erythroid stimulating agents (epoetin alfa [EPO]: Procrit, Aranesp)
Ineligible for radical cystectomy or refusal of radical cystectomy
For Cohort 1 (rhabdoid tumors only), the following test results must be available by local laboratory: morphology and immunophenotypic panel consistent with rhabdoid tumors, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss or mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
For Cohort 3, 5 and 7 (subjects with INI1-negative/aberrant tumors or any solid tumor with EZH2 GOF mutation only), the following test results must be available by local laboratory: Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss or mutation when INI1 IHC is equivocal or unavailable, or molecular evidence of EZH2 GOF mutation
Note: Subjects who are unable to undergo pre-dose (screening biopsy) will not be eligible
Fibrinogen >0.5 LLN
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Any history or evidence of opportunistic infection within 6 months of screening including tuberculosis, severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes)
Have Chronic Phase Chronic Myeloid Leukemia (CP-CML) and have received at least two prior tyrosine-kinase inhibitor (TKI) therapies and have demonstrated resistance to treatment OR have documented history of presence of T3151 mutation after receiving any number of prior TKI a. The diagnosis of CML will be made using standard hematopathologic and cytogenetic criteria; CP-CML will be defined by all of the following: i) < 15% blasts in bone marrow ii) < 30% blasts plus promyelocytes in bone marrow iii) < 20% basophils in peripheral blood iv) ? 100 × 109/L platelets (? 100,000/mm^3) v) No evidence of extramedullary disease except hepatosplenomegaly vi) No prior diagnosis of accelerated phase (AP-CML), and blastic phase (BP-CML) b. Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence of the t(9;22) Philadelphia chromosome i) Variant translocations are only allowed provided they are assessable for cytogenetic response utilizing conventional cytogenetic techniques c. Resistance to prior TKI therapy is defined as follows (participants must meet at least 1 criterion): i) Three months after the initiation of prior TKI therapy: No cytogenetic response (> 95% Ph+) or failure to achieve complete hematologic response (CHR) or new mutation ii) Six months after the initiation of prior TKI therapy: BCR-ABL1IS >10% and/or Ph+ >65% or new mutation iii) Twelve months after the initiation of prior TKI therapy: BCR ABL1IS >10% and/or Ph+ >35% or new mutation. iv) At any time after the initiation of prior TKI therapy, the development of a new BCR-ABL1 kinase domain mutation(s). v) At any time after the initiation of prior TKI therapy, the development of new clonal evolution vi) At any time after the initiation of prior TKI therapy, the loss of CHR, or complete cytogenic response (CCyR), or the confirmed loss of molecular response rate (MRR) in 2 consecutive tests, one of which has a BCR-ABL1IS transcript level of ?1% or new mutation d. > 1% of BCR-ABL1IS as shown by real-time polymerase chain reaction
Any revascularization procedure, including the placement of a stent
ANC ? 1,000/?L
Involved in other experimental protocols (except with permission of the other study PI)
Must be a candidate for treatment with either carboplatin plus paclitaxel or carboplatin plus PLD
Patients presenting for orthopaedic evaluation with a painful impending pathologic femur fracture or displaced pathologic femur fracture in the intertrochanteric, pertrochanteric, or subtrochanteric region of the proximal femur; the anatomic region of interest is defined by a line drawn from the base of the femoral neck to 5 cm below the base of the lesser trochanter or 2 diaphyseal shaft widths, whichever is greater
Radiographic evidence of an intramedullary occlusion by blastic metastases that would necessitate an alternative method of treatment, such as a plate/screw construct
Previous randomization for a contralateral procedure as part of this study
Histologic diagnosis of AT/RT or MRT as documented by institutional pathologist with loss of INI1 or BRG1 expression in tumor cells confirmed by immunohistochemistry, or by molecular confirmation of tumor-specific biallelic SMARCB1 loss/mutation or SMARCA4 loss/mutation if INI1/BRG1 immunohistochemistry is not available; patients with synchronous extraneural AT/RT are eligible; for Stratum A participants, histologic confirmation of the diagnosis of AT/RT or MRT may be from the original diagnosis or at the time of recurrence/progression\r\n* Whereas testing of INI1 expression by immunohistochemistry is widely available, Clinical Laboratory Improvement Amendments (CLIA)-certified sequencing of SMARCB1 in tumor samples is only done in limited institutions; therefore, we expect that the vast majority of patients will have confirmation of their diagnoses by immunohistochemistry only; exceptional cases may require gene sequencing\r\n* Of note, occasional patients with histologic diagnosis suggestive of AT/RT or MRT may display immunohistochemical and/or molecular characteristics which are equivocal (e.g., patchy loss of INI1 expression by immunohistochemistry, proof of monoallelic loss of SMARCB1 without confirmation of second hit by sequencing of exons only); these cases may be confirmed unequivocally to represent AT/RT or MRT only by research studies (e.g., whole genome sequencing); therefore, we propose that such patients be candidates for the current study but their outcomes be described separately
Biological parent of patient enrolling on SJATRT will be assigned to Stratum P
Subjects in the combination therapy arms must be eligible to receive erlotinib, or nivolumab per most current prescribing information, or at the discretion of the Investigator.
Proteinuria =< +1 on dipstick or =< 1 gram/24 hours
For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
Patients must be, after evaluation by the investigator, appropriate candidates for the administration of 5 to 6 cycles of standard platinum-based combination chemotherapy (carboplatin and paclitaxel, carboplatin and liposomal doxorubicin, or carboplatin and gemcitabine) following CRS with or without HIPEC
Tumors of low malignant potential (borderline carcinomas)
Immune deficiency: clinically significant primary or acquired immune deficiency (i.e. acquired immunodeficiency syndrome [AIDS] or on immunosuppressive medication after organ transplant)
Evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operating surgeon which prohibits intraperitoneal therapy
Plan for superficial inguinal dissection alone or combined superficial inguinal and deep pelvic node dissection is acceptable
American Society of Anesthesiologists (ASA) class 4 or greater
Creatinine clearance above limits set in the protocol for each cohort
Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
Rectal cancer located within 10 cm from the anal verge based on proctoscopy and digital rectal examination (DRE)
Complete preoperative colonoscopy demonstrating no synchronous colon cancer
Severely symptomatic rectal tumors (near-completely obstructing, symptomatic bleeding)
Tumors invading into the internal anal sphincter muscle based on DRE and pelvic MRI
Fecal incontinence at baseline
There should be no macroscopic intravascular invasion of tumors into the main portal vein, hepatic vein, or vena cava.
Negative for tuberculosis antigen (e.g. T-Spot test)
Prior diagnosis of rheumatoid arthritis
No evidence of dyspnea at rest
Enrollment in any other clinical study from screening up to day 100; enrollment in another clinical study not interfering with the endpoints of this study after day 100 according to the judgment of the PI (or PI designee) will be allowed, but will be clearly documented in the case report form (CRF) and in the patient’s medical file
Caution should be exercised when administering paclitaxel (Taxol) concomitantly with medicines known to inhibit (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir) OR induce (e.g. rifampicin, carbamazepine, phenytoin, efavirenz and nevirapine) either CYP2C8 or CYP3A4. Based on the in vitro data and SimCYP simulations, selumetinib is considered unlikely to perpetrate clinically significant drug-drug interaction via inhibition or induction of CYP enzymes
Caution should be exercised when administering paclitaxel (Taxol) concomitantly with medicines known to inhibit (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir) OR induce (e.g. rifampicin, carbamazepine, phenytoin, efavirenz and nevirapine) either CYP2C8 or CYP3A4.
Actively smoking 5 or more cigarettes per day for at least one year
Willing to set a quit date within 6 weeks
Willingness to take varenicline OR nicotine patch (patient choice)
Willingness to take bupropion
Carbon monoxide (CO) test under 7 parts per million (ppm)
3 or above on Patient Health Questionnaire (PHQ-2) Depression Scale
> 0 in PHQ-9 question 9
Daily use of a second form of tobacco or nicotine (e.g. e-cigarettes, cigars, chewing tobacco, snuff)
TURNSTILE I - SCREENING:
TURNSTILE I - SCREENING
Patient is mentally or legally incapacitated at the time of the study
Tumors involving the cerebellum
Unexplained febrile illness
IHC evidence of MUC16^ecto expression will be performed according to the technique and 0-5 scoring system
Only MUC16^ecto tumors with moderate to strong immunoreactive scores (3-5) will be considered positive
Clinical or radiographic evidence of bowel obstruction, or need for parenteral hydration and/or nutrition
Known or suspected extensive abdominal adhesions
Any concurrent active malignancies, defined as malignancies requiring any therapy other than expectant observation, since adverse events resulting from these malignancies or their treatment may confound our assessment of the safety of adoptive T cell therapy for ovarian cancer
Prior radiotherapy to any portion of the abdominal cavity or pelvis
ARM C COHORT 4: AST and ALT =< 5 x ULN
Patients must not have corrected QT (QTc)F (Fridericia Correction Formula) > 480 on 2 out of 3 electrocardiograms (EKG’s) (if first EKG is =< 480, no need to repeat, if first EKG is > 480 repeat twice for a total of 3 EKG’s)
PHASE II: Advanced RCC associated with 1) HLRCC or SDH (Cohort 1); OR 2) advanced non HLRCC-related papillary RCC (Cohort 2)
Proteinuria > 1gram/24 hrs
Active treatment-refractory diarrhea that may affect the ability of the patient to absorb the trial agents or tolerate further diarrhea
Relapsed Ph+ ALL, with no prior exposure to dasatinib and without known ABL kinase mutations predicted to be resistant to dasatinib (e.g. L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317I, F317L, F317S, F317V)
Relapsed or refractory Ph-like ALL without prior exposure to dasatinib and with mutations or rearrangements of genes conferring sensitivity to dasatinib (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP)
Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/fluorescence in situ hybridization [FISH]) and/or molecular tests (BCR-ABL1 transcripts)
Ph-negative ALL
Patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis
Mature B-cell (Burkitt’s) ALL
Unable to tolerate anti-viral and anti-Pneumocystis jirovecii prophylaxis while on pre-phase and remission induction therapy
Prisoners are excluded for this study
No active major medical or psychosocial problems that could be complicated by study participation
No histologic documentation of EOC
Signs or symptoms of gastrointestinal obstruction
Requirement for chronic parenteral hydration/nutrition
PHASE II STUDY COHORT 1 OVARIAN CANCER ELIGIBILITY CRITERIA (MEDI+O, MEDI+C AND MEDI+O+C): Documentation of germline breast cancer (BRCA)1 and BRCA2 mutation (gBRCAm) status will be requested; a documented deleterious germline BRCA1 and BRCA1 mutation (gBRCAm) obtained in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory will be requested, but it is not mandated for enrollment; Myriad testing will be accepted; if testing for BRCA is done by other organizations either by multi-gene panels or individual testing, genetic consultation report from a qualified medical professional listing the mutation and confirming that the laboratory results showed a recognized gBRCAm or germline deleterious BRCA rearrangement is required; if the patient refused genetic counseling, it should be documented in the medical records; variants of uncertain significance (VUS) of BRCA1 and BRCA2 are not considered deleterious; patients with VUS or deleterious mutation in other genes without gBRCAm or patients with negative BRCA testing are still eligible
PHASE II STUDY COHORT 5 TRIPLE NEGATIVE BREAST CANCER ELIGIBILITY CRITERIA (MEDI+O ONLY)\r\nDocumentation of germline BRCA1 and BRCA2 mutation (gBRCAm) status will be requested for eligibility; a documented deleterious gBRCAm obtained in a CLIA-certified laboratory, including but not limited to Myriad Genetics, either by multi-gene panels or individual testing, will be required prior to study enrollment; variants of uncertain significance (VUS) of BRCA1 and BRCA2 are not considered deleterious mutation; patients with VUS or deleterious mutation in other genes without gBRCAm or patients with negative BRCA testing are still eligible
Bilirubin =< 1.5 x UNL
Southwest Oncology Group (SWOG) performance status >= 2.0
No previous severe allergic reaction to hepatitis B vaccine, polio vaccine or tetanus, diphtheria, pertussis vaccine (DTP, Tdap, DT or Td)
Has not had a coma or long or multiple seizures within 7 days after a dose of DTP or Tdap unless a cause other than the vaccine was indicated
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: No previous severe allergic reaction to hepatitis B vaccine, polio vaccine or tetanus, diphtheria, pertussis vaccine (DTP, Tdap, DT or Td)
Medical conditions that may increase risk for poor cosmetic outcome (i.e. lupus, rheumatoid arthritis, scleroderma)
Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach for at least 1 hour
Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement
60 years of age or older or 50-59 with a low (0-17) oncotype score; oncotype is not required for women diagnosed with DCIS
Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus, rheumatoid arthritis, scleroderma)
Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach at length
Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement
Patients with microscopic hematuria OR biopsy proven BK nephritis and urine or blood polymerase chain reaction (PCR) positive for BK virus and/or JC viral encephalitis
Documented/locally determined AKT1 or PIK3CA mutation
Carboplatin Plus Paclitaxel Arm:
Paclitaxel Arm:
Hematological - Absolute neutrophil count (ANC) ? 1.5 x 109/L (Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm) or ? 1.0 x 109/L (Anastrozole Arm)
Hemoglobin (Hb) ? 9 g/dL (Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm) or ? 8 g/dL (Anastrozole Arm)
Metabolic - Glycated hemoglobin (HbA1c) ? 8%
Carboplatin and/or paclitaxel defined by the Investigator based on the Food and Drug Administration (FDA) approved labeling or institutional standard of care (SOC)
Anastrozole defined by the Investigator based on institutional SOC, scientific evidence, expert medical judgment, or published literature
Ki67 score/proliferative index =< 20% or low to intermediate mitotic index
Any serum aspartate aminotransferase (AST) is allowed but serum AST =< 34 IU/L is strongly encouraged
Gleason score =< 7, no tertiary pattern >= 5
American Urological Association (AUA) =< 18 with or without medical management
Up to a total of 1 year of androgen deprivation allowed
Confirmation that insurance will cover SBRT through normal hospital authorization process
FOR BOTH ARM A AND ARM B:
Significant urinary obstruction in spite of alpha blocker use (i.e. AUA symptom score > 18)
If sorafenib was previously administered, intolerance to sorafenib
Contraindications to sildenafil including:\r\n* Known retinitis pigmentosa\r\n* History of priapism related to PDE5 inhibitors (eg, sildenafil, vardenafil, tadalafil)\r\n* Presence of nonmalignant hematologic disorders, such as sickle cell disease, that may increase the risk of priapism
Adult men and women aged 18 and older
BM cellularity < 30% and
Symptomatic ischemia, or
FOR THE RANDOMIZED PORTION ONLY
FOR THE PILOT PORTION
Deemed by the treating physician to be unable to eat regular meals
Melanoma or renal histology
Coronary/peripheral artery bypass graft
Undergone molecular testing for integral biomarkers including immunohistochemical staining for vimentin
Patients must have probable (i.e., clinically suspicious) or histologically/cytologically confirmed, primary or recurrent, malignant neoplasm, malignant neuroendocrine tumor, or carcinoma in situ (any stage)\r\n* Malignant neoplasm, malignant neuroendocrine tumor, or carcinoma in situ will be defined as\r\n** Malignant neoplasm of lip, oral cavity, or pharynx (International Classification of Disease-9-Clinical Modification [ICD-9-CM] codes 140-149 [or corresponding ICD-10-CM codes]) \r\n** Malignant neoplasm of digestive organs or peritoneum (ICD-9-CM codes 150-159 [or corresponding ICD-10-CM codes])\r\n** Malignant neoplasm of respiratory or intrathoracic organs (ICD-9-CM codes 160-165 [or corresponding ICD-10-CM codes]) \r\n** Malignant neoplasm of bone, connective tissue, skin, or breast (ICD-9-CM codes 170-175 [or corresponding ICD-10-CM codes])\r\n** Malignant neoplasm of genitourinary organs (ICD-9-CM codes 179-189 [or corresponding ICD-10-CM codes])\r\n** Malignant neoplasm of other or unspecified sites (ICD-9-CM codes 190-199 [or corresponding ICD-10-CM codes])\r\n** Malignant neuroendocrine tumor (ICD-9-CM codes 209.0-209-3, 209.7 [or corresponding ICD-10-CM codes])\r\n** Carcinoma in situ (ICD-9-CM codes 230-234 [or corresponding ICD-10-CM codes])
Scheduled for curative or palliative major cancer surgery; patient must be scheduled for at least one of the following procedures (i.e., Common Procedural Terminology [CPT codes]), and may be scheduled for more than one of these procedures within or across each of the following procedure types (e.g., glossectomy, pharyngectomy, etc.) or procedure families (e.g., head and neck surgery, thoracic surgery, etc.)\r\n* Head and neck surgery\r\n** Glossectomy (CPT codes 41135,41140,41145,41150,41153,41155)\r\n** Pharyngectomy (CPT codes 42842,42844,42845,42890,42892,42894)\r\n** Laryngectomy (CPT codes 31360,31365,31367, 31368, 31370, 31375, 31380, 31382, 31390, 31395)\r\n** Neck dissection (CPT codes 38720, 38724)\r\n* Thoracic Surgery\r\n** Esophagectomy (CPT codes 43101, 43107, 43108, 43112, 43113, 43116, 43117, 43118, 43121, 43122, 43123, 43124)\r\n** Lung resection (CPT codes 32440, 32442, 32445, 32480, 32482, 32484, 32486, 32488, 32491, 32503, 32504, 32505, 32506, 32507, 32663, 32666, 32667, 32668, 32669, 32670, 32671, 32672)\r\n* Upper gastrointestinal/hepatico-pancreatico-biliary surgery\r\n** Gastrectomy (CPT codes 43620, 43621, 43622, 43631, 43632, 43633, 43634)\r\n** Pancreatectomy (CPT codes 48120, 48140, 48145, 48146, 48148, 48150, 48152, 48153, 48154, 48155, 48999)\r\n** Hepatectomy (CPT codes 47120, 47122, 47125, 47130)\r\n* Colorectal surgery\r\n** Colectomy (CPT codes 44140, 44141, 44143, 44144, 44145, 44146, 44147, 44150, 44151, 44160, 44204, 44205, 44206, 44207, 44208, 44210)\r\n** Proctectomy (CPT codes 44155, 44156, 44157, 44158, 44211, 44212, 45110, 45111, 45112, 45113, 45114, 45116, 45119, 45120, 45121, 45123, 45126, 45130, 45135, 45160, 45395, 45397, 45402, 45550)\r\n* Gynecologic surgery\r\n** Hysterectomy/Myomectomy (CPT codes 58140, 58145, 58146, 58150, 58152, 58180, 58200, 58210, 58240, 58260, 58262, 58263, 58267, 58270, 58275, 58280, 58285, 58290, 58291, 58292, 58293, 58294, 58541, 58542, 58543, 58544, 58545, 58546, 58548, 58550, 58552, 58553, 58554, 58570, 58571, 58572, 58573, 58940, 58943, 58950, 58951, 58952, 58953, 58954, 58956)\r\n** Gynecologic reconstruction (CPT codes 57260, 57265, 57267, 57268, 57270, 57280, 57282, 57283)\r\n* Urologic Surgery\r\n** Prostatectomy (CPT codes 55801, 55810, 55812, 55815, 55821, 55831, 55840, 55842, 55845, 55866)\r\n** Nephrectomy (CPT codes 50220, 50225, 50230, 50234, 50236, 50240, 50543, 50545, 50546, 50548)\r\n** Cystectomy (CPT codes 51550, 51555, 51565, 51570, 51575, 51580, 51585, 51590, 51595, 51596, 51597)\r\n* Soft tissue/plastic surgery\r\n** Breast reconstruction (CPT codes 19324, 19325, 19340, 19342, 19357, 19361, 19364, 19366, 19367, 19368, 19369)\r\n** Flap reconstruction (CPT codes 15731, 15732, 15734, 15736, 15738, 15740, 15750, 15756, 15757, 15758)
These procedures are commonly performed in patients with malignant neoplasms, malignant neuroendocrine tumors, or carcinomas in situ, and are commonly “tracked” by hospitals and cancer centers participating in the ACS NSQIP Procedure Targeted option because they are often associated with higher rates of postoperative morbidity and mortality (compared to other, less complex cancer procedures)
Geographical accessibility and willingness to return to FCCC for all preoperative and postoperative study assessments
Clinical or tissue diagnosis of benign neuroendocrine tumor, benign neoplasm, neoplasm of uncertain behavior, or neoplasm of unspecified nature \r\n* Benign neuroendocrine tumor (ICD-9-CM codes 209.4-209.6 [or corresponding ICD-10-CM codes]) \r\n* Benign neoplasms (ICD-9-CM codes 210-229 [or corresponding ICD-10-CM codes]) \r\n* Neoplasm of uncertain behavior (ICD-9-CM codes 235-238 [or corresponding ICD-10-CM codes]) \r\n* Neoplasm of unspecified nature (ICD-9-CM codes 239 [or corresponding ICD-10-CM codes])
Incarcerated individuals
Active infection requiring intravenous (IV) antibiotic usage within the last week prior to the dosimetry portion of the study
Both men and women of all races and ethnic groups are eligible for this trial
Active herpetic skin lesions
Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the principal investigator (PI) are excluded
Subject previously has entered this study
Lysate must meet release criteria
Subjects who screen fails can be re-enrolled if the causation of the screen fail has been corrected
Subject has a positive serum Yo antibody (does not need to be repeated if performed in the past)
Subject requires or is likely to require more than a two-week course of corticosteroids for intercurrent illness; subject must complete the course of corticosteroids 2 weeks before screening to meet eligibility
Subject has proteinuria > 3.5 gm over 24 hrs are not eligible for the study
Hematocrit < 30%
Potential donors under the age of 18 must have a single patient exemption approved by the Institutional Review Board (IRB); the donor must provide assent and the donor’s parent or guardian must provide permission for minor participation; donors under the age of 18 who cannot assent based on their developmental stage will not be included
Foundation for the Accreditation of Cellular Therapy (FACT) labs and final test results available prior to infusion into the patient (copy of labs included in appendices); in the second donation from the donor, the FACT labs must be redrawn within 30 days of initiation of apheresis; positive serologies are not repeated as they remain positive for lifetime
Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: ECOG performance 0-1
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: AST and ALT =< 2 X upper level of normal
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: Absolute lymphocyte count >= 500/mm^3
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: Major active medical or psychosocial problems that could be exacerbated by this treatment
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine
Dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
Has completed the baseline HRQOL questionnaires UNLESS is unable to complete because of literacy or limited vision
Bilateral orchidectomy or radical prostatectomy
Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
Adenocarcinoma of the prostate treated primarily with radical prostatectomy\r\n* Any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy
At least one additional non-contiguous lesion to the irradiated lesion amenable to radiographic evaluation
We will allow XRT prior to study entry to other sites, with no washout period, allowed prior to study entry as long as at least one measurable sites of disease is kept unirradiated
AT THE TIME OF PROCUREMENT: Recurrent or refractory GBM
AT THE TIME OF INFUSION: Intracranial catheter (such as Rickham or Ommaya) in place
AT THE TIME OF INFUSION: Available autologous transduced T lymphocytes with ? 15% expression of HER2 CAR determined by flow cytometry and killing of HER2-positive targets ? 20% in cytotoxicity assay
ALT =< 3 x ULN (5.0 x ULN if considered to be due to leukemic involvement)
Prior induction therapy with decitabine, clofarabine, idarubicin (DAC) + cytarabine (CIA)
Staging work-up prior to registration
MRI MONITORING SUB-STUDY: Engaged in occupations or activities which may cause accidental lodging of ferromagnetic materials, or have imbedded metal fragments from military activities
Clinical assessment score will be obtained, at baseline\r\n* Visual assessment (VA) in affected eye of at least 20/200 - 0/1\r\n* Ocular motility intact - 0/1\r\n* No diplopia - 0/1\r\n* Binocularity (fusion) +/- prism - 0/1\r\n* Normal tear lake, no complaint of persistent tearing - 0/1\r\n* Intact lacrimal system by probing/irrigation (both canaliculi to nasolacrimal duct [NLD]) - 0/1\r\n* Patient assessment of visual function on the affected side (good, fair, poor) - 0/1/2\r\n* Score maximum - 8
Medical oncology screening evaluation performed to assess medical indication/contra-indication to vismodegib treatment
Principal investigator (PI) to review the exam findings, photos and imaging study and determine whether the patient meets inclusion criteria in the study, based on BCCA size, location of tumor, and clinical assessment score\r\n* Orbital invasion or impending invasion by BCCA\r\n* Medial canthal BCCA within 7 mm of lacrimal apparatus
Patient will be approached for enrolling in the study by the PI, treating physician or a designee; informed consent will be obtained by the PI, co-investigator (co-I) or a qualified designee
If the patient consents to enroll, then blood will be drawn and stored for biomarker analysis
Prior to enrollment, the CA125 should have been elevated to at least double the level seen at the nadir value following the first complete response and measurable intraperitoneal disease that can be identified radiologically and accessed by laparoscopy/laparotomy for a biopsy and peritoneal catheter placement
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have subsequently grown unequivocally to be deemed a target lesion.
One or more evaluable or measurable lesions that do not demonstrate iodine uptake on any radioiodine scan; or
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as: BP less than 95th percentile for sex, age, and height/length at screening (as per National Heart Lung and Blood Institute guidelines) and no change in antihypertensive medications within 1-week prior to Cycle 1/Day 1. Osteosarcoma subjects 18 to 25 years should have BP ?150/90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1.
Two or more prior vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) targeted therapies.
< 1+ proteinuria
Tumors must be localized (non-metastatic) and classified as borderline resectable according to Americas Hepato-Pancreato-Biliary Association (AHPBA)/Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT) consensus criteria or be clinically node-positive via computed tomography (CT) or endoscopic ultrasound\r\n* AHPBA/SSO/SSAT criteria (any one of the following):\r\n** Tumor-associated deformity of the SMV (superior mesenteric vein) or PV (portal vein)\r\n** Abutment of the SMV or PV >= 180 degrees\r\n** Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction\r\n** Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction\r\n** Abutment of the superior mesenteric artery (SMA) < 180 degrees
Members of all races and ethnic groups will be included
Subjects with locally advanced, unresectable primary tumors will not be eligible\r\n* This includes any of the following:\r\n** Abutment of the SMA >= 180 degrees\r\n** Occlusion of the SMV or PV with insufficient normal vein above and below with which to perform venous reconstruction\r\n** Involvement of the hepatic artery with insufficient artery proximal and distal to perform reconstruction
Subjects with plastic biliary stents will be excluded; metal biliary stents are allowed and will not be excluded
Patients with MCL must be symptomatic and need immediate therapy; symptoms and nature of MCL include any of the following: \r\n* Blastoid variant\r\n* Pleomorphic variant\r\n* B symptoms\r\n* Mantle Cell International Prognostic Score (MIPI) > 3\r\n* Ki-67 >= 30%\r\n* Bulky tumors > 7 cm or in case of >= 2 tumors, each >= 5 cm in diameter\r\n* Disease threatening organ function\r\n* Elevated lactate dehydrogenase (LDH)\r\n* Peripheral blood white blood cell (PB WBC) > 50,000\r\n* Pancytopenia due to bone marrow MCL\r\n* Patient’s choice due to anxiety\r\n* Pain due to lymphoma\r\n* Somatic mutations in the TP53, c-MYC or NOTCH genes\r\n* Size of spleen >= 20 cm
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered
Serum M component (? 0.5 g/dL), or
Hb ? 9 g/dL (independent of transfusions or erythropoiesis-stimulating agents [ESA]).
Ability to understand and complete the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) instruments
PATIENT CRITERIA FOR PROCEEDING WITH CD8+ MEMORY T-CELL INFUSION:
Infection requiring current intravenous antibiotic therapy; the PI will serve as the final arbiter regarding eligibility
Documented genetic lesion(s) known to confer susceptibility to inhibition by either ruxolitinib or dasatinib or cytokine receptor-like factor 2 (CRLF2) positivity by flow cytometry (for the ruxolitinib cohort)
Have had complete (CC-0 or CC-1) CRS with HIPEC open or minimally invasive (laparoscopic or robotic)
Subjects with delayed healing of wounds, ulcers, and/or bone fractures
Absence of radiographic evidence of extrathyroidal extension
Serum transaminases =< 3 x ULN
Been treated with appropriate maximal medical therapy for heart failure
Able to perform 6 minute walk test
Significant valvular disease; (aortic stenosis [AS] with aortic valve area [AVA] < 1.5 and severe aortic regurgitation [AR] and mitral regurgitation [MR])
Inotropic dependence
Unstable or life-threatening arrhythmia
Mechanical or bioprosthetic heart valve
Cardiogenic shock
No deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and comprehensive rearrangement testing at an external reference laboratory; patients with variants of unknown significance will be eligible
Deleterious or suspected deleterious germline or somatic gene mutation implicated in the HR pathway, excluding BRCA1 or BRCA2, based on multiplex germline gene testing or direct tumor next generation deoxyribonucleic acid (DNA) sequencing; these genes include: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes (FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL), plus other HR-related genes at the discretion of the primary investigators
Any patient with a deleterious mutation in BRCA1 or BRCA2
ITP that has persisted for ? 3 months. ITP must be diagnosed in accordance The American Society of Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia (Neunert et al. 2011) or the International Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010), as locally applicable.
Not willing to stay at the study site for 4 hours after each PRTX-100 infusion
Patients must meet the diagnostic criteria for HPS (at least 5 of the following):\r\n* Fever\r\n* Splenomegaly\r\n* Cytopenia involving >= 2 cell lines\r\n* Hypertriglyceridemia or hypofibrinogenemia\r\n* Tissue demonstration of hemophagocytosis\r\n* Hepatitis\r\n* Low or absent natural killer (NK) cell activity\r\n* Serum ferritin >= 3000 ug/L\r\n* Soluble interleukin (IL)-2 receptor (cluster of differentiation [CD25]) > 2400 U/mL
Difficulty swallowing or malabsorption
First allogeneic hematopoietic stem cell transplantation (HSCT) using myeloablative conditioning (MAC), non-myeloablative (NMA), or reduced-intensity conditioning (RIC) preparative regimens.
At the time of allogeneic HSCT:
Azacitidine, decitabine or other demethylating agents
Lenalidomide, thalidomide and pomalidomide
Blood urea nitrogen (BUN) < 30 mg/dL
For Part B participants: SGPT (ALT) concentration < 2.5 x institutional ULN
Prior total body irradiation (TBI)
Existing chronic bone pain prior to pegfilgrastim usage
Chronic daily usage of antihistamine without an acceptable alternative non-antihistamine medication
Inability to complete the survey instrumentation accurately
Current or previous treatment with an 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG CoA) reductase inhibitor (any statin)
All metastatic lesions must be separated by a minimum of 3 cm as measured from the peripheral edges of the lesions which are in closest proximity to one another; if multiple lesions are present and are not all >= 3 cm away from each other, the patient will be deemed ineligible
For subjects currently on active systemic cancer therapy, the treating medical oncologist should be consulted to ensure proper washout (if appropriate) periods prior to SRS
Prior whole/partial brain irradiation or stereotactic radiosurgery
Lesion located in anatomic regions that are not amenable to SRS, including the brain stem, optic apparatus, or eloquent cortex
Serum cholesterol and serum triglyceride levels must be < grade 2
Category I drugs that are generally accepted to have a risk of causing torsades de pointes including: (patients must discontinue drug at least 7 days prior to starting dasatinib)\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, sotalol, ibutilide, dofetilide\r\n* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, sparfloxacin, lidoflazine
Patients must be post-menopausal based on either a history of an oophorectomy, or at least one year of amenorrhea; an elevated serum gonadotropin level can be used to confirm menopausal status in a subject with one year or more of amenorrhea
Presumed pediatric gliomas (grades I-IV) on MRI that are determined to be candidates for MLA by the treating neurosurgeon
Recurrent pediatric brain tumors determined candidates for MLA as determined by the treating neurosurgeon
Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA
More than 2 prior relapses (not counting the current relapse being treated on this study)
Evaluable myelofibrosis by IWG-MRT criteria including one or more of the following:\r\n* Spleen >= 5 cm below the left costal margin\r\n* MPN-SAF total symptom score (TSS) > 10 at baseline\r\n* Hemoglobin < 10 g/dL
Confirmed diagnosis of myelofibrosis (primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia vera) by World Health Organization (WHO) diagnostic criteria (3 major and 2 minor criteria: major criteria: megakaryocyte proliferation and atypia with either reticulin and/or collagen fibrosis, not meeting criteria for chronic myelogenous leukemia [CML], polycythemia vera [PV], myelodysplastic syndrome [MDS], or other myeloid neoplasm, JAK2V617F or other clonal marker or no evidence of reactive marrow fibrosis; minor criteria: leukoerythroblastosis, increased lactate dehydrogenase [LDH], anemia, palpable splenomegaly)
Ability to complete questionnaire(s) by themselves or with assistance
History of significant or major funduscopic findings including, but not limited to, retinal exudates, hemorrhage, detachment, neovascularization, papilledema, optic atrophy, micro-aneurysm or macular changes
Active neurologic disorder (i.e. weakness, altered mental status) – peripheral neuropathy alone does not exclude a patient
Documented penicillin or cephalosporin allergies
B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform, immunohistochemistry, Foundation One tests, etc.)
Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
at least 3 grade 3 CIRS-G comorbidities OR
at least 1 grade 4 CIRS-G comorbidity (if compatible to participation in the study).
Absence of any autoimmune syndrome typically associated with thymomas but not thymic carcinomas (myasthenia gravis, pure red cell aplasia, etc.)
Physician recruitment will consist of surveying the physicians involved in treating patients on this pilot study; physician participation will be voluntary; physicians will indicate their consent through completion of the survey; survey instructions will include information about the voluntary nature of participation, confidentiality of responses and the minimal risk related to involvement
Patients with Eastern Cooperative Oncology Group (ECOG) performance status worse than 2 (ie unable to perform their own activities of daily living [ADLs] without assistance, unable to spend less than 50% of day out of bed)
Diagnosis of hematologic malignancy meeting at least one of the disease status criteria outlined below; diagnoses from outside laboratories must be confirmed by review in the NCI laboratory of pathology
Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative overlap neoplasms\r\n* Myelofibrosis with adverse-risk features\r\n* Polycythemia vera\r\n* Essential thrombocythemia\r\n* Chronic myelomonocytic leukemia
Patient may have a hepatitis C infection; however, each patient will require a hepatology consultation; the risk/benefit profile of transplant and hepatitis C will be discussed with the patient and eligibility determined by the PI or the LAI
Has read, understood, and signed the ICF
SGPT (ALT) ? 110 U/L.
Patient deemed eligible for rectal spacer (Space OAR) placement by treating physician
Adenocarcinoma of the pancreas
Prior therapy with >= 1 prior systemic therapy over a period of at least 2 months (eg, at least two 4-week cycles of a regimen such as gemcitabine and nab-paclitaxel; or at least four 2-week cycles of a regimen such as fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX], fluorouracil/irinotecan/leucovorin calcium/oxaliplatin [FOLFIRINOX], or folinic acid-fluorouracil-irinotecan [FOLFIRI])
Persistent heart rate (HR) < 50 or > 120 beats per minute (bpm)
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered
Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
Lymphadenopathy exceeding 6 cm in short-axis diameter
Fecal incontinence
Clinical T-classification T1-3
American Urological Association Symptom Index (AUA SI) =< 15
AUA SI > 15
Diagnosis must be made by biopsy or excision
Tolerate one test dose (15 g) of ascorbate
G6PD (glucose-6-phosphate dehydrogenase) deficiency
Patients requiring daily finger-stick blood glucose measurements unless approved by the IND medical monitor, IND sponsor, and the study PI
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Stable, continuous antiretroviral treatment, defined as a multi-drug regimen (excluding zidovudine, also known as azidothymidine [AZT], Retrovir) prior to enrollment, as demonstrated by HIV plasma viral load < 50 copies/mL
Subjects must be on a prophylactic regimen for Pneumocystis jiroveci pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood
Dental braces or prosthesis that interferes with MR imaging
Aged ? 18 years, voluntarily consented to the study.
Adequate hematologic function, as defined by neutrophils ? 1.0 x 10^9/L and platelets ? 50 x 10^9/L; patients with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ? 1.0 x 10^9/L.
Any cytogenetic abnormality in the bone marrow that is known to be associated with or predictive of myelodysplasia is excluded; this includes, but is not limited to, del(5), del(7), del(11)
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Confirmation of active relapse involving the bone marrow of a hematologic malignancy >= 6 months after alloHCT employing PTCy as GVHD prophylaxis and more than 90 days after PTCy-MILs infusion
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: More than 2 years have elapsed since the patient’s initial PTCy-MILs infusion
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Most recent alloHCT performed did not utilize PTCy GVHD prophylaxis
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The use of immunosuppression for grade II-IV acute GVHD within 28 days prior to the infusion of PTCy-MILs
Patients with jaundice or clinical cholangitis, with new elevation of alkaline phosphatase, total bilirubin, and imaging findings supportive of stent occlusion (loss of stent patency, debris within stent, loss of or excessive pneumobilia)
Have altered gastro-duodenal or hepatobiliary anatomy such that endoscopic retrograde cholangiopancreatogram (ERCP) is felt to be unacceptably technically difficult or unsafe
Have additional sites of biliary strictures (intrahepatic/hilar) such that ERCP stenting is felt to be unlikely to provide adequate clinical benefit
Have biliary strictures not technically amenable to endoscopic therapy
Diagnosis of melanoma belonging to the following American Joint Committee on Cancer (AJCC) TNM stages:\r\n* Tx or T1-4 and\r\n* N1b, or N2b, or N2c, or N3 and \r\n* M0
Concurrent bisphosphonate or receptor activator of nuclear factor kappa-B (RANK)-ligand directed therapy for prevention of skeletal related events or treatment of osteoporosis is allowed
Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor (ARN-509) or androgen synthesis
Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
Chemotherapy, immunotherapy, radiotherapy, radiosurgery, interferon (e.g. Intron-A), allergy desensitization injections, growth factors (e.g. Procrit, Aranesp, Neulasta), interleukins (e.g. Proleukin) or any investigational therapeutic medication within 4 weeks of study entry
EUS evidence of vessel interfering with path of fiducial marker
Patient has not met criteria for withdrawal from the base protocol
Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, or
Man or woman >= 18 years old.
Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects).
Is willing to undergo malignancy genotyping for TP53 gene mutation, insertion, or deletion at screening.
Has a malignancy that contains a non synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening.
Biopsy-proven diagnosis of rectal adenocarcinoma
Primary surgeon indicates the need for an abdominal perineal resection (APR) at baseline
Other invasive malignancies within past 5 years from date of registration
Any conditions that would preclude a patient from completing all study assessments
Either resectable or borderline resectable as determined on staging imaging (as defined by National Comprehensive Cancer Network [NCCN])
Histological documentation of mCRC
Massive (i.e. > 6 cm below the left costal margin) or progressive/symptomatic splenomegaly OR
Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
Conditions that would prohibit administration of corticosteroids
Participants must have stable or responding systemic disease to TKI (no evidence of progression) on the most recent staging studies; the required staging studies are: (1) a re-staging computed tomography (CT) scan of the chest +/- abdomen with intravenous (IV) contrast (unless medically contraindicated) within 2 months of study enrollment; and (2) in patients with known brain metastasis, or to investigate patients with new onset of neurologic symptoms that may suggest metastasis to the brain, brain magnetic resonance imaging (MRI) with gadolinium, or head CT scan with IV contrast will be required within 2 months of study enrollment; the complete extent of the current residual systemic disease must be deemed amenable to SBRT as per review of imaging studies by a radiation oncologist involved in this trial; this will be based on the following criteria:\r\n* Lung: 1-3 lesions (including the primary) of maximum size 5 cm in longest diameter; a minimum size 1 cm in the longest diameter is recommended; (patients with a malignant pleural effusion prior to the start of TKI therapy will be considered eligible for SBRT if there is complete radiographic resolution of the effusion while on systemic therapy)\r\n* Spine: bone lesions must be limited to the spine; a maximum of 2 spinal metastases will be considered for SBRT, with each site spanning 1-3 vertebral bodies; a minimum size of 1 cm in longest diameter is recommended; SBRT may target sclerotic lesions that persist following TKI therapy\r\n* Gastrointestinal (GI): 1-4 liver metastases of maximum size 5 cm in longest diameter and/or 1-2 adrenal metastases of maximum 4 cm size in longest diameter; a minimum size of 1 cm in longest diameter is recommended\r\n* In addition:\r\n* Central nervous system (CNS): 1-4 brain metastases of maximum size 3cm in longest diameter; however, these should be treated with standard-of-care stereotactic radiosurgery (SRS) and will not be defined as target lesions for purposes of this protocol; there is no minimum size requirement for treatment of brain lesions but small foci of potential disease (1-4 mm size) detected on high-resolution MRI may not be clinically relevant and do not count towards the maximum number of 4 brain metastases as per the treating radiation oncologist’s discretion and in line with institutional practice\r\n* A maximum number of 5 target lesions outside the brain, excluding the lung primary, is recommended to ensure that enrollment is limited to patients with low-burden disease and that treatments can be delivered within the specified time frame; this is not an absolute requirement as situations may exist when more than 5 metastatic targets are appropriate in the treating radiation oncologist’s clinical judgment, for example when nearby lesions can be included in a single treatment field
Normal serum creatinine based on age/gender as defined by Seattle Children's Hospital (SCH) chemistry lab
Normal serum sodium level without need for supplementation
Patient is able to tolerate apheresis procedure including placement of temporary apheresis catheter if necessary or has prior apheresis product of 50 x 10^6 mononuclear (MNC) cells available for use
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: Patient has not received immunotherapy (for example- murine, chimeric or humanized monoclonal antibodies), T cell growth factors (such as IL-2, IL-7 or IL-15), interferons, vaccines, and other cellular products), pentoxifylline within the 7 days prior to the infusion of the T cell product
RETREATMENT WITH MODIFIED T CELLS: Subject has tolerated prior dose of modified T cell infusion without experiencing a dose limiting toxicity
RETREATMENT WITH MODIFIED T CELLS: Subject has modified T cell product available for release
RETREATMENT WITH MODIFIED T CELLS: Subject has < 5% detectable modified T cells in peripheral blood (can be done any time prior)
RETREATMENT WITH MODIFIED T CELLS: Subject has evidence of persistent NB
RETREATMENT WITH MODIFIED T CELLS: Normal serum creatinine based on age/gender
RETREATMENT WITH MODIFIED T CELLS: Normal serum sodium level without need for supplementation
RETREATMENT WITH MODIFIED T CELLS: ALT (SGPT): =< 5 x ULN
Primary lung cancer or metastatic disease to the lungs to be treated with either conventionally-fractionated radiotherapy (CFRT) or hypo-fractionated stereotactic ablative radiotherapy (SABR)
There are no ethnic restrictions
Prior radiotherapy for thoracic cancer or other malignancy leading to any overlap of planned radiotherapy fields
Children (< 18 years of age), pregnant women, University of California employees or students, or prisoners will be excluded from this study
Presence of an index lesion >= 1 cm amenable to hypofractionated radiotherapy
Patients who have metastatic cancer must have at least one lesion that is outside the radiation field that measures greater than one cm that can be followed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; this lesion, if it is close to the radiated lesion, must receive no more than 10% of the dose prescribed to the target lesion
Ability to tolerate hypofractionated radiation therapy (e.g. lie flat and hold position)
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy
Histological confirmation of pheochromocytoma (PH)/paraganglioma (PG)
Histologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC with mutations, rearrangement and fusion involving RET oncogene, or abnormalities (non-synonymous single nucleotide variant [SNV] or amplification) in the nintedanib target genes VEGFR1-3, TP53, PDGFR-A, PDGFR-B, or FGFR1-3; Clinical Laboratory Improvement Act (CLIA) certified lab testing for nintedanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable
Radiographic evidence of cavitary or necrotic tumors
Potassium before the first dose of ceritinib
Magnesium before the first dose of ceritinib
Phosphorus before the first dose of ceritinib
Total calcium (corrected for serum albumin) before the first dose of ceritinib
Barcelona Clinic Liver Cancer stage B or C; segmental and subsegmental portal vein thrombosis is allowed
Consultation with interventional radiologist and deemed an appropriate candidate for TARE
Prior 90Y TARE or sorafenib is not allowed
Inability to perform y90 TARE due to: (1) inability to catheterize the hepatic artery, (2) portal vein thrombosis/occlusion without the ability to perform selective infusion, (3) technetium Tc 99m-labeled macroaggregated albumin (Tc-99m MAA) hepatic artery perfusion scintigraphy shows unfavorable shunt fraction between the liver and the pulmonary parenchyma as determined by the interventional radiologist, or (4) other contraindication to TARE identified by interventional radiologist
Subjects with active herpes simplex or herpes zoster; subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded; subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study
Target lesion size for re-irradiation must be =< 2 vertebral bodies
Systemic chemotherapy delivered or planned to be delivered within (+/-) 5 days of SRS re-irradiation
Patients who may not receive therapeutically effective doses via an external beam approach to the lesion of interest as specified by the Dose Limit Guidelines \r\n* Evaluation of doses previously delivered to spinal cord/cauda equina and other critical structures (bowel, esophagus, kidneys, rectum) will be taken into consideration\r\n* If repeat irradiation would exceed any normal tissue constraint the patient will be ineligible \r\n* If the total prior radiation dose to the spinal cord/cauda equina and/or sacrum over all prior treatments exceeds 100 Gy BED (biologically effective dose), the patient will be ineligible
Subjects who have received at least one vaccine under protocol University of Pennsylvania Cancer Center (UPCC)-19809 or UPCC-29810
Hematocrit >= 30%
Subjects who are positive for serum anti-Yo (cerebellar degeneration-related protein 2 [cdr2]) antibodies are not eligible; (Yo antibody does not need to be repeated if performed in the past)
Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym-A infusion.
Available Viralym-A T cell line.
Endotracheal intubation and mechanical ventilation at any FiO2
Hemodynamic instability requiring continuous infusions of inotropes or vasopressors
Patient able and willing to complete the QoL, economics and other questionnaires. The baseline assessment must already have been completed within required timelines prior to randomization. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible
Patients must have activating genomic alterations in FGFR (mutations, fusions or amplifications [> 6 copies]) or activating genomic alterations in mast/stem cell growth factor receptor kit (KIT), platelet-derived growth factor receptor alpha (PDGFR alpha), ret proto-oncogene (RET), ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) and fms-related tyrosine kinase 3 (FLT3) by any validated Clinical Laboratory Improvement Amendments (CLIA)-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable
Patients with known ponatinib-resistant gene alterations\r\n* Platelet derived growth factor receptor, alpha polypeptide (PDGFRA) D842V mutation\r\n* Mast/stem cell growth factor receptor Kit (cKIT) D816V mutation\r\n* FLT3 D835V/Y/H/F or Y842C mutations\r\n* Fibroblast growth factor receptor 3 (FGFR3) K652E mutation
Have an address and telephone number where he/she may be reached
Individuals rated as moderate (9-16) to high (17 or greater) on suicidality as assessed by Module B of the MINI
Psychiatric hospitalization within 1 year of screening date
Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, phencyclidine (PCP), or tetrahydrocannabinol (THC); a. participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded; b. participants failing the toxicology screen will be allowed to re-screen once; if they test positive again, they will not be allowed to return
Diagnosis: patients with recurrent/refractory medulloblastoma (MB), atypical teratoid (AT)/rhabdoid tumors (RT) or ependymoma involving the brain and/or spine at original diagnosis or relapse; they must have histological verification at diagnosis and/or relapse; patient must have presented with these tumors in the posterior fossa (PF) or relapsed in the PF
Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles to receive NK cell infusion
Presence of nodules considered neoplastic in contralateral lobes (M1a)
Willingness to take everolimus orally and maintain a pill diary
PART 2: Comorbidity Index < 5 at the time of pre-transplant evaluation
DONOR: Umbilical cord blood units will be selected according to the following umbilical cord blood graft selection criteria; one or 2 cord blood (CB) units may be used to achieve the required cell dose
DONOR: Selection of two CB units is allowed to provide sufficient cell dose (see below for algorithm to determine single versus double unit transplant); when multiple units are selected, the following rules apply:\r\n* The CB unit with the least HLA disparity (with the patient) will be selected first (i.e., selection priority is 6/6 match > 5/6 match > 4/6 match); additional CB units then may be selected to achieve the required cell dose, as outlined below; if a second unit is required, this unit will be the unit that most closely HLA matches the patient and meets minimum size criteria outlined below of at least 1.5 x 10^7 total nucleated cells (TNC)/kg (i.e. a smaller, more closely matched unit will be selected over a larger, less well matched unit as long as minimum criteria are met)\r\n* If two CB units are used:\r\n** The total cell dose of the combined units must be at least 3.0 x 10^7 TNC per kilogram recipient weight\r\n** Each CB unit MUST contain at least 1.5 x 10^7 TNC per kilogram recipient weight\r\n* Algorithm for determining single versus double unit cord blood transplant:\r\n** Match grade 6/6: TNC dose >= 2.5 x 10^7/kg\r\n** Match grade 5/6, 4/6: TNC dose >= 4.0 (+/- 0.5) x 10^7/kg
DONOR: General comments:\r\n* Units will be selected first based on the TNC dose and HLA matching\r\n* Cluster of differentiation (CD)34+ cell dose will not be used for unit selection unless 2 units of equal HLA-match grade and similar TNC dose (+/- 0.5 x 10^7 TNC/kg) are available; in this case, the unit with the larger CD34+ cell dose (if data available) should be selected\r\n* A CB unit that is 5/6 mismatched but homozygous at the locus of mismatch should be chosen over a 5/6 unit with bidirectional mismatch even if the latter unit is larger (has more cells); this also applies to 4/6 units; this is only applicable to choosing units within a given match grade\r\n* Other factors to be considered: \r\n** Within the same HLA match grade, matching at DR takes preference\r\n** Cord blood banks located in the United States are preferred\r\n* Up to 5% of the cord blood product(s), when ready for infusion, may be withheld for research purposes as long as thresholds for infused TNC dose are met; these products will be used to conduct studies involving the kinetics of engraftment and immunobiology of double cord transplantation
Hematopoietic cell transplantation (HCT) co-morbidity index score > 3; the principal investigator is the final arbiter of eligibility for comorbidity score > 3
DONOR: Non-inherited maternal antigen (NIMA), inhibition of platelet aggregation (IPA), and natural killer cell (NK) reactivity will not be included in selection criteria
Must be scheduled for laparoscopic robot assisted partial nephrectomy of renal mass
Masses located close to the hilar vessels or at locations that cannot be accessed with the HIFU probe
Patient with only 1 kidney
Multiple or bilateral renal masses
Abdominal obesity that would, in the assessment of the principal investigator (PI), make the HIFU ablation difficult
Subjects with tumors lying < 1 cm from sensitive structures
All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions
Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician
Conditions that would prohibit intermittent administration of corticosteroids for T-DM1 premedication.
Bilirubin =< 1.5 x UNL
Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency
Arms 1E, 2E and 3E: solid tumor that demonstrate anaplastic lymphoma kinase (ALK) positivity; ALK positivity can be assessed using the assays below, and documentation of ALK positivity using one of the tests below is required\r\n* Fluorescence in situ hybridization (FISH) test for ALK positivity using the Food and Drug Administration (FDA)-approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); OR\r\n* Harboring a confirmed ALK positivity, as determined by positivity to the Ventana immunohistochemistry (IHC) assay
Arms 1E: previously treated with and progressed on gemcitabine-containing therapy
Subjects will be required to agree to a biopsy performed at baseline and again at week 8 of the study in order to be eligible for enrollment in stage 1 of the study
Known sensitivity to lenalidomide or other thalidomide derivatives or anti cluster of differentiation (CD)20
Smoke an average of 5 or more cigarettes or little cigars per day (CPD) prior to telephone screen
Produce an expired carbon monoxide (CO) level greater than or equal to 6 parts per million (ppm) or a NicAlert reading of > 2
Have a working telephone
Taking psychotropic, anticonvulsive, or narcotic medication
Meet criteria for a current major depressive episode or suicidality
Report uncorrected vision problems
Involved in current smoking cessation activity
Considered by the investigator to be an unsuitable or unstable candidate (e.g., due to cognitive impairment)
Unwilling to alter or remove hairstyle, hair extensions, or wig during the clinic visits to allow for correct electroencephalography (EEG) sensor placement
Have a diagnosis of primary aHUS, persistent HSCT-associated TMA or TTP
No clinically apparent alternative explanation for thrombocytopenia and anemia
Have STEC-HUS
Have a positive direct Coombs test
Histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2, CIN3, or CIN2/3); a copy of the pathology report is required at the time of enrollment; only patients that had their biopsy performed at the University of Alabama at Birmingham (UAB) Colposcopy clinic will be included
Focal lesion visualized in its entirety colposcopically and involving =< 2 quadrants of the cervix
Satisfactory (adequate) colposcopy
Lives within 100 miles of the University of Alabama at Birmingham
Glandular abnormalities on cytology or histology
Cervical lesion incompletely visualized (e.g., extending into the endocervical canal)
Endocervical curettage positive for high-grade cervical intraepithelial neoplasia
Unreliable for follow-up (drug use, planning to move out of region ,etc.); any patient that lives more than 100 miles away will be excluded
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Granulocytes >= 1,500/mcL
STEP 1: Within 30 days of study entry: Patients with a history of bone marrow disorders including hematological malignancies and aplastic anemia, myelodysplastic Syndrome (MDS) and myeloproliferative disorder (MPD) planning to undergo allogeneic HSCT with reduced intensity or myeloablative conditioning regimens
CMV seropositive
STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells (adoptive immunotherapy): CMV reactivation defined as CMV DNA present in the blood (DNAemia) >= 137 copies/ml
CMV seronegative
STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells (adoptive immunotherapy): documented CMV end-organ disease
Research participants must not require more than 2 mg TID of dexamethasone during T cell therapy
Research participants with any other active malignancies
Unresectable disease or borderline resectable disease assessed by a multidisciplinary panel of pancreas surgeon, medical and radiation oncologist, and a radiologist; criteria defining unresectable and borderline resectable patients will be based on the National Comprehensive Cancer Network (NCCN) Guidelines (version [v] 1.2014)\r\n* Unresectable\r\n** Greater than 180 degrees of superior mesenteric artery (SMA) encasement\r\n** Any celiac abutment\r\n** Unreconstructible superior mesenteric vein (SMV)/portal occlusion\r\n** Aortic invasion or encasement\r\n** Nodal metastases beyond the field of resection\r\n* Borderline resectable\r\n** Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen\r\n** Encasement of the SMV/portal vein but without encasement of the nearby arteries\r\n** Short-segment venous occlusion resulting from either tumor thrombus or encasement with suitable proximal and distal vessel for reconstruction/grafting.\r\n** Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to celiac axis\r\n** Tumor abutment to SMA but not to exceed greater than 180 degrees of circumferential vessel wall
Relief of biliary obstruction if present (percutaneous transhepatic cholangiography [PTC] tube or endobiliary stent)
Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered
Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for the eligible injection sites (left and right medial deltoid region) exceeds 40 mm
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
T1/2N0-2M0 SCC of the oropharynx, hypopharynx or larynx
Nutrition evaluation with consideration of percutaneous endoscopic gastrostomy (PEG) tube placement
T3/4 or N3
Histological confirmation of SCLC.
Accessibility to the site that ensures the subject will be able to keep all study-related appointments.
Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin.
Anion gap > 16 meq/L or arterial blood pH < 7.30.
Women of all races and ethnic groups are eligible for this trial
Gynecologic Oncology Group (GOG) performance status =< 2
Surgery achieves either no gross residual disease or optimal cytoreductive status defined as no single lesion measuring more than 1 cm in its greatest diameter (this protocol calls for the intentional delay in resection of up to 3 tumors per patient until the HIPEC procedure is complete; the surgeon will identify these tumors as easily resectable from a technical and safety aspect)
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
No appropriate caregivers identified
Within 2 weeks of enrollment: Blood urea nitrogen (BUN) =< 25 mg/dl
Metastases detected below the tentorium or beyond the cranial vault
Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization\r\n* Myocardial infarction within the last 6 months\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol\r\n* Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
Histologically confirmed diagnosis of advanced (metastatic or unresectable) non-small cell lung cancer (NSCLC) with mutations, rearrangement and fusion involving RET oncogene, or abnormalities in the pazopanib target genes defined as vascular endothelial growth factor receptors 1-3 (VEGFR1-3), platelet-derived growth factor receptor-alpha (PDGFRA), or platelet-derived growth factor receptor-beta (PDGFRB), or tumor protein p53 (TP53) with abnormalities including deletion, insertion, early stop codon, and/or nonsynonymous mutations with functional consequences; Clinical Laboratory Improvement Act (CLIA) certified lab testing for pazopanib target genes using cell free deoxyribonucleic acid (DNA) from peripheral blood and/or assays performed on tumor tissues are acceptable
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage; Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions); large protruding endobronchial lesions in the mail or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed; lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of thee bronchi are allowed
Recent hemoptysis (>= 1/2 teaspoon of red blood within 8 weeks before first dose of pazopanib)
Homozygous negative for the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT 1A1)*28 allele
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrilomus; consult principal investigator for questions, including necessary washout period for the specific drug
Prior treatment with fractionated radiation therapy (up to 60 Gy) is an eligibility criterion, however there should not have been a second course of fractionated radiotherapy to the supratentorial area
COHORT I:
The biopsy site must have been demarcated by a clip(s)
Patient must be able to tolerate lying in the prone position with arms extended forward
COHORT II: Patient must be >= 60 years
COHORT II: The biopsy site must have been demarcated by a clip(s)
COHORT II: Patient must be able to tolerate lying in the prone position with arms extended forward
Mastectomy intended
Suspicious microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
Candidates for reduced intensity conditioning regimens
Subjects must have a back-up umbilical cord on the registry in addition to the umbilical cord being used in this study
Patient must be scheduled to receive temozolomide concurrent with and following radiation (temozolomide may be started late due to insurance reasons, insufficient counts, or other reasons)
Bilirubin =< 1.5 x UNL
MIBG scan with positive uptake at minimum of one site
There is no limit on number of prior regimens
No hematuria and/or proteinuria greater than 1+ on urinalysis
Prior therapy with fenretinide, or fenretinide + ketoconazole, if DLT's were experienced
Choose bilateral mastectomy followed by bilateral immediate tissue expander breast reconstruction
Understand the study purpose, requirements, and risks
Having a tattoo on the back that is too large to permit PVB injections (as determined by the provider performing the procedure)
MAIN STUDY COHORT EXCLUSION CRITERIA: Pregnancy (as determined by point of care test administered in accordance with the policies of the Department of Nuclear Medicine)
Glycosylated hemoglobin (HbA1c) < 7.0%
Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >= 38 degree Celsius)
Presence of close (< 2 mm) or positive margins
Patient is medically fit to receive cisplatin
Patients taking Coumadin, other agents containing warfarin, rivaroxaban, or dabigatran; (exception: low dose Coumadin [1 mg or less daily] administered prophylactically for maintenance of in-dwelling lines or ports is allowed)
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
The last dose of cytotoxic chemotherapeutic agents that are not considered lymphotoxic must be at least one week before the leukapheresis procedure; oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis
The last dose of lymphotoxic chemotherapeutic agents (e.g. cyclophosphamide, ifosofamide, bendamustine, etc) must be at least 2 weeks before the leukapheresis procedure
Note: exceptions may be made at the discretion of the principal investigator (PI)/study team
The last dose of cytotoxic chemotherapeutic agents that are not considered lymphotoxic must be at least one week before lymphodepletion; oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to lymphodepletion
The last dose of lymphotoxic chemotherapeutic agents (e.g. cyclophosphamide, ifosofamide, bendamustine, etc) must be at least 2 weeks before lymphodepletion
KPS >= 70%
Platelets > 50 K without growth factor or transfusion support for a week at least
Preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal range
STUDY-SPECIFIC EXCLUSIONS:
Any known contraindications to cyclophosphamide, fludarabine, etoposide, bendamustine, cetuximab or tocilizumab
Borderline-resectable or locally-advanced pancreatic cancer (based upon impression of the surgical oncologist, in conjunction with radiologic consultations) as defined per the Alliance consensus:\r\n* Borderline-resectable\r\n** An interface between the primary tumor and superior mesenteric vein (SMV)/portal vein measuring 180 degrees or greater of the circumference of the vein wall\r\n** Short-segment occlusion of the SMV/portal vein but with suitable vessel proximal and distal to the obstruction to allow safe resection and reconstruction\r\n** Short-segment interface (of any degree) between the tumor and the hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction\r\n** An interface between the tumor and the superior mesenteric artery (SMA) or celiac trunk measuring less than 180 degrees of the circumference of the artery wall \r\n* Locally-advanced\r\n** Encasement of the SMA/celiac artery (> 180 degrees)\r\n** Involvement of the SMV/portal vein without options for reconstruction\r\n** Aortic invasion or encasement
Evidence of gross duodenal invasion, gastric outlet obstruction
RAI-refractory disease on structural imaging, defined as any one of the following:\r\n* A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed prior to enrollment in the current study, or\r\n* A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to entry in the study; there are no size limitations for the index lesion used to satisfy this entry criterion\r\n* The presence of at least one fluorodeoxyglucose (FDG) avid lesion
Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration; those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been cleared after the last intravenous contrast administration
Plasma creatinine phosphokinase (CK) < 1.5 x ULN
Inability to tolerate first-line treatment with sorafenib (e.g., unacceptable toxicity), tumor progression on sorafenib, patient preference to stop sorafenib and for alternative therapy/trial, or patient preference to forgo sorafenib for alternative therapy/trial\r\n* Note:\r\n** Unacceptable toxicities due to sorafenib include, but are not limited to, the following drug-induced adverse events including: hepatitis, skin rash (grade 3 or higher), hypertension (grade 3 or higher), hand-foot skin reaction (grade 3 or higher), QT prolongation (grade 3 or higher), and/or diarrhea (grade 3 or higher)\r\n** Patient preference to stop sorafenib for alternative therapy/trial will include the following indications: the aforementioned adverse events at lesser grades for which the patient is unwilling to continue therapy, as well as situations in which the patient deems the side effects to be intolerable with their quality of life; examples include, but are not limited to, intolerable nausea, vomiting, abdominal pain, fatigue, loss of appetite, and weight loss\r\n** Patient preference to forgo sorafenib for alternative therapy/trial is based upon the patients' right for autonomy; this allows them to refuse or choose their treatment; the practitioner will always act in the best interest of the patient and recommend that the patient start with known life-prolonging therapies before enrolling in a clinical trial of an investigational agent that has not been determined to be safe and effective in patients with liver cancer
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting sonidegib study treatment; if it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
Hematocrit >= 27.0%
COH pathology review confirms that research participant’s diagnostic material is consistent with ALL; additionally, CD19 positivity must be documented in a pathology report; however it is not a requirement that the CD19 testing be performed by a COH pathologist
Research participant’s absolute leukemic blast count does not exceed 10,000 cells/uL
KPS >= 70%
Preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal reference range
Any known contraindications to cyclophosphamide, fludarabine, etoposide, cetuximab or tocilizumab
Renal mass =< 5 cm\r\n* The treating renal mass must be =< 5 cm; other renal masses (cysts etc.) of any size will not make the subject ineligible
Biopsy proven renal neoplasm\r\n* All histology of renal cancers are included, including oncocytoma
Growth of renal mass > 4 mm in radiographic scans must be demonstrated within a one year period
Absence of occlusive thrombus in the main portal vein
Encephalopathy not adequately controlled medically
Any contra-indication to angiography
Any known contra-indication to chemoembolization according to the treating physician
Able to take daily aspirin (325 mg) for the duration of INCB7839 treatment and 1 week after the last dose to reduce the risk of thrombosis (not applicable if on other anti-coagulant therapy at time of study registration)
Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
BSA (m2) of <0.25
Pre-existing vocal cord paralysis
Chronic neurologic condition which affects voice or swallow (for instance, multiple sclerosis or Parkinson disease)
Baseline laryngeal pathology that would warrant intervention that could affect voice or swallow function
Evidence of nodal involvement identified in the operating room (OR)
The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or
The patient must have microbiological evidence of CMV viremia or tissue invasion as attested by viral culture, or detection of levels of CMV DNA in the blood or body fluids consistent with CMV infection.
The patient's CMV infection is clinically progressing or CMV viremia is persistent or increasing (as evidenced by quantitation of CMV DNA in the blood) despite two weeks induction therapy with antiviral drugs. Or
The patient has developed CMV viremia as attested by viral culture, or detection of levels of CMV DNA in blood or body fluids while receiving prophylactic doses of antiviral drugs to prevent CMV infection post transplant. Or
The patient is unable to sustain treatment with antiviral drugs due to drug associated toxicities (e.g. myelosuppression [ANC< 1000?l/ml without GCSF support] or nephrotoxicity [corrected creatinine clearance ? 60 ml/min/1.73 m^2 or serum creatinine > 2 mg/dl]) CMV infections are life threatening, and may involve multiple organ systems such as the lungs, liver, gastrointestinal tract, hematopoietic and central nervous systems. Antiviral drugs used for treatment may also compromise renal and hematopoietic function. Therefore, dysfunctions of these organs will not affect eligibility for this protocol.
Stable blood pressure and circulation, not requiring pressor support
Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal
Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
Progressive intracranial ependymoma after prior focal irradiation
Prior craniospinal irradiation
Patient must be able to lie still in full body cast for 45 minutes
Circulating peripheral blood myeloblasts or lymphoblasts on morphologic analysis from time of last treatment to time of enrollment
Negative purified protein derivative (PPD) test
Non-healed infected skin ulcers
Subjects on cisapride, oral midazolam, nisoldipine, felodipine, pimozide, quinidine, dofetilide, triazolam, methadone, levacetylmethadol (levomethadyl), lovastatin, simvastatin, dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), cisapride, pimozide, methadone, levacetylmethadol (levomethadyl), quinidine
Blood urea nitrogen (BUN) < 25
Prior radiosurgery
Prior intracavitary irradiation or Gliadel wafers
Subjects meeting the American Association for the Study of Liver Disease (AASLD) criteria may be randomized without a biopsy, but will undergo a biopsy during the RFA procedure unless contraindicated or unattainable.
The position and accessibility of the target lesion allows for the safe administration of multiple ablation cycles or deployments to achieve a probe dwell time of ? 45 minutes.
Expected ablation volume > 30% of total liver volume or removal of 3 hepatic segments
More than 1 lesion identified during baseline.
Baseline laboratories (repeat lab tests are permitted to evaluate eligibility during the Screening Period. Lab results must be within protocol range prior to study treatment.)
Baseline Chemistry
Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjects who are therapeutically anticoagulated for medical conditions unrelated to HCC such as atrial fibrillation. Subjects may be re-screened after condition is treated or anticoagulant is withheld.
Have contraindications to receiving doxorubicin hydrochloride (HCl).
Evidence of hemachromatosis.
Willing to sign a durable power of attorney
Subjects must be co-enrolled in protocol 03-C-0277
Cytoreduction therapy with plasmapheresis or hydroxyurea acceptable
CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy; for CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir\r\n* CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in broncheoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates or changes consistent with CMV retinitis on ophthalmologic examination\r\n* CMV infection: defined as the presence of CMV positivity as detected by polymerase chain reaction (PCR) or pp65 antigenemia or culture from ONE site such as stool or blood or urine or nasopharynx\r\n* Failure of antiviral therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR or pp65 antigenemia after 7 days of antiviral therapy
Adenovirus: Treatment of persistent adenovirus infection or disease despite standard therapy; standard therapy is defined as antiviral therapy with cidofovir^13 or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function\r\n* Adenovirus infection: defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or nasopharynx\r\n* Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, direct fluorescent antibody (DFA) or culture from two or more sites such as stool or blood or urine or nasopharynx\r\n* Failure of therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease (as measured by PCR or any other quantitative assay) after 7 days of antiviral therapy
EBV: For treatment of persistent EBV infection despite standard therapy; for EBV infection, standard therapy is defined as rituximab given at 375 mg/m^2 in patients for 1-4 doses with a cluster of differentiation (CD)20+ tumor\r\n* EBV infection: defined as\r\n** Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR\r\n** Or clinical or imaging findings consistent with EBV lymphoma and/or elevated EBV viral load in peripheral blood\r\n* Failure of therapy is defined as\r\n** Increase or less than 50% response at sites of disease for EBV lymphoma OR\r\n** Increase or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease after 1st dose of rituximab
BK virus: Treatment of persistent BK virus infection or BK virus disease despite antiviral treatment with cidofovir or leflunomide; no clear standard treatment is defined; cidofovir has been administered in low doses as well as high doses to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy; in small trials leflunomide had activity against BK virus, therefore we will consider this agent an acceptable alternative to cidofovir, given the absence of a clear first line option\r\n* BK virus infection is defined as the presence of BK virus positivity as detected by PCR or culture in one site such as blood or urine\r\n* BK virus disease is defined as the presence of BK virus detectable by culture or PCR in blood or urine or other body fluids and symptoms of disease including, but not limited to persistent microscopic or macroscopic hematuria or detectable BK virus in more than one site\r\n* Failure of therapy is defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease (as measured by PCR or any other quantitative assay) or worsening hematuria after 7 days of antiviral therapy
HHV6: Treatment of persistent HHV6 infection or disease despite antiviral treatment with ganciclovir, cidofovir and foscarnet; no clear standard treatment is defined; ganciclovir, cidofovir and foscarnet all have variable in vitro activity against HHV-6, and may have a role in treating HHV-6-associated disease – therefore antiviral treatment with one or more of these agents will we acceptable initial therapy\r\n* HHV6 virus infection is defined as the presence of elevated HHV-6 levels as detected by PCR or positive culture in one site such as cerebrospinal fluid (CSF) or blood\r\n* HHV6 disease is defined as defined as the presence of HHV6 detectable by culture or PCR in one or more sites such as blood or CSF and symptoms of disease including symptoms of HHV6 encephalitis OR detectable HHV6 by PCR or culture in more than one site\r\n* Failure of therapy is defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease (as measured by PCR or any other quantitative assay) after 7 days of antiviral therapy
JC virus: Treatment of progressive or persistent JC virus infection or disease without suitable alternative treatment option; pepmixes specific for antigens on adenovirus, EBV, CMV, HHV6 and BK virus are used to generate multivirus-specific VSTs; no pepmix specific for the rare JC virus is used for generation of these cytotoxic T lymphocytes (CTLs), however given the high homology (> 90%) between JC and BK and the fact that BK virus-specific T cells targeting polyomavirus capsid protein (VP1) and large T (as targeted in multivirus VSTs) have been administered to treat JCV-progressive multifocal leukoencephalopathy (PML), resulting in viral clearance from the cerebrospinal fluid it is likely that VSTs are efficacious against JC virus; given the current lack of treatment options for JC virus infection or reactivation after HSCT and the risk of progression to PML, which is almost uniformly fatal, and the apparent activity of BK virus-directed T cells against JC virus infected cells, this trial proposes including patients with progressive or persistent JC virus on this study, unless a suitable alternative therapy is available\r\n* JC virus infection is defined as the presence of elevated JC virus levels as detected by PCR or positive culture in one site such as CSF or blood\r\n* JC virus disease is defined as defined as the presence of JC virus detectable by culture or PCR in one or more sites such as blood or CSF and symptoms of disease including symptoms of PML OR detectable JC virus by PCR or culture in more than one site
Available multivirus-specific VSTs
Adequate blood cell counts (i.e. absolute neutrophil count [ANC] > 1000) at baseline, or willingness to accept supportive measures such as transfusions, filgrastim, and epoetin
Patients are in CR/VGPR or have primary refractory NB in BM - i.e., NB resistant to standard therapy, as evidenced by persistence of NB in the BM by histology or metaiodobenzylguanidine (MIBG) scan, but all other findings in scans show VGPR
Human anti-mouse antibody (HAMA) titer > 1000 enzyme-linked immunosorbent assay (Elisa) units/ml
Patients must have histologically confirmed, BRAF-mutant (V600E/K) solid tumor (molecularly confirmed using Cobas assay or a comparable Food and Drug Administration [FDA]-approved assay) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy, and for which standard curative measures do not exist or are no longer effective\r\n* If test at Clinical Laboratory Improvement Act (CLIA)-certified laboratory (lab) used a non-FDA approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Potassium > 3 and < 5.5 mEq/L
Magnesium > 1.2 and < 2.5 mEq
Documented (signed) informed consent; the patient, family member and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed:\r\n* A. No Research Imaging – for patients for whom one or more of the following applies:\r\n** Is a minor (< 18 years of age)\r\n** Acute lymphoblastic leukemia (ALL) diagnosis\r\n** Does not agree to optional imaging (WF-MRI, DECT)\r\n* B. With Research Imaging – all of the following must apply:\r\n** Adult (>= 18 years of age)\r\n** Acute myeloid leukemia AML diagnosis\r\n** Agree to optional imaging: WF-MRI and DECT\r\n** Do not agree to optional FLT-PET, or there are no FLT-PET slots available\r\n* C. With Research Imaging plus FLT-PET\r\n** Adult (>= 18 years of age)\r\n** AML diagnosis\r\n** Agrees to optional imaging: WF-MRI and DECT\r\n** Agrees to optional FLT-PET\r\n** FLT-PET accrual remains open
Electrocardiogram (EKG) showing no ischemic changes and no abnormal rhythm
For Cohort A (enzalutamide) and Cohort B (abiraterone acetate): patients who have progressed on both enzalutamide and abiraterone acetate are eligible and post-BAT will be retreated with the last second line agent they had received (e.g. patient receiving abiraterone acetate [abiraterone] then enzalutamide would receive retreatment with enzalutamide post-BAT)
For Cohort A (enzalutamide) and Cohort B (abiraterone acetate): patients must be withdrawn from enzalutamide or abiraterone acetate for >= 4 weeks and have documented PSA increase after the withdrawal period
For Cohort A (enzalutamide) and Cohort B (abiraterone acetate): patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone prior to starting BAT
Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia
Hematocrit > 50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure (per Endocrine Society Clinical Practice Guidelines)
Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Plasma creatine phosphokinase (CK) < 1.5 x ULN
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 5-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment; NOTE: if it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
Prior allogeneic SCT
One of the following must be satisfied:\r\n* The patient is undergoing mobilization to collect and store for an autologous PBSC transplant in the future\r\n* The patient is eligible to undergo autologous PBSC transplantation on institutional protocols in the future
No prior attempt at mobilizing PBSC
Patients must not have received radiation therapy to more than 20% of hematopoiesis forming bones (spine, pelvis and proximal long bones) during lifetime
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs in a single treatment
Evidence of any detectable technetium-99m macroaggregated serum albumin (Tc-99m MAA) flow to the stomach or duodenum, not correctable by using established angiographic techniques to stop or mitigate such flow
Co-morbid disease of condition that would preclude safe delivery of TheraSphere treatment or, in the judgment of the physician, place the patient at undue risk
Willing to provide all biologic specimens as required by the protocol
Cluster of differentiation (CD)4 count >= 200/uL or >= 15% of peripheral blood lymphocytes
Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of the ovary
Requiring blood product support
Active treatment with valproic acid for non-oncological conditions, if this cannot be safely switched to an alternative agent
Current evidence of hematemesis, melena or gross hematuria
Patients with a history of gallbladder problems or gall stones or biliary obstruction, unless patient had cholecystectomy
Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment
Active herpes lesion
Concurrent therapy with any drug active against simplexvirus (HSV) (acyclovir, valacyclovir, penciclovir, famcyclovir, gancyclovir, foscarnet, cidofovir)
Receipt of bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration; (receipt of bevacizumab [Avastin] greater than 4 weeks of scheduled M032 administration does not exclude patient)
Patients will have no more than 3 distinct lesions within the brain; at least 1 lesion must be a minimum of 3 cm in greatest dimension, no larger than 5 cm which will be treatable by fractionated stereotactic radiosurgery
The additional lesions will each be treated with single fraction stereotactic radiosurgery
Patient may be on steroids or anti-epileptics
Fractional shortening (FS) > 27%
Pathologic or cytologic documentation of pancreatic adenocarcinoma
Serum calcium >= LLN
Serum magnesium >= LLN
Serum potassium >= LLN
The patient who has not previously received hyperthermic intraperitoneal chemotherapy must have histopathologically or cytologically confirmed cancer from peritoneal mesothelioma, pseudomyxoma, or gastrointestinal malignancies (excluding pancreatic and hepatobiliary) with known synchronous or metachronous disease dissemination limited to the peritoneal surfaces
Psychiatric or addictive disorders or other conditions that would preclude the patient from meeting the study requirements
Sickle cell disease - patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end-organ damage (A, B, C, D, or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F):\r\n* A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral magnetic resonance imaging (MRI) or an abnormal trans-cranial Doppler examination (>= 200 m/s); or\r\n* B. Sickle cell related renal insufficiency defined by a creatinine level >= 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy or nephrotic syndrome or creatinine clearance < 50 mL/min or requiring peritoneal or hemodialysis; or\r\n* C. Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of >= 2.5 m/s at least 3 weeks after a vaso-occlusive crisis; or\r\n* D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting >= 4 hours involving the corpora cavernosa and corpus spongiosa; or\r\n* E. Sickle hepatopathy defined as either ferritin > 1000 mcg/L or direct bilirubin > 0.4 mg/dL at baseline; or
F. Any one of the below complications\r\n* Vaso-occlusive crises; eligible for hydroxyurea*: at least 3 hospital admissions in the last year; eligible for hematopoietic stem cell transplantation (HSCT): more than 1 hospital admission per year while on maximal tolerated dose of hydroxyurea*\r\n* Acute chest syndrome (ACS); eligible for hydroxyurea*: 2 prior ACS while > 3 years of age and adequately treated for asthma; eligible for HSCT: any ACS while on hydroxyurea*\r\n* Osteonecrosis of 2 or more joints; eligible for hydroxyurea*: and significantly affecting their quality of life by Karnofsky score 50-60; eligible for HSCT: and on hydroxyurea* where total hemoglobin increase less than 1 g/dL or fetal hemoglobin increases < 2.5 times the baseline level\r\n* Red cell alloimmunization; eligible for hydroxyurea*: transfusion-dependent; eligible for HSCT: total hemoglobin increase < 1 g/dL while on hydroxyurea*\r\n* Note: hydroxyurea at maximum tolerated dose
Thalassemia - patients with thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:\r\n* Portal fibrosis by liver biopsy \r\n* Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with desferroxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week)\r\n* Hepatomegaly of greater than 2 cm below the costochondral margin
Major ABO mismatch
Patients will have unresectable disease, defined radiographically as > 180 degrees involvement of the superior mesenteric artery or celiac trunk or superior mesenteric vein (SMV)/portal vein impingement that cannot be surgically reconstructed, in the absence of distant metastasis
Total bilirubin =< 3, (with relief of biliary obstruction if present [percutaneous transhepatic cholangiography (PTC) tube or endobiliary stent])
No contraindications for leukapheresis
Successful T cell test expansion (first 10 subjects)
Results of ATRX and/or 1p/19q chromosomal status: if ATRX is lost, 1p/19q status is not required; if ATRX is intact, 1p/19q chromosomal status must be available to permit treatment selection
Results of pRAS40 testing
Patient not candidate for orthotopic liver transplantation at the Hospital of the University of Pennsylvania based on review of patient imaging and history at multidisciplinary Hepatic Tumor Conference at the Hospital of the University of Pennsylvania
Prior TACE
Pregnant women are excluded from this study because propranolol is an agent with the potential for teratogenic or abortifacient effects
The patient is a prisoner
Radiologic workup must demonstrate that the thoracic disease is confined to only one hemi-thoracic cavity and must be deemed potentially resectable by the surgical team
Histologic diagnosis of melanoma
Ocular melanoma
Evidence ongoing transformation into aggressive NHL
Positive test results for human T-lymphotropic 1 (HTLV 1) virus; HTLV testing is required in patients from endemic countries (Japan, countries in the Caribbean basin, South America, Central America, Sub Saharan Africa, and Melanesia)
Biopsy proven pancreatic adenocarcinoma
Borderline resectable per National Comprehensive Cancer Network (NCCN) criteria (no distant metastases, venous involvement of the portal vein/superior mesenteric vein [SMV], demonstrating tumor abutment and narrowing of the lumen, encasement of the portal vein/SMV without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal or distal to this area of vessel involvement, allowing for safe resection and reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; tumor abutment of the superior mesenteric artery [SMA] not to exceed 180 degrees of the circumference of the vessel wall)
Able to get a Whipple resection per surgeon assessment performed within 4 weeks of registration
Documentation of pre-existing hearing deficits
Other invasive malignancies within the past 5 years from date of registration
Ultrasound visible lesion(s)
If younger than 40, there must be comorbidities which preclude the patient to undergo cyclophosphamide (Cy) TBI conditioning regimen
No appropriate caregivers identified
Patients who have neuromuscular disorders that are associated with elevated creatinine phosphokinase (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Bisphosphonates are allowed, at the treating investigator’s discretion
Hypercalcemia at baseline, defined as any corrected calcium greater than the laboratory’s normal parameters
Subjects with biopsy-proven potentially resectable or borderline adenocarcinoma of the pancreas as determined by National Comprehensive Cancer Network (NCCN) criteria
PTT WNL; if patient on warfarin for prophylactic clot presentation for indwelling catheter, PT/PTT may be +/- 15 %
Symptomatic evidence of gastric outlet obstruction
Current anticoagulant therapy; (acetylsalicylic acid [ASA] =< 325 mg per day is allowed)
Patients must have lymphocytosis with white blood cells between 30,000-100,000/uL in order to collect adequate leukemia cells for vaccine production
Histologically proven recurrent meningioma or aggressive meningioma; note: confirmation of ESO expression and pathology is not required in patients with definitive radiologic evidence of meningioma who are unresectable, and in whom radiation therapy without biopsy is the standard treatment
Willing to sign a durable power of attorney
Subject must be co-enrolled in protocol 03-C-0277
Lymphocytes >= 500/mcL
Patients with a known or suspected hypersensitivity to GM-CSF (sargramostim), Cytoxan, pentastarch or hetastarch, corn, or dimethyl sulfoxide (DMSO)
Positive serology for HBV defined as a positive test for HBsAg; in addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HepB DNA test will be performed and if positive the subject will be excluded
Patients must have adequate TIL available (Turnstile II); pre-rapid expansion procedure (Pre-REP) TIL generated in the similar clinical trial 2004-0069 may also be utilized for Turnstile II
Any form of primary or secondary immunodeficiency; must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm^3), white blood cell (WBC) (> 3,000/mm^3) or absence of opportunistic infections (Turnstile II)
ANC <1500/?L
Phosphorus < LLN
Potassium < LLN
Willingness and ability to complete the EPIC questionnaire
Patients must have histological evidence of a metastatic well differentiated or moderately differentiated mucinous appendiceal epithelial neoplasm (AEN)
Radiographic images demonstrating the presence of mucinous peritoneal carcinomatosis (PMP)
Patients must not be considered a candidate for a complete surgical cytoreductive surgery; this determination will be made through either discussion at MD Anderson peritoneal surface malignancy multidisciplinary review or consultation with MD Anderson peritoneal surgeon
Patients must be able to understand and provide answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30)/ovarian (OV)-28 QOL questionnaires in order to participate in the trial
The presence of complete or partial bowel obstruction based upon clinical assessment
No prior irinotecan or carfilzomib
Pedunculated polyps (as defined by Paris Classification type Ip or Isp)
Poor general health (ASA class>3)
Poor bowel preparation
History of central nervous system (CNS) radiotherapy: radiation of 60 gray (Gy) in 30 fractions, 59.4 Gy in 1.8 Gy fractions, 75 Gy in 30 fractions or equivalent or lower doses
Patients with active implanted medical or electronic device or bullet fragments including pacemakers, defibrillators, deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, and programmable shunts
Known sensitivity or allergy to conductive hydrogels (like the gel used on electrocardiogram [ECG] stickers or TENS [transcutaneous electrical nerve stimulation] electrodes)
Up to 3 tumors all less than 3 cm
No gross vascular invasion or regional nodal or distant metastases
Childs’ class A or B7
Prior TACE, radiofrequency ablation (RFA), or liver transplant
Complete obstruction of portal venous flow to the segment of liver that includes the target lesion
Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale (assessed verbally)
Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or artificial nails) that are likely to alter pain perception during testing
Uncontrolled narrow-angle glaucoma
Currently taking selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), or tricyclic antidepressant (TCA) regimen for treatment of major depressive disorder or generalized anxiety disorder (without approval and involvement of the patient’s treating psychiatrist)
Current Grade 3 or higher coagulopathy, thrombosis and/or hemostasis disorders,
transaminases (AST or ALT) levels, 5 times greater than the ULN, except if related to ALL/LBL,
History of Grade 3 or higher blood transfusion incident according to US Biovigilance Network which refers to any transfusion followed by a major intervention (vasopressors, intubation, transfer to intensive care) to prevent death.
Presenting with anti-erythrocyte antibodies leading to the unavailability of phenotype compatible red blood cells.
Patient undergoing yellow fever vaccination.
Multifocal progression or involvement of the leptomeninges
Patient receiving or planning to receive trastuzumab, trastuzumab with pertuzumab or ado-trastuzumab emtansine, for at least 3 months, alone or in combination with other systemic treatment or radiation
Current signs or symptoms of heart failure (HF) or ischemia
First or second relapse of glioblastoma
If prior therapy with gamma knife or other focal high-dose radiation, must have subsequent histologic documentation of local relapse, or relapse with new lesion outside the irradiated field
Prior receipt of bevacizumab or other vascular endothelial growth factor (VEGF) negative (-) or VEGF receptor-targeted agents
Men refusing to exercise a reliable form of contraception
Patient is diagnosed with benign or malignant stricture, fistula, perforation, or leak
Physician plans to remove the stent within the duration of study follow-up
Patient that is contraindicated to upper GI endoscopy and/or any procedure to be performed in conjunction with esophageal stent placement
Disease should be determined as \borderline resectable\ according to the Expert Consensus Statement published by Callery et al:\r\n* No distant metastasis\r\n* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction\r\n* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis\r\n* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
Patient must have > 1 lesion; combined diameter of the lesions must be of size > 1.5 cm
Patient must be eligible for SABR to one or more extra cranial sites
Adequate cardiac function (adequate perfusion; no ischemia) on thallium (or technetium [Tc]) stress test
Patients with electrolyte abnormalities at study entry defined as follows: Serum potassium < 3.5 mEq/L despite supplementation, or > 5.5 mEq/L; Serum magnesium above or below the institutional normal limit despite adequate management; Serum calcium (corrected for albumin levels) above or below institutional normal limit despite adequate management.
Patient can have prior SRS to lesions other than the one planned for neoadjuvant SRS and resection
At the time of planning, unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm
No irreversible coagulopathies
Irreversible coagulopathies that preclude fiducial placement
Prior upper abdominal external beam irradiation
Inability to deliver target dose with CyberKnife due to normal tissue dose constraints
Decreased platelet count and/or anticoagulation parameters that would preclude transcutaneous placement of fiducials
Relapsed/refractory MCL: Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty
Serum sodium >= LLN
Must not have taken a hypomethylating agent
Right bundle branch block and left anterior hemiblock (bifascicular block)
Patients who have received prior therapies will be allowed to enroll after a wash-out period as follows assuming they have recovered from the side effects of such therapies:\r\n* Chemotherapy – 3 week wash-out period\r\n* Oral agents – 2 week wash-out period (except vemurafenib, which will require no wash-out period)\r\n* Investigational agents – 3 week wash-out period\r\n* Immunotherapy – 4 week wash-out period\r\n* Palliative radiation therapy to bone/brain – 2 week wash-out period\r\n* Major radiation or surgical procedure – 3 week wash-out period
Confirmation of diagnosis
MATCHED RELATED DONOR: History of prior malignancy; however, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis; risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient
HAPLOIDENTICAL RELATED DONOR: History of prior malignancy; however, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis; the risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient
Plasma creatine phosphokinase (CK) < 1.5 x ULN
Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the following:\r\n* Children < 1 year with International Neuroblastoma Staging System (INSS) stage 2a, 2b, 3, 4 or 4S disease and MYCN amplification (> 10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal)\r\n* INSS 2a or 2b disease and MYCN amplification, regardless of age or additional biologic features\r\n* INSS stage 3 and:\r\n** MYCN amplification (> 10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features)\r\n** Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status\r\n* INSS stage 4 and:\r\n** MYCN amplification, regardless of age or additional biologic features\r\n** Age > 18 months (> 547 days) regardless of biologic features\r\n** Age 12 – 18 months (365 – 547 days) with any of the following three unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminate/unknown\r\n* Children >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who have progressed to a stage 4 without interval chemotherapy
Children with INSS 4 disease, age < 18 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and deoxyribonucleic acid [DNA] index > 1)
Must consent to participate in study I 03103: Roswell Park Cancer Institute (RPCI) Data Bank and Biorepository (DBBR)
Disease must be evaluable by metaiodobenzylguanidine (MIBG) scan; a positive MIBG scan must be present within 8 weeks prior to study entry and subsequent to any intervening therapy; if the patient has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done at least 4 weeks after radiation was completed and must show viable neuroblastoma
Platelets >= 50,000 X 10^9 /L without transfusion if stem cells are not available
ANC >= 500 X 10^9 /L with transfusions allowed if stem cells available
Platelets >= 20,000 X 10^9 /L with transfusions allowed if stem cells available
Lesions to be treated under this protocol must be > 2 cm, but =< 4.0 cm in diameter
Conformality index 2.0 or less cannot be achieved, or homogeneity index is > 2.0
Unable to deliver 10 gray (Gy) or less to optic nerve/chiasm (typically 3 mm or more separation of the tumor from the optic nerve/chiasm is necessary)
Brainstem location is excluded from this study
Invasive ductal, medullary, papillary, colloid (mucinous) or tubular histologies
All tumors (invasive and non-invasive disease) must be excised with a minimum margin width of >= 2 mm; re-excision of surgical margins is permitted; focally close (< 2 mm) or positive (tumor cells at the inked edge of the specimen) margins determined to be at an anatomic boundary of resection by the surgeon, such as posterior fascia for posterior margins or skin for anterior margins, are also acceptable
Patients presenting with abnormal microcalcifications on a screening mammogram must have radiographically confirmed excision of the suspicious microcalcifications, either by specimen radiograph or post-biopsy mammograms
Pure DCIS
Lobular or mixed ductal and lobular histology
Clear delineation of the extent of the lumpectomy cavity is not possible
Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless these were biopsied and found to be benign
Collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
Actively being treated on any other therapeutic research study
Prior wide excision with diameter of the excision > 3 cm
Primary melanoma arises from the eye or mucus membranes
Clinical evidence of regional, intransit ,or distant metastases
Second invasive melanoma
Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy; the protocol principal investigator (PI) is the final arbiter of eligibility
Infratentorial and multi-focal tumors are eligible
Blood urea nitrogen (BUN) =< 30 mg/dl
Metastases beyond the cranial vault
Subject must be capable and reliable to participate in all study related procedures
The presence of cervical conglomerate nodal mass or extracapsular spread (ECS) on imaging
Subject presents an increased surgical risk including abnormally positioned carotid artery or an inability to obtain adequate exposure for transoral surgery
The subject has previously been treated for the primary diagnosis of OP-SCCA or SG-SCCA
Subjects with metastatic disease exclusively present within a previously irradiated field\r\n* Subjects with metastasis within and outside of previously irradiated field that is eligible for SABR are eligible
Use of any of the following within the past 14 days: megestrol acetate (Megace), diethyl stilbestrol (DES), or cyproterone acetate, ketoconazole, high dose calcitriol [1,25(OH)2VitD] (i.e., > 7.0 ug/week)
Subjects with pathologic long-bone fractures
Any condition that would prohibit patient from initiating valproic acid; current or prior valproic acid treatment is allowed (do not need to be >= lower limit of normal [LLN] for laboratory for enrollment)
Known mitochondrial disorder caused by mutations in mitochondrial deoxyribonucleic acid (DNA) polymerase gamma
Persistent heart rate (HR) < 50 or > 120 beats per minute (bpm)
Diffusely multifocal lesion
Lesions not amenable to GTR
Tumors infiltrate the cerebellum, bilateral corpus callosum (“butterfly glioma”), ventricular system, or brain stem
Blood counts no restrictions
Failure to obtain insurance/payment authorization for Zevalin, unless the subject agrees to cover the cost
Positive leukocytotoxic crossmatch
Patient has at least one medically fit family member expected to be HLA mismatched at 1-9/10 more commonly and preferred: 4-6/10 loci (e.g. parent, sibling, niece/nephew, etc. but adult children preferred)
Subjects must have >= 0.5 cm of inflammatory breast cancer (IBC) on core (5 cores)\r\n* NOTE: If the core is less than 0.5 cm, the subjects may be considered for inclusion based on the pathologists’ review of biopsy slides
Blood urea nitrogen (BUN) < 2 x ULN
Subjects must not have allergies to any compounds similar to CDB-4124
Patient has participated in a Novartis sponsored combination trial where pasireotide was dispensed in combination with another study medication and is still receiving combination therapy. (only patients receiving pasireotide monotherapy can be included)
Patients must demonstrate active noninfectious inflammatory pustular skin lesions resembling pustular psoriasis and involving >= 5% total body surface area, or palmoplantar involvement; conditions may include, but are not be limited to, pustular psoriasis, Sneddon-Wilkinson disease, subcorneal pustular dermatosis, reactive arthritis, palmoplantar pustulosis, acrodermatitis continua of Hallopeau and palmoplantar pustular psoriasis
Quantiferon tuberculosis (TB) gold must be performed for screening for mycobacterium tuberculosis infection; however, a tuberculin skin test may be placed if the Quantiferon TB gold test is indeterminate; patients must have a negative Quantiferon TB Gold (or tuberculin skin test) or evidence of appropriate treatment prior to study entry
Subjects who experience a significant flare after discontinuation of a tumor necrosis factor (TNF) inhibitor as part of this study that requires urgent medical management or hospitalization, or in the estimation of the principal investigator poses excessive risk to the patient to enter the study
Other defined dermatologic conditions which may include pustules as part of the clinical presentation, but which clinically and/or histologically do not resemble pustular psoriasis; examples include, but are not limited to acute generalized exanthematous pustulosis (AGEP, a drug-induced pustular dermatosis typically caused by beta-lactam antibiotics, tetracyclines, oral antifungals and other drugs), bacterial or fungal folliculitis, cutaneous candidiasis, tinea pedis, tinea corporis, neutrophilic eccrine hidradenitis or eosinophilic pustular folliculitis (Ofuji syndrome)
Known diagnosis of deficiency of the interleukin-1 receptor antagonist (DIRA)
Presence of active infection; history of exposure to TB (positive purified protein derivative [PPD] or Quantiferon TB gold) who have not been treated with a TB prophylaxis regimen for at least one month
Chest x-ray (if Quantiferon TB Gold is positive) demonstrating pleural scarring and/or calcified granuloma consistent with prior or current untreated TB
Other immunoregulatory or immunodeficiency diseases, such as multiple sclerosis
Individuals with life-threatening or disabling inflammation of the eyes, gut or joints requiring urgent or immediate medical attention, or at the physician's discretion
Previously treated participants
Participants must not have an invasive infection at time of protocol entry
Chronic (>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not responded to antifungal therapy.
Developed the current episode of IA infection during receipt of >13 days of antifungal prophylaxis with an agent considered to be a mold-active antifungal agent.
Known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
On artificial ventilation or receiving acute Continuous Positive Airway Pressure (CPAP)/Bilevel Positive Airway Pressure (BPAP) at the time of randomization.
Pancreatic or periampullary tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning
Must be a patient to be treated with SBRT only at Johns Hopkins Hospital
Diagnosis of probable pancreatic cancer, distal common bile duct (CBD) cholangiocarcinoma and other periampullary cancers (histology not required)
Biliary obstructive symptoms or signs
Distal biliary obstruction consistent with pancreatic cancer, distal CBD cholangiocarcinoma or other periampullary malignancy
Location of distal biliary obstruction is such that it would allow the proximal end of a stent to be positioned at least 2cm from the hilum
Biliary strictures caused by confirmed benign tumors
Biliary strictures caused by malignancies other than pancreatic cancer, distal CBD cholangiocarcinoma and other periampullary cancers
Surgically altered biliary tract anatomy, not including prior cholecystectomy
Previous biliary drainage by ERCP/PTC
One of the following criteria must be met: (a) Tumors that are microscopically multifocal must be 3.0 cm or less in total aggregate size and encompassed within a single scar (b) Patient does not have microscopically multifocal tumor.
For tumors that are invasive, HER2 must be performed (positive or negative is acceptable).
If image guidance with daily cone beam CT with direct physician visual assessment is used for treatment positioning, the presence of markers or clips in the surgical bed is recommended but not required. If cone beam CT imaging will NOT be used for image guidance, then the patient must be prepared to have 2 fiducial markers minimum, 3 preferred, placed prior to treatment (if not previously done).
Any clinical or radiographically suspicious nodes, unless biopsy proven benign.
Suspicious residual microcalcifications on mammography of either breast, unless negative for malignancy on pathology.
Lymphovascular space invasion (LVSI) on pathology specimen.
Histologic examination showing invasive lobular histology.
Breasts technically unsatisfactory for radiation treatment upon the discretion of the treating physician.
Significant infection or other co-existing medical condition that would preclude protocol therapy such as pregnancy, HIV/AIDS or collagen vascular diseases specifically systemic lupus erythematosus, scleroderma, or dermatomyositis.
Known BRCA 1 or BRCA 2 mutation.
Histologically and cytologically proven bile duct cancer of any type (including intrahepatic cholangiocarcinomas, extrahepatic primary cholangiocarcinomas, hilar cholangiocarcinomas, cholangiocarcinomas located in the gall bladder or hepatic capsule effraction, and carcinoma of the Ampulla of Vater, etc.) that is not amenable to surgery, radiation, or combined modality therapy with curative intent, and has failed or is not eligible for available chemotherapies such as gemcitabine with or without platinum
No evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN)
Bilirubin =< 1.5 x UNL
Dyspnea with moderate exertion
Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of white blood cells [WBCs], red blood cells [RBCs], and platelets)
Human anti-hu3F8 antibody (HAHA) titer > 1300 Elisa units/ml
In cases of SLL, subjects must have at least one bidimensionally measurable lesion; one of the measurements must be >= 1.5 cm in one dimension
Waldenström’s macroglobulinemia
Patients 18 years or older with Philadelphia chromosome (Ph)-positive or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR).
Patients must have detectable BCR-ABL transcript levels meeting at least 1 of the following criteria: Patient has never achieved a major molecular response (MMR, as defined by a BCR-ABL/ABL </=0.1% in the international scale (currently equivalent to 0.28 in the MDACC molecular diagnostic laboratory), & transcript levels have shown in at least 2 consecutive measures separated by at least 1 month to have increased by any value; or achieved a major molecular response which has been lost, with an interim increase in transcript levels by at least one-log, confirmed in two consecutive analyses separated by at least 1 month; or patient has received therapy for at least 2 years & lacks a sustained major molecular response; or patient has received therapy for at least 5 years & lacks a sustained complete molecular response (CMR, defined as transcript levels still detectable in the MDACC molecular diagnostic laboratory).
Patients should have a confirmed diagnosis of chronic lymphocytic leukemia defined as all of the following:\r\n* Absolute lymphocyte count (ALC) > 5000\r\n* Positive for either CD19 or CD 20 together with CD23 and CD5\r\n* Less than 55% atypical cells
Patients should have findings of relapse by one or both of the following:\r\n* ALC > 5000 on 2 consecutive occasions and increasing\r\n* Any increase in lymphadenopathy over best response that has persisted for more than 3 months
Patient with confirmed del11q mutation may be included if untreated
Patient must be able to drink and eat more than 75% of their usual daily meals
Must receive a myeloablative or reduced intensity conditioning regimen for stem cell transplant (SCT) as defined by the Center for International Blood and Bone Marrow Transplant Research (CIBMTR)\r\n* Cyclophosphamide (Cy) and single dose total body irradiation\r\n* Fludarabine (Flu) and busulfan\r\n* Fractionated total body irradiation (TBI) and cyclophosphamide\r\n* Busulfan and cyclophosphamide
Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate
Must not have nonmyeloablative conditioning as defined below:\r\n* TBI =< 2 Gy +/- purine analog\r\n* Flu + Cy +/- antithymocyte globulin (ATG)\r\n* Flu + cytarabine (AraC) + idarubicin (Ida)\r\n* Cladribine + AraC\r\n* Total lymphoid irradiation + ATG
Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens
Blood urea nitrogen (BUN) =< 1.5 x ULN
Any form of primary or secondary immunodeficiency; must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm^3), white blood cell (WBC) (> 3,000/mm^3) or absence of opportunistic infections (Turnstile II)
Patients must be willing to stay within 2 hours drive of MD Anderson Cancer Center whilst receiving Ipilimumab therapy. Patient must also agree to present to MD Anderson emergency center while on Ipilimumab therapy.
Patients with non-organ confined renal masses (invading renal vein, inferior vena cava, peri-renal tissue, ipsilateral adrenal gland, or metastasis)
Patients with renal lesions determined to be too complex to perform a RAPN without clamp by the surgeon; (the renal mass may be deemed too difficult based on pre-operatively radiological findings; the surgeon’s decision to exclude a mass from a robotic assisted partial nephrectomy would be based on a higher risk of positive margin or complication if a RAPN was performed)
Rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR), or viral culture positive for influenza
Immunocompromised
Symptoms/signs suggestive of influenza like illness (ILI)
Infants with post-menstrual age (PMA) <36 weeks
Hereditary fructose intolerance
MPN-associated myelofibrosis
Anemic patient OR red blood cell (RBC)-transfusion-dependent patient
Prior sotatercept
Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or progressed within 6 months of the last dose of brentuximab vedotin
Intolerance to brentuximab vedotin
Adequate hematocrit independent of red cell transfusions
NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies
For patients with skin metastases, lesions selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)
No restriction based on prior treatments
Symptoms or manifestations of: a) gastroparesis; b) refractory gastroesophageal reflux disease (GERD) including persistent esophagitis, refractory heartburn, reflux-related laryngitis, and respiratory symptoms; or c) severe dyspepsia
Potassium between range of 3.0 to 5.5
Magnesium level between 1.8-2.9 mg
Patients who are receiving antiarrhythmic medications with action on repolarization times (with prolongation of the QTc interval such as amiodarone, disopyramide, dofetilide, flecainide, ibutilide, quinidine, sotalol, dronedarone etc.)
Serum lactate dehydrogenase (LDH) > 1.5 x institutional ULN
Have a target tumor that is accessible for intratumoral administration by PTA (Percutaneous transluminal approach) or EUS (Endoscopic Ultrasound) guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection.
Bulky celiac adenopathy (?2.5 cm) or nonadenocarcinoma histology.
Established refractoriness to CMC-544
Total bilirubin < 2.0 mg/dl with relief of biliary obstruction if present (percutaneous transhepatic cholangiography [PTC] tube or endobiliary stent)
Moderate or severe aplastic anemia defined by one of the following: peripheral blood neutrophils < 0.5 x 10^9/L; platelets < 30 x 10^9/L or platelet transfusion dependence; reticulocytes < 50 x 10^9/L in anemic patients or red cell transfusion dependence
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Subjects must be co-enrolled in National Institutes of Health (NIH) protocol 08-HG-0059
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects must have a diagnosis of atopic dermatitis on the basis of the criteria defined by UK Working Party's Diagnostic Criteria for Atopic Dermatitis
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects must have an Objective SCORAD (SCORing Atopic Dermatitis) of >= 15 indicating AD severity of moderate to severe
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Known allergic reaction to sulfa, beta-lactam, or tetracycline class drugs; or lidocaine or epinephrine
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Any chronic past or present medical illness, including chronic skin diseases like psoriasis
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Subjects receiving or planning to receive an investigational new drug (IND) agent, ultraviolet light therapy, monoclonal antibodies, or systemic immunosuppressants
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Subjects who provide direct healthcare or reside in healthcare facilities or in non-hospital settings such as clinics, assisted living facilities, homeless shelters, jails and prisons as well as subjects with frequent exposure to laboratory animals
The gross target volume (GTV) is suitable for motion management using 4 dimensional computed tomography (4D CT), internal target volume (ITV), or respiratory gating; in addition, the target coverage and normal tissue constraints must be met as specified in protocol accounting for the respiratory motion of anatomy as a whole (not just the tumor)
Prior radiotherapy to any anatomic regions that would result in overlap of radiation dose distribution to critical structures (esophagus, heart, spinal cord, brachial plexus)
Patient refusal
Disease amenable to biopsy via percutaneous approach or other minimally invasive procedures such as thoracoscopy, bronchoscopy, laparoscopy, or gastrointestinal (GI) endoscopy
Patients with ATP-binding cassette, sub-family B (MDR/TAP) (ABCB)4 and ABCB11 genotypes associated with mithramycin-mediated hepatotoxicity
Consideration by the Investigator, for any reason, that the subject is an unsuitable candidate to receive veliparib (ABT-888) and/or breast irradiation
Postmenopausal woman
Certain scores on an anxiety and depression mood questionnaires
Presence of LGL clone prior to enrollment will not be an exclusion criterion if the LGL clone is < 25% of T cell population
Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (patients must discontinue drug 7 days prior to starting dasatinib):\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, sotalol, ibutilide, dofetilide\r\n* Erythromycin, clarithromycin\r\n* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Patient agrees that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Prisoners or subjects who are involuntarily incarcerated
Participants must have undergone simple, modified radical, or radical abdominal hysterectomy or vaginal hysterectomy and lymphadenectomy (pelvic nodes, para-aortic nodes, or both nodal basins) by open or laparoscopic assisted technique
Participants with cervical cancer may undergo chemotherapy in conjunction with adjuvant proton therapy; the agents, doses, routes and schedule of administration will be determined by their attending gynecologic oncologist or medical oncologist
Prior therapeutic radiation exposure to tissues for which protocol irradiation is anticipated is an exclusion criterion
Patients must have histological confirmation of the diagnosis (it is recommended that the immunohistochemical panel includes: CD45, CD20, CD30, CD15, CD10, BCL6, BCL2, MUM-1), and in addition have a dominant mass within the anterior mediastinum.
Histological diagnostic material available for review.
Other rare lethal disorders of hematopoiesis and lymphohistiocytosis for which a T-cell depleted transplant is indicated (e.g., hemophagocytic lymphohistiocytosis; refractory; non-severe combined immunodeficiency [SCID] lethal genetic immunodeficiencies such as Wiskott Aldrich syndrome, CD40 ligand deficiency, autoimmune lymphoproliferative syndrome [ALPS])
< 2.0 x ULN serum bilirubin, unless there is congenital benign hyperbilirubinemia
Patients must have available archived tissues of 20-30 unstained slides; if frozen tissues are available, at least 200 mg would be preferred, but not mandatory for study eligibility
Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide
For dose expansion phase: patients must have EphA2 overexpression overall H-score of 3 or above in immunohistochemistry (IHC) evaluation; Clinical Laboratory Improvement Amendments (CLIA) certified EphA2 IHC staining to be performed on formalin fixed, paraffin-embedded tissue sections using monoclonal EphA2 antibody; EphA2 expression to be assessed through a combo of % of positive cells and staining intensity; the % of positive cells will be rated: 0 points (pts), 0 to 5%; 2 pts, 6 to 50%; 3 pts, 50%; the staining intensity will be rated as follows: 1 pt, weak intensity; 2 pts, moderate intensity; 3 pts, strong intensity; pts for expression and % of positive cells will be added; an overall score will be assigned; tumors to be categorized into 4 groups: negative (overall score 0), 5% cells stained, regardless of intensity; weak expression (overall score 1), 1 - 2 pts; moderate expression (overall score 2), 3 - 4 pts; and strong expression (overall score 3), 5 - 6 pts; overall H-score of 3 or above will be defined as EphA2 overexpression in tumor cells
Must have clinically severe SCD (SS, SC or SBeta0 Thal) or thalassemia major and be eligible for myeloablative SCT
Sufficient physiological reserves
Patients with biopsy proven locally advanced sinus, nasal cavity, hard palate, soft palate, major or minor salivary gland tumors, or lacrimal apparatus, with nasal cavity, sinus, auditory canal, or skull base involvement are eligible
No active alcohol addiction that will interfere with participation in this study, as assessed by medical caregiver
Presence of a symptomatic bradyarrhythmia or uncompensated heart failure
Evidence of distant metastases (excluding para-aortic nodes)
Prior radiotherapy to the pelvis (or abdomen if para-aortic nodes are involved)
Lansky performance status of >= 60% for participants 16 years old or younger
Triglyceride level of no more than 400 mg/dL
Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT
Patients using any of the following medications: mesoridazine, dronedarone, thioridazine, ziprasidone, levomethadyl, and saquinavir for vemurafenib/sorafenib arm
Patient must otherwise be a candidate for ASCT as determined by the treating physician
Patient must not have a diagnosis of hepatic encephalopathy
Patient must not have a diagnosis of sclerosing cholangitis
Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine
Untreated symptomatic hydrocephalus determined by treating physician
Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma or other EBV-associated malignancy, OR
Evaluable disease as demonstrated by clinical and/or radiologic studies with current or prior elevated blood levels of EBV-deoxyribonucleic acid (DNA) exceeding 500 copies/ml by quantitative real time polymerase chain reaction (PCR), OR
Stable blood pressure and circulation not requiring pressor transport
Patients who develop EBV lymphomas or lymphoproliferative diseases or other EBV-associated malignancy as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy; for these patients, normal, EBV specific T-cells from third party seropositive donors who are HLA compatible in 1) at least 2 HLA antigens and 2) one restricted allele shared by the patient will be used; again, selection of T cells known to be restricted by an allele shared by the patient will be given priority
Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and non-Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma; normal, EBV specific T-cells from third party seropositive donors who are HLA compatible in 1) at least 2 HLA antigens and 2) one restricted allele shared by the patient will be used; again, selection of T cells known to be restricted by an HLA allele shared by the patient will be given priority
DONORS: Donors in groups 1 and 2 would have already been determined to be eligible and will have donated blood or leukocytes to establish EBV-specific T-cells under IRB # 05-065, 07-055, 95-024, or 12-086; there are no additional eligibility requirements for these donors
DONORS: Donors in group 3, however, will need to meet the following eligibility requirements prior to donation:\r\n* Donors must satisfy the criteria specified in Food and Drug Administration (FDA) 21 Code of Federal Regulations (CFR) 1271\r\n* Donors must be typed for HLA-A, B, C, and DR\r\n* Donors must have a hemoglobin value > 10 g/dl\r\n* Donors must be capable of undergoing, at least, a single standard 2 blood volume leukapheresis or a donation of one unit of whole blood
At least five measurable KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion
Any abnormality that would be scored as a >= grade 3 toxicity by CTCAE, except:\r\n* Obesity is not considered an abnormality for the purposes of eligibility assessment unless in the opinion of the principal investigator or lead associate investigator its clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study\r\n* Lymphopenia\r\n* Asymptomatic hyperuricemia, hypophosphatemia, or creatine kinase (CK) elevations\r\n* Direct manifestations of KS\r\n* Direct manifestations of HIV infection, except for neurologic or cardiac manifestations\r\n* Direct manifestations of HIV therapy, except for neurologic or cardiac manifestations
Known hypersensitivity to thalidomide, lenalidomide or pomalidomide including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or pomalidomide
ABT-888 is primarily excreted in the urine, and is not even metabolized by the liver; thus such degree of hepatic impairment is not expected to affect the dosing of ABT-888
Any patient with either progressive aGvHD or steroid refractory (SR) aGvHD after hematopoietic stem cell transplant (HSCT) will be eligible; prophylactic GvHD therapy with cyclosporine, tacrolimus, mycophenolate mofetil (MMF), or sirolimus can be continued; biopsy/pathological confirmation of skin/gastrointestinal or liver GvHD is not required, but it is encouraged
Patient should not be getting any other experimental therapy for aGvHD
Pathology confirmation of HL with City of Hope (COH) pathology review
All pre-study and follow-up imaging studies preferably performed at City of Hope
Co-morbid illnesses that preclude protocol participation (to be determined by PI)
Any cytogenetic abnormality in the bone marrow that is known to be associated with or predictive of myelodysplasia is excluded; this includes, but is not limited to, del(5), del(7), del(11)
Persistent marrow involvement (> 10%) with HL after salvage cytoreductive therapy and before stem cell mobilization
Patient must present with indications for diagnostic or therapeutic approaches for benign and/or malignant diseases of the oral cavity or laryngopharynx (including the neoplastic lesions of the tongue, tongue base, retromolar trigone, tonsils, palate, posterior and lateral pharynx, glottic, supraglottic and subglottic larynx)
Karnofsky rating 70-100.
Able to communicate sensations during the ExAblate MRGFUS procedure.
Brain edema and/or mass effect that causes midline shift or shift in wall of the third (3rd) ventricle of more than 10-mm.
Targeted area (i.e.: ROT) less than 5 millimeters from primary branches of cerebral vessels, dural sinuses, the hypophysis or cranial nerves
Containing calcifications in the focused ultrasound sonication beam path in the event system tools cannot tailor the treatment around these calcification spots
More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.
The subject presents with:
Symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
Unstable hemodynamic status including:
Symptomatic coronary artery stenosis.
Known sensitivity to gadolinium-DTPA.
Patients with histologically proven glioblastomas or gliosarcomas that express EGFRvIII as assessed by immunohistochemistry (IHC) or polymerase chain reaction (PCR) confirmed by the National Cancer Institute (NCI) Laboratory of Pathology
Willing to sign a durable power of attorney
Subjects must be co-enrolled on protocol 03-C-0277
Tumors arising in the skull and spine
Actively being treated on any other therapeutic research study
Pathologically confirmed KSHV-MCD
Elevated C-reactive protein (CRP) (CRP > 3 mg/L) probably or definitely attributable to KSHV-MCD
No life- or organ-threatening manifestations of MCD
Willingness to complete tuberculosis evaluation and start prophylactic antituberculosis therapy as soon as is medically feasible if patients have a reactive tuberculin skin test and/or positive QuantiFERON-tuberculosis (TB) Gold test and have not completed an adequate course of prevented anti-tuberculosis therapy, following American Thoracic Society/Centers for Disease Control recommended guidelines
Any abnormality that would be scored as NCI Common Toxicity Criteria (CTC) grade 3 toxicity that is unrelated to HIV, its treatment, or to MCD that would preclude protocol treatment; exceptions include:\r\n* Lymphopenia\r\n* Direct manifestations of Kaposi sarcoma or MCD\r\n* Direct manifestation of HIV (i.e. low cluster of differentiation [CD]4 count)\r\n* Direct manifestation of HIV therapy (i.e. hyperbilirubinemia associated with protease inhibitors)\r\n* Asymptomatic hyperuricemia\r\n* Hypophosphatemia\r\n* Elevated creatinine kinase (CK) attributed to exercise
Subjects must not be candidates for intensive high-dose chemotherapy, with or without an autologous stem cell transplant (ASCT), due to one or more of the following factors:\r\n* Age >= 65 years: Patients < 65 years of age must be ineligible for high-dose chemotherapy (HDT)/ASCT on the basis of comorbidity, organ dysfunction or patients refusal for HDT/ASCT\r\n* Comorbid disease, such as coronary artery disease (CAD), congestive heart failure (CHF), pulmonary dysfunction, liver or kidney dysfunction, precluding high dose therapy secondary to expected increased morbidity and mortality: poor performance status (Karnofsky performance scale [KPS] 70% or less); ejection fraction < 45%; impaired pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO) < 50% expected\r\n* Patient refusal\r\n* Medical conditions which in the opinion of the treating physician and DMT preclude HDT/ASCT
Any malabsorption problem
Medical condition that would contraindicate allogeneic transplantation as per standard practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc)
Patients with mixed chimerism (present of more than 5% recipient chimerism) at 6 months post transplant will not be started on the protocol until the chimerism changes back to > 98%
DONOR: Related donors < 18 years of age requiring placement of a leukapheresis catheter will donate peripheral blood collected by phlebotomy (including a unit of blood if weight permits) and shall not undergo catheter placement for leukapheresis
Previous infusion of CD19 CAR T cells at another institution
Existing major organ dysfunction > grade 2, with the exception of hearing loss and myelosuppression (defined as suppression of all types of white blood cells [WBCs], red blood cells [RBCs] and platelets)
Exposure to more than one prior anti-tubulin/microtubule agent
Written Authorization for Use and Release of Health and Research Study Information (Health Insurance Portability and Accountability Act [HIPAA] authorization per institutional requirements)
Serum potassium >= 3.5 mEq/L
Self-reported race of either African American or Caucasian
Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509), galeterone (TOK-001), orteronel (TAK-700), or similar agent
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index; if an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
Patients with active implanted electronic devices in the brain or spinal cord such as programmable VP shunts, deep brain stimulators, vagus nerve stimulators, are not allowed
Patients with foreign body intracranially, such as bullet fragments, are not allowed, with the exception of VP-shunts (non-programmable) and Ommaya catheters
Had prior exposure to an immuno-oncology or pyrrolobenzodiazepine (PBD)-based drug
Presence of diffuse lepto or pachy meningeal carcinomatosis (focal/localized involvement from limited meningeal based metastases acceptable), greater than 1 cm mid-line shift, uncal herniation, or severe hemorrhage/hydrocephalous (small intra-lesional hemorrhage or anticipated surgical cavity is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Potassium within normal institutional range, or correctable with supplements
Immunohistochemically negative for IDH1 R132H mutation
Genotyping data available or in process (data must be available at time of initial registration if randomization probabilities differ across biomarker subgroups as determined by the Dana-Farber Cancer Institute [DFCI] Coordinating Center) to assign biomarker subgroups through whole exome sequencing, whole genome copy number analysis, or a combination
Participants who have had any prior cranial radiotherapy
Known acute or chronic pancreatitis
Therapy-related MDS (t-MDS)
MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
For the romidepsin arm of the study, prior therapy with romidepsin if discontinued due to toxicity
Subjects with active Epstein-Barr virus (EBV) unrelated to underlying lymphoma (positive serology for anti-EBV virus capsid antigen [VCA] IgM antibody and negative for anti-EBV Epstein-Barr nuclear antigen [EBNA] IgG antibody, or clinical manifestations and positive EBV PCR consistent with active EBV infection)
Subjects with active cytomegalovirus (CMV) (positive serology for anti-CMV IgM antibody and negative for anti-CMV IgG antibody and positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy will be excluded from participation in the study; carriers will be monitored per institutional guidelines
A HER2 exon 20 insertion including A775_G776insYVMA, G776_V777insVC, or P780_Y781insGSP, or any other in-frame exon 20 insertion mutation.
An activating point mutation in HER2 including, but not limited to, L755S, G776V, and V777L.
Have not received a TKI with pan-HER activity (eg, afatinib, neratinib, or dacomitinib).
A HER2 exon 20 insertion: A775_G776insYVMA, G776_V777insVC, P780_Y781insGSP, or any other in-frame exon 20 insertion mutation.
An activating point mutation in HER2 including, but not limited to, L755S, G776V, and V777L.
Have at least one target (ie, measurable) intracranial CNS lesion (?10 mm in longest diameter by contrast enhanced magnetic resonance imaging [MRI]). Lesions previously treated by stereotactic radiosurgery (SRS) or surgical resection should not be included as a target lesion. Lesions previously treated with whole brain radiation therapy (WBRT) may be included as a target lesion if (1) the last administration of WBRT was >3 months prior to the first dose of AP32788 and (2) unequivocal radiological progression of the lesion has been observed. Expansion Cohort 4 Specific Inclusion Criteria:
Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the lung (typical and atypical according to the World Health Organisation (WHO criteria), evaluated locally)
Has a mitotic index <2 mitoses/2 mm2 for typical carcinoid (TC) and <10 mitoses/2 mm2 and/or foci of necrosis for atypical carcinoid (AC)
Positive Somatostatin receptors (SSTR) imaging
Has been treated with Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization
Patients must weigh ? 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System).
Patients with a history of gastrinoma, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.
Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.
Parts 1 and 2:
Parts 3 and 4:
Part 1: 0 or 1
Parts 2, 3 and 4: 0, 1, or 2
Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PCA) who present for first line chemotherapy treatment
Acute or sub-acute intestinal obstruction
Be between the ages of ?18 and ?65 years
Have other life-threatening illness
Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG
For patients with non-measurable, structural disease the following must apply:\r\n* Undetectable thyroglobulin antibody AND\r\n* A serum thyroglobulin of 10 ng/ml or greater in the context of suppressed thyroid-stimulating hormone (TSH) (TSH =< 0.4 mcU/ml) =< 28 days prior to study registration; use of any thyroglobulin assay is allowed, though all serum thyroglobulin measurements for study purposes must be conducted with the same thyroglobulin assay
Having been treated with a total cumulative (lifetime) 131I therapeutic activity > 800 mCi (excluding 131I activity administered for diagnostic scans)
Unable to follow a low iodine diet or requiring medication with high content in iodide (e.g., amiodarone)
Received iodinated intravenous contrast within =< 2 months of registration; avoidance of iodinated oral contrast is also preferred but not strictly required for study enrollment; NOTE: those who have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that excess iodine has been cleared (defined as urinary iodine documented to be < 300 mcg/day by either a spot urinary iodine or 24-hour urinary iodine measurement)
-  Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks first dose
Group A : Individuals > 18 years of age with previously untreated AML who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
Participants in Part D must have NSCLC of any subtype.
Participants in Part E must have melanoma of any subtype.
For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.
Have a preexisting chronic condition resulting in persistent diarrhea.
Patients with unmutated IGHV who also have a complex karyotype on a stimulated karyotype
SCREENING:
Participants must have classical histology posterior fossa medulloblastoma as determined by institutional neuro-pathological evaluation
Sufficient pathologic material must be available for central analysis and review
Tumors will be deemed Wnt positive if, at the time of central analysis, there is:\r\n* Monosomy 6 as determined by array comparative genomic hybridization (CGH)\r\n* Gene transcript detection by NanoString supporting Wnt+ medulloblastoma\r\n* Absence of large-cell, anaplastic histology\r\n* Nuclear b-catenin immunohistochemistry (IHC) result will be determined, but not required for the diagnosis
Diagnostic imaging (pre and post contrast) must be forwarded to Dana-Farber Cancer Institute (DFCI) for central review to confirm eligibility
Histological or cytological documentation of adenocarcinoma of the colon or rectum
UGT1A1 genotype other than *1/*1, *1/*28, or *28/*28
Known dihydropyrimidine dehydrogenase (DPD) deficiency
ELIGIBILITY CRITERIA FOR REGISTRATION: subjects for whom neoadjuvant chemotherapy followed by interval cytoreductive surgery is planned must have fine needle aspirate (FNA) or other cytology showing adenocarcinoma OR core biopsies OR surgically directed biopsies showing adenocarcinoma AND CA125 over 250 OR CA125:CEA ratio > 25 OR CA =< 250 with no evidence of GI cancer; they should have presumed stage III or IV disease, generally based on abdominal carcinomatosis, omental caking, pleural effusions or ascites
ELIGIBILITY CRITERIA FOR REGISTRATION: the subject and her physician must agree to 6 cycles (a total of up to 8 cycles will be allowed) of one of the standard of care regimens allowed on this protocol; these regimens (starting dosage) include:\r\n* < 70 years of age:\r\n** R1: IV paclitaxel 175 mg/m^2 and carboplatin area under the curve (AUC) 5-6 every 21 days\r\n** R2: IV docetaxel 75 mg/m^2 and carboplatin AUC 5-6 every 21 days\r\n** R3: IV paclitaxel 80 mg/m^2 day 1, 8, and 15 and carboplatin AUC 5-6 day 1 every 21 days\r\n* >= 70 years of age may (but not required to) choose one of the following alternative regimens:\r\n** R4: IV paclitaxel 135 mg/m^2 plus IV carboplatin AUC 5 plus optional filgrastim (G-CSF) every 21 days\r\n** R5: IV paclitaxel 60 mg/m^2 day 1, 8, and 15 plus IV carboplatin AUC 5 day 1 every 21 days (day 15 paclitaxel optional)\r\n** R6: IV paclitaxel 60 mg/m^2 plus IV carboplatin AUC 2 day 1, 8, and 15 every 21 days\r\n*** Use of granulocyte colony stimulating factor is permitted, but additional chemotherapy agents (e.g. gemcitabine) or biologic agents (e.g. bevacizumab) are not; dose modifications for patients >= age 70 are allowable as indicated above; patients >= age 70 for whom the physician deems carboplatin AUC 5 to be unsafe may be treated with AUC 4
EXCLUSION CRITERIA FOR REGISTRATION: subjects should not be participating in other clinical trials of interventions designed to reduce risk of ovarian cancer recurrence or plan to receive off –protocol maintenance therapy (e.g. paclitaxel or bevacizumab)
A minimum of 2 x 10^6 cluster of differentiation 34 positive (CD34+) cells must have been collected
Treatment-related mortality (TRM) score < 9.21 corresponding to a TRM rate of 3% when chemotherapy of similar intensity as proposed here is administered to inpatients
Blast count =< 10,000
Fibrinogen > 200
Patient must have an outpatient caregiver available
Patient must live within 30 minutes of the treating physician’s office during outpatient treatment
Patient must be willing to return to the treating physician’s office for outpatient follow-up once outpatient treatment is completed
Logistical requirements:\r\n* Space available in infusion room\r\n* Outpatient infusion pump available if continuous infusion required\r\n* Case discussed with infusion room nursing staff
Platelets >= 100,000 microliter (transfusion independent)
No evidence of dyspnea at rest
No exercise intolerance
Epithelioid or biphasic histology subtype (Note: patients with biphasic histology can have < 10% sarcomatoid)
> 10% Sarcomatoid or desmoplastic histology
Prior nephrectomy on the contralateral side of malignant pleural mesothelioma (MPM)
Bulky disease in the fissure preventing lung-sparing pleural IMRT
A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by cytogenetics, polymerase chain reaction (PCR), or POD test
Patients will have no more than 3 distinct lesions, all being =< 3 cm in greatest dimension, OR 1 lesion =< 6 cm in greatest dimension
Renal failure requiring hemo- or peritoneal dialysis
Other baseline neurocognitive or emotional disorders or deficits, including but not limited to head injury, cardiovascular accident (CVA), transient ischemic attack (TIA), or other cerebral insults with residual neuropsychiatric deficits, psychiatric disorders, learning disabilities, human immunodeficiency virus (HIV) positivity or other medical conditions at high risk of causing neurocognitive decline or emotional instability
Planning target volume (PTV) must be encompassed in a reasonable SBRT “portal” as defined by the treating radiation oncologist
Non-adenocarcinomas, adenosquamous carcinomas, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas are not eligible
Diagnosis of NF2 by National Institutes of Health (NIH) criteria (1988) with evidence of either:\r\n* Bilateral vestibular schwannomas, or\r\n* First-degree family relative with NF2 and either unilateral vestibular schwannomas (VS) or any 2 of: meningioma, schwannoma, glioma, neurofibroma, or juvenile posterior subcapsular lens opacity
Inability to tolerate periodic audiologic testing or to understand a language with established scoring for word recognition testing
Inability to adequately perform volumetric measurement of at least 1 target lesion (e.g., due to the presence of artifacts from cochlear or auditory brainstem implants, ill-defined tumor margins resulting from the juxtaposition of tumors abutting each other, or sequela from prior irradiation to the target lesion); Note: patients with cochlear or auditory brainstem implants may participate if a target lesion can be accurately assessed
Active lupus or scleroderma
FA complementation group A as determined by somatic cell hybrids, molecular characterization, western blot analysis, acquisition of mitomycin C resistance after in vitro lentiviral transduction with a vector bearing the complementary deoxyribonucleic acid (cDNA) for Fanconi complementation group A, or other clinically certified method of complementation group analysis
Pregnancy or lactation; females of childbearing potential and males who are admitted to the study will be advised that the study procedures and study drugs may be teratogenic, and they will be required to take adequate measures to prevent conception for the duration of the study
Total abstinence or
Lumbar cerebrospinal fluid (CSF) must be assayed for cytology, alpha fetoprotein (AFP) and beta human chorionic gonadotrophin (HCGB); a quantitative serum determination of AFP and HCGB should be performed at the time of the lumbar CSF assay
For the diagnosis of pure germinoma, HCGB (serum and CSF) must be =< 100 mIU/ml, serum AFP must be =< 10 IU/l (ng/ml) and =< institutional norm and CSF AFP =< 2 IU/l (ng/ml) and =< institutional norm with histologically proven diagnosis of germinoma at diagnosis or relapse
For histologically unconfirmed MMGCT, serum and/or CSF tumor markers of HCG? > 100 mIU/ml or any elevation of AFP > 10 IU/L (ng/ml) and/or institutional norm in the serum and CSF AFP > 2 IU/L (ng/ml) and/or institutional norm
Axillary nodes with definite evidence of microscopic or macroscopic extracapsular extension
Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters
Clear delineation of the extent of the target lumpectomy cavity not possible
Documented diagnosis of collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
EBV seropositivity (can be pending at this time)
Absolute lymphocyte count (ALC) > 500
Diagnosis - CD30+ HL or CD30+ NHL
After Dose Escalation: any patient (children or adults) with relapsed CD30+ HL or CD30+ NHL or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and autologous stem cell transplantation
EBV seropositivity
Available autologous transduced EBV-specific cytotoxic T lymphocytes with >= 15% expression of CD30CAR determined by flow-cytometry
Patient requiring allogeneic SCT
Psychiatric disturbance
Allogeneic SCT recipient requiring additional cellular therapy
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs in a single treatment
Evidence of any detectable Technetium-99 Macroaggregated Albumin (Tc-99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop or mitigate such flow.
Complete occlusion of the main portal vein.
Co-morbid disease of condition that would preclude safe delivery of TheraSphere treatment or, in the judgment of the physician, place the patient at undue risk
Forced expiratory volume in one second (FEV1) >= 50% of expected value obtained within 90 days of enrollment\r\n* Note: For children who are unable to cooperate for positron emission tomography (PFT)s, the criterion is: No evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen therapy
MATCHED RELATED DONOR: History of prior malignancy; however, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis; the risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient
Able to lie supine for approximately 60 minutes, the anticipated duration of each treatment session
Major medical or psychiatric disorders that would seriously compromise patient tolerance of this regimen
Actively being treated on any other therapeutic research study
Presence of pleural effusions > 5 mm as measured by treating physician using standard radiologic measuring tools
Other rare lethal disorders of hematopoiesis and lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or congenital cytopenias; non-severe combined immunodeficiency [SCID] lethal genetic immunodeficiencies such as Wiskott Aldrich syndrome, CD40 ligand deficiency or, autoimmune lymphoproliferative syndrome [ALPS], as well as refractory autoimmune cytopenias, paroxysmal nocturnal hemoglobinuria [PNH], metabolic storage diseases or heavily transfused congenital hemoglobinopathies)
Actively being treated on any other therapeutic research study
For tumors other than DSRCT, 8H9 reactivity must be confirmed by immunohistochemistry
Histologic proof of phyllodes tumor of borderline or malignant grade, as first defined by Pietruszka and modified by Azzopardi and adopted by the World Health Organization:\r\n * Borderline malignant: 5-9 mitoses/10 high-power fields (HPF), pushing or infiltrating margins, 2+ (moderate) stromal cellularity and atypia\r\n * Malignant: 10 or more mitoses/10 HPF, predominantly infiltrating margins, usually 3+ (severe) stromal cellularity and atypia but occasionally 2+
History of noncompliance during previous vaccination cycles with study treatment and/or monitoring which is concerning for continued noncompliance
CD19 expression must be detected on the majority of the malignant cells by immunohistochemistry or by flow cytometry in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH; definition of which cells are malignant must be determined for each patient by the Laboratory of Pathology using techniques to demonstrate monoclonality such as kappa/lambda restriction (other techniques can be used to determine monoclonality at the discretion of the Laboratory of Pathology); the choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient. Immunohistochemistry will be used for lymph node biopsies and bone marrow biopsies; flow cytometry will be used for peripheral blood, fine needle aspirate, and bone marrow aspirate samples
Blood blast percentage higher than 5%
Creatinine =< 1.2 mg/dl (urinary diversion is permitted to improve renal function)
Actively being treated on any other research study
HSV-1 Seropositive
Clinical or pathological diagnosis of cirrhosis, hemochromatosis, or hepatic fibrosis
Ascites, or complete occlusion of main portal vein
Known existing uncontrolled coagulopathy, hemorrhagic disorder, or inability to discontinue Coumadin or Plavix for 5 days prior to each treatment (except for prophylaxis against portacath-associated thrombosis, which does not require cessation of therapy)
Magnesium (triplet combination only) >= 1.8 mg/dL
NSCLC expanded cohort only: total of 20 never smokers and non-smokers; never smokers are defined as individuals who have never smoked and non-smokers are defined as individuals with a =<10 pack year history and have quit > 15 years
NSCLC cohort only: current smoker
Evidence of HCL by flow cytometry of blood or a solid (lymph node) mass, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for CD19, CD22, CD20, and CD11c; patients with flow cytometry consistent with HCL variant (HCLv) are eligible, including those with CD25 and/or CD103 negative disease
One of the following:\r\n* At least 2 prior courses of purine analog\r\n* 1 prior course of purine analog plus >= 1 course of rituximab if the response to the course of purine analog lasted < 1 year\r\n* Diagnosis of HCL variant (HCLv)\r\n* Unmutated (> 98% homology to germline) IGHV4-34+expressing HCL/HCLv
Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material; Gleason score must be in the range of 2-6; (the highest Gleason score in any core reported on the pathology report will be used for determining inclusion)
Subjects must complete all required tests listed in the protocol within the specified time frames
Members of all races and ethnic groups are eligible for this trial
Clinical stages T2c or greater (AJCC Criteria 6th Ed.)
DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy
DONOR: In the case that PBMC will be used as stem cell source, ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
The Target Lesion must be determined to be amenable to percutaneous injection by the treating physician.
Target Lesion(s) must not be contiguous with, encompass or infiltrate major blood vessels.
Completion of patient questionnaires
No active major medical or psychosocial problems that could be complicated by study participation
Breast adenocarcinoma that is amplified for HER-2/neu gene expression by 2-fold or more by FISH analysis, or that is IHC 3+
Subjects on medications that may not be safely stopped during the fasting portion of the study, or which may not be safely consumed without food
INCLUSION FOR INTRAMURAL INJECTION: \r\n* Subject must have lesion(s) amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk\r\n* Lesion(s) must meet size criteria\r\n* In the first two dose levels, subjects must have localized disease that meets size criteria; localized is defined as a single lesion; however, more than one lesion may be acceptable if they are contiguous\r\n* In the third dose level, subjects must have one to three lesions meeting size criteria\r\n* The arm (route of administration) will be chosen by the investigator and patient/parent based on multiple considerations and subject to approval by the principal investigator
At the time of enrollment, specified baseline CNS conditions must be =< grade II toxicity per Common Terminology Criteria for Adverse Events (CTCAE) 3.0 criteria; this includes the following conditions: arachnoiditis/meningismus/radiculitis, ataxia, CNS cerebrovascular ischemia, CNS necrosis/cystid progression, cognitive disturbance, confusion, dizziness, encephalopathy, hydrocephalus, leak - cerebrospinal fluid, leukoencephalopathy (radiologic findings), mental status, psychosis, seizure, somnolence/depressed level of consciousness
No focal wall motion abnormalities as determined by either of the above studies
Electrocardiography (EKG) without evidence of ischemia or significant arrhythmia
Ductal carcinoma in-situ or invasive ductal, medullary, papillary, colloid (mucinous), or tubular histologies; invasive lobular carcinomas are allowed
Unifocal or multifocal (confined to one quadrant, lesions less than 4 cm apart) breast cancer (1 or 2 foci which can be encompassed by one lumpectomy)
Negative inked histologic margins of lumpectomy (no invasive cells at margin) or negative re-excision specimen to be confirmed prior to radiation
Tamoxifen, Arimidex or other hormonal therapy is allowed; it may begin any time relative to the radiation at the discretion of the treating physician
Available autologous transduced cytotoxic T lymphocytes with >= 15% expression of HER2 CAR and killing of HER2-positive targets >= 20% in cytotoxicity assay
Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center
Corrected serum calcium level of > 10.5 mg/dL (serum corrected calcium = serum calcium + 0.8[4-serum albumin])
Prior radioimmunotherapy
Patients must have had a visual analog scoring of pain >= 4 at the planned treated site within 14 days of registration; pain must be ongoing or require narcotic pain medicine to control
Narcotic pain prescription and usage information must be available and documented
Clinical stages T1a-T2b
DONOR (FHCRC only): Up to 5% of the unmanipulated cord blood product (s), when ready for infusion, may be withheld for research purposes as long as thresholds for infused TNC dose are met; these products will be used to conduct studies involving the kinetics of engraftment and immunobiology of double cord transplantation
DONOR: Any cord blood units without full maternal testing and negative results for hepatitis A, B, C, HIV, and human T-lymphotropic virus (HTLV)-1 viruses; any additional available virology results on the unit itself will be reviewed but are not mandated, complete or always available; cord blood units are presumed to be CMV negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
Patients must have had a response to chemotherapy, which the investigator feels is likely to resulting systemic control of the cancer; in most instances, this would reflect a major response (i.e. > or = 90% reduction of tumor), though a lower percentage may be acceptable if the investigator feels the residual reflects another component, such as transitional cell carcinoma (TCC); Dr Arlene Siefker-Radtke will serve as the final arbiter when questions regarding response arise
Supranormal values judged to be of benign or inconsequential etiology will be acceptable
Prior cranial irradiation
Admission for UCBT must be within an acceptable time period after the pre-allograft chemotherapy
Units with attached segments for confirmatory typing will be given preference
Seropositivity for human T-lymphotropic virus type 1 (HTLV-1)
Myeloproliferative syndromes
DONOR: Any cord blood units without the full maternal testing and negative results for hepatitis A, B, C, HIV, and human T-lymphotropic virus (HTLV-1) viruses; any additional available virology results on the unit itself will be reviewed but are not mandated, complete or always available; cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
Willingness to undergo MDACC Audiology and Ophthalmology Assessment
Evidence of distant metastases (below the clavicle) by clinical or radiographic measures.
The donor and the patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policy approved by the United States (U.S.) Department of Health and Human Services
Must not be taking a drug specifically known to interact with VPA for at least 2 weeks prior to initiating the trial; including but not limited to: Aspirin, Felbamate, Rifampin, Amitriptyline/Nortriptyline, Carbamazepine, Clonazepam, Diazepam, Ethosuximide, Lamotrigine, Phenobarbital, Primidone, Phenytoin, Tolbutamide, Warfarin, Zidovudine
Members from all ethnic and race groups are eligible for this study
Umbilical cord blood used as an unrelated stem cell source will provide > 2.0 x 10^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci; cord blood grafts may include a single or pair of cord units depending on the cell dose
Verified by morphology and confirmed by cytochemistry and immunophenotyping
MLL status unknown
WBC ? 300 x 10^9/L AND/OR prednisone poor response
Mature B-ALL, defined by the immunophenotypical presence of surface immunoglobulins or t(8;14) and breakpoint as in B-ALL
Presence of the t(9;22) (q34;q11) or bcr-abl fusion in the leukemic cells (if data are not known, patient still may be eligible)
Relapsed ALL PATIENT CHARACTERISTICS:
History of severe allergy or intolerance to any contrast media, narcotics, sedatives, or atropine, that cannot be controlled using basic angiographic techniques
Portal hypertension with portal venous shunt away from the liver
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs on either: 1) first TheraSphere administration; or 2) cumulative delivery of radiation to the lungs over multiple treatments
Evidence of any detectable technetium (Tc)-99 macroaggregated albumin (MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow
Confirmed diagnosis of intrahepatic carcinoma; the histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alpha fetoprotein (AFP)
History of severe allergy or intolerance to any contrast media, narcotics, sedatives, or atropine, that cannot be controlled using basic angiographic techniques
Portal hypertension with portal venous shunt away from the liver
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs on either: 1) first TheraSphere administration; or 2) cumulative delivery of radiation to the lungs over multiple treatments
Evidence of any detectable Technetium macroaggregated albumin (Tc-99 MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow
Plus any of the following: \r\n- Stroke or central nervous system event lasting more than 24 hours\r\n- Magnetic resonance imaging (MRI) changes indicative of brain parenchymal damage\r\n- Magnetic resonance angiogram (MRA) evidence of cerebrovascular disease\r\n- Acute chest syndrome requiring exchange transfusion or hospitalization\r\n- Recurrent vaso-occlusive pain crisis (more than 2/year for the last 2 years)\r\n- Stage I or II sickle lung disease\r\n- Sickle retinopathy\r\n- Osteonecrosis\r\n- Red cell alloimmunization (> 2 antibodies) during long-term transfusion\r\n- Constellation of dactylitis in the first year of life and a baseline hemoglobin < 7 g/dL and leukocytosis (> 13.4 x 10^3/mm^3) in the absence of infection during the second year of life\r\n- History of invasive pneumococcal disease\r\n- Pitted red blood cell (RBC) count > 3.5% during the first year of life\r\n- Abnormal transcranial Doppler\r\n- Transfusion dependence\r\n- Beta thalassemia major
DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) and will be screened per the American Association of Blood Banks (AABB); (AABB guidelines and the recipients will be informed of any deviations)
DONOR: ABO compatibility (in order of priority) \r\n- Compatible\r\n- Major incompatibility\r\n- Minor incompatibility\r\n- Major and minor incompatibility
Poor mouth opening, with maximal opening less than 1.5 cm
Hemophagocytic lymphohistiocytosis (HLH), familial hemophagocytic lymphohistiocytosis (FLH), viral-associated hemophagocytic syndrome (VAHS), X-linked lymphoproliferative disease (XLP), severe chronic active Epstein Barr virus infection (SCAEBV) with predilection for T- or natural killer (NK)-cell malignancy
Patients with severe hepatic disease (direct bilirubin greater than 3 ug/dl or serum glutamic pyruvate transaminase [SGPT] greater than 500 ug/dl)
Diagnosis of Fanconi anemia
Suitable UCB units available according to Umbilical Cord Blood Graft selection algorithm; the UCB graft may consist of one or two UCB units
Myeloproliferative syndromes
UCB units will be selected according to current University of Minnesota umbilical cord blood graft selection algorithm; one or 2 UCB units may be used to achieve the required cell dose
If 2 UCB units are required to reach the target cell dose, each unit must be a 4-6 HLAA, B, DRB1 antigen match to each other, as well as a 4-6 antigen match to the recipient
All diseases are advanced hematologic malignancies not curable by conventional chemotherapy; responses to conventional treatment range from zero to 30% but are typically short lived
Natural killer cell malignancies
Myeloproliferative syndromes
Subjects with radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration, and/or spinal cord block
Subjects who have contraindications to carboplatin, melphalan, etoposide phosphate, or sodium thiosulfate
Patient must recover fully from hepatic resection
Bilirubin < 2 x UNL
Active acute infection, except for Herpes viruses (cytomegalovirus [CMV], Epstein Barr virus [EBV], herpes zoster virus [HZV], herpes simplex virus 1 [HSV 1]).
A known allergy to one or more components of SV, namely soy beans, mushrooms, mung beans, red dates, scallion, garlic, lentil beans, leek, hawthorn fruit, onions, ginseng, angelica root, Chinese licorice, dandelion root, Senegal root, ginger, olives, sesame seed and parsley.
INCLUSION CRITERIA FOR CCT: patients must have the diagnosis of malignant chromaffin cell tumor (CCT) i.e. malignant pheochromocytoma or malignant paraganglioma
INCLUSION CRITERIA FOR CCT: patients must have MIBG-avid malignant CCT and evaluable disease on MIBG scan at time of enrollment on protocol
Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate
Platelet >= 75,000/mm^3 (unless impairment due to idiopathic thrombocytopenic purpura [ITP])
No prior systemic chemotherapy; patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome)
Patient compliance and geographic proximity (as determined by the Principal Investigator) that allow adequate follow-up.
Pure sarcomas or borderline tumors or mucinous tumors
Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
Female subject must either:
postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to Screening, or
Subject has known dihydropyrimidine dehydrogenase deficiency.
Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would exclude the subject from participation.
Must have indication for treatment (adapted from National Comprehensive Cancer Network [NCCN] 2015 guidelines)\r\n* Any of the following constitute an indication for treatment:\r\n** Significant symptoms due to any iBCL: Which may include pain/discomfort, limitation of function, fatigue/malaise/constitutional symptoms, B-symptoms (fever, weight loss, night sweats), pruritus\r\n** Threatened end-organ function due to any iBCL\r\n** Progressive cytopenia secondary to any iBCL\r\n** Steady progression of follicular lymphoma (FL) and marginal zone lymphoma (MZL)
Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
Confirmation of diagnosis:
In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Is or has an immediate family member (example, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion.
Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ?21 days after the completion of interleukins, interferons, or cytokines (other than hematopoietic growth factors)
Cellular therapy: ?42 days after the completion of any type of cellular therapy (eg, modified T-cells, natural killer cells, dendritic cells, etc)
ANC ?1.0 × 10^9/Liter (L)
Total abstinence (if it is their preferred and usual lifestyle);
Are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as participants having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy).
Are planning to undergo SCT prior to PD on this study (ie, these participants should not be enrolled in order to reduce disease burden prior to transplant).
Presence of lesions that are amenable for injections as determined by interventional radiology\r\n* NOTE: Nodal or extranodal sites must be palpable and easily accessible; sites such as mediastinum, retroperitoneum, within solid organs, spinal sites, central nervous system (CNS) sites, etc., are NOT allowed
Any of the following:\r\n* Pregnant persons\r\n* Nursing persons\r\n* Persons of childbearing potential who are unwilling to employ adequate contraception
Clinical diagnosis of TDT with ? 8 documented RBC transfusion events per year on an annualized basis in the 2-years prior to screening
Confirmed beta-thalassemia diagnosis by molecular genetic testing
Participants willing to undergo all protocol-specified biopsies
Must have determination of biomarker (BM) status (either BM positive [+] or BM negative [-]) by the sponsor's blood based assay
Willingness to have a central venous line (peripherally inserted central catheter [PICC] or PORT)
Willingness to follow the requirements of the intravenous ascorbic acid program schedule
Any of the following:\r\n* Pregnant persons\r\n* Nursing persons\r\n* Persons of childbearing potential who are unwilling to employ adequate contraception
Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
Patients with uncontrolled or symptomatic kidney stones; NOTE: Patients with calcium oxalate crystals on baseline urinalysis or a history of symptomatic calcium oxalate stones must be seen by the Nephrology Stone Clinic and placed on a low oxalate diet (< 100 mg oxalate/day) prior to enrollment
Known paroxysmal nocturnal hemoglobinuria (PNH)
Has carcinomatous meningitis;
Group 1: BRAF mutant melanoma (Part B)
Group 2: NRAS or HRAS mutant solid tumors(Part B)
Group 3: KRAS mutant CRC.(Part B)
Group 4: KRAS mutant NSCLC (Part B)
Group 5: Pancreatic Ductal Adenocarcinoma (Part B)
Screening heart function lab test
creatinine kinase - MB, troponin-I, and troponin-T within normal limits
Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
Current evidence of endocrine alteration of calcium Phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia)
Expansion cohort only: Plasma cell fluorescence in situ hybridization (FISH) test demonstrating presence of t(11;14)
Active infection or an unexplained fever >38.5°C during Screening or on the first scheduled day of dosing.
Previous radiotherapy to the lung or mediastinum
Confirmed diagnosis of primary cold agglutinin disease (CAgD) based on the following criteria: a) Chronic hemolysis; b) Polyspecific direct antiglobulin test (DAT) positive; c) Monospecific DAT strongly positive for C3d; d) Cold agglutinin titer >= 64 at 4 degree celsius; e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+, and f) No overt malignant disease
Bilirubin level above the normal reference range
Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening
Relapsed post-autologous HSCT
Has undergone prior allogeneic HSCT:
Patients must have erythematous manifestations of cutaneous aGvHD. Characteristics of the rash must indicate active inflammation (red coloration) as distinct from resolving inflammation (brown coloration).
Evidence of end-organ Cytomegalovirus (CMV) infection
Patients known to have CMV, adenovirus, human herpes virus 6 (HHV6), Epstein Barr virus (EBV) or any hepatitis viremia from screening according to institutional standard practice
Ileus, abdominal pain, extensive denudation of intestinal mucosa or stage 4 GI GvHD.
IA involving sites other than lungs and sinuses
Advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term.
History of prior ? grade 3 hypersensitivity reaction or any toxicity attributed to trastuzumab or murine proteins that warranted permanent cessation of these agents (applicable for Cohort 1 only).
Previous exposure to vinorelbine (applicable for Cohort 1 triplet combination only)
Natural killer cell malignancies
Related donors will be assessed and collected through University of Minnesota BMT protocol MT2012-14C: “Procedure Guidelines For Related Hematopoietic Stem Cell Donors.”
CML in blast crisis
Has male sexual partner with vasectomy
Practice total abstinence from sexual intercourse (minimum 1 complete menstrual cycle)
Sexually active with female partner only
Prior treatment of chronic HCV infection with a direct acting antiviral agent(s): telaprevir, boceprevir, sofosbuvir, simeprevir, or other direct acting antiviral
HCV genotype performed during screening indicates infection with genotype 2 or 3
Vaccinations against encapsulated bacterial pathogens (Neisseria meningitis, including serogroup B meningococcus, Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment
Clinical diagnosis of systemic lupus erythematosus (SLE) or other autoimmune disorders with anti-nuclear antibodies (ANAs) at Screening
cT1N0- tumour invasion into submucosa, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
cT2N0 - tumour invasion into muscularis propria, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
cT3a,bN0- tumour invasion through the muscularis propria no more than 5 mm into the subserosa/perirectal tissue and clear of the circumferential radial margin (CRM). Absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or lymphovascular invasion.
Mid to low-lying tumour eligible for local tumour excision in the opinion of the treating surgeon.
ANC ? 1.5 x 109/L
Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires.
Must have operable gastric adenocarcinoma, T2-T4a, N0-N3, M0
Prior radiotherapy that overlaps with planned radiotherapy portal
completed the base trial and have shown a clinical benefit of SD or better and have never met any withdrawal criteria as defined in the tisotumab vedotin base protocol, or
not completed treatment as defined in the base protocol for reasons that are not considered critical and unmanageable for the safety of the patient (as evaluated by the investigator and/or the sponsor) and the patient clearly showed response of PR or better.
Acceptable hematological status
Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of human papillomavirus (HPV) status or PDL-1 status
ANC >= 1000 K/CUMM
Platelets >= 75,000 K/CUMM
Subject has HNSCC with carotid artery encasement
Subjects with active hemorrhagic diathesis
Glycosylated hemoglobin (HbA1c) =< 7 % (Gedatolisib can cause hyperglycemia)
Second active neoplasia
Planned to receive either primary or post-operative CRT
Planned IMRT (Intensity-Modulated Radiotherapy)
Planned administration of cisplatin administered weekly or tri-weekly during RT
Herbal, alternative remedies, and alcohol containing over-the-counter mouthwashes are excluded during the course of the study
Chronic immunosuppression
Experienced a previous response to pembrolizumab or nivolumab
ANC ? 750/µL (?0.75 x 10^9/L)
Planned to receive IMRT with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative dose of at least 60 Gy and a maximum of 72 Gy
Radiation fields to include at least two mucositis sites at risk (buccal mucosa, floor of mouth, ventral and lateral tongue, soft palate) in which both sites receive a minimum cumulative dose of 55 Gy
Planned to receive concomitant single agent chemotherapy with cisplatin given either weekly or tri-weekly
Prior exposure to isatuximab or participated clinical studies with isatuximab.
Participants with light chain and free light chain (FLC) only may be enrolled if they meet all the criteria for a diagnosis of MM.
Participants must be considered by their physician eligible to receiving the IRD regimen.
Criteria 1 Waldenström macroglobulinemia
Receiving other treatments for the condition (with exceptions and time limits)
Other hematologic/biochemistry requirements, as per protocol
The tumor must have been determined to be mismatch repair proficient or microsatellite stable through CLIA approved testing (Immunohistochemistry [IHC], polymerase chain reaction [PCR], or Next-Generation Sequencing [NGS] assays).
Symptomatic arrhythmia
Functioning intraperitoneal catheter
Gynecological Oncology Group (GOG) performance status =< 2
Consecutive patients with a newly diagnosed, objectively confirmed: symptomatic or unsuspected, proximal lower-limb DVT or symptomatic PE or unsuspected PE in a segmental or more proximal pulmonary artery;
3 or more doses of a vitamin K antagonist before randomization;
thrombectomy, vena cava filter insertion, or thrombolysis used to manage the index episode;
bacterial endocarditis;
Late-Gadolinum enhancement (LGE) on CMR indicative of cardiac amyloidosis
Transthyretin amyloid (ATTR) cardiomyopathy (CM)
Subjects with a diagnosis of hereditary ATTR amyloidosis should have a known amyloidogenic transthyretin (TTR) mutation demonstrated by genotyping AND is recognised to be primarily associated with cardiomyopathy AND one of the following: Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarised light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis. Or Scintigraphy: 99m^Tc-DPD with Grade 2 cardiac uptake or 99m^Tc-PYP with either Grade 2 or 3 cardiac uptake.
Subjects with a diagnosis of wild type ATTR-CM must be negative by genotyping and have one of the following: Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarised light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis OR Scintigraphy 99m^Technetium-dicarboxypropane diphosphonate (99m^Tc-DPD) with Grade 2 cardiac uptake or 99m^ Technetium-pyrophosphate (99m^Tc-PYP) with Grade 2 or 3 cardiac uptake.
Subject medically diagnosed with AL amyloidosis that has required chemotherapy or an autologous stem cell transplant based upon: AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type, in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
Newly diagnosed AL amyloidosis based upon: AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
Sustained / symptomatic monomorphic ventricular tachycardia (VT), or rapid polymorphic VT, at screening
Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening. Implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM) at screening
N-terminal pro b-type Natriuretic Peptide [(NT)-proBNP] >8500 nanograms (ng)/ Liter (L)
Any active and persistent dermatological condition
Existing diagnosis of any type of dementia
Acute coronary syndrome, or any form of coronary revascularization procedure (including coronary artery bypass grafting [CABG]), within 6 months of screening.
Urine dipstick positive (>1+) for blood during screening with investigation indicating glomerular haematuria. If other causes are identified, subjects may be enrolled on resolution of the abnormality
Orthopnoea of sufficient severity to preclude supine scanning as determined at screening
Inability to fit inside scanner due to body size (girth)
Intra- orbital metal fragments that have not been removed
Inner ear implants
Orthopnoea of sufficient severity to preclude supine scanning as determined at Screening
Fulfilment of diagnostic criteria for AL amyloidosis
TTR polyneuropathy and / or intracranial TTR involvement including ophthalmological disease
Screening CLEC12A level ? 20%;
Patient has Glucose-6-phosphate deficiency
Symptomatic cardiomyopathy
Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with total bilirubin < 2 mg/dL for dose-escalation) with no encephalopathy and no clinical ascites (ascites controlled by diuretics is also excluded in this study).
Normal electrocardiogram at screening
Has documented HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
Subjects experiencing toxicity with ibrutinib
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
ANC ?1.5×10^9/L.
Subjects experiencing toxicity with ibrutinib
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
Total bilirubin within the reference range during screening evaluation
A history of retinal pigment epithelial detachment (RPED) or risk factors for RPED
If undergoing myeloablative allogeneic HCT:
If undergoing non-myeloablative allogeneic HCT:
Willing to undergo blood transfusions as deemed clinically necessary.
Any prior exposure to Hu5F9?G4 or other CD47 targeting agents.
Haematologic and biochemical indices within the ranges shown below at the screening visit
ANC 1500 cells/?l
Postmenopausal defined as:
Age 55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range
Age 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range
AR positive tumours defined as any nuclear AR staining by IHC (enrolment may be based on local pathology findings; subsequent review of AR expression by central pathology laboratory will be carried out)
Triple-negative tumours, i.e. tumour cells are negative for
HER2 with 0, 1+ or 2+ intensity on IHC and no evidence of amplification of the HER2 gene on ISH
Any approved or investigational agent that blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700)
Hypersensitivity to the active pharmaceutical ingredient or any of the excipients of the IMPs, including Labrasol, butylated hydroxyanisole, and butylated Hydroxytoluene
Indication to initiate androgen deprivation therapy (ADT)
Symptomatic lymphadenopathy
Excluding the lesion intended to undergo radiation, subjects must have at least 1 unresectable, non-bony lesion that is measurable radio-graphically (based on RECIST 1.1).
Any contraindications for ipilimumab (Yervoy®) or nivolumab (Opdivo®) as per the package inserts.
Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival.
?12 weeks for total skin electron beam irradiation,
?3 weeks for systemic retinoids, interferons, vorinostat, romidepsin, fusion proteins
Patient currently has unresolved toxicities for which ceritinib dosing has been interrupted in the parent study.
Subject is at least 65 years old at the time of signing the consent form.
Pathological diagnosis of pancreatic adenocarcinoma before first treatment but may be enrolled with presumed diagnosis based on clinical and radiologic evaluation with confirmation made by biopsy at time of EUS prior to AdV-tk injection
FLT3 mutation positive (ITD, TKD or other)
1 week from non-cytotoxic agents
Acceptable blood sugar control
Requiring renal dialysis
Receiving hematopoietic growth factors
Fever (> 38.1°C)
Enrollment in a concomitant clinical study
Expression of one (1) or more of the following TAPAs: Sp17, AKAP-4, Ropporin, PTTG-1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1, by either RT-PCR and/or immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood. For HER-2/neu expression, positive FISH results are acceptable.
Participation in any other intraoperative margin assessment protocol that would affect data acquisition.
Serum potassium, magnesium, and calcium levels normal per current Yale-New Haven Hospital (YNHH) lab medicine standards (may be corrected to those levels by supplementation during screening period) within 2 weeks prior to start of any therapy
High-grade (second degree or above) atrioventricular (AV) block or persistent sinus bradycardia of less than 50 beats per minute (BPM)
Anti-arrhythmia medication other than beta-blockers or digoxin
Treatment with an H2 blocker, other than famotidine; if the subject requires a proton pump inhibitor (PPI), then esomeprazole, pantoprazole, or rabeprazole may be given
Subjects must have been treated with at least 2 prior therapies including a proteasome inhibitor and a cereblon-binding agent\r\n* Subjects who are refractory to carfilzomib may enroll throughout the trial; carfilzomib refractory status is defined by IMWG criteria: disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course\r\n* In the twice weekly dosing cohort of the study, enrollment will be limited to patients meeting carfilzomib refractory status\r\n* In the weekly dosing cohort, it will be required that one of the expansion cohorts (20 subjects) enrolls carfilzomib refractory subjects and the other (20 subjects) enrolls carfilzomib/proteasome inhibitor (PI) naive/sensitive subjects
Previous selinexor exposure
Previous inability to tolerate any dose of paclitaxel (i.e., the subject required a paclitaxel dose reduction or discontinuation).
Health care coverage.
Alkaline phosphatase > UNL or > 2.5 x UNL in case of liver metastases, or > 5 x UNL in case of bone metastases.
Has a mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance with the study requirements.
Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible)
Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or other conditions with iron overload from repeated blood transfusions (see exclusion criteria for exceptions);
Thalassemia syndromes;
Diamond Blackfan anemia;
Written documentation of local or central laboratory determination of amplification or translocation to FGFR1-TACC1, FGFR3-TACC-3 fusion and/or activating mutation in FGFR1, FGFR2,or FGFR3
Aged between 18 and 75 years, inclusive.
Patient is currently enrolled in a Novartis-sponsored, CD&MA study receiving everolimus or everolimus plus Sandostatin LAR Depot and has fulfilled all their requirements in the parent study
Patient is currently benefiting from treatment with everolimus, as determined by the guidelines of the parent protocol.
Patient has participated in a Novartis sponsored combination trial where imatinib was dispensed in combination with another study medication and patient is still receiving combination therapy.
Men and women from all ethnic and racial groups
Diarrhea ( >=3 loose bowel movements per day)
Duration of diarrhea of at least 1 week
Absolute neutrophils >= 1,500/mm^3
Able to take acetaminophen
Primary amyloidosis
Patient is currently receiving medication(s) that are principally metabolized via the cytochrome P450 3A4 enzyme pathway.
Abnormal LVEF (< LLN for the institution for a patient of that age) on echocardiogram
Gynecologic Oncology Group (GOG) Performance Status of 0, 1, or 2
Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.
Have identified a backup cells source in case of engraftment failure; the source can be autologous, related or unrelated
Adequate renal and hepatic function (creatinine ? 1.5 x IULN, bilirubin ? IULN, AST and ALT ? 3.0 x IULN or 5 x IULN if know liver metastases).
Sufficient tumor available to determine if expresses wild-type or mutated BRAF if result not already known; the presence or absence of BRAF mutation needs to be determined at Brigham and Women's Cancer Center (BWH), or by Drs. Christopher Corless and Michael Heinrich at Cancer Pathology Shared Resource Oregon Health & Science University, or in context of eligibility assessment after signing consent to a previous clinical trial
Potassium within normal range or correctable with supplements
Magnesium within normal range or correctable with supplements
Corrected serum calcium within normal range, or correctable with supplements
Agreement to provide blood samples for pharmacodynamic studies utilizing Peripheral Blood Mononuclear Cells (PMBCs) as outlined in the protocol
Melanoma of ocular primary
Active suppurative cholangitis (hypotension, acidemia, mental status changes)
Complex stenoses (Bismuth grade IV) will not be eligible for the trial
No prior malignancy is allowed except for cancers that have been definitively treated with a risk of recurrence of < 30% based on the treating oncologists assessment
Patient must consent to mandatory correlative sample collection
Patients has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of >= 10 on the Patient Health Questionnaire (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of ‘1, 2, or 3’ to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)\r\n* Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety\r\nNote: The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment
Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
Hypercalcemia: serum calcium > 11.5 mg/100 ml or
Renal insufficiency: serum creatinine > 173 µmol/l
Patient with contra-indication to high dose of steroids (including ongoing active infection, use of live vaccines, virosis such as hepatitis, herpes, varicella, herpes zoster)
Known malabsorptive disorder
Patient with detectable c-kit JM mutation confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma)
lesion(s) diameter is ? 2 cm
HER2 status negative
Hypercalcemia
Hepatic blood flow abnormalities and/or large-volume ascites
One to 3 painful lesions.
Targeted tumor(s) are ExAblate device accessible and are located in ribs, extremities (excluding joints), pelvis, shoulders and in the posterior aspects of the following spinal vertebra: Lumbar vertebra (L3 - L5), Sacral vertebra (S1 - S5)
Patients with persistent distinguishable pain associated with up to 3 tumors of which a maximum of 2 tumors will be treated: o If patient has pain from additional sites that are not planned for treatment, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the NRS compared to the site(s) to be treated.
Patient with NRS (0-10 scale) pain score ? 4 at the targeted tumors (i.e: both tumors targeted for treatment must have NRS ? 4) irrespective of medication
Targeted tumors (most painful) size up to 8 cm in diameter
Able to communicate sensations during the ExAblate MRgFUS treatment
Need surgical stabilization of the affected weight bearing bony structure (>7 fracture risk score, see Section 6.9) OR
Unstable angina pectoris on medication
Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 4 hrs of total table time.)
Are participating or have participated in another clinical trial for the palliation of their targeted bone metastasis tumors in the last 30 days
Targeted (most painful) tumors size > 8 cm in diameter
Targeted (most painful) tumors:
NOT accessible to ExAblate device
Patients must meet all the University of Alabama at Birmingham (UAB) diagnosis and disease status criteria for clinical appropriateness for allogeneic HSCT derived from American Society for Blood and Marrow Transplantation (ASBMT) and National Comprehensive Cancer Network (NCCN) guidelines and updated annually
secondary AML and ALL in 1st or 2nd relapse or primary refractory
DLCO > 50%
Infections requiring administration of ganciclovir, valganciclovir or acyclovir at the time of infusion: HSV-Tk cells can be administered after a 24-hour discontinuation interval of antiviral therapy
Administration of G-CSF after haploidentical HCT
CD3+ cells ? 100/µl at day of planned experimental infusion after haploidentical HCT
Chronic diarrhea
Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis
Currently being treated with hematopoietic growth factors other than erythropoietin (EPO). Treatment with hematopoietic growth factors may be started during the study with development, or worsening, of cytopenia
Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis, Cutaneous Mastocytosis
Handicapped status defined as at least two of the following handicaps, including at least one among pruritus, flushes, depression and asthenia: pruritus score ? 6, number of flushes per week ? 7, Hamilton rating scale (depression) ? 10, number of stools per day ? 4, number of mictions per day ? 8, Fatigue Impact Scale total score (asthenia) ? 40
Patient with one of the following mastocytosis: Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
C-Kit (CD117) positive tumours detected immuno-histochemically or PDGF positive if c-kit negative
Ki 67 < 10%
Normal EKG and LVEF >40%, measured by EKG and MUGA scan, radionuclide ventriculogram, or echocardiogram
Legal incapacity or limited legal capacity, unless authorization is granted by a legal guardian
DCIS with microinvasion on histology on core needle biopsy
Palpable mass
Mass on mammography
Prior exposure to carboplatin (related to current or past diagnosis)
Presence of ulcerating or fungal skin lesions or infection of the breasts
Poor nutritional state (as determined by clinician)
Allergies to lidocaine or marcaine
Allergies to imaging dyes
Inferior margin of the cancer located within 15 cm from the anal verge as determined by rigid sigmoidoscopy
Patient is a candidate for elective rectal resection
ASA class 4 or 5
Patient is receiving sorafenib (Nexavar) as a monotherapy in their originating protocol. Patients who were being treated with sorafenib (Nexavar) in combination with other chemotherapies in the original study, but continued on single agent sorafenib (Nexavar) after discontinuation of the combination agent will be eligible.
Patient who are receiving concurrent combination with sorafenib (Nexavar) and TACE (transarterial chemoembolization) in their originating study will be eligible.
Undergone complete resection of primary tumour
Satisfactory haematological or biochemical functions (tests should be carried out within 8 weeks prior to randomisation): Results of clinical investigations carried out within 8 weeks prior to randomisation can be used in place of the required screening investigations. Patients with mild laboratory abnormalities can be included at the discretion by the site principal investigator, and after approval by ASCOLT Trial Management Group
ANC ? 1.0 x 109/L
Active gastritis or active peptic ulcer
History of erosive GERD or active erosive GERD on gastroscopy.
Unexplained rise of CEA (i.e. smoker with elevated CEA will not be excluded)
Histological diagnosis of relapsed or refractory classical HL
Received growth factor support or transfusions to achieve hematology entry criteria (platelets, hemoglobin, absolute neutrophil count)
Smoked at least 10 cigarettes/day for at least 1 year.
Willingness to reduce alcohol consumption during study to 2 or fewer standard drinks/day (3 oz. of alcohol or two beers (12 oz.), or two 5 oz. glasses of wine).
Evidence of problem alcohol consumption based on AUDIT.
Suicidal or homicidal ideation.
Current major depression.
Karnofsky rating 70-100 (See Appendix A).
Able to communicate sensations during the ExAblate MRGFUS procedure.
The subject presents with:
Symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papaedema).
Immunosuppression (corticosteroids to prevent brain edema are permitted)
Known sensitivity to gadolinium-DTPA
Patients with a history of uncontrolled seizures or who are not on anti seizure medication (e.g., Phenytoin 100 mg PO t.i.d. or Keppra 500 mg po bid) before the procedure
Prior enrollment in NCI protocol 09-C-0139 with receipt of at least 5 doses of TARP peptide vaccine (i.e. completion of primary vaccination series)
Hepatitis B and C negative, unless the result is consistent with prior vaccination or prior infection with full recovery
Discontinued study participation in Verastem-sponsored IPI-145-07 study
Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus (HSV)
Currently enrolled in Studies GS-US-352-0101, GS-US-352-1214, or GS-US-352-1154
Non-smokers, former smokers and/or smokers who have not smoked within 1 month before surgery, and who agree to not smoke or utilize e-cigarettes during the post-operative period
Pre-pectoral implant placement
Undergoing delayed reconstruction
Requiring Wise pattern reduction of mastectomy skin flap
Subject is undergoing robotic partial nephrectomy being performed by participating surgeon
Subject is willing to be randomized between intervention and control arms
Cases in which the subject has a solitary or horseshoe kidney
Cases in which the subject has more than two masses in the applicable kidney
Cases involving a bilateral operation
Participation in a TRACON Pharmaceuticals sponsored parent TRC105 study and, thought to have potential to derive clinical benefit from continued treatment with TRC105 in the opinion of the parent study investigator.
ability to begin TRC105 dosing on this protocol within 6 weeks from the subjects last dose of TRC105 in the parent TRC105 study
Any clinical event that would make TRC105 therapy inappropriate under the parent protocol
For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving chromosome 7 or chromosome 17.
AST(SGOT)/ALT(SGPT): ?3 x UNL
creatinine: ?2 x UNL
Nonlactating female between the ages of 21 to 65 years, inclusive;
Pap test documenting atypical squamous cells of undetermined significance (ASCUS)/HPV+, atypical squamous cells high grade (ASC-H), low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL) within 4 months prior to screening Visit 1;
History of pathologically confirmed CIN1 by colposcopically-directed punch biopsy, within 12 weeks prior to administration of first study vaccination (CIN 2/3 subjects will not be eligible);
For the diagnosis of CIN1, has a documented satisfactory colposcopy, ie, the entire lesion as well as the entire squamocolumnar junction is visualizible by colposcopy;
Current recognized immunodeficiency disease, including infection with HIV, cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies.
Previously enrolled in this study.
Erythropoietin and darbopoietin-? are permitted;
Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis (i.e., LHRH agonist/antagonist) are permitted. No other hormonal therapy is permitted;
Subjects with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) < 500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) >= 45 percent.
For France only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Lumbar CSF cytology is not required, but may be performed if clinically indicated prior to study enrollment. If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible \r\n* Note: False positive cytology can occur within 10 days of surgery
Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD)
Lactating females are not eligible unless they have agreed not to breastfeed their infants
204 Prior allogeneic HSCT.
BRCA1, BRCA2 and/or ATM gene defect.
Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination.
Deemed eligible for and willing to undergo RC by the attending urologist.
GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200.
Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
Indwelling catheters are not permitted.
Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
Bladder post-void residual volume of >500 mL.
Difficulty providing blood samples.
Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
Willingness to avoid pregnancy or fathering children.
Subject does not meet protocol-specified washout periods for prior treatments
Tumors must be supratentorial in location.
Participant has a visual condition that compromises the ability to accurately measure visual acuity or assess visual activities of daily living (vADLs).
cervical cap or diaphragm with a spermicidal agent,
tubal sterilization, or
Barcelona Clinic Liver Cancer (BCLC) stage B or C that cannot benefit from treatments of established efficacy such as resection, local ablation, chemoembolization.
Liver function status Child-Pugh (CP) Class A. CP status should be calculated based on clinical findings and laboratory results during the screening period.
Transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast cancer resistance protein (BCRP)
Presence of other active invasive cancers that do not harbor CCNE1 amplification
Leptomeningeal carcinomatosis
Symptomatic peripheral ischemia
A recognized single pathogen cultured from 1 or more blood cultures; OR
Inpatient or outpatient with presence of indwelling CVC (ie, totally implantable port, tunneled or non-tunneled CVC, hemodialysis catheter, or peripherally inserted CVC) that has been in place for greater than5 days from which a bloodstream infection has been documented within 96 hours prior to enrollment (and from which an isolate of the baseline pathogen(s) is still available for analysis at the central laboratory) and demonstrates the protocol definition of CRBSI/CLABSI; NOTE: For the treatment arm only (MLT Arm and Control Arm), the CVC is expected to be in place through the end of treatment.
Subjects who refuse to have their catheter removed or subjects for whom, in the Investigator's opinion, catheter retention for the duration of the study is reasonable or required;
Subjects eligible for the Observation Arm must have had their central line removed and replaced within 96 hours of the qualifying blood culture (120 hours with Medical Monitor approval);
Subjects with septic shock that requires inotropic support or is unresponsive to fluid resuscitation;
Subjects taking disulfiram or disulfiram-like drugs;
Subjects with the presence of a deep-seated intravascular source of infection (eg, endocarditis [as evidenced by vegetations on an echocardiogram or clinical suspicion] or septic thrombosis);
Subjects with polymicrobial CRBSI/CLABSI caused by pathogens that would require multiple antibiotics to be used for adequate lock therapy treatment. For example, a subject with methicillin-resistant Staphylococcus aureus and Escherichia coli requiring treatment with vancomycin and meropenem would be excluded from the study. A subject with S. aureus and Staphylococcus epidermidis, where both are identified as pathogens and where both could be treated with vancomycin, would be eligible;
Subjects with the presence of a tunnel or catheter exit site infection or an infusion port pocket abscess as manifested by purulence at the exit site, or inflammation with erythema, or induration of greater than 1 cm in diameter;
Subjects who have been previously randomized into the present study;
Subjects with a central line-related mycobacterial infection; or
Echocardiogram with normal ejection fractions
The total sum of Ad-p53 Injection Doses (mL) based upon the tumor volumes shown in Table 2 should be less than or equal to 25 mL as the MTD of Ad-p53 is 2.5 x1013 vp/treatment day.
No macroscopic intra-vascular invasion by tumors of the main portal vein, hepatic vein or vena cava.
Subjects must not have tumors adjacent to vital structures such as carotid arteries.
Diagnosis of intrahepatic cholangiocarcinoma.
Histologically-confirmed T1b, T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
Resectable disease at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the chest, abdomen, and pelvis (C/A/P)
Unresectable gallbladder cancer at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the C/A/P
Known dihydropyrimidine dehydrogenase deficiency
The presence of homologous recombination deficiency defined by either; A) Inherited pathogenic variant of BRCA2, ATM, BRCA1, PALB2 by a Clinical Laboratory Improvement Act (CLIA) level germline assay or B) have evidence by somatic sequencing using a CLIA level assay of biallelic inactivation of BRCA1, BRCA2, PALB2, FANCA or biallelic inactivation or monoallelic inactivating mutation of ATM.  It is anticipated that the majority of patients will be germline carriers of a pathogenic variant of BRCA1, BRCA2 or ATM.
Must be candidates for radical prostatectomy and considered surgically resectable by urologic evaluation.
2. Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included.
Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy.
Patient is ineligible, declines, or is considered ineligible to undergo radical cystectomy
Has reached the age of majority in their country
FLT3-ITD mutant (> 3% FLT3-ITD/total FLT3) AML (primary AML or secondary to MDS) is ineligible for intensive induction chemotherapy by meeting at least 1 of the protocol-defined criteria
analysis of results
Meeting the protocol definition of TNmCRC assessed in the screening blood test.
Non-healing wounds on any part of the body.
Radiotherapy as specified in the protocol
Blood urea nitrogen (BUN) =< 40 mg/dL.
A lesion that either:\r\n* Is intended to be accessed bronchoscopically OR\r\n* Is intended to be accessed with computed tomography (CT) guided transthoracic injection and in the estimation of the radiologist performing the procedure will not require transversing a bullae that significantly increases the risk of pneumothorax.
Known meningeal involvement of MM.
AML or MDS relapse following allo-HSCT (morphological relapse, or MRD positive by flow cytometry, cytogenetics, molecular mutations)
Medically fit, as defined by treatment-related mortality (TRM) score ?13.1 calculated with simplified model
Concomitant illness associated with a likely survival of < 1 year
Willingness to avoid pregnancy or fathering children as per protocol-defined criteria.
Radiographic evidence of major blood vessel invasion/infiltration
The study will require that 50% of enrolled subjects have homozygous deletions, deleterious mutations, or both in one or more of the DNA damage response (DDR) genes; the other 50% of patients must have an intact DDR pathway
Previous enrollment in this study
Tumor causing urinary outlet obstruction that requires catheterization for voiding; patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll
Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.
Presence of a known ibrutinib resistance mutation at ? 4% variant allele frequency OR < 4% with two separate measurements at least 4 weeks apart with increasing variant allele frequency
Germline BRCA 1/2 Mutation Positive
Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS). If available, NGS sequencing report should be submitted to Gradalis.
For Part 2, any menopausal status
Active retinal pigment epithelium (RPE)/photoreceptor disorders such as; retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular degeneration.
Waldenstrom's macroglobulinemia
Amyloidosis
Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
Documented evidence of at least ONE or MORE of the following:\r\n* Biallelic inactivation of genes involved in homologous recombination repair in the tumor\r\n* Biallelic inactivation of other genes involved in homologous DNA recombination repair in the tumor may be included at investigator’s discretion\r\n* Homologous recombination repair deficiency by genomic signature in the tumor\r\n* Clearly pathogenic or likely pathogenic germline mutation in BRCA2, BRCA1 and/or ATM\r\n* (Note: the following are not alone sufficient for eligibility and require additional criteria to be met: germline variant of uncertain significance in BRCA1, BRCA2 and/or ATM; germline mutations in other HR genes)
Patient's tumor must express specified biomarkers. Note: Patients who were previously screened for participation in other Immatics' sponsored clinical trials and whose biomarkers are positive for IMA202-101 based on IMA_Detect may enter IMA202-101 screening
Acceptable coagulation status
Available IMA202 product passed all required release tests
Any condition contraindicating leukapheresis
Patient unable to tolerate lymphodepletion, low-dose IL-2 and/or IMA202 product
Prior daratumumab or other anti-CD38 antibody
Subject has known moderate or severe persistent asthma within 2 years, or currently has uncontrolled asthma of any classification; (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)
Patient declines participation in NANT 2004-05, the NANT Biology Study
Bisphosphonates and/or denosumab are allowed
Urgent need of treatment to prevent acute neurologic deterioration, including urgent neurosurgery or radiotherapy
Blood urea nitrogen < 2 X ULN
Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of study agent dosing
The presence of gross skin invasion/ulceration by the breast cancer, or inflammatory changes with skin edema AND erythema; Note: Paget’s disease is permitted
Women receiving a “nipple delay” procedure prior to mastectomy
Women with skin diseases (psoriasis, eczema)
Taken tamoxifen or other selective estrogen/progesterone receptor modulators (SERMs/SPRMs) within two years prior to entering study or been required to discontinue SERM therapy due to thromboembolic or uterine toxicity
Lymphocyte count ? 0.5 x 109/L (500/µL)
Uncontrolled autoimmune hemolytic anemia (Hgb < 11g/deciliter) or idiopathic thrombocytopenic purpura (< 100,000/µl)
Has received prior therapy with IL-2 or other investigational systemic cytokine therapy signaling through a common gamma-chain cytokine receptor including IL-7, IL-15 or IL-21
Presence of FLT3-ITD and/or D835 mutation(s)
Willing to undergo routine surveillance with breast ultrasound and/or mammography
DCIS with focal invasion
Women with biopsy confirmed high grade cervical intraepithelial lesions (diagnosis confirmed by\r\npositive p16 immunohistochemistry staining) within 12 weeks of baseline visit
Pathologic findings consistent with\r\n* atypical endometrial cells or serious glandular-cell atypia (atypical glandular cells, favor neoplasia cytology diagnosis)\r\n* evidence of cervical carcinoma on Pap smear or biopsy\r\n* more than two cervical quadrants of cervical intraepithelial neoplasia grade 3 (CIN 3) as visualized by colposcopy\r\n* nonvisual squamous columnar junction on colposcopy with no concurrent endocervical sampling performed
Biopsy proven ccRCC
Inability to stop anticoagulants/antiplatelet therapy peri-operatively
Currently enrolled in a Valor-sponsored IGN002 study
Derived clinical benefit from IGN002, defined as CR, PR, or SD, in another Valor-sponsored IGN002-101 study (e.g., IGN002-101)
Tolerated IGN002 therapy in the other Valor-sponsored IGN002 study
Discontinued from another Valor IGN002 study due to an AE considered by the Investigator to be related to IGN002 treatment
Researchers think that any life-threatening illness, condition or organ system dysfunction can damage the safety of subjects
Donors will be selected from among the subject’s relatives, adult children preferred
If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will be preferred; CMV serology of the donor will be tested prior to the allogeneic cell donation; donations from CMV-positive donors to CMV-negative recipients will be given if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment given as per guidelines below
Positive infectious disease test as dictated by blood collection center’s standard operating procedure (SOP)
Patient is deemed by the investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
Neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy)
Subjects planning on embarking on a new strenuous exercise regimen after first dose of study treatment that can result in significant increases in plasma CK levels
A diagnosis of basal cell nevus syndrome (BCNS) as defined in the Consensus Statement (Bree et al, American Journal of Medical Genetics [Am J Med Genet] Part A 155:2091-2097)\r\n* Major criteria are: \r\n** BCC prior to age 20 years, or excessive number of BCCs out of proportion to prior sun exposure and skin type\r\n** Keratocyst of the jaw prior to age 20\r\n** Palmar or plantar pitting\r\n** Lamellar calcification of the falx cerebri\r\n** Medulloblastoma\r\n** First degree relative with BCNS\r\n* Minor criteria are: \r\n** Rib anomalies, or other specific skeletal malformations including kyphoscoliosis and short 4th metacarpals\r\n** Macrocephaly\r\n** Cleft/lip or palate\r\n** Fibroma of the heart or ovary\r\n** Ocular abnormalities\r\n** Other rare abnormalities listed in the article by Bree et al\r\n* For diagnosis of BCNS, the patient must have either 2 major criteria, one major and two minor criteria, or one major criterion plus molecular confirmation of a patched 1 (PTCH1) gene mutation
At least two BCC tumors, preferably more; these tumors must be located in different body regions or alternatively, located > 10 cm apart at sites that can be reproducibly separated into red and blue illumination fields
Laboratory requirements: \r\n* If the patient has never had a skin biopsy to establish the histological diagnosis of BCC as part of his/her syndrome, then one lesion must be biopsied prior to entry into the trial\r\n* Any suspected BCC lesion of > 10 mm in diameter must be biopsied at the start of the trial, to establish the histological subtype of the BCC\r\n* Any presumed BCC lesion that fails to respond by the end of the trial must be biopsied to rule out an incorrect diagnosis as a reason for the lack of response\r\n* If a female patient suspects she is pregnant during the course of the trial, a serum pregnancy test will be administered and if positive, any further PDT treatments will be halted
Currently participating in another clinical trial
Both men and women of all races and ethnic groups are eligible for this trial
PREREGISTRATION (STEP 0): Peripheral blood must be collected for submission to Fred Hutchinson Cancer Research Center for central assessment of the establishment of BCR/ABL status to confirm patient’s eligibility for registration to Step 1; Fred Hutchinson will forward results within 1-2 business days of receipt of the peripheral blood to the submitting institution
Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma); or exceptionally raised tumour markers (alpha-fetoprotein [AFP] >= 1000ng/mL and/or human chorionic gonadotropin [HCG] >= 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with germ cell tumor (GCT), high tumour burden, and a need to start therapy urgently
Primary arising in testis, ovary, retro-peritoneum, or mediastinum
Intermediate or poor prognosis as defined by International Germ Cell Cancer Consensus Classification (IGCCC) classification (modified with different lactate dehydrogenase [LDH] criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries); see below\r\n* Primary site: Testis or retro-peritoneum or mediastinum\r\n** Histology: Non-seminoma\r\n*** Prognostic category: Intermediate\r\n**** Clinical Factors: Testes/retroperitoneal primary and no liver, bone, brain or other non-pulmonary visceral metastases and intermediate markers – any of:\r\n***** AFP >= 1000 ng/mL and =< 10 000 ng/mL\r\n***** HCG >= 5000 IU/L and =< 50 000 IU/L\r\n***** LDH >= 3.0 x upper limit of normal (ULN) and =< 10 x ULN\r\n*** Prognostic category: Poor\r\n**** Clinical Factors: Mediastinal primary or liver, bone, brain or other non-pulmonary visceral metastases or poor markers – any of:\r\n***** AFP > 10 000 ng/mL or\r\n***** HCG > 50 000 IU/L or\r\n***** LDH > 10 x ULN\r\n** Histology: Seminoma\r\n*** Prognostic category: Intermediate\r\n**** Clinical factors: Any primary site and liver, bone, brain or other non-pulmonary visceral metastases and normal AFP, any HCG, any LDH\r\n* Primary site: Ovary\r\n** Histology: Malignant germ cell tumour histology (any of yolk sac, choriocarcinoma, embryonal carcinoma, mixed malignant GCT)\r\n*** Prognostic category: Federation of Gynecology and Obstetrics (FIGO)/Children's Oncology Group (COG) stage IV\r\n**** Distant metastases involving liver/spleen parenchyma and/or extra-abdominal organs (including but not limited to inguinal lymph nodes and lymph nodes outside abdominal cavity, lungs, bone, brain) and/or pleural effusion with positive cytology
Immuno-magnetically purged PBSCs are permitted, however a special exception protocol must be filed with the FDA and local IRB where patient will be infused to allow infusion of immunomagnetically purged PBSC; CD34+ selected cells are not permitted
PBSCs from identical twins are permitted, but no other allogeneic cells are allowed; sse of autologous stored umbilical cord blood stem cells is not allowed
Absolute T-cell count (ATC) at screening >= 0.07 K/microL. This is defined as CD3+ T-cell percent (expressed as fraction of 100%) multiplied by the absolute lymphocyte count (ALC, expressed in K/microL).
Negative human anti-mouse antibody (HAMA) result.
Presence of other active invasive cancers.
Platelets (plt) ? 100 x 10^9/L for paclitaxel cohort, and ? 75, 000 for endocrine therapy cohort
Active herpetic skin lesions or prior complications of HSV-1 infection (e.g. herpetic encephalitis or keratitis)
Subjects who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV 1 induced complications (immunosuppressed individuals, HIV positive individuals, pregnant women, or children under the age of 1 year) during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
Part 1: be willing to engage in follow-up telephone calls with a research nurse
Part 2: presence of fatigue as defined FACIT-F subscale of ? 34 on a 0 to 52 scale (in which 52 = no fatigue and 0 =worst possible fatigue)
Part 2: able to complete the baseline assessment forms
Part 2: able to understand the recommendations for participation in the study
Part 2: currently receiving anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and/or tricyclic drugs (imipramine, clomipramine, or desipramine)
Must have undergone a surgical resection with definitive intent, either by open or laparoscopic resection of the primary gastric or GE junction cancer. Patients must have undergone a total gastrectomy, subtotal gastrectomy, or distal gastrectomy (depending on the location of primary gastric lesion) with at least a modified D2 lymphadenectomy.
Patients have elected to undergo radical prostatectomy (RP) as treatment of choice and have to be a surgical candidate for RP; this determination will be made by the patient in conjunction with their treating urologist and is current standard of practice
Medical or surgical history that in the treating physician’s opinion would make the subject not a suitable candidate for i.p. therapy; examples would include surgically documented extensive intraperitoneal adhesions or large volume ascites
Subjects must have had histologic verification of a malignancy at original diagnosis or relapse; all subjects with relapsed or refractory solid tumors are eligible, excluding CNS tumors
Absolute neutrophils >= 1500/mm^3.
Evidence of cerebrospinal fluid (CSF) dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).
Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a class D agent with the potential for teratogenic or abortifacient effects.
Nursing mothers declining to discontinue breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide.
Prior receipt of cumulative RAI doses in excess of 1000 mCi
Prior radical prostatectomy
At least one but no more than 5 discrete PSMA-avid metastases on baseline PSMA-PET scan; all PSMA-avid lesions must be amenable to SBRT in judgment of treating radiation oncologist; there are no restrictions on site of metastasis (e.g. bone, lymph node, visceral); equivocal lesions on PSMA PET scan that are not definitive for metastasis will not count towards the limit of metastases and will not undergo SBRT
Presence of visceral metastases (e.g. lung, liver) detectable on cross-sectional imaging or bone metastases requiring the use of opioid analgesic or focal radiation treatment at the time of study entry
Creatine kinase (CPK) =< 2.5 x ULN
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation; neutropenic fever is defined as the presence of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as: 2) single oral temperature measurement of > 101 degree Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0 degree C) sustained over a 1-hour period
Requires hospitalization for IV empiric antibiotic therapy
Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
Participation in any other ongoing ceftolozane/tazobactam trial
Intolerance of ibrutinib
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
Is or has an immediate family member (spouse or children) who is investigational site or staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject
Patient must state willingness to undergo pre- and post-treatment biopsies. According to the investigator’s judgement, the planned biopsies should not expose the patient to substantially increased risk of complications
RENAL & BLADDER COHORT: Consent to Monroe Dunaway (MD) Anderson laboratory protocol PA13-0291
BLADDER: Histological documentation of urothelial cancer either on outside transurethral bladder biopsy or on initial transurethral bladder biopsy at MD Anderson under PA13-0291
BLADDER: Subjects must be considered cisplatin ineligible as per treating physician due to renal dysfunction, hearing impairment, or co-morbidities
RENAL & BLADDER: Currently enrolled in another interventional study
Patient has developed a rash or symptoms of a rash (cutaneous burning) characteristic of an EGFR inhibitor (health-care provider report of the rash with no other documentation is permitted)
Patient is willing to provide a skin biopsy for correlative research; Note: Can be waived with permission of study chair (documentation such as an email must be provided)
Patient must complete baseline quality of life (QOL) packet
Within 7 days before the first dose of cabozantinib: Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
Willing to sign a durable power of attorney
Confirmed MGMT-promoter unmethylated status
Use of valproate in any of its indications (epilepsy, mood disorder). Valproate, due to its HDAC inhibiting activity is contraindicated. For those patients on valproate, valproate will need to be discontinued and switched to a different anti-epileptic agent or psychotropic agent. A washout period of 4 days from valproate acid will be allowed prior to enrolling into the trial.
Previous enrollment in the present study
Prior administration of other NY-ESO-1 targeting immunotherapeutics.
No prisoners or children will be enrolled on this study.
At sites in the Southeastern U.S., subject must have negative serum test for galactose-alpha-1,3-galactose IgE (Note: positive test result is predictive of immediate-onset anaphylaxis reaction during first exposure to cetuximab, which is prevalent predominantly in limited geographic region of the Southeastern U.S.
Histologically or cytologically confirmed diagnosis of cervical, anal, penile, vulvar, or vaginal cancer positive for HPV-16 and/or HPV-18 by the Cervista assay. Tumors may be positive for more than 1 HPV subtype as long as HPV-16 and/or HPV-18 is present. Note: for the first 6 patients, only cervical, vulvar, or vaginal cancers will be enrolled.
Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed)
Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after dosing with C. novyi-NT
The patient has a caregiver for 28 days after dosing with C. novyi-NT
Asplenia
Antibiotic allergies that would preclude treatment for a C. novyi-NT infection
Glasgow Coma Score of less than 15
Consented to genome sequencing and the database of genotypes and phenotypes (dbGaP)-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/ribonucleic acid (RNA) samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done as part of routine care or another research project.)
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
As this study aims to assess the immunogenicity of various vaccine plus adjuvant combinations, no prior immunotherapy will be permitted.
Inadequate tissue acquisition to allow for neoantigen screening.
No candidate neoantigen identified during screening.
PRE-REGISTRATION: Chronic corticosteroid dependence that is unable to be weaned to discontinue.
ENROLLMENT: Patients where the burden of pulmonary metastasis, location, or bulkiness of disease may cause high morbidity if localized swelling such as causing uncontrolled symptoms, oxygen dependence, or location near a major bronchi as determined by investigator.
Prior cystectomy
Intermediate intensity regimen: 18 =< 65 years
DONOR: A domestic backup unit must be identified and reserved prior to the start of the treatment plan for possible infusion in the unlikely event of poor post-thaw viability of the primary CB unit
CD30-positivity by immunohistochemistry of >= 1%
May have received either brentuximab vedotin or lenalidomide/immunomodulatory imide drugs (IMiD) without dose modification/delay due to toxicity\r\n* IMiDs defined as thalidomide analogues
Sickle cell disease (SCD)\r\n* If diagnosis of SCD must meet one or more of the following disease characteristics:\r\n** Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing\r\n** Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions\r\n** Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,\r\n** Impaired neuropsychological function and abnormal cerebral MRI scan\r\n** Stage I or II sickle lung disease,\r\n** Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value)\r\n** Bilateral proliferative retinopathy and major visual impairment in at least one eye\r\n** Osteonecrosis of multiple joints with documented destructive changes\r\n** Requirement for chronic transfusions\r\n** Red blood cell (RBC) alloimmunization
Transfusion dependent alpha- or beta-thalassemia
Other non-malignant hematologic disorders\r\n* Transfusion dependent or involve other potential life-threatening cytopenias, including but not limited to paroxysmal nocturnal hemoglobinuria, Glanzmann’s thrombasthenia, severe congenital neutropenia and Shwachman-Diamond syndrome
Cerebral adrenoleukodystrophy (cALD)\r\n* Diagnosis of adrenoleukodystrophy (ALD) by abnormal plasma very long chain fatty acid (VLCFA) profile or ABCD1 gene mutation\r\n* Cerebral disease on MRI\r\n* Absence of a major functional disability (cortical blindness, loss of communication, wheelchair dependence) on the ALD Neurologic Function Scale\r\n* Performance intelligence quotient (IQ) of 70 or higher
Other inherited metabolic disorders\r\n* Any other inherited metabolic disorder for which alloHCT is indicated and for whom, in the opinion of the treating physician, the patient’s best treatment option is with a haploidentical donor following non-myeloablative conditioning
DONORS: In general good health as determined by the medical provider
Acute leukemias of ambiguous lineage
Pathologically confirmed diagnosis of liposarcoma; all subtypes are eligible
Presence of distant metastases; intra-abdominal (regional) spread is allowable if meets inclusion criterial indeterminate or small volume pulmonary nodules may be eligible, if the treating physicians recommend curative-intent resection of the primary tumor despite the presence of possible lung metastases
Prior eribulin
Monocytes >= 300/uL
Any of the following\r\n* Pregnant persons\r\n* Nursing persons\r\n* Persons of childbearing potential who are unwilling to employ adequate contraception
Men must have osseous metastases, but the presence of visceral metastases will not exclude patients from participation\r\n* Prior external beam radiation therapy (> 4 weeks prior to enrollment) for palliation of osseous metastatic disease is allowed, provided there is at least one osseous metastasis which has not been irradiated and which can be biopsied
At least one risk factor predicting higher likelihood of bone marrow sample yield: elevated alkaline phosphatase, low hemoglobin, or elevated lactate dehydrogenase (LDH)
Prior treatment with ARN-509 or enzalutamide (there is a grace period for men who wish to enroll and who have recently started enzalutamide for the first time but have taken less than 15 days of therapy)\r\n* Concurrent use of androgen deprivation therapy aside from LHRH agonist or antagonist (i.e. bicalutamide, flutamide, nilutamide, abiraterone, ketoconazole, estrogen); there will be a 2 week wash-out period from the last dose of any of these agents until the first dose of enzalutamide on study; patients who have just started enzalutamide for fewer than 5 doses prior to enrollment in the trial are still considered eligible and not subject to wash-out
Received systemic therapy with radionuclides (e.g., strontium-89, samarium- 153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
Chronic diarrhea > grade 1, or a diagnosis of Crohn’s or ulcerative colitis
Phase II only: Patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD) or BRCA1 or BRCA2 or PALB2 mutation, or HRD (non-BRCA, non-PALB) who have not received any systemic therapy in the metastatic setting\r\n* NOTE: In pancreatic cancer: exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
Metastatic colorectal, pancreatic, gastroesophageal or biliary tract adenocarcinoma not amenable to curative resection
Be appropriate candidates for resection and curative intent therapy in general
Ability to swallow epacadostat tablets. In case Incyte at a later time point provides support to administer epacadostat tablets parenterally (via gastrostomy [G]-tube), such administration would also be acceptable as an alternative (once official documentation has been obtained from Incyte)
Known human papillomavirus (HPV) status for oropharyngeal primary tumors
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Unresolved partial or complete small or large bowel obstruction.
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LVEF < LLN on screening exam
Creatinine =< 1.5 x IULN
Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not required)
Ki-67 >= 50%.
FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Reasonable expectation that the patient can wait 3-6 months for generation of data for subsequent treatment selection.
FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH STANDARD OF CARE (PART 2): The patient PDXs must have generated informative mouse xenograft data during Part 1 to participate in Part 2.
Philadelphia chromosome-positive (Ph+) ALL
Subject has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification. NOTE: subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study
Patient has an AR-positive and PTEN-positive tumor as determined by using Clinical Laboratory Improvement Amendments (CLIA) compliant assays to identify AR-positive and PTEN-positive disease (AR positivity is defined as >= 1% of nuclear staining, PTEN positivity is defined as > 0% of nuclear staining).
Expression of AR-V7 is not required as expression of AR-V7 can occur during enzalutamide and contribute to resistance to enzalutamide
Known diagnosis of bipolar depression or psychosis
Hepatic impairment as judged by clinical investigator or bilirubin > 2
Hispanic or Spanish speaking women
Conditions that preclude SGB or sham intervention (e.g., anatomic abnormalities of the anterior neck or cervical spine; goiter, cardiac/pulmonary compromise; acute illness/infection; coagulopathy or bleeding disorder; allergic reactions/contraindications to a local anesthetic or contrast dye); pregnancy
Individuals who are not yet adults (infants, children, teenagers)
Prisoners
Anti-CD20 mAb-naive or anti CD20 mAb-sensitive (defined as progression of FL >= 6 months following prior anti-CD20 mAb containing therapy).
Patients must not have any systemic illness which precludes them from being an operative candidate as determined by anesthesia preoperative evaluation. This includes but is not limited to, sepsis, liver failure, renal failure, cardiovascular failure, pulmonary failure
Patients must have fully intact mental status and normal neurologic abilities. Intact mental status is defined by ‘the capacity to identify and recall one's identity and place in time and space. Assessment of mental status and documentation of fully intact mental status by pediatric criteria, will be completed using physical and mental exam by the referring doctor or oncologist
Confirmed wild-type status in KRAS exons 2, 3, and 4; NRAS exons 2, 3, and 4; and BRAF, by standard of care testing of tumor specimen; tissue used for testing may have been collected prior to treatment with cetuximab
Clinical stages IIA –IIIC (American Joint Committee on Cancer [AJCC] 2009)
No other therapy with demonstrated clinical benefit in relapsed/refractory B-cell NHL available to the patient
No evidence of ischemic heart disease based on 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines
Been treated with appropriate maximal medical therapy for heart failure
Significant valvular disease; (aortic stenosis [AS] with aortic valve area [AVA] < 1.5 and severe aortic regurgitation [AR] and mitral regurgitation [MR])
Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram
Inotropic dependence
Unstable or life-threatening arrhythmia
Mechanical or bioprosthetic heart valve
Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days
Subject must be willing to undergo protocol directed biopsies and blood draw for immune profiling
Absence of a biopsiable lesion as determined by radiologist
Subjects with existing periorbital edema
Subjects with creatine kinase > ULN
Tolerate one test dose (15g) of ascorbate
G6PD (glucose-6-phosphate dehydrogenase) deficiency
Patients requiring daily finger-stick blood glucose measurements unless approved by the IND medical monitor, IND sponsor, and the study PI
Participants must have an image guided biopsy performed to yield fresh tissue for the in vitro organoid bio-assay and two biomarker testing (western blot and immunohistochemistry)
Participant is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is an investigational site or sponsor-investigator staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is granted allowing exception to this criterion for a specific subject
All types of urinary diversions
Bulky lymphadenopathy (> 2 cm)
Ineligible for curative loco regional treatment and have progressed on or did not tolerate approved treatments of Erivedge (vismodegib, also known as GDC 0449) and Odomzo (sonidegib, also known as erismodegib or LDE225) and have progressed on did not tolerate or are unwilling to try other investigational agents
Receiving potassium wasting diuretics or amphotericin must be noted to have theoretically increased arrhythmia risks with arsenic trioxide (potassium wasting diuretics or amphotericin are not excluded)
Histological evidence of primary stage III or IV or recurrent endometrial carcinoma who have had definitive surgery for endometrial cancer (at least hysterectomy and bilateral salpingo-oophorectomy); pathologic documentation of the recurrence (i.e., biopsy) is required if there is only a single site of disease on imaging and that site is less than 2 cm; if a subject with recurrence is undergoing a biopsy for clinical indications and is willing and able, an optional collection of 3 frozen tissue cores of the recurrence site is requested for correlative analysis
Subjects with recurrence must have a documented complete response upon completion of initial definitive therapy
Subjects with carcinosarcoma
The regimen under study must constitute a reasonable therapeutic option
Per good clinical practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with DA-EPOCH-A +/- imatinib (imatinib mesylate) +/- rituximab, should be resolved to grade 1 or less
For patients with Philadelphia chromosome positive (Ph+) ALL, they must not have progressed within 3 months of receiving imatinib or have a documented ABL kinase mutation known to confer resistance to imatinib (e.g., T315I)
Patient agrees to undergo a baseline and a follow-up 11C-alpha-methyl-L-tryptophan (AMT)-PET scan during immunotherapy (IMT)
Granulocytes >= 1,000/mm^3
Blood urea nitrogen (BUN) =< 1.5 times normal
No other investigational agents, immunomodulating agents, or cancer chemotherapy are permitted for the duration and 12 months following the study IMT unless there is disease progression; radiotherapy is not permitted; appropriate antibiotics, blood products, antiemetics, fluids, electrolytes and general supportive care are to be used as necessary
Renal insufficiency requiring dialysis
Willing to undergo pharmacogenetic testing
Carcinoma must be HPV-associated, which is defined as positive for p16 protein by immunohistochemistry (IHC); p16 positivity is defined as >= 70% of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p16 by immunohistochemistry in a Clinical Laboratory Improvement Amendments (CLIA) certified pathology lab. p16 testing is standard at participating institutions and may be conducted locally
Southwest Oncology Group (SWOG) performance status 0-1
Renal failure requiring hemo-or peritoneal dialysis
Sodium 136-146 mEq/L
Potassium 3.5-5.0 mEq/L
Bicarbonate 21-31 mEq/L
Chloride 98-107 mmol/L
Blood urea nitrogen (BUN) 8-26 mg/dL
No single lesion can be larger than 3 cm in maximal diameter; there may not be midline shift exceeding 5 mm or hydrocephalus
AML, any French- American- British (FAB) subtype except M3, with confirmed mutation in the NPM1 gene
Minor surgical procedures must be completed >= 7 days prior to randomization with documentation of adequate recovery from associated complications to grade =< 1; these include (but are not limited to) laparoscopy, thoracoscopy, bronchoscopy, mediastinoscopy, endoscopic ultrasonography, skin biopsy, percutaneous needle biopsy, and routine dental procedures; as a precautionary measure, it is recommended, but not strictly required, that placement of a central venous access device, thoracentesis, or paracentesis be done 7 days before the initiation of protocol directed chemotherapy with documentation of adequate recovery from associated complications to grade =< 1
Ability to complete questionnaire(s) independently or with assistance
Ability to comprehend and respond to questions using a telephone keypad
Prior exposure to eribulin mesylate
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621C based on the presence of an actionable mutation
AR expression detected by immunohistochemistry by central review
Blood Urea Nitrogen (BUN) < 30 mg/dL
Subjects must have at least one positive DTH skin response (more than 5 mm) to test item challenge prior to randomization.
Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
Subjects require or are likely to require more than a 2-week course of corticosteroids for intercurrent illness. Subjects must have completed the course of corticosteroids at the time of apheresis to meet eligibility.
Fanconi anemia (FA)
Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
Documented RAS-mutated tumor without activating PIK3CA mutations or PTEN mutation (loss of PTEN or silencing)
Neuromuscular disorders associated with elevated creatine kinase (CK, e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, or spinal muscular atrophy)
Prior intolerance to a fluoropyrimidine
Unable to obtain confirmation of payment coverage (insurance or other) for either possible treatment
Have an isocitrate dehydrogenase 1 (IDH1) mutation
Be willing to complete Quality of Life assessments during the study
Are candidates for and willing to receive intensive IC for their AML.
Have a condition that limits the ingestion or absorption of drugs administered by mouth
If WBC ?20,000/?L, cytoreduction with hydroxyurea is permitted prior to enrollment.
Cardiopulmonary function criteria:
Inclusion Criteria:\n\n        Cohort A only\n\n        • Receiving ruxolitinib dose of less than 20 mg daily with no dose increase or no dose\n        modification in the last 8 weeks before screening visit.\n\n        Cohort B only\n\n        • Must have had initial reduction in spleen on ruxolitinib treatment:\n\n          -  Followed by documented evidence of progression in spleen length or volume OR\n\n          -  Discontinued ruxolitinib for hematologic toxicities, after the initial reduction in\n             spleen length or volume.\n\n        All subjects\n\n          -  Confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or\n             post-essential thrombocythemia myelofibrosis according to revised World Health\n             Organization 2016 criteria.\n\n          -  Must have palpable spleen of ? 5 cm below the left subcostal margin on physical\n             examination at the screening visit.\n\n          -  Eastern Cooperative Oncology Group performance status of 0, 1, or 2.\n\n          -  Screening bone marrow biopsy specimen available or willingness to undergo a bone\n             marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week\n             24.\n\n          -  Life expectancy of at least 24 weeks.\n\n          -  Willingness to avoid pregnancy or fathering children\n\n        Exclusion Criteria:\n\n          -  Lack of recovery from all toxicities from previous therapy (except ruxolitinib) to\n             Grade 1 or better.\n\n          -  Previous treatment with itacitinib or JAK1 inhibitors (JAK1/JAK2 inhibitor ruxolitinib\n             is permitted).\n\n          -  Inability to swallow food or any condition of the upper gastrointestinal tract that\n             precludes administration of oral medications.\n\n          -  Recent history of inadequate bone marrow reserve as demonstrated by protocol-defined\n             criteria.\n\n          -  Inadequate liver function at screening and baseline visits as demonstrated by\n             protocol-defined criteria.\n\n          -  Inadequate renal function at screening and baseline visits as demonstrated by\n             protocol-defined criteria.\n\n          -  Active bacterial, fungal, parasitic, or viral infection that requires therapy.\n\n          -  Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of\n             reactivation: HBV DNA and HCV RNA must be undetectable. Subjects cannot be positive\n             for hepatitis B surface antigen or anti-hepatitis B core antibodies. Subjects who have\n             positive anti-HBs as the only evidence of prior exposure may participate in the study\n             provided that there is both 1) no known history of HBV infection and 2) verified\n             receipt of hepatitis B vaccine.\n\n          -  Known human immunodeficiency virus infection.\n\n          -  Clinically significant or uncontrolled cardiac disease.\n\n          -  Active invasive malignancy over the previous 2 years except treated basal or squamous\n             carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix,\n             and completely resected papillary thyroid and follicular thyroid cancers. Subjects\n             with malignancies with indolent behavior such as prostate cancer treated with\n             radiation or surgery may be enrolled as long as they have a reasonable expectation to\n             have been cured with the treatment modality received.\n\n          -  Splenic irradiation within 6 months before receiving the first dose of itacitinib.\n\n          -  Use of any prohibited concomitant medications.\n\n          -  Active alcohol or drug addiction that would interfere with their ability to comply\n             with the study requirements.\n\n          -  Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5\n             half-lives (whichever is longer) before the first dose of itacitinib or anticipated\n             during the study.\n\n          -  Use of concomitant treatment of fluconazole at a dose > 200 mg (for ruxolitinib\n             subjects treated in Cohort A only).\n\n          -  Inadequate recovery from toxicity and/or complications from a major surgery before\n             starting therapy.\n\n          -  Currently breastfeeding or pregnant.
Part 2 patients must have tumor MGMT methylation status of unmethylated; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction [MSPCR] or quantitative polymerase chain reaction [PCR]) are acceptable
Biopsy-proven KS involving skin (with or without visceral involvement) without need for urgent cytotoxic therapy; there should be no evidence of improvement in KS in the 4 weeks immediately prior to study enrollment
HIV seropositive participants must be on antiretroviral therapy (ART) with the following criteria:\r\n* A complete ART regimen that does not include the study drug as one of a minimum of 3 active drugs, which may include an integrase inhibitor or efavirenz in combination with nucleoside reverse-transcriptase inhibitors (NRTIs)\r\n* The ART regimen must not include protease inhibitor (PIs); participants must not have received a PI-based regimen for at least 4 weeks prior to enrollment\r\n* Participants must either have an undetectable HIV plasma ribonucleic acid (RNA), or if plasma RNA detectable, must be on the same stable regimen for a minimum of 12 weeks prior to study enrollment\r\n* No minimum cluster of differentiation (CD)4 count, but maximum HIV plasma RNA of 1,000 copies/mL
Chronic diarrhea as defined by loose or watery stools occurring more than 3 times daily at baseline lasting more than 4 weeks or not abating on condition-appropriate therapy prior to study enrollment
Meets criteria for 1 of the 4 defined study cohorts
In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
Patient is postmenopausal woman defined as either:
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range. Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
Patient is premenopausal defined as either:
If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
Patient must have:
Group 1 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET rearrangement that was previously treated with a tyrosine kinase inhibitor (TKI) that inhibits RET, such as cabozantinib, vandetanib, ponatinib, sorafenib and alectinib.
Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work
Participants with mature B-cell (Burkitt’s) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); (FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for patients with surface immunoglobulin expression or L3 morphology)
Participants who have ever previously received any anti-neoplastic agent, including methotrexate, 6-mercaptopurine, 6-thioguanine, vincristine cyclophosphamide, cytarabine (except for IT cytarabine), or any anthracycline, for any reason (e.g., rheumatologic or autoimmune condition) are not eligible
One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen
Structurally unstable bone lesions suggesting impending fracture
Signs of leukostasis requiring urgent therapy
Acceptable hematological status
Prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload.
Known positive serology for hepatitis B (unless due to vaccination or passive immunization due to immunoglobulin therapy)
Participants must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary
To be eligible for the study all participants (Cohort 1 and 2) are required to provide genomic profiling data from assays performed in a Clinical Laboratory Improvement Act (CLIA)-certified lab that demonstrate the following with respect to relevant biomarkers required for enrollment to the study as listed below; results from genomic profiling must be sent to the DFCI Coordinating Center prior to enrollment of the participant for central pathology review\r\n* Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence or more than single copy loss for any of the genes defined as array comparative genomic hybridization [CGH] log2 ratio of < 0.3 by array CGH; or from sequencing data with sufficient coverage for evaluation) AND\r\n* Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations by sequencing)
Prior evidence of 1p/19q co-deletion
IDH1/2 mutation in any prior biopsy
Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL184, sunitinib etc)
Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is suitable for intralesional injection, with or without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because the area cannot be properly contained with an occlusive dressing
Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for human herpesvirus 1 (HSV-1) induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
Exposure to household contact with known immunodeficiency
Diagnosis of scleroderma
Diagnosis of active lupus
Diagnosis of active dermatomyositis
Poorly-differentiated GEP-NEC based on local pathology report
Well-differentiated grade 3 neuroendocrine tumors; poorly-differentiated neuroendocrine carcinoma of any origin (other than GEP-NEC); including NEC of unknown origin, adenocarcinoid, and goblet cell carcinoid
Cryoablation, radiofrequency ablation, or trans-arterial embolization of hepatic metastases
Non-adenocarcinoma histology
Adenocarcinoma originating in the ampulla or appendix; (duodenal tumors that involve the ampulla but originate in the duodenum are eligible)
The subject must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central speciality laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
The subject must have a current CMV infection refractory or resistant to treatment. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after 2 or more weeks of continuous treatment with intravenous (IV) ganciclovir, oral valganciclovir, IV foscarnet, or IV cidofovir. This definition applies to the current CMV infection and the most recently administered anti-CMV agent. Resistant is defined as documented failure to achieve > 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after 2 or more weeks of continuous treatment with IV ganciclovir, oral valganciclovir, IV foscarnet, or IV cidofovir. This definition applies to the current CMV infection and the most recently administered anti-CMV agent. AND Documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir, valganciclovir, foscarnet, or cidofovir.
The Investigator must be willing to treat the subject with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.
Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).
Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
Intolerance of dexamethasone
Subjects must have either:
Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization.
Pre-study evaluation must include an ophthalmologic exam by an ophthalmologist (not optometrist) and should minimally include visual acuity testing, slit lamp examination, and funduscopic examination; follow up eye-exams will only be performed if subjects develop/report any visual impairment; visual impairment may include peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; follow up eye-exams will minimally include visual acuity testing, slit lamp examination, and funduscopic examination; additional testing will be based on symptoms, what is observed and ophthalmologist recommendations
Able to tolerate daily supplementation of calcium and vitamin D
Prior administration of denosumab
Planned invasive dental procedures during the course of study
Multiple (? 2) separate enhancing tumors
Uncontrolled blood-sugar levels defined as HbA1c > 7%
Patient must be available for follow-up
Any electrocardiograph (ECG) changes that interfere with QT interval interpretation (e.g., left bundle branch block, frequent premature ventricular contractions)
The trial is open to both genders
Hypersensitivity to thalidomide, lenalidomide, pomalidomide, bortezomib, or dexamethasone (such as Stevens-Johnson syndrome); rash to immunomodulatory drug that can be medically managed is allowable
Ongoing toxic manifestations of previous treatments.
HER2+ as 3+ by IHC or in-situ hybridation (ISH) amplified.
Must have two biopsy accessible lesions:
* one lesion must be ?10 mm and <100 mm in longest diameter, accessible for repeated intratumoral (IT) injection and accessible for baseline and on-treatment biopsies.
a second (distal) lesion must be accessible for baseline and on-treatment biopsy and must be distinct from the injected lesion.
tumors encasing major vascular structures (i.e., carotid artery or tumors close to other vital organs), are not considered appropriate
OATP1B1/3 substrates
LVEF below institutional LLN or below 50%, whichever is lower
Tumors in which the invasive component is present only as micro-invasion
Significant comorbidity associated with an estimation of < 5 remaining life years
Current addictive or psychiatric disorder which may preclude protocol adherence
Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy)
Pre-registration: Diagnostic bone marrow and peripheral blood specimens must be submitted for eligibility testing by multiparameter flow cytometry; testing will be performed by the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Leukemia Translational Studies Laboratory and reported to the institution
Any significant medical complications related to consolidation cycle 2 must have resolved
Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
Subjects must be willing to undergo myeloma genotyping for TP53 mutation, insertion, or deletion at screening
Subjects with a malignancy that contains a non-synonymous mutation, insertion, or deletion in the TP53 gene determined prior to screening; TP53 mutation status at screening is NOT required prior to AMG-232 dosing; however, subjects found to have TP53 mutation and/or deletion from screening bone marrow biopsy as assessed by central deoxyribonucleic acid (DNA) sequencing conducted at Dr. Jeffrey Sklar’s laboratory at Yale University Cancer Center, will be removed from study after C1 and continue on standard-of-care KRd alone
Subjects with known central nervous system involvement of myeloma should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Known homozygous DPD (dihydro pyrimidine dehydrogenase) deficiency
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Subject has an air leak ? 100 mL/min, as measured by a digital thoracic drainage system (DTDS)
Subject has air leak only on forced exhalation or cough
Subject has sepsis
Subject has pneumonia
Subject is not an appropriate candidate for, or unable to tolerate, flexible bronchoscopy procedures
Subject has a primary pneumothorax
Serum lactate dehydrogenase (LDH) =< 10 X ULN
Subjects with radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal cord block
Subjects who have contraindications to carboplatin, melphalan, or STS
If both of the following conditions are present, the patient is ineligible:\r\n* < 10 pack-year smoking history\r\n* p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-2b (AJCC 7th Edition)\r\n** Note: in the event that a registered patient has a p16-positive result on central review with the tumor and nodal stage T0-3, N0-2b (AJCC 7th Edition), then the site will be notified that the patient is ineligible
Respiratory illness requiring hospitalization at the time of step 1 registration\r\n* Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
Clinically apparent jaundice and/or known coagulation defects
Patients must have tumor MGMT methylation status of unmethylated as determined by local pathologist using a Clinical Laboratory Improvement Act (CLIA)-approved diagnostic test; results of routinely-used methods for MGMT methylation testing (e.g. methylation-specific [MS]- polymerase chain reaction [PCR] or quantitative PCR) are acceptable
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
The subject is a prisoner
The subject requires or is likely to require more than a 2-week course of corticosteroids of > 4 mg
Lack of ability of a patient for immunological and clinical follow-up assessment
Has known sensitivity to retinoic acid derivatives
Uncontrolled symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dl or corrected serum calcium > ULN)
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however they must still undergo pregnancy testing\r\n* Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy; investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly
Carcinomatous meningitis
Prisoners or individuals who are involuntarily incarcerated
Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
Patients who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec (T-VEC) treatment and through 30 days after the last dose of talimogene laherparepvec (T-VEC)
Recurrent, unresectable, or metastatic RCC or STS (any histologic type) for which pazopanib is an appropriate therapy
Known or suspected malabsorption condition or obstruction
The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chlorine (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator’s discretion
Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
Subject has clinical evidence of Disseminated Intravascular Coagulation (DIC)
AGS67E
L-Histidine
?-trehalose dihydrate or
polysorbate 20
Diagnosis of MDS (participants with therapy-related MDS are eligible)
Failure to achieve complete or partial response or hematological improvement after at least six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine OR
Relapse after initial complete or partial response or hematological improvement after six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine administered within the past 2 years For participants in Cohorts C1 and C2:
Phase II: inoperable PN causing morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions in patients with NF1; histologic confirmation of PN tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF1 confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or have at least one other diagnostic criterion for NF1 listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more café-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
oral, intra-vaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition for ovulation
vasectomised partner
Patient has or is willing to have a central venous catheter (e.g. PICC, Port-A-Cath®, Hickman® catheter) for drug administration.
Known intolerance to steroids or H1/H2-antagonists.
Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV \r\n* Note: a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory\r\n* For T-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LLy defined by the submitting institution will be accepted
Lactating females who plan to breastfeed
It is deemed ethical to provide an experimental drug (e.g., Mylotarg) that is associated with hepatotoxicity (veno-occlusive disease [VOD]) and myelosuppression
Patient may have more than one site of recurrence/metastatic disease but only one lesion will be injected that is >= 1 cm in size (if in the lung, the lesion must be >= 2 cm and adjacent to the pleura in the lung)
Requiring blood product support
Patients who require anti-arrhythmic treatment with Amiodarone or any drug with a quinidine-like effect on the heart or who have history of a malignant ventricular arrhythmia unless they have a functioning Automatic Implantable Cardio Defibrillator (AICD) implanted
The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator’s discretion
Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
ARM A: Willingness to provide all biological specimens as required by the protocol
ARM A: Child Pugh Score A (patients with ascites must have paracentesis performed within scope of standard of care, to be able to successfully perform intratumoral injection procedure)
ARM B: Willingness to provide all biological specimens as required by the protocol
Lactating females are not eligible unless they have agreed not to breastfeed their infants
PRE-REGISTRATION:
Willingness to provide the biologic specimens
Dose Escalation cohort only: Willingness to participate in the SPECT/CT imaging as required by the protocol
Presence of a pleural effusion with the ability to safely place an intrapleural catheter or have pre-existing intrapleural catheter
Anti-measles immunity as demonstrated by serum immunoglobulin (Ig)G anti-measles antibody levels of >= 1.1 EU/ml as determined by BioPlex Measles IgG multiplex flow immunoassay
PRE-REGISTRATION
Requiring ongoing blood product support at time of pre-registration
Prior myeloablative allotransplant
Willingness to provide the biologic specimens is required by the protocol; this is part of the mandatory correlative research component; these specimens include:\r\n- PHASE I: peripheral blood for plasma pharmacokinetic analysis and peripheral blood mononuclear cell (PBMC) polymer assessment from 0-24 h after drug administration on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; urine for assessment of ABT-888 renal clearance for 24 h after administration of drugs on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; and a pretreatment peripheral blood sample for possible sequencing of the BRCA1, BRCA2 loci as well as possible pharmacogenomic analysis
Available core biopsies from the time of diagnosis; these may include sections paraffin-embedded material
Proteinuria < 1+ on dipstick testing (if 2+ seen on first test, retest >= 24 hours later)
Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by needle core biopsy; fine-needle aspiration is not sufficient; incisional/excisional biopsy is not allowed; in case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint
DOSE ESCALATION COHORT: Subjects who have received sirolimus, everolimus, temsirolimus, or any other agent for current malignancy that theoretically targets PI3K, AKT and / or mTOR
DOSE ESCALATION COHORT: Subjects with clinical condition where subjects may not tolerate immune mediated hepatotoxicity; this includes extensive liver metastasis, excessive intake of alcohol (male > 4 drinks/day, female > 2 drinks/day), and the use of acetaminophen > 2 gms/day; per epacadostat investigator’s brochure
DOSE ESCALATION COHORT: Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
DOSE EXPANSION COHORT: ALT(SPGT) ? 2.5 X ULN
DOSE EXPANSION COHORT: ALP ? 2.5 X ULN
DOSE EXPANSION COHORT: Subjects who have received sirolimus, everolimus, temsirolimus, or any other agent for current malignancy that theoretically targets PI3K, AKT and / or mTOR
DOSE EXPANSION COHORT: Subjects with clinical condition where subjects may not tolerate immune mediated hepatotoxicity; this includes extensive liver metastasis, excessive intake of alcohol (male > 4 drinks/day, female > 2 drinks/day), and the use of acetaminophen > 2 gms/day; per epacadostat investigator’s brochure
DOSE EXPANSION COHORT: History or presence of an abnormal ECG which, in the investigator's opinion, is clinically meaningful; screening QTcF interval > 480ms is excluded; subjects with left bundle branch block are excluded
DOSE EXPANSION COHORT: Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
Previous enrollment in the present study
Diagnosis of immunodeficiency
Oropharyngeal primaries have to be human papillomavirus (HPV) p16 negative, unless by American Joint Committee on Cancer (AJCC) 7th edition staging they are cT4a, cT4b, cN2 and/or cN3 tumors
Patients with known contraindications to radiotherapy, including inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome)
Serum free light chain (FLC) assay: involved FLC assay ? 10 mg/dL (? 100 mg/L) and an abnormal serum FLC ratio (< 0.26 or > 1.65)
Has received high-dose melphalan and autologous stem cell transplant (HDM-ASCT) within 12 weeks before the first infusion or are planning for HDM-ASCT
Major abnormalities identified by electrocardiogram (ECG) or echocardiogram (ECHO), at the investigator’s discretion
Presence of aneurisms of the ascending aorta or aortic stress
Histologically confirmed breast cancer that overexpresses HER2 (defined by American Society of Clinical Oncology [ASCO]- College of American Pathologists [CAP] 2013 guidelines performed using Food and Drug Administration [FDA]-approved tests by laboratories with demonstrated proficiency) that is metastatic or unresectable
Comorbidity or incurrent illness
History of neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Subjects with FAB M3 (t(15;17)(q22;q21)[PML-RARalpha]) are not eligible
Subjects must not be receiving growth factors, except for erythropoietin
Subjects with bacteremia must have documented negative blood cultures prior to study entry
As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with nivolumab-containing regimen.
Patients must have received at least 6 months fluorouracil (5-FU)- or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil, leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others)
Patients with known ophthalmologic conditions, such as:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or upper limit of normal [ULN] adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal plexiform neurofibroma (PN) (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); (this will not apply to subjects with confirmed Gilbert’s syndrome [persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology], who will be allowed only in consultation with their physician)
Have received at least 1 treatment of either fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX) or gemcitabine/abraxane based regimens in the neoadjuvant setting; modifications of FOLFIRINOX including leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX), leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI), fluorouracil (5FU) and capecitabine and modifications of gemcitabine/abraxane including single agents gemcitabine or abraxane are allowed
DMG biopsy/resection is planned for the clinical care of the patient independent of study participation by the treating pediatric neurosurgeon and neuro-oncologist
Complete or partial intestinal obstruction at the time of study enrollment
Germline ABCB4 (CC) and ABCB11 (GG or GC) genotypes determined by pharmacogenomics analysis of peripheral blood mononuclear cells
Disease amenable to biopsy via percutaneous approach or other minimally invasive procedures such as thoracoscopy, bronchoscopy, laparoscopy, or gastrointestinal (GI) endoscopy
All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions
Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study
Concomitant radiotherapy
Cohort 2 (MTD) only: patient is thought to be a short- or long-term candidate for gemcitabine in the opinion of the treating oncologist
Cohort 2 (MTD) only: patient willing to undergo muscle biopsies at baseline and after 28 to 35 days of disulfiram/gemcitabine or gemcitabine/placebo therapy as required by the protocol
Patient willing to complete a medication diary
Receiving phenytoin
Participants must be able and willing to follow protocol instructions and schedules
Any signs, symptoms, and/or radiographic evidence of a complete or partial bowel obstruction
STAGES 1 AND 2
Renal insufficiency requiring hemodialysis or peritoneal dialysis
Intrathecal cytotoxic therapy:\r\n* No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone\r\n* At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
Children are excluded from this study, but will be eligible for future pediatric trials
Prior exposure to gemcitabine
Blood urea nitrogen (BUN) < 25 mg/dL
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
Cytomegalovirus colitis or enteritis as defined by cytomegalovirus (CMV) shell vial or culture positivity from endoscopic biopsy the discretion of the treating physician based upon PCR positivity, clinical presentation and histology
Respiratory insufficiency with oxygen requirement > 4 L nasal cannula
Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib; bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
Dependency on IV hydration or total parenteral nutrition (TPN)
Blood urea nitrogen (BUN) =< 40 mg/dl
Tolerate a 15 g ascorbate infusion (screening dose)
Active hemoptysis within 1 week of screening (more than 1/2 teaspoon per day)
Actively receiving insulin at time of ascorbate infusion (unless an exception is granted by the Investigational New Drug [IND] sponsor, medical monitor, and the principal investigator [PI])
G6PD (glucose-6-phosphate dehydrogenase) deficiency
Subjects must be on a prophylactic regimen for pneumocystis carinii pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood
Receipt of a vaccine for HIV-1 or any prior gene modified cell product, at any time
Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
Ulcerated skin lesions
MGMT promoter methylation testing will be performed by an institutional Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory using a methylation specific polymerase chain reaction (PCR) assay to detect deoxyribonucleic acid (DNA) methylation within the promoter region of the MGMT gene\r\n* Participants with an MGMT promoter that is unmethylated will be enrolled to cohort 1a, while those with tumor MGMT promoter that is methylated, partially methylated, indeterminate or unknown will be enrolled to cohort 1b
ADDITIONAL CRITERIA FOR COHORTS 1A AND 1B PARTICIPANTS ONLY: Cohort 1a: MGMT promoter unmethylated
ADDITIONAL CRITERIA FOR COHORTS 1A AND 1B PARTICIPANTS ONLY: Cohort 1b: MGMT promoter methylated, partially methylated, indeterminate or unknown
No new or worsened existing acute medical condition that would require a dose hold or delay
No dexamethasone (or other corticosteroid bioequivalent) within one week of vaccination initiation
Stereotactic biopsy (without further resection)
Radiographic or cytologic evidence of diffuse leptomeningeal extension - tumors with limited subependymal involvement are eligible
Participants who have received or plan to receive any additional treatment for glioblastoma aside from surgical resection and conventional radiotherapy (cohort 1), pembrolizumab (cohorts 1a and 1b) and temozolomide (cohort 1b) including but not limited to temozolomide (cohort 1 & 1a participants), stereotactic radiosurgery, placement of Gliadel (carmustine; BCNU) wafers, any other intratumoral or intracavitary treatment, brachytherapy, novo-tumor treating fields (Optune), or investigational therapeutic agents
COHORT 1A & 1B PARTICIPANTS ONLY:
Patients must have BRAFV600E or BRAFV600K mutations, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Amendments (CLIA)-certified lab; if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Inability to travel to the National Institutes of Health (NIH) Clinical Center
Auto-immune hemolytic anemia
Ability to undergo up to 90 minutes of PEM imaging
Willing to adhere to the prohibitions and restrictions specified in the protocol
Peripheral bilateral edema requiring active medical management
Hyponatremia (serum sodium value less than 130 mEq/L)
Gynecologic Oncology Group (GOG) performance status >= 2
Platelets >= 80,000 x 10^9/L, unsupported by transfusions
Able to tolerate intraperitoneal (IP) port placement and IP treatment administration in the opinion of the enrolling investigator
Use of any uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid from screening through follow-up period
Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia
Massive (i.e., >6 cm below the left costal margin), progressive or symptomatic splenomegaly
Massive nodes or clusters (i.e., >10 cm in longest diameter) or progressive lymphadenopathy
Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
A treatment regimen containing cytotoxic agents (eg, fludarabine, pentostatin, cladribine, cyclophosphamide, chlorambucil, bendamustine) AND
Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ? 500 mU/mL and off ESA for at least 8 weeks before Screening.
Willing to adhere to the prohibitions and restrictions specified in the protocol.
Hypoplastic MDS (cellularity < 10%).
Hyponatremia (defined as serum sodium value of < 130 mEq/L).
Evidence of leptomeningeal dissemination
Patient is unable to tolerate placement of a stereotactic head frame
Mucosal melanoma and uveal melanoma are not allowed
Serum calcium or magnesium outside the institutional range of normal
Serum potassium < 4.0 mmol/L or above 5.0 mmol/L
Previous exposure to vandetanib
Previous enrollment or randomization in this study
Up to 2 prior relapses allowed
1 week for non-cytotoxic agents, such as interferon, tamoxifen, & cis-retinoic acid
Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
Positive antinuclear antibody (ANA) lab result
Mini Mental Status Exam (MMSE) >= 18 prior to study entry
Recursive partitioning analysis (RPA) class I-II/Karnofsky performance status >= 70%
Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
Myelodysplastic syndromes
Myeloproliferative syndromes
Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
Clinical stages T1c-T3c (American Joint Committee on Cancer [AJCC] sixth edition)
Must have a baseline American Urological Association (AUA)/International Prostate Symptom Score (IPSS) score of < 20
Note: patients with mature B-cell (Burkitt's) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
For lymphoblastic lymphoma: diagnosis may be made by i) biopsy of involved site (e.g., node, mediastinal mass), or ii) by cytology from pleural fluid or other fluid collection or iii) by marrow aspirate/biopsy demonstrating < 30% involvement by lymphoblasts (confirmed by flow cytometry, immunohistochemistry, cytogenetics and/or FISH studies) in a patient with evidence of lymphomatous masses by radiographic studies; note: marrow aspirate and/or biopsy must be performed in patients with lymphoblastic lymphoma prior to study entry to confirm that patient does not meet definition of ALL; in rare circumstances, lymphoblastic lymphoma patients may be registered prior to marrow aspirate/biopsy if it is felt that the procedure cannot be safely performed; permission in advance by principal investigator or designee is required
A diagnosis of CD established by referring physician(s) and confirmed by our review of the clinical presentation, clinical course, endoscopic and imaging findings, and histology of mucosal tissue specimens
Endoscopic and histologic evidence of active intestinal inflammation consistent with CD; in the event that the involved mucosa cannot be readily reached by endoscopic biopsy, an imaging test that shows typical changes of CD in the intestinal tract will suffice as evidence of active intestinal inflammation; the presence of intestinal stomas does not exclude the patient from study
A current complication of CD that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: \r\n * Abscess, phlegmon, necrotizing skin lesion, or inflammatory fistula\r\n * Intestinal fibrotic stricture and intestinal obstruction\r\n * Uncontrolled mucosal, organ, or systemic infection with a bacterial, viral, fungal, or parasitic organism\r\n * Sclerosing cholangitis
pStat3+ upon central testing of archival tumor specimen\r\n* Cohort A: pStat3 score of >= 5 by central testing\r\n* Cohort B: pStat3 score of 3-4 by central testing (Note, Cohort B will only open if there are at least 2 objective responses observed in the first stage of Cohort A)
Willing not to smoke
Willing to complete a pill diary each day
Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren’s syndrome), congenital abnormality (e.g., Fuchs' dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
Screening urinalysis < 5 white blood cell/high power field (WBC/hpf) (unless alternate urinary diagnosis not consistent with infection)
Participants with known or suspected allergies to any component of the vaccine
Participants may not have been vaccinated previously with any of the synthetic peptides included in this protocol
The subject is able to lie flat for up to 45 minutes for imaging studies
Kidney: 500 cGy
Lungs: 500 cGy
An estimated progression-free survival of less than one year
DONOR: Determination of histocompatibility will be made by deoxyribonucleic acid (DNA) oligotyping (low resolution for class I antigens and high resolution for class II antigens)
Each lesion must be less than or equal to 5 cm in maximal diameter and multiple lesions must be less than or equal to 18 cm for the sum of the diameters in 3 dimensions; Example: 3 lesions each 2 + 2 + 2 cm have an aggregate diameter of 18 cm which is acceptable
Within or touching the zone of proximal bronchial tree defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when taking cyclophosphamide; aprepitant should also be used with caution with etoposide or vincristine chemotherapy
Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity\r\n* Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
Candidate for gross total or subtotal resection
Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay
Willing to provide biologic specimens as required by the protocol
Requiring blood product support
Known BRCA1/2 status is not required for study entry; however patients known to have a germline deleterious BRCA1/2 mutation should be encouraged to consider a preoperative trial specifically designed for BRCA1/2 carriers, if available
Prior non-taxane or platinum containing chemotherapy will be allowed if the prior exposure was at least 5 years ago and the exposure is thought not to potentially interact with the primary outcome of the trial or put the patient at undue risk, and should be reviewed with study principle investigator (PI) on a case by case basis
Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification
Any condition that would prohibit administration of corticosteroids
Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):\r\n* Bone disease\r\n** At least one metaiodobenzylguanidine (MIBG) avid bone site or diffuse MIBG uptake\r\n*** For recurrent/progressive or refractory disease a biopsy is not required regardless of number of MIBG avid lesions\r\n*** For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at the time of enrollment (bone marrow, bone, or soft tissue) is required to be obtained at any time point prior to enrollment and two weeks subsequent to most recent prior therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score of >= 3 then no biopsy is required for eligibility\r\n** If a tumor is known to be MIBG non-avid, then a patient must have at least one fludeoxyglucose (FDG)-positron emission tomography (PET) avid bone site present at the time of enrollment with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma obtained at any time prior to enrollment and two weeks subsequent to most recent prior therapy\r\n* Any amount of neuroblastoma tumor cells in the bone marrow based on routine morphology (with or without immunocytochemistry) in at least one sample from bilateral aspirates and biopsies\r\n* At least one soft tissue lesion that meets the criteria for a TARGET lesion as defined by:\r\n** SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter >= 10 mm, or for lymph nodes >= 15 mm on short axis; lesions meeting size criteria will be considered measurable\r\n** In addition to size, a lesion needs to meet ONE of the following criteria:\r\n*** MIBG avid; for patients with persistent disease only: if a patient has only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at time of enrollment (either bone marrow, bone and/or soft tissue) is required to be obtained at any time point prior to enrollment and at least two weeks subsequent to most recent prior therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score of >= 3 then no biopsy is required for eligibility\r\n*** FDG-PET avid (only if tumor is known to be MIBG non-avid); these patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy\r\n*** Non-avid lesion (both MIBG and FDG-PET non-avid); these patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one non-avid lesion present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy
Absolute phagocyte count (APC = neutrophils and monocytes): >= 1000/mm^3
Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving clinically
No dyspnea at rest
=< grade 2 hypercalcemia (applicable only for dose levels that include cis retinoic acid [RA])
Patient declines participation in NANT 2004-05; unless the institution has been granted special exemption from mandatory enrollment on NANT 2004-05 by the NANT Operations Center
For the purpose of obtaining a RECIST v1.1 baseline scan, participants must have a\n             radiological evaluation conducted no more than 28 days prior to beginning study\n             therapy (PLD).  NOTE: For participants with a history of CNS metastasis, baseline\n             radiological imaging must include an evaluation of the head.
Participants must have adequate organ function including:\n\n               1. Bone Marrow Reserve:\n\n                    1. Absolute neutrophil count (ANC) ? 1.5x10^9/L prior to treatment.\n                       Participants on maintenance doses of granulocyte colony stimulating factor\n                       (G-CSF) are eligible.\n\n                    2. Platelets ? 100x10^9/L\n\n                    3. Hemoglobin ? 9 g/dL\n\n                    4. Use of supportive care measures (eg, use of white blood cell [WBC] growth\n                       factors, antiemetics, epoetin) should follow the ASCO guidelines as listed\n                       at www.asco.org.  Participants should receive full supportive care,\n                       including transfusion of blood as mandated by clinical need; however,\n                       transfusions administered for the sole purpose of meeting the study\n                       inclusion criteria between the time informed consent is signed and first\n                       dose of EC145/placebo/PLD is administered are not allowed.\n\n               2. Hepatic: Total bilirubin level < 1.5 x ULN and ALT, AST, GGT, and alkaline\n                  phosphatase levels < 2.5 x ULN.\n\n               3. Renal: Serum creatinine level ? 1.5 x ULN or for participants with serum\n                  creatinine levels above 1.5 x ULN, creatinine clearance ? 50 mL/min/1.73m^2\n\n               4. Cardiac: Left ventricular ejection fraction (LVEF) equal to or greater than the\n                  institutional lower limit of normal.
Prior exposure to FR-targeted therapy (eg, EC145, EC0225, EC0489, farletuzumab).
Subject meets institutional requirements for IL-2 therapy
Has primary ocular melanoma
Subjects with aphakia
Pulmonary metastasis permissible; appropriate candidates with lung lesions may be considered for ablative hypofractionation using stereotactic body radiation therapy (SBRT)
Diagnosis of immunodeficiency
No active second cancers
Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
No prior cranial radiotherapy will be permitted
Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: anti-convulsants (carbamazepine, phenobarbital, phenytoin), anti-mycobacterial (rifabutin), PDE5 inhibitors (sildenafil, vardenafil, tadalafil), HMG-CoA reductase inhibitor (atorvastatin, rosuvastatin), immunosuppressants (cyclosporine, tacrolimus, sirolimus), narcotic analgesic (methadone), oral contraceptive (ethinyl estradiol), macrolide antibiotic (azithromycin), Inhaled/nasal steroid (fluticasone), antidepressant (trazodone)
Evidence of nodal disease greater than or equal to 15 mm in short axis as these findings are concerning for metastases that would not be targeted with radium-223 alone (Arm B); however, lymph nodes with short axis measurements between 1.5-3 cm that have not enlarged more than 5mm (to account for reader variability) over the last 6 months and which are not inducing symptoms, causing obstruction, or in the opinion of the investigator pose a risk of impending obstruction of any structures, will be allowed
Soft tissue components of bone metastases >= 1.0 cm in longest axis\r\n* Soft tissue components of bone metastases < 1.0 cm that have been stable for > 6 months (must not have enlarged > 5 mm) are permitted
Has a diagnosis of immunodeficiency
Subjects with certain medical conditions
Subjects who have recently been enrolled in other experimental clinical trials of\n             investigational agents
Pretreatment electrocardiography (EKG).
Both men and women of all races and ethnic groups are eligible for this trial
Vaccinations other than those given as part of this research study (with the exception of influenza vaccine) are prohibited throughout the duration of study participation\r\n* NOTE: Influenza vaccination (inactivated) is permitted during the flu season; the preferred time is 7 to 14 days after CDX-1401 administration
Subjects of either sex, of all races and ethnic groups, and ?18 years of age
For the Diabetes Expansion Cohort - Subjects who currently require insulin,\n             thiazolidinediones, dual proliferator-activated receptors (PPAR) agonists,\n             glucagon-like peptide (GLP-1) analogues, dipeptidyl peptidase (DPP-IV) inhibitors or\n             have received the same in the 4 weeks prior to screening.
Subjects with known complications of diabetes like diabetic nephropathy or diabetic\n             retinopathy
If an ovarian cancer patient has a different histology than HGSC, but has a known germline BRCA1 or BRCA2 mutation and meets all other criteria listed, that patient is eligible
No current dependency on intravenous (IV) hydration or total parental nutrition (TPN)
No current or active dermatologic diagnoses that would preclude interpretation of skin toxicities of BKM120 and BYL719
Grade 2 or higher proteinuria and hematuria
Diagnosis of NF2
Presence of vestibular schwannomas
Evidence of progressive increase in vestibular schwannoma size or worsening hearing\n             loss due to vestibular schwannoma
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Resting bradycardia less than 55 beats/min
Presence of any serious or unstable concomitant systemic disorder incompatible with\n             the clinical study
Patients must not have had any infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within 4 weeks prior to randomization
Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
Both men and women of all races and ethnic groups are eligible for this trial
Peripheral lung nodule =< 2 cm on preoperative CT scan and presumed to be lung cancer; the center of the tumor, as seen on CT, must be located in the outer third of the lung in either the transverse, coronal or sagittal plane; patients with pure ground glass opacities or pathologically confirmed N1 or N2 disease are not eligible
Histologic confirmation of NSCLC (if not already obtained)
Confirmation of N0 status by frozen section examination; right sided tumors require that node levels 4, 7, and 10 be sampled and diagnosed as negative on frozen section; left sided tumors require that node levels 5 or 6, 7 and 10 be sampled and diagnosed as negative on frozen section; levels 4 and 7 nodes may be sampled by mediastinoscopy, endobronchial ultrasound (EBUS) and/or endoscopic ultrasound (EUS), or at the time of thoracotomy or VATS exploration; nodes previously sampled by mediastinoscopy (or EBUS and/or EUS) either immediately prior to or within 6 weeks of the definitive surgical procedure (thoracotomy or VATS) do not need to be resampled
No evidence of dyspnea at rest
Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal excretion of methotrexate is inhibited by these agents
Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
In the opinion of the investigator do not require rapid cytoreduction due to bulky disease (e.g. painful lymphadenopathy or organomegaly, or impending end-organ dysfunction
Current pancreatitis
Tumor MGMT methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. methylation-specific polymerase chain reaction [MSPCR ] or quantitative polymerase chain reaction [PCR]) are acceptable
Patient must not have known sensitivity to TRC102 or any formulation excipients
There is no limit to the number of prior chemotherapies
United Network for Organ Sharing (UNOS) stage T1, T2, or T3 disease
Candidates for liver transplantation (listed or screened) according to one of the following criteria:\r\n* Milan criteria (one lesion < 5 cm or 3 or fewer lesions each < 3 cm)\r\n* University of California San Francisco (UCSF) Downstaging criteria (one lesion less than 8 cm or 2-3 lesions each less than 5 cm with sum of maximum dimensions less than 8 cm, or 4-5 lesions each less than 3 cm with sum of maximum dimensions less than 8 cm)\r\n* UCSF All-Comers criteria (UNOS stage T3 disease beyond UCSF Downstaging criteria)
Imaging evidence of common bile duct obstruction
Previous sphincterotomy or bilio-enteric anastomosis
Significant hepatic arterial to portal vein shunting in the area to be treated
Systemic amyloid light chain amyloidosis
Total bilirubin =< 3.0 x the upper limits of normal (ULN) (biliary stenting or percutaneous biliary drainage are allowed for cancer related biliary obstruction)
Renal failure requiring hemo-or peritoneal dialysis
Tumor must be HER2-positive and retinoblastoma (RB)-proficient; RB-proficiency is determined by tumor biopsy demonstrating RB normal and cyclin-dependent kinase inhibitor 2A (p16in4a) low by immunohistochemistry; RB proficiency means that there is an intact RB pathway indicative of responsiveness to PD-0332991; RB staining is scored on an absent (no nuclear staining), weak (nuclear staining less than observed in endothelial cells and stromal cells surrounding the tumor), positive (nuclear staining at or above surrounding tissue) (0, 0.5, 1 respectively); p16ink4a is a routine clinical stain that is scored using absent, weak, positive, strong (0, 1, 2, 3 respectively); tumors will be scored using (p16)/(RB), where a score of less than 3 is required for inclusion; RB loss is expected to occur in less than 15% of cases; RB – proficiency will be done locally as standard of care and made available for central review at later time points in the study
Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the CD4 counts are < 200 cells/uL
Subjects must complete the filgrastim (G-CSF)/plerixafor mobilization of peripheral blood progenitor cells and must have collected at least 7.5 x 10^6 CD34+ cells/kg, sufficient for preparation of both, a back-up of 2.5 x 10^6 CD34+ cells and the research product
Research product must pass all release tests
Any AIDS-related opportunistic infection occurring within the past year and for which treatment has been unsuccessful would be considered exclusionary, but this is done on a case-by-case basis as determined by the principal investigator
Patients with a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide (DMSO), fetal bovine serum, or trypsin (porcine origin)
Consensus following presentation of the case at the multidisciplinary Pediatric Neuro-Oncology conference, which includes participation of neuro-oncology, neurosurgery, radiation oncology, interventional neuroradiology and neurology
Chronic myeloproliferative disorder, i.e. myelofibrosis
Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of TBI
DONOR: Able and willing to have up to 3 separate mobilized apheresis collections performed or if unable to undergo apheresis agrees to a bone marrow harvest (requires additional consent)
Any of the following:\r\n* Pregnant persons\r\n* Nursing persons\r\n* Persons of childbearing potential who are unwilling to employ adequate contraception
Tumors must have a Ki-67 index greater than 20% and/or > 20 mitotic figures/10 high-power fields
Proteinuria (>= 2 g/24 hours)
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Participants must have tumors with anticipated transurethral resection time =< 1 hour
Subjects with resected primary tumors who have documented metastases are eligible
Subjects who have a heart rate >= 100 beats per minute (bpm) or =< 45 bpm determined by the ECG recorder’s algorithm on the screening ECG
Subjects with corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy, or may interfere with diagnosis of treatment-emergent corneal epitheliopathy at the discretion of the investigator in consultation with the ophthalmologist/optometrist; low grades of superficial punctate keratitis, within the range seen in the normal population, should not lead to the exclusion of the patient
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Subject must be willing and able to take pazopanib with a low-fat meal every day as specified in the protocol
Serum HCV ribonucleic acid (RNA) levels of > 1,000 IU per milliliter or higher
HCV genotype 1, 2, 3, 4
Lymphomas of other histologies other than the ones listed in inclusion above
Patients must have an adequately functioning bladder after thorough evaluation by a urologist and have undergone as thorough a transurethral resection of the bladder tumor as is judged safely possible
Patient’s comprehensive metabolic panel (CMP) must be done no more than 6 weeks prior to informed consent and the CMP levels must be within acceptable institutional limits or to the discretion of the treating physician, which may be the principal investigator of the study
Documentation of HTLV infection (enzyme linked immunosorbent assay [ELISA]) in individual with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction [PCR]) or a consistent clinical picture (including two of the following: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean or South American birthplace)
Current or prior HTLV-1 associated inflammatory diseases, including but not limited to myelopathy, uveitis, arthropathy, pneumonitis, or a Sjogren’s disease-like disorder
Hemoglobin A1c (HbA1c) =< 8%
Patient has a score >= 12 on the Patient Health Questionnaire (PHQ)-9 questionnaire
Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
Patient has a Generalized Anxiety Disorder (GAD)-7 mood scale score >= 15
For escalation cohorts, if no measurable disease is present, then at least one predominantly lytic bone lesion must be present
Previous radiotherapy to the lesion(s) of interest
Patients with a history of cardiac disease are excluded; baseline electrocardiography and assessment of serum troponin (I) are included the screening exams; subjects in whom these assays are abnormal (electrocardiogram [EKG] excluding 1st degree bundle branch block, sinus bradycardia, sinus tachycardia or non-specific T wave changes, serum troponin >= grade 2)
Potassium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
Magnesium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
Sodium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
Phosphorus above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
Breastfeeding mothers must agree to discontinue nursing if the mother is treated with selinexor
Proteinuria =< +1 on dipstick or =< 1 gram/24 hours
Presence of distance metastases (M1)
Clinically significant sensorineural hearing impairment which may be worsened via cisplatin exposure (audiometric abnormalities without corresponding clinical deafness are not grounds for exclusion)
Subject has previously been treated with nab-paclitaxel\t\r\n* NOTE: Subjects who have had previous treatment with nab-paclitaxel will NOT be excluded if given in the adjuvant or neoadjuvant setting\r\n* Only in the metastatic setting, will subjects previously treated with nab-paclitaxel be excluded from this trial; exceptions may be made for subjects who discontinued treatment with a previous nab-paclitaxel inhibitor for reasons other than progression and as long as it has been > 12 months since discontinuation of the previous nab-paclitaxel; this exception will require prior approval from the study principal investigator (PI) at University of Kansas Medical Center (KUMC)
American Society of Anesthesiologists (ASA) criteria of IV or higher
Unfit for minimal sedation anesthesia
Rectal fissure, fibrosis, stenosis, or other anatomic abnormality precluding insertion of transrectal device
Urinary tract or rectal fistula
Subjects must complete the filgrastim (G-CSF)/plerixafor mobilization of peripheral blood progenitor cells
Any AIDS-related opportunistic infection occurring within the past year and for which treatment has been unsuccessful would be considered exclusionary, but this is done on a case-by-case basis as determined by the principal investigator (PI)
Recurrent malignant gliomas
Metastases detected below the tentorium or beyond the cranial vault
Is or has an immediate family member (spouse or children) who is investigational site or sponsor staff directly involved with this study, unless prospective institutional review board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject
Pre-enrollment biopsy parameters (as per H.L. Moffitt C.C. review)\r\n* Minimum of 10 biopsy cores\r\n* Gleason score 6 or 7\r\n* Unilateral cancer (only right-sided or left-sided, not bilateral)
Medically unfit for anesthesia
Histology other than adenocarcinoma
Mammogram or ultrasonography (USG) performed
Presence of distant metastases documented clinically or radiographically with the exception of ipsilateral supraclavicular nodes
Significant dermatological disease including but not limited to, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg. blepharitis, cheilitis, cellulitis, cyst)
Life-threatening, visceral metastases
Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane
Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle
Clear BCMA expression must be detected on greater than 50% of malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry; these assays must be performed at the National Institutes of Health; it is not required that the specimen used for BCMA determination comes from a sample that was obtained after the patient’s most recent treatment; BCMA expression will need to be documented on the majority of malignant plasma cells at some time after the original anti-BCMA CAR T-cell infusion in all patients undergoing a second anti-BCMA CAR T-cell infusion; if paraffin embedded unstained samples of bone marrow involved with MM or a plasmacytoma are available, these can be shipped to the National Institutes of Health (NIH) for BCMA staining, otherwise new biopsies will need to be performed for determination of BCMA expression
PHASE II: The patient is participating in the trial at an institutional which has agreed to perform the imaging research studies, completed the American College of Radiation Imaging Network (ACRIN) defined scanner qualification procedures and received ACRIN approval
Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry)
Baseline serum calcium < 8.4 mg/dL (calcium supplementation may be given to restore the serum calcium above this level prior to study entry)
Prisoners or subjects who are involuntarily incarcerated
Hematocrit >= 28%
A blood pressure (BP) =< the 95th percentile for age, height, and gender measured, and not receiving medication for treatment of hypertension; please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
Pathology review by the study institution is required
Lack of appropriate caregivers
Significant ST depression of >= 1.5 mm in 2 or more leads and/or T wave inversions in >= 2 leads
Complete left bundle branch block
Right bundle branch block + left anterior hemiblock (bi-fascicular block)
Requirement of inotropic support (excluding digoxin)
Ischemic myocardial event including angina requiring therapy and artery revascularization procedures
Other concomitant active malignancies
Both men and women of all races and ethnic groups are eligible for this trial
Response to first infusions:\r\n* Subjects who had a PR, or SD with clinical benefit may elect to receive a second infusion of cells; subjects that initially had a CR may only receive a second dose if evaluable disease recurs; clinical benefit is indicated by an improvement in the subject’s health status (eg, improved performance status or quality of life, decreased pain, etc.)
Patients will NOT receive a second infusion of GD-2 CAR T cells if >= 5 % of the circulating T cells are GD2-CAR positive by flow cytometry
An adequate number of cryopreserved GD2-CAR cells must be available, or an adequate number of cryopreserved PBMC from the original apheresis must be available to generate a second dose of GD2-CAR T cells; post-GD2 CAR apheresis will not be used to harvest peripheral blood mononuclear cell (PBMC) cells for the transduction for the second infusion
The cell dose (based on CAR transduced cells) for the second infusion shall not be greater than the current dose level completed or the MTD if this has been determined and not less than the first dose level of this study (1 x 10^5/kg)
Creatinine < 2.0 milligrams per deciliter
Claustrophobia
KPS < 70
Must be either initiating therapy with romidepsin (Arm A) or currently receiving romidepsin with documented stable disease (SD) or partial response (PR) (Arm B)
Serum potassium >= lower limit of normal (LLN) and serum magnesium >= LLN (electrolyte levels may be achieved with repletion or other supportive medications like potassium sparing diuretics)
Prior participation in a randomized controlled study that included MLN9708 (ixazomib) in one of the treatment arms independent of whether assigned to MLN9708 (ixazomib) or not
Women of all races and ethnic groups are eligible for this trial
Use of any UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, gefitinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine, ketoconazole, linoleic acid, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, and probenecid propofol, quinidine, ritonavir, sorafenib, sulfinpyrazone, valproic acid, and verapamil; patients must avoid UGT1A9 inhibitors from the screening period through active treatment with INCB024360 and for one week after discontinuation of INCB024360
Low-dose Coumadin (1 mg) is acceptable; however, doses that increase INR are not permitted; if an alternative to Coumadin-based anticoagulants cannot be used, the INR should be monitored weekly after initiation of therapy and upon discontinuation of INCB024360, until INR normalization
Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
Patient is allergic to 5-FC, leucovorin, or 5-FU
Patients have failed at least one previous induction course of intravesical BCG, defined as histologically confirmed persistent or relapsing tumor present on post-BCG endoscopic evaluation; all BCG failures will be considered for inclusion into the study, including BCG-refractory, -resistant, and -relapsing; for the purposes of the study, “BCG-refractory” and “BCG-resistant” subjects will be considered to have “BCG-persistent” disease
Patients unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV)
Excisional biopsy or lumpectomy performed prior to randomization
Conditions that would prohibit administration of corticosteroids
Patient agrees that intravenous (IV) bisphosphonates will be withheld during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Electrocardiogram (ECG) abnormalities indicative of arrhythmia (at the discretion of the investigator)
Patients currently taking drugs that are generally accepted to have a high risk of causing torsades de pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine, ranolazine, and St. John’s wort
Patients requiring comedication with potent P-glycoprotein (P-gp) inhibitors (including cyclosporine, azithromycin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) or inducers (including rifampicin)
T4 within normal limits; if abnormal and patient is receiving thyroid replacement therapy, the thyroid medication may be adjusted and the T4 may be re-tested
History of peripheral vascular disease (PVD) that has required surgical or percutaneous intervention or documented PVD that requires medical management with medications such as acetylsalicylic acid (ASA) + clopidogrel; patients with diabetes that is not well controlled are excluded from participation; not well controlled is defined as a hemoglobin (Hgb) A1C of greater than 7.5%
Use of any UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, geftinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine, ketoconazole, lineoleic acid, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid propofol, quinidine, ritonavir, Sorafenib, sulfinpyrazone, valproic acid and verapamil from screening through follow-up period
Low-dose Coumadin (1 mg) is acceptable; however, doses that increase INR are not permitted; if an alternative to Coumadin-based anticoagulants cannot be used, the INR should be monitored weekly after initiation of therapy and upon discontinuation of INCB024360, until INR normalization
The tumor is considered to be radioactive-iodine refractory by any of the following criteria:\r\n* Total lifetime dose of radioactive iodine > 600 mCi\r\n* Absent or insufficient radioactive iodine uptake in either all lesions or an index lesion which has never been resected or received external beam radiation therapy as documented on a radioactive iodine scan (insufficient uptake must be confirmed by either an endocrinologist or nuclear medicine physician)\r\n* Progression of disease (by imaging or thyroglobulin) within 6 months of radioactive iodine treatment\r\n* Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan
Gynecologic Oncology Group (GOG) performance status of 0 or 1
Cancer antigen 19-9 (CA19-9); NOTE: in the event that a stent has been placed and biliary obstruction has been relieved, the CA19-9 should be drawn post stent placement
More than one primary lesion
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines, or romidepsin; agents that alter gastric pH may change MLN8237 absorption are not permitted; proton pump inhibitors need to be stopped 4 days prior to the first dose of MLN8237; histamine-2 (H2) receptor antagonists are not permitted from the day prior (day -1) through to the end of MLN8237 dosing; antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237
Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
Receiving umbilical cord blood
Patient agrees to stay within a reasonable distance (i.e. 30 minutes travel time) of the study site for the duration of the first treatment cycle through 24 hours after the last dose
Post-transplant lymphoproliferative diseases (often referred to as Epstein-Barr virus [EBV]-associated lymphomas)
Known allergies to clofarabine, melphalan, sirolimus or tacrolimus
Patient must agree to take lenalidomide with low dose dexamethasone as their initial therapy
Diagnosis of amyloidosis
Patients must have elevated calcitonin levels, greater than 8 pg/mL in females and 16 pg/mL in males
Patients with minimal or no disease related-symptoms (minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly scheduled narcotics)
Willing to travel to the National Institutes of Health (NIH) for follow-up visits
Participation in another interventional clinical trial at the time of enrollment
Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site
No clinical or radiographic evidence of pancreatitis
Histologically proven adrenocortical carcinoma (ACC) with the majority of disease confined to the peritoneal cavity and resectable or amenable to radiofrequency ablation
Childs B or C cirrhosis
Evidence of severe portal hypertension by history, endoscopy, or radiologic studies\r\n* Note: any diagnosis of portal hypertension or clinical stigmata of such including but not limited to gastric or esophageal varices, umbilical vein varices or telangiectasias
Willing to sign a durable power of attorney
Participation in any previous study involving sipuleucel-T
Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to registration
Patients who are not a candidate for an unrelated donor allogeneic HSCT based on the current institutional BMT program clinical practice guidelines; organ function criteria will be utilized per the current institutional BMT program clinical practice guidelines; there will be no restriction to study entry based on hematological parameters
Bilirubin =< 1.5 x UNL
Previous enrollment (or assignment) in the present study
Patients must have non-metastatic pancreatic cancer not immediately amenable to surgical resection; these are defined as follows\r\n* No distant metastases\r\n* Any involvement (defined as loss of fat plane on contrast CT) of any of the following vessels:\r\n** Hepatic artery \r\n** Superior mesenteric artery \r\n** Celiac axis \r\n** Superior mesenteric vein \r\n** Aorta\r\n* Metastases to lymph nodes beyond the field of resection
Charlson index of comorbidity score =< 4
Biopsy proven NSCLC
Pathologic assessment of the mediastinum to document involved nodal stations
The dose of nilotinib for patients receiving the drug in the second line setting due to failure of a first line TKI is generally 400 mg PO BID; in addition, if a patient is unable to tolerate second line nilotinib at 400 mg PO BID their dose may be decreased to 300 mg PO BID; in both instances they will be eligible for phase I
Total granulocytes of 1000 per mcL or more
Patients must have a positive screening Epstein Barr virus (EBV) antibody titre on screening test as this is required to protect against EBV infection during the time of lymphodepletion
Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics
Vasopressor requirement
Uncontrolled hyperlipidemia (total cholesterol > 350 or triglycerides > 300)
Pregnant or lactating women are excluded from this study because temsirolimus and sorafenib are drugs with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temsirolimus or sorafenib, breastfeeding should be discontinued if the mother is receiving temsirolimus/sorafenib treatment
Circulating human anti-mouse antibody (HAMA), to be determined before each infusion
Southwest Oncology Group (SWOG) performance status >= 2.0
Willingness and ability to complete the bowel and urinary domains of the EPIC prior to registration
Mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions
Smoking history < 10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana); one cannabis joint is equivalent of 5 cigarettes; smoking status definitions (National Health Interview Survey and Behavioral Risk Factor Surveillance System):\r\n* Smokers: smoking now every day or some days in past month\r\n* Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months\r\n* Former smoker: at least 100 cigarettes/lifetime and not smoking > 12 months\r\n* Never smokers: < 100 cigarettes (or equivalent)/lifetime
Total granulocytes of 1000 per mcL or more
Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics
Cumulative lifetime dose of anthracycline chemotherapeutic > 80 mg/m^2
Subject has circulating blast count > 50,000/?L (subjects may be enrolled if circulating blast count is controlled by hydroxyurea and/or, if clinically indicated, by leukophoresis)
Absence of a regular red blood cell transfusion requirement
Adequate absolute CD3 count estimated to be required to obtain target cell dose based on discussion with Department of Transfusion Medicine (DTM) apheresis and Cell Processing Section, DTM
Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested\n             and negative
Baseline BNP > 2 x IULN
Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or\n             clinical evidence of other conditions known to associated with hypocalcemia,\n             including:, hypoalbuminemia, hyperphosphatemia, hypomagnesemia
Asymptomatic or minimally symptomatic disease as demonstrated by Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and no need for opiate pain medications to control pain/symptoms
Cluster of differentiation (CD)4 count > 400 cells/mm^3
Clinically significant oral cGVHD after allogeneic hematopoietic stem cell transplant (HSCT) with severity score of at least 2 on erythema subset and/or at least 1 on ulceration subset and a composite score >= 20 of the OMRS scale confirmed by the principal investigator (PI), clinical study chair (CSC), or lead associate investigator (LAI)
< Grade 2 hypo/hyperkalemia
Willingness to provide mandatory blood samples for pazopanib drug level assessments required for dosage adjustments, as well as for required pharmacogenomic studies
-
Approval for hydroxychloroquine treatment by an eye doctor, based on a screening eye exam; examples of disqualifying baseline conditions may include macular degeneration and other retinal disease such as cataracts that would interfere with required funduscopic examinations, or severe baseline visual impairment, retinopathy or visual field changes; all patients must undergo a screening eye exam prior to enrollment
Must not have psoriasis or porphyria
Total calcium (corrected for serum albumin) within normal limits (ongoing requirement for bisphosphonate to control malignant hypercalcemia is not allowed but prophylactic use of bisphosphonate to prevent skeletal complication of bone metastasis is allowed)
Patients has any of the following mood disorders as judged by the Investigator or a psychiatrist, or who meets the cut-off score of >= the Patient Health Questionnaire-9 (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7 (GAD-7) mood scale, respectively, or selects a positive response of ‘1, 2, or 3’ to questions number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)\r\n* Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety\r\n* Note: the psychiatric judgment overrules the mood assessment questionnaire result or the investigators judgment
Patients with evidence of myelodysplasia, leukemia by morphology, immunostains flow cytometry or abnormal cytogenetics on a bone- marrow aspirate or biopsy; the diagnosis of myelodysplasia will be made by an independent investigator of the Laboratory of Pathology, National Cancer Institute (NCI) taking into consideration the totality of the clinical, pathological, flow cytometric and cytogenetic and present in a particular individual’s evaluation
Both men and women and members of all races and ethnic groups are eligible for this trial
Hematocrit > 25%
Any acute medical problems requiring active intervention
Patient must agree to submit tissue (i.e., the original haematoxylin/eosin [H/E]-stained slides and immunohistochemistry studies) for central pathology review post-registration
Prior cranial irradiation
Complete blood count, differential and platelet count must be within normal limits (WNL) or verified by the study chair to be related to conditions not interfering with normal health status
Accessible for follow up
Bilateral prophylactic mastectomy
Acute or chronic pancreatitis
Electrolyte abnormalities (particularly hypokalemia or hypomagnesemia)
HER2/neu negative disease (performed on primary tumor and/or metastatic lesion using commercially available/approved assay in local institutional or reference laboratory), according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Any malabsorption problem
Pre- or post-menopausal women with stage I and II breast cancer, triple negative tumors (upper limit of positivity < 10% for estrogen receptors, < 20% for progesterone receptors)
Active connective tissue disorders, such as lupus or scleroderma
Lymphopenia, cluster of differentiation (CD)4 lymphopenia, leukopenia, and anemia will not render patients ineligible
Fanconi anemia
In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling; specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting the exclusion criteria will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis
Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on cerebrospinal fluid [CSF] cytology) are excluded
Mini Mental Status Exam (MMSE) >= 18 prior to study entry
Recursive partitioning analysis (RPA) class I (KPS >= 70, primary cancer controlled, age < 65, metastases in brain only) or class II (lack of one or more of class I criteria)
RPA class III (KPS < 70)
No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm)
Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication
Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm
Endoscopy with biopsy
HER2 expressing adenocarcinoma of the esophagus centrally
Prior anthracycline or taxane
Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
Medical contraindications to esophagectomy
Total bilirubin =< 1.5 institutional upper limit of normal (ULN), unless elevated secondary to lymphomatous involvement of liver or biliary system, or due to other HIV medications (e.g., indinavir, tenofovir, or atazanavir); for direct bilirubin > 1.2 due to hepatic involvement by tumor for the initial dose of EPOCH drug adjustment
Any acute, inter-current infection that may interfere with planned protocol treatment; participants with mycobacterium avium will not be excluded from study entry; chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met
Positive staining of the most recently resected tumor tissue with antibodies to 1 or more of the following: human melanoma black (HMB) 45 for glycoprotein (gp) 100, NY-ESO-1, and/or melanoma-associated antigen recognized by T cells (MART)-1
Patients must not be taking ketoconazole, dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice within two weeks of randomization and during the course of therapy; topical and inhaled steroids are permitted
All potential subjects should be evaluated for whether breast cancer (BRCA)1-2 testing is medically appropriate; individuals who have a 10% or higher risk of having a BRCA1-2 mutation (Myriad tables at www.myriad.com) are encouraged (but not required) to have mutation testing and results known; information regarding mutation status (positive [including specific mutation], negative, or unknown) and projected risk of having a mutation (as determined by Myriad tables) will be collected at the time of diagnosis
Prior azacitidine, decitabine, or midostaurin
Patient must not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
Patient must not have had clinically significant hemoptysis, defined as greater than 1 tablespoon of bright red blood, within one year prior to registration; although hemoptysis has not been associated with cediranib, it may be a class effect for anti-angiogenic agents and therefore a risk factor for this experimental agent
Poorly-controlled DM
Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT
CTEP CTCAE version 4.0, grade 2 or higher peripheral ischemia (brief [< 24 hours (hrs)] episode of ischemia managed non-surgically and without permanent deficit)
No segmental, lobar or main portal vein thrombosis as evidence by cross sectional imaging
Childs score of A or B
Diagnosis of acute or lymphomatous ATL by flow cytometry of blood or immunohistochemistry of biopsy tissue, confirmed by National Cancer Institute (NCI) Laboratory of Pathology, and previously treated unless the patient is ineligible for or refuses other protocols or treatments for ATL
Neutralizing antibodies less than or equal to 75% neutralization of 200 ng/ml of LMB-2
Current or prior features of acute (corrected calcium [Ca]++ > 2.73 or lactate dehydrogenase [LDH] > 2-fold above ULN) or chronic (LDH 1.5-2-fold above ULN or absolute lymphocyte count > 4 x 10^9/L with T-cells > 3.5 x 10^9/L) ATL; patients with smoldering ATL (no acute or chronic features) and symptomatic ATL skin lesions are also eligible
AT TIME OF PROCUREMENT:
Diagnosis of advanced stage or metastatic HER2-positive cancer (immunohistochemistry or reverse transcriptase-polymerase chain reaction [RT-PCR] is used to determine HER2 positivity)
EBV seropositive
EBV-seropositive
Available autologous transduced EBV-specific cytotoxic T lymphocytes with >= 15% expression of HER2 CAR determined by flow-cytometry and killing of HER2-positive targets >= 20% in cytotoxicity assay
AT TIME OF PROCUREMENT:
Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required
Circulating human anti-mouse antibody (HAMA), to be determined before each infusion
Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected PBSC are to be used (patients with cryopreserved stem cells which are negative [=< 0.1% involved] by flow cytometry will also be considered eligible)
Southwest Oncology Group (SWOG) performance status >= 2.0
Unable to perform self-care during radiation isolation
OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
Available autologous transduced peripheral blood T-cells with >= 15% expression of CD19CAR determined by flow-cytometry
Subjects should be willing and able to take folic acid and vitamin B12 supplementation and should interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8-day period for long acting agents such as piroxicam) before entering the study
Presence of third space fluid which cannot be controlled by drainage
Primary immunodeficiency disorder or other nonmalignant inherited disease (except aplastic anemia and Fanconi anemia) treatable by allogeneic HCT
Donors: Identical twin
Histopathological evidence of CD25+ HCL confirmed by the National Institutes of Health (NIH) pathology department; this will require a monoclonal population of peripheral malignant lymphocytes that are CD25 positive by fluorescence activated cell sorting (FACS) with anti-CD25 antibody; positive expression in a FACS assay is defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody by FACS; HCLv (HCL variant) is usually CD25 negative, and eligibility would require CD25+ HCLv
Previous treatment with or inability to receive BL22 or HA22 recombinant immunotoxin; patients must have had at least 2 prior systemic therapies, including 2 courses of a purine nucleoside analog (PNA), or 1 course of either rituximab or B-RAF proto-oncogene, serine/threonine kinase gene (BRAF) inhibitor following a single prior course of PNA
Serum that neutralizes =< 75% of the activity of 1 ug/mL of LMB-2 using a bioassay
Chronic Epstein-Barr virus (EBV)-associated lymphoproliferative disease\r\n* At any point after diagnosis, including upfront therapy
Myeloproliferative disorders\r\n* Idiopathic myelofibrosis\r\n* Polycythemia vera\r\n* Essential thrombocytosis\r\n* Chronic myelomonocytic leukemia\r\n* Patients with myeloproliferative disorders must be end-stage, which is primarily defined as disease severity refractory to splenectomy
Serum total bilirubin < 2.5 mg/dl; values above these levels may be accepted, at the discretion of the principal investigator (PI) or lead associate investigator (LAI), if such elevations are thought to be due to liver involvement by malignancy or GVHD
DONOR:\r\n* First-degree relative with genotypic identity at 6/6 HLA loci (HLA- A, B, and DR)\r\n* Age 11 to 90 years and able to give consent or assent; for donors < 18 years old, the legal guardian must be able to provide informed consent\r\n* Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis\r\n* Donors must be human immunodeficiency virus (HIV) negative\r\n* Donors with a history of hepatitis B or hepatitis C infection may be eligible; however, eligibility determination of such patients will require a hepatology consultation; the risk/benefit of the transplant and the possibility of transmitting hepatitis will be discussed with the patient and eligibility will then be determined by the principal investigator and LAI\r\n* Lactating donors must substitute formula feeding for her infant during period of filgrastim administration (to prevent any filgrastim effect on infant)
DONOR:\r\n* History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent\r\n* History of hypertension that is not controlled by medication, stroke, autoimmune disease, or severe heart disease (donors with symptomatic angina will be excluded); donors with a history of coronary artery bypass grafting or angioplasty who are symptom free will receive a cardiology evaluation and be considered on a case-by-case basis\r\n* History of prior malignancy; however, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis; in addition, donors with localized cancer such as prostate cancer that are on a watch-and-wait management due to the low-risk of disease progression may also be considered for stem cell donation on a case-by-case basis; the risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient\r\n* Donors must not be pregnant (unknown effect of filgrastim on fetus); donors of childbearing potential must use an effective method of contraception\r\n* Anemia (hemoglobin [Hb] < 11 gm/dl) or thrombocytopenia (platelets < 100,000 per ul); however, potential donors with Hb levels < 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy and the case is individually approved by NIH or Hackensack Blood Bank
Primary amyloidosis (AL) or myeloma complicated by amyloidosis
A diagnosis of ET or PV shall be made in accordance with the World Health Organization (WHO) (2008) criteria as shown below (Values below are at the time of diagnosis, not study entry):\r\n* Polycythemia Vera (2 major criteria required)\r\n** Hemoglobin (Hb) > 18.5g/dl (male) or 16.5g/dl (female) or \r\n** Hematocrit (HCT) > 99 percentile reference range or \r\n** Elevated red cell mass (> 25% above mean predicted value) or \r\n** Hb > 17g/dl (male) or 15g/dl (female) if associated with a sustained rise from baseline with no apparent cause (e.g. treated iron deficiency)\r\n** Presence of JAK2V617F\r\n* Essential Thrombocythemia (all 4 major criteria required)\r\n** Platelets count >= 450 x 10^9/L\r\n** Megakaryocyte proliferation with large and mature morphology; no significant increase or left shift of neutrophil granulopoiesis or erythropoiesis\r\n** Not meeting WHO criteria for chronic myelogenous leukemia (CML), PV, myelodysplastic syndromes (MDS) or other myeloid neoplasms\r\n** Demonstration of JAK2V617F, clonal cytogenetic marker or no evidence of reactive thrombocytosis\r\n** May participate in study without presence of JAK2V617F
In addition patients must EITHER be intolerant or resistant to hydroxyurea according to previously modified established criteria as follows:\r\n* Any ONE of the following:\r\n** Platelet count > 600 x 10^9/L after 3 months of at least 2g/day of hydroxyurea or maximally tolerated dose (MTD) of hydroxyurea (2.5 g/day in patients with a body weight greater than 80 kg)\r\n** White blood cell (WBC) < 2.5 x 10^9/L or Hgb < 11g/dl at any dose of hydroxyurea not to exceed 2g/day (for a period of at least 2 months)\r\n** Progressive splenomegaly or hepatomegaly (> 5cm from initiation of hydroxyurea) or the appearance of new splenomegaly or hepatomegaly while on maximum tolerated dose (MTD) of hydroxyurea\r\n** Not achieving a Hct < 45% in order to eliminate the need for supplemental phlebotomies after 3 months of at least 2g/day MTD of hydroxyurea\r\n** Not achieving a WBC of < 10 x 10^9/L after 3 months of at least 2g/day MTD of hydroxyurea\r\n** Having a platelet count < 100 x 10^9/L on hydroxyurea at any dose without eliminating the need for supplemental phlebotomy or having progressive splenomegaly as defined above\r\n** Development of a major thrombotic episode (cerebral vascular accident [CVA], myocardial infarction, severe migraines requiring medication, abdominal vein thrombosis, deep vein thrombosis) while being treated with maximal tolerated doses of hydroxyurea\r\n** Presence of leg ulcers or other unacceptable hydroxyurea-related-nonhematological toxicities, such as unacceptable mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of hydroxyurea\r\n* OR have Splanchnic Vein Thrombosis (SVT) (includes Budd-Chiari, abdominal vein thrombosis, portal vein thrombosis, splenic vein thrombosis); for these patients the following additional inclusion/exclusion criteria apply:\r\n** > 3 months since onset of SVT\r\n** SVT treated with oral anticoagulants but no aspirin\r\n** Liver enzymes not > 2 times the normal value\r\n** Absence of encephalopathy, refractory or infected ascites, esophageal varicose of grade > 1 at time of trial entry\r\n** Bone marrow biopsy confirmed diagnosis of PV or ET\r\n** JAK2-V617F present\r\n** These patients may have a normal blood count at trial entry
Willing to participate in associated correlative science biomarker study
Presence of any life-threatening co-morbidity
Any contraindications to pegylated or non-pegylated interferon
History of autoimmune disorder (e.g. hepatitis; idiopathic thrombocytopenic purpura [ITP]; scleroderma; severe psoriasis affecting > 10% of the body, rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory drugs [NSAID] for management)
Evidence of severe retinopathy (e.g. cytomegalovirus [CMV] retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension)
Thyroid dysfunction not adequately controlled
Presence of JAK2 exon 12 mutation
No previous exposure to any formulation of interferon
No detectable PNH (paroxysmal nocturnal hemoglobinuria) clone where tested
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
> 20% blast in the PB or BM prior to hematopoietic cell transplantation (HCT) or had leukemic transformation (> 20% blasts in PB or BM any time prior to HCT)
Registration of patients who have not yet undergone Oncotype DX screening must occur no later than 56 days after definitive surgery; (for all patients, Step 2 Registration must occur within 84 days after definitive surgery); if the Oncotype DX Breast Cancer Assay has not been performed, patients must be willing to submit tissue samples for testing to determine the Recurrence Score value; a representative block or unstained sections from the representative block are sent directly to Genomic Health for Oncotype DX Breast Cancer Assay which will be performed according to the standard commercial process\r\n* If the Oncotype DX Recurrence Score is already known and is 25 or less, the patient must be registered to Step 2 immediately following Step 1 registration; if the Oncotype DX Recurrence Score is already known and is greater than 25, the patient is ineligible
The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete QOL forms per their expectation report; patients who are able to complete a questionnaire in English must be offered the opportunity to participate in the Quality of Life and Economic Substudy; (The Quality of Life and Economic Substudy is available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a questionnaire in English are registered to S1007 without participating in the Quality of Life and Economic Substudy\r\n* Patients who consent to participate in the Quality of Life and Economic Substudy and who do not yet know the results of their Oncotype DX screening must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment between 14 days prior to and 7 days after Step 1 Registration\r\n* Patients who consent to participate in the Quality of Life and Economic Substudy and who do already know their Oncotype DX Recurrence Score (and it is 25 or less) will proceed to Step 2 Registration without completing the S1007 Health-Related Quality of Life Questionnaire Enrollment Form (but will complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Recurrence score (RS) by Oncotype DX must be =< 25
The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form after Recurrence Score results and randomized treatment status are known but before treatment has been initiated
Diagnosis < 3 years prior to entry
Essential Thrombocythemia (all 4 major criteria required)\r\n* Platelets count >= 450 x 10^9/L\r\n* Megakaryocyte proliferation with large and mature morphology; no significant increase or left shift of neutrophil granulopoiesis or erythropoiesis\r\n* Not meeting WHO criteria for chronic myelogenous leukemia (CML), PV, myelodysplastic syndromes (MDS) or other myeloid neoplasms\r\n* Demonstration of clonal cytogenetic marker or no evidence of reactive thrombocytosis\r\n* May participate in study without presence of JAK2V617F
Willing to participate in associated correlative science biomarker study
No known PNH (paroxysmal nocturnal hemoglobinuria) clone
Any contraindications to pegylated interferon or hydroxyurea
Presence of any life-threatening co-morbidity
Evidence of severe retinopathy (e.g. cytomegalovirus [CMV] retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension)
Splanchnic vein thrombosis (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
Thyroid dysfunction not adequately controlled
JAK2 exon 12 mutation: PV that lacks the JAK2V617F mutation but is characterized by the exon 12 mutation
No previous exposure to any formulation of pegylated interferon
Willing to undergo testing for gBRCA.
Known history of allergic reaction to Cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.
Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose
Have received at least 2 previous courses of BCG within a 12 month period - defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3 instillations of maintenance BCG, or at least two of six instillations of a second induction course, where maintenance BCG is not given
No maximum limit to the amount of BCG administered
Available for the whole duration of the study
Presence of lymphovascular invasion and/micropapillary disease as shown in the histology of the biopsy sample
Subject is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A subject with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Subjects can be enrolled from a local test result if they have any of the following FLT3 mutations: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD)/D835 or FLT3- TKD/I836.
Female subject must either:
post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
Subjects with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal [LLN]).
Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Subject has an FLT3 mutation other than the following: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
Significant ongoing immunologic rejection based on pathology and clinical diagnosis (from time of transplant until randomization)
Use of direct acting antivirals for hepatitis C virus (HCV) recurrence, with the exception of sofosbuvir and ledipasvir/sofosbuvir
Clinically active serious infection documented by positive cultures or an incomplete course of treatment for bacteremia or fungemia
Use of direct acting antivirals for HCV recurrence\r\n* Sofosbuvir and ledipasvir/sofosbuvir are not excluded therapies
PTT ?1.5 ULN
Fibrinogen ?0.75 LLN
ATRT
MRT
RTK
Selected tumors with rhabdoid features
Extraskeletal myxoid chondrosarcoma
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
For subjects with ATRT, MRT, RTK, or selected tumors with rhabdoid features only, the following test results must be available: Morphology and immunophenotypic panel consistent with rhabdoid tumor and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss/mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
For subjects with INI1 negative tumor only, the following test results must be available: Morphology and immunophenotypic panel consistent with INI1-negative tumors, and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss/mutation when INI1 IHC is equivocal or unavailable
Cohort 1 - ATRT
Cohort 2 - MRT/RTK/selected tumors with rhabdoid features
Cohort 3 - INI-negative tumors:
Extraskeletal myxoid chondrosarcoma
Chordoma (poorly differentiated or de-differentiated)
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
For subjects with ATRT/MRT/RTK only - Has the following test results available: Morphology and immunophenotypic panel consistent with rhabdoid tumor, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss/mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
Morphology and immunophenotypic panel consistent with INI1-negative tumors, and
Molecular confirmation of tumor bi-allelic INI1 loss/mutation when INI1 IHC is equivocal or unavailable
Cytogenetics or FISH and/or molecular confirmation (e.g., deoxyribonucleic acid [DNA] sequencing) of SS18 rearrangement t(X;18)(p11;q11)
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Known urinary tract obstruction
Patients with the following ocular conditions: corneal disorders, monocular vision (i.e., best corrected visual acuity greater than or equal to 20/200 in one eye), or active ocular disorders requiring treatment
Target Population
Steroids for physiological replacement are allowed.
Brain lesions >3 lesions which were previously treated with SRT
Prisoners or subjects who are involuntarily incarcerated
Patient may have received or plan to receive concurrent bone targeting agents that do not have an effect on PSA (e.g. denosumab or bisphosphonate)
A dual-energy X-ray absorptiometry (DEXA) scan must be obtained within 2 years prior to registration
Specimen Submission Criteria:
As a part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Tumors that are amenable to serial biopsy
Eligible for treatment with a taxane-containing regimen (for example, docetaxel), unless taxane-containing regimen was declined after an informed decision
Prior radium-223 dichloride or hemibody external radiotherapy
Unmanageable fecal incontinence
Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood (allelic ratio as determined by a central laboratory with a cutoff of ?3% FLT3-ITD/total FLT3). If a specimen has been sent for FLT3-ITD testing at the central laboratory but the subject requires treatment for AML before the central FLT3-ITD test result is available, a local test result may be acceptable for randomization after consultation with the Medical Monitor.
Serum potassium, magnesium, and calcium (serum calcium corrected for hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.
In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion. Additionally, for women randomized to chemotherapy, unwillingness to adhere to the restrictions in the respective locally established guidelines and local approved label (prescribing information, Summary of Product Characteristics, or US product insert) from the manufacturer and the Patient Information Leaflet (package insert) as instructed by the Investigator.
For subjects in the UK only: Refusal of permission to allow the subject's General Practitioner to be notified of their participation in the study.
NSCLC patients must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus or;
Patients with tumor types such as HNSCC, papillary renal carcinoma, gastric adenocarcinoma, and other solid tumors must meet criteria for amplification of the MET gene locus, defined MET mutations, or rearrangements involving the AXL or MET gene locus
Immunocompromised subjects;
Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
Or known cases of hepatobiliary diseases (e.g., primary biliary cholangitis, primary sclerosing cholangitis, history of immune-mediated cholangitis);
Subjects with cholangitis attributed to infectious etiology (e.g., ascending cholangitis, bacterial cholangitis) are eligible if the infection has been fully resolved prior to the screening visit.
Or known cases of drug-induced hepatobiliary toxicities.
Absolute neutrophil count ?1.5 × 10^9/liter (L), platelets ?100 × 10^9/L, and hemoglobin ?9 grams/deciliter (5.58 millimoles/L).
Nonsteroidal anti-inflammatory agents.
Diagnosis of PMF according to the revised WHO criteria; or PET-MF or PPV-MF according to the IWG-MRT criteria
Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring greater than or equal to (>=) 5 cm below the left costal margin OR spleen volume of >= 450 cm^3 measured by MRI
Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms
Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) < 35%.
Participants with prior chemotherapy or radiotherapy (RT) for current NSCLC. Participants curatively treated for past early stage NSCLC greater than 3 years ago may be included.
Patients must not be known to have hypersensitivity to cisplatin, gemcitabine (gemcitabine hydrochloride), doxorubicin (doxorubicin hydrochloride), vinblastine (vinblastine sulfate), methotrexate or filgrastim/pegfilgrastim
Patients must consent, if residual tumor is present at the time of cystectomy, to the submission of 20 (10 micron) unstained slides with 2 (5 micron) slides at the start and stop of the series (total of 22 unstained slides)
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of Institutional Review Board approval for this study has been entered in the system
Testing for MSI Status (by an accredited lab)
Subjects with microsatellite instability high (MSI-H) tumors will enroll in the MSI-H Cohort (mStage and cStage groups), the C3 Cohort, and the C5 Cohort.
Subjects with phenotypes that are non-microsatellite instability high (non-MSI-H) will enroll in the non- MSI-H Safety Cohort and the C6, C4 Cohorts.
Patients must be assigned to S1400G; S1400G biomarker eligibility defined as homologous recombination repair deficiency (HRRD) positive is as follows\r\n* Biomarker-positive group\r\n** HRRD by FMI\r\n*** Homologous recombination repair deficiency by Foundation Medicine Inc., criteria\r\n* Alteration type\r\n** Truncating mutation, frameshift deletions, indels missense and nonsense mutations predicted to have functional consequence in any of the specified genes\r\n* Eligible alteration\r\n** Mutation in any one of the following critical HRR pathway genes: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1
Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin
Any non-squamous subtype
Has documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib.
Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug.
Patient has undergone more than 2 debulking surgeries
Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
Physiologic dosing of hydrocortisone is permitted.
All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program.
Male subjects, as appropriate to age and the discretion of the study physician:
Subjects must have received adequate BCG treatment defined as at least 2 courses of BCG, i.e., at least one induction and one maintenance course or at least 2 induction courses. The initial induction course must be at least 5 treatments within a 7-week period. The second course (induction or maintenance) must be at least 2 treatments within a 6-week period. The \5+2\ doses of BCG must be given within approximately 1 year (i.e., the start of one course to start of the second course within 12 months ±1 month) and for the same disease episode for which the subject is enrolling. Treatment must be considered \full-dose\ BCG (see Section 10). If additional doses or courses of BCG above the minimum \5+2\ are given, these do not have to be within the same approximate 12 month timeframe. Subjects who were unable to receive at least 5 doses of BCG in a first course and at least 2 doses of BCG in a second course due to intolerance are not eligible. Subjects who began their initial course of BCG with \full-dose\ BCG and required dose-reductions due to adverse events but are still able to tolerate at least \5+2\ doses of BCG are considered to meet the requirement for \adequate BCG.\ Subjects who received less than \full dose\ BCG (e.g., 1/3rd dosing) as a standard regimen and not due to dose reductions because of AEs are not eligible. The BCG may have been given in combination with interferon. When BCG is given simultaneously in combination with interferon, 1/3rd dosing of BCG is acceptable.
Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years) and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval.
Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the Investigator, would predispose the subject to the development of complications from the administration of intravesical therapy and/or general anesthesia.
Subjects must have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for ?12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.
ANC ?1,500/µl
Subjects must have potassium (K+) >3.5 mEq/l.
Active diverticulitis.
Maintenance of castrate conditions
Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation.
Adequate sections or a paraffin block from the original diagnostic specimen must be submitted for review by the lymphoma pathology group
The lymphoma must express the cluster of differentiation (CD)20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections; a report providing confirmation of CD20 expression must be submitted
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Clinically suspected Grades II to IV acute GVHD as per MAGIC guidelines, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
Unresolved toxicity or complications (other than acute GVHD) due to previous allo-HSCT.
Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
Parts 1 and 3: 0 or 1
Parts 2 and 4: 0, 1, or 2
Willingness to avoid pregnancy or fathering children
HbA1c of ? 8% (all subjects will have HbA1c test at screening)
Coagulation panel within protocol-specified parameters
Subjects with carcinomatous meningitis
Radiologic evidence of new and/or progressive parenchymal brain metastasis, spinal cord metastases (intramedullary), or leptomeningeal disease (LMD) by magnetic resonance (MR) imaging of the brain and/or spine, or CSF cytology evidence of new LMD or persistent LMD
Ineligible to receive treatment with auto-SCT due to age (?65 years old) or any significant coexisting medical condition (cardiac, renal, pulmonary or hepatic dysfunction), likely to have a negative impact on tolerability of auto-SCT. Participants <65 years of age who refuse auto-SCT are not eligible for this study.
Has lactose intolerance.
PMBCL:
Has relapsed after autologous stem cell transplant (auto-SCT) or has failed to achieve a Complete Response or Partial Response within 60 days of auto-SCT. Participants may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment. OR
RS:
All Participants:
Prior treatment with other immune modulating agents within fewer than 4 weeks prior to the first dose of REGN2810. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments.
Subjects with histologically or cytologically confirmed NSCLC, MEL (including I/O relapsed MEL or I/O refractory MEL), CRC, SCCHN, ovarian cancer, recurrent B cell NHL or HL, or glioblastoma
Ocular MEL
Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Documentation of V600E-activating BRAF mutation status.
Subjects enrolling in the primary refractory or relapsed melanoma must be willing to undergo mandatory pretreatment and on-treatment biopsies.
Ocular melanoma is excluded.
Must have progressed on, refused, or were intolerant of sorafenib.
The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment.
Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation.
Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.
Non-malignant disorders deemed curable by allogeneic transplantation: a. primary immune deficiencies, b. severe aplastic anemia not responding to immune suppressive therapy, c. osteopetrosis d. selected cases of erythroid disorders such as ?0 ?0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia. e. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML). Note: Subjects will be eligible if they meet either item 5 OR item 6.
A minimum genotypic identical match of 5/10 is required.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with > 3 residual lesions on end-induction MIBG scan.
They can't cooperate with the special precautions that are needed for this trial.
Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation from Myriad Genetics or other laboratory approved by the Sponsor
Not a candidate for treatment with at least 1 of the treatments of protocol-specific physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)
Subjects with leptomeningeal carcinomatosis are not permitted
Presence of primary or associated amyloidosis (AL)
Participants who plan to proceed with ASCT as part of first line therapy
Key
A morbidity (per the prescribing information) that would require starting a patient at a reduced dose of axitinib.
Willingness to be transfused to treat low hemoglobin levels
Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.
Biopsy confirmation of GVHD is not required. Enrollment should not be delayed for biopsy or pathology results unless local institutional practice mandates biopsy confirmation to make a GVHD treatment decision.
Collection of a 5 ml blood sample (red top for serum) from the patient for Ann Arbor Scoring and ready to be shipped immediately after randomization.
A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment.
Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating gastric/GEJ cancer; previously received trastuzumab as part of a regimen in the metastatic setting with evidence of progression; 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted
Non epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors
have postmenopausal status
have visceral crisis
Legal incapacity or limited legal capacity
Prior administration of other NY-ESO-1-targeting immunotherapeutics.
Pathologically confirmed HER2-positive MBC
LVEF at least 50%
Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site; nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by hematoxylin and eosin (H & E) stained slides
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Participants with known or suspected COPD must have a FEV1 test during Screening
Relapsed or refractory pediatric B-cell ALL:
Ineligible for allogeneic SCT
Pegylated-asparaginase must be stopped > 4 weeks prior to CTL019 infusion e. CNS disease prophylaxis:
CNS directed radiation must be completed > 8 weeks prior to CTL019 infusion g. Anti T-cell Antibodies: Administration of any T cell lytic or toxic antibody (e.g. alemtuzumab) within 8 weeks prior to CTL019 is prohibited since residual lytic levels may destroy the infused CTL019 cells and/or prevent their in vivo expansion. If such an agent has been administered within 8 weeks prior to CTL019, contact the Sponsor, consider consultation with an pharmacology expert, and consider measuring residual drug levels, if feasible, prior to CTL019 infusion Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CTL019 infusion. Highly effective contraception methods include:
Use of IUDs are excluded due to increased risks of infection and bleeding in this population. However, IUD inserted prior to consent may remain in place, and a second method of contraception is mandated
Physician report/letter
Operative report or other source documentation in the patient record
Discharge summary
Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
For the dose-escalation phase, a phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation is also required; Memorial Sloan-Kettering Cancer Center (MSKCC) or outside documentation is acceptable
High levels of calcium requiring bisphosphonate therapy or denosumab.
Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are elgible for study after discussion and approval by the Medical Monitor.
If a subject has de novo DLBCL, the diagnosis is confirmed by biopsy and is immunohistologically characterized as de novo germinal center B-cell-like (GCB) DLBCL or de novo non-GCB DLBCL.
If the subjects has Richter's Syndrome (RS), the diagnosis is confirmed by biopsy and is immunohistologically characterized as transformation to DLBCL.
Diagnosis of PMBCL.
Procedure involving Total Mesorectal Excision by an abdominal or transanal approach.
Subject has a known dysfibrinogenemia, hypofibrinogenemia or a fibrinogenemia, without preoperative correction of fibrinogen levels.
Subject with American Society of Anesthesiology (ASA) status higher than 3.
Subject received intra-operative sealant, glue or any buttressing material other than the LifeSeal™ Surgical Sealant.
Subject has peritoneal carcinomatosis.
Excessive bleeding (above 500cc) identified prior to anastomosis formation with the need for intra-operative blood transfusion.
REGULATORY CRITERIA: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Isolated extramedullary relapse (i.e., testicular, CNS).
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
A score higher than 6 on the Cumulative Illness Rating Scale-Geriatric.
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
Must have an apheresis product of non-mobilized cells accepted for manufacturing
Prior allogeneic HSCT
Eligible for and consenting to ASCT
Intolerance to the excipients of the CTL019 cell product
If female, patient is postmenopausal
Patient has identified PIK3CA status
Prior administration of other NY-ESO-1-targeting immunotherapeutics
For melanoma: Uveal melanoma or LDH >1.1 x ULN
Associated with symptoms and/or findings; OR
Participants with paraspinal, paratracheal and mediastinal pathologic lesions larger than 2 centimeters unless they are previously irradiated
Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
Suitable candidate for single agent nab-paclitaxel as assessed by the investigator.
WBCs ? 2000/uL,
Potassium within normal range, or correctable with supplements,
Subject has known acute or chronic pancreatitis.
Subject has active hepatitis B or C. Subject with hepatitis in medical history may be eligible if infection considered cleared, ie core Ab+, surface Ab+, surface Ag- for hep B and Ab+/DNA- for hep C.
Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations
For RCC:
For gastric or GEJ adenocarcinoma:
For CRC:
For all cohorts:
For all cohorts:
Kaposi sarcoma (KS) (following prior KS-specific therapy (Cohorts 1-3)\r\n* (KS) impacting physical and/or psychological wellbeing and not amenable to local therapy and one or more of the following: \r\n** Stable KS despite 6 or more cycles of liposomal doxorubicin or paclitaxel or other active cytotoxic agents (i.e. etoposide, bleomycin, anthracyclines, vincristine [vincristine sulfate], vinblastine); or\r\n** Progressive disease despite 3 or more cycles of liposomal doxorubicin or paclitaxel or other active cytotoxic agents (i.e. etoposide, bleomycin, anthracyclines, vincristine, vinblastine); or\r\n** Patient who received a cumulative lifetime dose of anthracycline of >= 550 mg/m^2; or\r\n** Recurrent or progressive KS after completion of prior first line chemotherapy\r\n** Intolerant of or refuses further cytotoxic chemotherapy\r\n** No KSHV-associated multicentric Castleman disease in past 5 years\r\n** For KS patients, the following laboratory values supersede values below:\r\n*** Platelets > lower limit of normal\r\n*** Hemoglobin > 10 g/dL
Treatment naive Kaposi sarcoma impacting physical and/or psychological wellbeing and not amenable to local therapy. (Cohort 4)\r\n* On antiretroviral therapy (ART) with suppressed HIV viral load for > 3 months (Note: an extended washout period is needed to avoid treatment during the period of risk for the highly toxic and often fatal “Immune Reconstitution Inflammatory Syndrome (IRIS)”\r\n* No KSHV-associated multicentric Castleman disease in past 5 years\r\n* No prior systemic chemotherapy \r\n* No symptomatic pulmonary KS or chest X-rays positive for un-evaluated abnormalities \r\n* Disease evaluable by AIDS Clinical Trial Group (ACTG) KS response criteria\r\n* CD4+ T-cell count >= 100 cells/uL \r\n* For KS patients, the following laboratory values supersede values below:\r\n** Platelets > lower limit of normal\r\n** Hemoglobin > 10 g/dL
Creatine kinase < 5 X institutional ULN
Presence of diffuse leptomeningeal carcinomatosis (focal/localized involvement is acceptable), > 1 cm mid-line shift, uncal herniation or significant hemorrhage/hydrocephalous (small intra-lesional hemorrhage is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
Expression of CD30
A diagnosis of renal AML > 3 cm confirmed on pre-enrollment DCE-MRI; a previous diagnosis or treatment of a different AML lesion is allowed
Chest radiograph
Performed within 14 days of patient registration: Serum magnesium > 1.8 mg/dL(can be achieved with replacement)\r\n* NOTE: The package insert for the study drug, romidepsin, does not require subject blood levels of potassium (K) and magnesium (Mg) to be at a certain level; therefore in this study, we will require K > 3.8 and Mg > 1.8 for eligibility, but for the rest of the treatment parameters during the course of the study we will require these electrolytes to be within normal range (WNL)
Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma
Subjects must have at least one lesion amenable to biospy
Previous immunotherapy
HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing confirmed by central testing (NeoGenomics Laboratories): \r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense AND/OR\r\n* FISH positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at NeoGenomics Laboratories, Inc. (formerly Clarient Laboratories) do not need to undergo retesting for central confirmation of HER2 status; ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status
Bilateral breast cancers are allowed as long as both cancers are HER2-positive; however, only the primary cancer’s status requires central review
Patient is fit to receive the randomization options for which he is being considered
Pure verrucous carcinoma of the penis
Notes: subjects may not have had a transfusion within 7 days of screening assessments; concomitant elevation of bilirubin and AST/ALT above the IULN is not allowed
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage; Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions); large protruding endobronchial lesions in the mail or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed; lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
Recent hemoptysis (>= 1/2 teaspoon of red blood within 8 weeks before first dose of pazopanib)
WT TP53 status
Acceptable coagulation profile
Patients with cancers likely to be Human Papilloma Virus (HPV)-positive such as cervical cancers, oropharyngeal cancers or anal cancers must undergo additional screening to determine eligibility
For Dose Escalation:
For Cohort Expansion:
Other concomitant malignancies (with some exceptions per protocol)
Has histological and/or cytological evidence of BPDCN in the peripheral blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is either previously untreated or is persistent/recurrent following prior treatment for BPDCN.
The patient is ? 18 years old.
Has histological and/or cytological evidence of BPDCN in the peripheral blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is either previously untreated or is persistent/recurrent following prior treatment for BPDCN.
The patient is ? 18 years old.
Phase II only:\r\nArms 1 and 2: disease must be determined to be HPV-unrelated; HPV-unrelated SCCHN is defined as either p16-negative oropharyngeal squamous cell carcinoma (OPSCC) or non-OPSCC (larynx, hypopharynx, oral cavity) or p16-negative unknown primary SCC presenting with a level 2 or 3 neck node; p16 will be assessed by IHC; a specimen showing any staining will be considered p16-positive\r\nArm 3: disease must be HPV-related SCCHN (defined as OPSCC or unknown primary presenting with a neck mass that is either p16 positive or HPV in situ hybridization [ISH] or polymerase chain reaction [PCR] positive)
Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
For the Monotherapy MET Amplified cohort only: MET amplification by prospective screening assay from peripheral blood; the amplification score must be “strongly positive” (++ or +++), which is defined as amplification present at a level that is observed in the upper 50th percentile of samples with amplifications
Calcium >= LLN
Magnesium >= LLN
Potassium >= LLN
Clinical diagnosis of appendiceal or colorectal neoplasm with peritoneal mucinosis or metastasis
Subjects with classical carcinoid
Tumors of low malignant potential
Subjects with a history of coronary artery disease may be included if they have had a normal stress test within 60 days of enrollment and/or were cleared by Memorial Sloan Kettering (MSK) cardiology
Evidence of extensive intraperitoneal adhesions at the time of surgery which prohibits intraperitoneal therapy, as determined by the operating surgeon
Any condition that would preclude the ability to deliver appropriate IP therapy
Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and nonamyloid forming [uninvolved] free light chain [FLC]) ? 50 mg/L.
Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required):
Renal involvement is defined as proteinuria (predominantly albumin) >0.5 g/day in a 24-hour urine collection. Note: Amyloid involvement of other organ systems is allowed, but not required.
Must meet criteria for 1 of the following AL Amyloidosis Risk Stages (as defined by N-terminal proBNP [NT-proBNP] cut-off of < 332 pg/mL and troponin T cut-off of 0.035 ng/mL as thresholds):
Stage 1: both NT-proBNP and troponin T under threshold
Stage 2: either NT-proBNP or troponin T (but not both) over threshold;
Stage 3: both NT-proBNP and troponin T over threshold (but NT-proBNP < 8000 pg/mL)
Female participants who:
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis.
Hypercalcemia, defined as a calcium of > 11 mg/dL
Must have baseline efficacy images with measurable target tumors in the liver according to RECIST 1.1 using standard imaging techniques taken within 28 days prior to randomization. Images must be taken after, or at the time of completion of first line chemotherapy
Intervention for, or compromise of, the Ampulla of Vater
Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per MSKCC or a participating site attending urologic oncologist
Serious medical co-morbidities precluding radiotherapy
Acceptable blood sugar control:
Total abstinence from sexual intercourse (? 1 complete menstrual cycle before the baseline/randomization visit).
Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream
>2 previous systemic anti-neoplastic regimens for CCA.
Men or women the age of majority in their country
has HER2 positive expression confirmed per protocol
Is suspected to have certain other protocol-defined diseases based on imaging at screening period
analysis of results
Participants with documented diagnosis of primary Myelofibrosis, post polycythemia Vera Myelofibrosis or post-essential thrombocythemia myelofibrosis
Completion of adjuvant radiotherapy according to standard guidelines (e.g. AGO Mamma, NCCN) is strongly recommended. If radiotherapy is not performed the reason for this needs to be documented in the eCRF.
A clinical-pathologic stage - estrogen/grade (CPS-EG) score of ?3, or score 2 if nodal status at surgery is ypN+, calculated using local estrogen receptor status and grade assessed on either core biopsies taken before start of neoadjuvant treatment or surgical specimen (see chapter 21.1).
Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypo¬magnesemia).
Recent (within the past year) or active suicidal behavior.
Prior histologic diagnosis of GBM or gliosarcoma at first occurrence
First or second recurrence of GBM or gliosarcoma considered to be surgically resectable
Availability of >= 4 clinical vials of HSPPC-96
No serious, non-healing wounds or ulcers
No clinical deterioration at the time of registration/randomization
Vaccination within 2 weeks of enrollment (except for annual flu vaccine).
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution’s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Subjects with HNSCC:
Carcinomas of the nasopharynx, salivary gland, or nonsquamous cell histology are excluded.
Subjects with melanoma:
Currently receiving nivolumab and considered by Investigator to have the potential to derive clinical benefit from continuing treatment with nivolumab.
Has a pre-existing condition that is contraindicated including
Non-secretory or oligo-secretory MM
Waldenström's macroglobulinemia
Primary amyloidosis
Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field.
Prior intracerebral agent.
Need for urgent palliative intervention for primary disease (e.g., rapidly increasing intracranial pressure, impending herniation, uncontrolled seizures).
In the absence of therapeutic intent to anticoagulate the patient: INR > 1.5 or PT > 1.5 xULN or aPTT > 1.5 xULN Therapeutic anticoagulation.
Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (refer to Appendix 5). A stable regimen (? 4 weeks) of antidepressants of the selective serotonin re-uptake inhibitor (SSRI) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine).
Eligible for general anesthesia (ASA category ? 3)
Acute unresolved Urinary Tract Infection (UTI)
Interest in future fertility
History of urethral and bladder outlet disorders, including urethral stricture disease, urethral diverticulae, bladder neck contracture, urethral fistulae, urethral stenting, urethral sling, urethroplasty or chronic indwelling urethral catheter
Untreated bladder stones
Active untreated gross hematuria for any cause
Post Void Residual (PVR) bladder volume > 250 mL
Obstructing median lobe enlarged out of proportion to the rest of the prostate and protruding significantly into the bladder, sometimes referred to as \ball valve\ median lobe, determined on Baseline MRI
Current unilateral or bilateral hydronephrosis
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
be intolerant of sorafenib (defined as Grade 2 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards AND 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily) AND/OR Grade 3 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards OR 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily); OR must have documented refusal of sorafenib;
Subject has been previously treated with mogamulizumab;
MM diagnostic criteria (all 3 required);
(C) Calcium elevation (serum calcium >11.5 mg/dl )(> 2.65 mmol/L)
Abnormal serum free light-chain ratio ?100 (involved kappa) or < 0.01 (involved lambda)
Cytogenetic abnormalities finding in malignant myeloma clone with t(4; 14); and / or del(17p); and / or 1q amplification; and / or t(14:16);or
Have a post-transplant response as Partial response (PR) or better at the time of enrollment to this study;
Cytogenetic abnormalities finding in malignant myeloma clone with t(4; 14); and / or del(17p); and / or 1q amplification; and / or t(14; 16); or
Serum LDH > 2 x ULN; c. Minimal residual disease (MRD) positive (defined as more than 1 malignant cell in 105 cells) measured by ClonoSIGHT NGS assay of a BMA sample) at the time of enrollment to this study; BMA sample collected at the time of multiple myeloma diagnosis, prior to induction therapy available for central MRD assessment by ClonoSIGHT NGS assay
Renal failure requiring hemodialysis or peritoneal dialysis
Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by amyloidosis
Subjects with vitiligo or alopecia;
If central pathology review indicates a diagnosis other than ATC, the participant may continue treatment with lenvatinib per standard of care, at the discretion of the treating investigator. Participants deemed to have another diagnosis (not ATC) will be taken off this study and replaced for the purpose of efficacy analyses.
Differentiated thyroid carcinoma (DTC) with focus loci of ATC is allowed. If a participant has pathology showing a small focus of ATC arising out of DTC and the measurable disease is not fully consistent with ATC, confirmation of ATC by biopsy is required.
Differentiated thyroid cancer (DTC) or MTC. However, ATC arising out of DTC is allowed, as long as the measurable disease is clinically consistent with ATC i.e., rapidly progressive and/or 18F fluorodeoxyglucose (FDG)-avid.
Radiographic evidence of major blood vessel invasion/infiltration.
HBsAg positive
For Dose Escalation:
For Cohort Expansion:
Other concomitant malignancies (with some exceptions per protocol)
Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study
Known sensitivity to any component of cisplatin, carboplatin or pemetrexed.
Agree to provide core biopsies at baseline and at Cycle 2 Day 15
Inaccessible tumors or for whom biopsy is contraindicated
Require parenteral nutrition
Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
CT scans or MRIs used to assess disease at baseline must be submitted for central review
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Are at least:
Has certain serious illnesses or medical conditions
Histological or cytological confirmation of ER+ BC as assessed by a local laboratory using slides, paraffin blocks, or paraffin sample or by medical history: ER+ (confirmed as ER expression more than or equal to 1% positive tumor nuclei)
Postmenopausal women. Postmenopausal status is defined by the National Comprehensive Cancer Network as either:
Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/mL
Current treatment with intravenous bisphosphonate or denosumab with elevated serum calcium corrected for albumin or ionized calcium levels outside institutional normal limits at screening
Relapsed or refractory pediatric B-cell ALL.
Ineligible for allogeneic SCT.
Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.
Anti T-cell therapy: Administration of any T cell or toxic agent is strongly discouraged since residual lytic levels may destroy the infused CTL019 cell or prevent their in vivo expansion.
For relapsed/refractory subjects only:
Subjects age ? 18 years with relapsed or refractory AML after ? 2 prior induction regimens, at least one containing anthracyclines
Medically eligible to receive MEC
Absolute blast count (ABC) ? 40,000/mm
Medically eligible to receive \7+3\ cytarabine/idarubicin
ABC count ? 40,000/mm
Serum free light chain (FLC) assay: Involved FLC assay ?10 mg/dL (?100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
Solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
Neuroendocrine tumors
NSCLC with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
k-RAS wild-type CRC with documented NTRK1, NTRK2, or NTRK3 rearrangement
Other solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
Hematological malignancies
Subject must not have evidence of clinically significant immunosuppression or active herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
Prior administration of other NY-ESO-1-targeting immunotherapeutics.
Associated with symptoms and/or findings; OR
Hemoglobin >= 90 g/L\r\n* Blood transfusions are allowed at any time during the screening, treatment or follow-up period, according to the center recommendations
Current participation in another therapeutic clinical trial.
No CVA21 neutralising antibody (? 1:16)
T2N1-2 or T3N0-2b tumors at =< 14 cm from the A-V margin (below the peritoneal reflection) or the rectosigmoid junction
Tumors with a lumen sufficient to allow the positioning of the rectal applicator (standard probe/scope) confirmed by the treating physician
Tumors of less than 4 cm thickness from the rectal mucosa documented at the time of staging images
Evidence of signet ring involvement on histology
Evidence of necrotic or > 1.5 cm in diameter pelvic (iliac/inguinal) nodes
Part 2, Cohort 1: For subjects with only PAM pathway alterations, subjects must have only PAM alterations, excluding Akt2 activating mutations or amplifications, and no other genomic alterations.
Part 2, Cohort 2: Histologically confirmed local laboratory testing (immunohistochemistry 3+ staining and/or fluorescence in situ hybridization ratio >= 2.0) HER2+ metastatic breast cancer subjects who are resistant to trastuzumab-containing treatment and progressed on trastuzumab, pertuzumab, a taxane, and/or trastuzumab emtansine. There is no limit regarding the number of prior lines of therapy. Subjects may be enrolled regardless of whether or not their tumor harbors a PAM pathway alteration (documentation of PAM pathway alteration for this cohort is not required).
Legal incapacity or limited legal capacity
Has ocular conditions such as:
Monocularity
Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder
Participants no longer need to be able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid
Have a known BRCA 1/2 mutation status (for participants who do not have a known BRCA 1/2 status at screening, a blood sample will be collected to determine the status with the results available prior to randomization
Participants unwilling or unable to have a central venous catheter placed will not be excluded from receiving single-agent Doxil
Men and women of all races and ethnic groups are eligible for this trial.
Have acquired, hereditary or congenital immunodeficiencies including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.
Have a known history of HIV are excluded due to the possibility that Gemcitabine or NPC-1C(NEO-102) may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to Gemcitabine or NPC-1C(NEO-102).
Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
Ongoing or recent hepatic encephalopathy
AML with inv(16), t(8;21), t(16;16), t(15;17), or t(9;22) or molecular evidence of such translocations
Have a documented diagnosis of MDS
Anemia that requires red blood cell transfusions
Must agree to follow pregnancy precautions as required by protocol.
Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
Abnormal coagulation parameters
Abnormal kidney function test results
South Western Oncology Group (SWOG) performance status 0-2
Prior fenretinide oral capsules is allowed; please consult study chair if prior history of intravenous fenretinide emulsion (allowable if drug stopped due to hypertriglyceridemia); prior 13-cis, 9-cis or all-trans retinoic acid are allowed
Extensive prior RT.
Impending need for immediate RT for symptomatic relief.
Myocardial infarction or cerebrovascular accident within one year from consultation, or other major vascular risk factor which would prevent a patient from receiving appropriate androgen deprivation therapy
Patient must be appropriate for reduced intensity regimen, according to the treating physician
Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy
The following assessments are required within 2 weeks prior to the start of registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator’s discretion
Acute paronychia developing during the course of their monotherapy or combination chemotherapy
Involvement of at least one nail with a Paronychia Severity Grading score of 1 or higher
Individuals who are already on antibiotics as prescribed by oncologist for any condition except paronychia
HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab
Individuals with inaccessible tumors or for whom biopsy is contraindicated
Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
PTT <1.5 ULN
Be vasectomized, or
Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Regular alcohol consumption averaging more than seven drinks/week for women and 14 drinks/week for men within 6 months of screening.
Histological or cytological diagnosis of ductal adenocarcinoma of the pancreas.
allow bilirubin up to 2.5 times ULN if elevation is not associated with other signs of liver toxicity or can be explained by mechanical obstruction - requires clinical research physician approval.
HER-2 positive BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (>=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
KPS > 70
Seizures occurrence or the requirement of escalation (or addition) of anti-epileptic drugs
Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
Malabsorption, total gastric resection
Coronary/peripheral artery bypass graft
For both cohorts:
has achieved menarche at some point
Male subject must:
For both cohorts:
Thrombopoiesis-stimulating agents (eg, romiplostim, eltrombopag, Interleukin-11)
Subjects with vitiligo or alopecia;
Unwilling or unable to complete subject reported outcome assessments without assistance or with minimal assistance from trained site personnel and/or caregiver.
Serum total bilirubin > 1.5 × ULN. Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis). Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs' test or over 50% of indirect bilirubin
Absolute WBC count ? 15 × 109/L. AML Cohort:
Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia.
Massive or progressive or symptomatic splenomegaly.
Massive nodes or progressive or symptomatic lymphadenopathy.
fevers higher than 100.5°F or 38.0°C for >=2 weeks without other evidence of infection
either ALC >10 000/µL, or
Eligible and able to secure sourcing for ibrutinib
Chronic persistent atrial flutter or atrial fibrillation. Patients with intermittent atrial fibrillation may be enrolled if without episode for >= 6 months and without indication for anti-coagulation
Is undergoing transplant for the treatment of nonmalignant hematological disorders (for example: aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia).
Intolerant of ibrutinib
Ongoing AE attributed to ibrutinib therapy
Post-menopausal
Patient has disease amenable to biopsy and is agreeable to undergo a biopsy; NOTE: under unusual circumstances, submission of ascites material may be acceptable if a biopsy is not possible; this exception will require approval by one of the study principal investigators
Unable to tolerate thromboembolic prophylaxis while on the study
Is a current smoker
Subjects in Cohort A may have asymptomatic LM detected by MRI. (Subjects with symptoms or signs attributed to LM will be enrolled in Cohort B whether or not they have brain metastases)
Has an active infectious process
Histologically confirmed non-keratinizing differentiated NPC or undifferentiated NPC
Urinalysis with < 2+ proteinuria
SGOT (AST) ? 3 x ULN
Anti-nuclear antibody (ANA) negative or low-positive institutional range, as determined within 28 days from registration. Intermediate values (usually defined by a titer of ?1:80, or as indicated by institutional range) are acceptable if there are, in the opinion of the Investigator, no early signs of an autoimmune disease.
Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin).
Hematological function, as follows, without transfusion support:
Disease that is measurable as defined by RECIST v1.1, mINRC, Revised Response Criteria for Malignant Lymphoma, RANO criteria (as appropriate) or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures
Prior administration of other intratumoral immunotherapeutics
Postmenopausal status as defined by the protocol
No current evidence of visceral crisis or lymphangitic spread
No visceral crisis, lymphangitic spread or known brain metastases: visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
Documentation of menopausal status: post menopausal or premenopausal subjects are eligible.
Known presence of osteonecrosis of jaw.
Lymphangitic carcinomatosis.
Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
Legal incapacity or limited legal capacity
In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Recent hemoptysis
Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene;
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Site has received notification from Mayo Clinic – Rochester Division of Hematopathology of the central confirmation of diagnosis and tissue adequacy for mandatory research studies
International Prognostic Index (IPI) of 2 or greater
Part B: Pancreatic Adenocarcinoma
Part B: NSCLC
Absence of known translocation or inversion events involving the ALK gene locus (resulting in EML4-ALK fusion)
Part B: Esophagogastric Adenocarcinoma:
Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion)
Cohort 3: Participants must have cholangiocarcinoma.
For Part E: Participants must have adenoid cystic carcinoma (ACC).
For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway.
Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).
Prior allogeneic SCT
Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and Expansion Cohorts A & B and optional, but encouraged in Escalation Cohorts 2 & 3 and Expansion Cohort C)
Diagnosis of one of the following: Part 1 Only: NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by IHC and/or detection of NUT gene translocation as determined by FISH. Subjects may be treatment naïve or have had prior therapy; SCLC, CRC, NB, TNBC, ER positive BC, CRPC, NSCLC and any other solid tumor which has been confirmed by clinical testing to be MYCN amplified (defined as a MYCN gene copy number gain of >=5). Subjects should have tumor progression after receiving at least one prior standard/approved chemotherapy, or where there is no approved therapy, or where standard therapy is refused. Part 2 only: NUT Midline Carcinoma as diagnosed by the Central Laboratory. Subjects may be treatment naïve or have had prior therapy. SCLC, CRPC, TNBC and ER+BC .
Adequate organ function as follows: Hematologic system: Absolute neutrophil count (ANC), Lab values - >=1.5 X 10^9/L; Hematologic system: Hemoglobin, Lab values - >=9.5 grams/deciliter (g/dL) (subjects that required transfusion or growth factor need to demonstrate stable haemoglobin for 7 days of 9.5 g/ g/dL); Hematologic system: Platelets, Lab values - >=100 X 10^9/Liter [L] ); Hematologic system: Prothrombin time /International normalized ratio and partial thromboplastin time, Lab values - <=1.5 X upper limit of normal (ULN). Renal system: Creatinine, lab values - <=1.5 X ULN; or Renal system: Calculated creatinine clearance [calculated by Cockcroft Gault formula], lab values - >=50 milliliter (mL)/minute (min); or Renal system: 24-hour urine creatinine clearance>=50 mL/min; Hepatic system: total Bilirubin <=1.5 X ULN (isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% or subject has a diagnosis of Gilbert's syndrome), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >=2.5 x ULN. Cardiac system: Ejection fraction, lab values - >=lower limit of normal (LLN) by Echocardiogram (ECHO) (minimum of 50%); Cardiac system: Troponin ( T), lab values - <=ULN; Cardiac system: Potassium, lab values - >=LLN and <=ULN; Cardiac system: Magnesium, lab values - >=LLN. Thyroid system: thyroid stimulating hormone, lab values >=LLN and <=to ULN. Reproductive /endocrine system: testosterone <50 nanogram (ng)/dL (only for subject with CRPC)
Besylate Sub-Study only: unable or unwilling to eat the FDA recommended high-fat high-calorie breakfast (two eggs fried in butter, two strips of bacon, 4 ounce [oz]) of hash brown potatoes and 8 oz of whole milk) within the recommended 30 minutes.
Fanconi Anemia
Participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor
Tumors must have been completely resected; in patients with tumor adherent to adjacent structures, en bloc R0 resection must be documented in the operative report or otherwise confirmed by the surgeon; near or positive radial margin are NOT exclusions as long as en bloc resection was performed; positive proximal margin or distal margin is an exclusion
Pathology confirmed by treating institution’s pathology department
Ability of patient or durable power of attorney (DPA) for healthcare to give informed consent
Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety
Clinical Masaoka stage II (> 5 cm), III, or IVA, including suspected invasion of mediastinum, pericardium, lung, great vessels or chest wall, and/or pleural metastases
Medically operable
Thymic carcinoid
History and/or current evidence of ectopic mineralization/ calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymphnodes and asymptomatic coronary calcification
Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination.
Eligibility for crossover registration from Arm A (lenalidomide alone) to Arm B (lenalidomide and epoetin alfa):
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S0919; specimens must be submitted to the site’s preferred cytogenetics laboratory
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
SGOT (AST) =< 3.0 x IULN and SGPT (ALT) =< 3.0 x IULN
History of allergic reactions attributed to the following: \r\n* Camptothecin derivatives (e.g., topotecan [topotecan hydrochloride], irinotecan, or exatecan [exatecan mesylate]) \r\n* Any ingredients contained within the liquid irinotecan solution (e.g., sorbitol) or\r\n* Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta, Neupogen)
MDS: MDS classifiable by the World Health Organization (WHO) system as RA, RARS, refractory cytopenia with multilineage dysplasia (RCMD), RCMD and ringed sideroblasts (RCMD-RS) or RAEB
MPD: Chronic idiopathic myelofibrosis with peripheral blood cytopenias
Uveal or ocular melanoma
LDH level ? 1.5 × ULN at screening
PNH diagnosis confirmed by documented by high-sensitivity flow cytometry
Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab.
Eligible 19 years and older in South Korea
Patient has been permanently discontinued from ribociclib (LEE011) in the parent protocol for any reason.
Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation.
Has mesothelioma (pleural, peritoneal, pericardial, tunica vaginalis) of any histology that is relapsed or refractory after treatment with at least one pemetrexed-containing regimen
Part 2: Molecular evidence of BAP1 loss of function mutation present on local pathology, e.g., lack of nuclear BAP1 staining by immunohistochemistry (IHC) or evidence of loss of function by gene sequencing
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment throughout their time on study
Patients with the following ocular conditions: corneal disorders, monocular vision (ie. best corrected visual acuity greater than or equal to 20/200 in one eye), or active ocular disorders requiring treatment
Hematological:
Hematocrit ?30%
Coagulation:
The trial is open to both genders
Must have documented ALK rearrangement.
Subjects must not be on home oxygen therapy (intermittent or continuous).
The patient must have completed at least 4 months of adjuvant chemotherapy (i.e., FOLFOX, CapeOx, or other, such as 5-fluorouracil, leucovorin, oxaliplatin (FLOX), 5-fluorouracil/leucovorin (5FU/LV), capecitabine).
Isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Gastroduodenal ulcer(s) determined by endoscopy to be active.
Symptomatic peripheral ischemia.
Karnofsky performance status (KPS) >= 70% at time of enrollment; an exception will be made for those with lower KPS at enrollment with an acute worsening that is likely to resolve in the treating physicians judgment (e.g., reversible infection, trauma, medication reaction, etc)
Patient willing to consider HCT
Prior formal search was instituted
Identification of a drug target/targets through molecular profiling performed as a part of routine clinical care and treatment recommendation by the Mayo Clinic Genomics Tumor Board (GTB); NOTE: If profile matches more than 1 treatment arm, final decision for treatment arm assignment to be made by patients treating physician; it will be required for the genomic aberration to be identified through a test in a Clinical Laboratory Improvement Amendments (CLIA) workflow; assays used will range from single gene abnormalities (e.g. fluorescent in situ hybridization [FISH] for human epidermal growth factor receptor 2 [ERBB2] amplifications) to next generation sequencing based gene panels (Foundation One®) to more comprehensive assays such as whole exome sequencing; the Mayo Clinic GTB will serve as the centralized point of data synthesis to allow for assessment of molecular profiling accomplished through a heterogeneous array of tests
Patient meets all sub-protocol specific criteria of each applicable sub-protocol
Ability to complete questionnaire(s) by themselves or with assistance
SUB-PROTOCOL AIM A: Confirmation of advanced cancer with mTOR pathway aberrations as determined through routine clinical care using pathway aberrations performed in a CLIA certified laboratory; cancer genomic profiling tests incorporating next generation sequencing from archival formalin-fixed paraffin-embedded tissue (FFPE) are validated with sensitivities and specificities of 99% and 99%, respectively; in the assay, hybrid-capture–selected deoxyribonucleic acid (DNA) libraries are sequenced to depths targeting > 500 × coverage by non-polymerase chain reaction (PCR) duplicate read pairs, with > 99% of exons at coverage > 100 ×); multiplatform profiling may include immunohistochemistry and in situ hybridization methods with previously established negative/positive cutoffs performed in a CLIA certified lab; at least one pathway aberration must be identified; these must be confirmed in a CLIA certified lab; the potential mTOR aberrations that could be identified are listed below, please note that this list is not all inclusive; if a CLIA validated report lists an mTOR pathway inhibitor as a target drug for a genetic aberration, then it can be considered eligible for the purposes of this study; v-akt murine thymoma viral oncogene homolog 1 (AKT1), MTOR, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tuberous sclerosis (TSC)1, TSC2, retrovirus-associated DNA sequence (Ras) homolog enriched in brain (RHEB), serine/threonine kinase 11 (STK11), neurofibromin (NF)1/2
SUB-PROTOCOL AIM A: Serum cholesterol =< 350 mg/dL
SUB-PROTOCOL AIM A: Serum triglyceride =< 300 mg/dL
Known CD20-negative status at relapse or progression
Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib.
Female subject must either:
Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
No prior therapy with IL-15 or IL-15 analog
No positive Hep C serology or active Hep B infection
The 'worst pain' in the last 24 hours must be reported to be 4 or above on a scale of 0 (no pain) to 10 (pain as bad as subject can imagine)
First or second progression of Glioblastoma;
Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
HPV- negative SCCHN tumor as determined per institutional standard (eg, p16 IHC; multiplex nucleic acid sequence based amplification [NASBA] or other polymerase chain reaction [PCR]-based assays).
Difficulty swallowing capsules.
May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.
Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
Blood sample sent for free IGF-1 testing
at least one bidimensionally measurable, PET positive disease site (transverse diameter of ?1.5 cm and perpendicular diameter of ?1.0 cm at baseline)
refrain from breastfeeding and donating blood or oocytes
Males (if sexually active with a FCBP) must
refrain from donating blood or sperm
be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events
be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and give written acknowledgement of this.
primary refractory DLBCL
were previously treated with CD19-targeted therapy or IMiDs® (e.g. thalidomide, LEN)
CRLX101 or with any topoisomerase I therapy;
Ocular or uveal melanoma
Documented IDH1R132-mutant tumors
HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA
Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc positive, but viral DNA negative are not eligible
LVEF < 50%
Primary mediastinal DLBCL.
Moderate eye disorders
A valid cobas PIK3CA mutation result by central testing is required
Proteinuria < trace
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population.
Soft-tissue progression defined as an increase ? 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions.
Soft-tissue progression defined as an increase ? 20% in the sum of the diameter (SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD, or the appearance of one or more new lesions, since the onset of the most recent prior therapy
Subjects may be Brentuximab vedotin- naïve, or may have had prior Brentuximab vedotin treatment (cohort A, B & C - enrolment closed)
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
Currently enrolled in study CCL09101E, or YM387-II-02, or successfully completed 24 weeks of study GS-US-352-1672
History of prior cumulative exposure to >= 300 mg/m^2 cisplatin, area under the curve (AUC) of 18 of carboplatin, or their combined equivalent within one year prior to enrollment
Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV; patients must be at least 3 months from the last dose of BV
Untreated for metastatic colorectal cancer or progression on any first line fluorouracil (5-FU) containing regimen (such as leucovorin calcium, fluorouracil, oxaliplatin [FOLFOX] or irinotecan, fluorouracil, leucovorin calcium [FOLFIRI])
Subjects must voluntarily sign an ICF;
Subjects must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
Subjects must not be candidates for ruxolitinib based on EITHER:
Patients with ventricular tachycardia or supraventricular tachycardia that requires treatment with a class Ia antiarrhythmic drug or class III antiarrhythmic drug
Complete left bundle branch block (LBBB)
Serum potassium levels outside the laboratory’s reference range
Serum magnesium levels outside the laboratory’s reference range
Serum calcium levels outside the laboratory’s reference range
Adults (aged ? 18 years)
Serum cardiac troponin (cTn) level ? 99% percentile of the upper reference limit
Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks before the first dose of CPI-0610
Off all other treatments for MDS, CMML, or AML including an erythropoiesis-stimulating agent (ESA), for at least 4 weeks prior to Screening. Filgrastim (G-CSF) is allowed before and during the study, as clinically indicated.
Willing to adhere to the prohibitions and restrictions specified in this protocol.
Hyponatremia (defined as serum sodium value of < 130 mEq/L).
Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
Postmenopausal women. Postmenopausal status is defined either by:
Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
Resting heart rate 50-90 bpm
Documented cardiomyopathy
Newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib
Potassium, magnesium, phosphorus and total calcium values ? LLN (lower limit of normal)
Sufficient physiological reserves
Prior allogeneic HSCT
Exudative, bloody, or cytologically malignant effusions
Patient must have magnesium, calcium, glucose, potassium and sodium levels within normal limits
Hepatic insufficiency resulting in clinical jaundice and/or Coagulation defects
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Main portal vein thrombosis
Contraindications to angiography and selective visceral catheterization
Taking any other systemic anticancer agent (docetaxel, doxorubicin, irinotecan)
Taking any substrate agents for CYP 2B6 (bupropion, cyclophosphamide, efavirenz, ifosfamide, methadone, paclitaxel, amodiaquine, repaglinide)
Taking any UGT 1A1 and UGT 1A9 substrates (e.g. irinotecan)
Taking P-Gp substrates (e.g. Digoxin)
Intervention for, or compromise of, the Ampulla of Vater
Patients who meet International Federation of Gynecology and Obstetrics (FIGO) stage I, II, or III criteria for low-risk gestational trophoblastic neoplasia (GTN): post molar GTN or choriocarcinoma (as defined below); patients may have had a second curettage but must still meet GTN criteria below:\r\n* Post molar GTN\r\n** For the purposes of this study, patients must have undergone evacuation of a complete or partial hydatidiform mole and then meet the criteria for GTN defined as:\r\n*** A < 10% decrease in the hCG level using as a reference the first value in the series of 4 values taken over a period of 3 weeks (> 50 mIU/ml minimum) OR\r\n*** A > 20% sustained rise in the hCG taking as a reference the first value in the series of 3 values taken over a period of 2 weeks (> 50 mIU/ml minimum) OR\r\n*** A persistently elevated hCG level a period of 6 months or more following the initial curettage (> 50 mIU/ml minimum)\r\n* Choriocarcinoma\r\n** Histologically proven non-metastatic choriocarcinoma OR\r\n** Histologically proven metastatic choriocarcinoma if the metastatic site(s) is restricted to one (or more) of the following: vagina, parametrium, or lung
Granulocytes >= 1,500/mcL
Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy
DLBCL-2 cohort:
For PCNSL cohort:
Primary GBM or gliosarcoma
No prior or scheduled Gliadel® wafer implant unless area of assessment and planned resection is outside the region previously implanted.
No prior interstitial brachytherapy or stereotactic radiosurgery unless area of assessment and planned resection is outside the region previously treated.
Must be Pomalidomide naïve.
Known symptomatic acute or chronic pancreatitis.
Complete left bundle branch, or bifasicular block.
Troponin-T value > 0.4 ng/ml or BNP >300 pg/mL. ° Subjects with baseline troponin-T >Upper Limit of Normal (ULN) or B-type Natriuretic Peptide (BNP) >100 pg/mL are eligible but must have cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy.
Submission of original biopsy for review by hematopathologist at local institution
Plts > 75,000/mcL
Complete supportive and palliative care will continue to be provided to ameliorate signs and symptoms that were pre-existing or may arise while on study and which do not interfere with the objectives of the study
All subjects must be capable of swallowing multiple capsules
Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.
Known or suspected defect in the function of the urea cycle.
Adenocarcinoma of the prostate treated primarily with radical prostatectomy\r\n* Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy
Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (?50%) epithelial component
Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
Appendiceal adenocarcinoma basket\r\n* Metastatic appendiceal adenocarcinoma\r\n* Not considered candidate for curative surgery
Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
Appendiceal adenocarcinoma basket\r\n* Complete or partial bowel obstruction
Epstein-Barr virus-associated nasopharyngeal carcinoma basket:\r\n* None
Human papilloma virus-associated cancers basket\r\n* None
Peritoneal mesothelioma basket:\r\n* None
Creatine phosphokinase (CPK) ? 2.5 × ULN.
Concomitant diseases/conditions:
Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart).
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
The trial is open only to women with primary endometrioid adenocarcinoma of the uterine corpus (all histologic grades and stages) who are planned and appropriate for primary surgical treatment
Granulocytes (ANC) >= 1,500/mcl
Adequate iron stores, defined as transferrin saturation greater than 20 percent (%) and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain
Platelets inferior to 75 000 cells per µL if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per µL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within three days before the screening visit.
Corrected serum calcium superior to 14 mg per dL (superior to 3.5 mmol per L).
Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt), and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, or H2 blockers that would prohibit further treatment with these agents.
Part B only: 5. Histologically or cytologically confirmed, molecularly selected (i.e. BRAFV600 positive and/or PI3K mutation positive) advanced solid tumors. Prior molecular characterization should be based using a regulatory approved assay or analytically validated assay.
known glaucoma or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities.
PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
LDH level ? 1.5 × ULN at screening.
Non-epithelial, including malignant mixed Mullerian tumors
Ovarian tumors with low malignant potential (i.e. borderline tumors)
Any prior radiotherapy to the pelvis or abdomen
Must be in need of therapy as evidenced by at least one of the following criteria: \r\n* Bulky disease defined as:\r\n** A nodal or extranodal (except spleen) mass > 7 cm in its greater diameter or,\r\n** At least 3 nodal or extranodal sites >= 3 cm in diameter\r\n* Presence of at least one B symptom:\r\n** Fever (> 38 C) not due to infectious etiology\r\n** Night sweats\r\n** Weight loss > 10% in the past 6 months\r\n* Fatigue due to lymphoma\r\n* Splenomegaly (> 13 cm)\r\n* Compression syndrome (ureteral, orbital, gastrointestinal)\r\n* Any of the following cytopenias due to lymphoma:\r\n** Hemoglobin =< 10 g/dL\r\n** Platelets =< 100 x 10^9/L\r\n** Absolute neutrophil count (ANC) < 1.5 x 10^9/L\r\n* Pleural or peritoneal effusion\r\n* Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta-2 microglobulin > ULN
No indication of distant metastases
adenocarcinoma of the pancreas,
cholangiocarcinoma
Subjects must have normal or clinically insignificant ECG at screening
Corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy, or may interfere with diagnosis of treatment-emergent corneal epitheliopathy at the ophthalmologist's or the investigator's discretion
biliary cirrhosis
malignant biliary obstruction unless the bile flow to the gastrointestinal tract is maintained by a fully operational biliary stent
Poor CYP2D6 metabolizers based on the screening test for genetic polymorphisms in CYP2D6 metabolizing capacity
Study Arm 1:
Study Arm 2
All Study Arms:
Study Arm 1
Study Arm 2
All Arms:
5. Subject who is willing and able to undergo biopsy.
Arm A only: ImiDs (eg, lenalidomide, thalidomide);
Arms C only: bendamustine
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures;
Prior therapy with agents that target Phosphatidylinositide 3-kinases (PI3K), Protein kinase B (AKT), or mechanistic target of rapamycin (mTOR). Participants with known hypersensitivity to everolimus or rapamycin derivatives are also excluded.
Available CD34+ stem cells
Other active serious illnesses
Lack of availability for immunological and clinical follow-up assessments.
Subjects with ocular melanoma
Have adequate biliary drainage.
For Cohort 1: has documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib
Participants unwilling to exclude grapefruit juice and grapefruit from their diet.
Diagnosis of leptomeningeal carcinomatosis
Active herpetic skin lesions or prior complication of herpes simplex virus (HSV)-1 infections (e.g. herpetic encephalitis or keratitis)
ANC ?1.5×10^9/L
Clinically suspected Grades IIB to IVD acute GVHD as per modified MN-CIBMTR criteria, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
Inadequate recovery from toxicity and/or complications from the prior allo-HSCT.
Vertebral body site to be treated is located from C3 to L5
Requires open spinal procedure or a percutaneous procedure without the use of image guidance
Unable to tolerate general anesthesia and prone position
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, has not been treated). If re-enrolled, the subject must be re-consented.
EPd Cohort:
EN Cohort:
Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cells dyscrasia
Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cells [WBC] <20,000 per microliter [/mcL]) or low blast AML based on 1 of the following: French American British (FAB) Classifications:
Female participants who:
Are postmenopausal for at least 1 year before the Screening visit , or
involvement of pterygopalatine fossa, maxillary sinus, or facial skin;.
pterygoid plate erosion;
direct extension to involve prevertebral fascia;
extension to superior nasopharynx or Eustachian tube;
suspected invasion (encasement) of the common or internal carotid arteries. Encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270º or greater;
direct extension to mediastinal structures;
regional metastases to the supraclavicular neck (low level IVB or VB)
RB status
Diffuse Intrinsic Pontine Glioma (DIPG) Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined on neuroimaging as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation.
Note: Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, pleomorphic xanthoastrocytoma with or without anaplasia, gangliogliomas, or other mixed gliomas without anaplasia are not eligible.
Bi-thalamic tumors, biopsied and noted to have intact RB. Bi-thalamic tumors that are not biopsied will be eligible to enroll on the DIPG/bi-thalamic non-biopsied arm.
AND RB positive noted on immunohistochemistry.
ALT (SGPT) ? 2.5 X ULN for age
Documented cardiomyopathy
Note: If a BP reading prior to enrollment is above the 95th percentile for age, height and gender, it is to be rechecked and documented to be ? 95th percentile for age, height and gender prior to patient enrollment.
Relapsed or refractory with at least one (FL) or two (MCL), but not more than four, prior lines of antineoplastic regimens.
Sensitive CYP2D6 substrates or CYP2D6 substrates with NTI
Selected dual substrates of CYP3A4/5 and CYP2C8
Selected dual substrates of CYP3A4/5 and CYP2D6
Selected dual substrates of OATP and CYP450
Selected dual substrates of CYP3A4/5 and P-gp
NTI P-gp substrates
For participants with DLBCL: preplanned consolidative radiotherapy
Diagnosis of advanced or metastatic NSCLC. Group A must be ALK negative NSCLC and Group B must be ALK positive NSCLC
Group B any number of prior regimens.
All subjects must have radiologic or pathologic evidence of ? 2 skeletal lesions with or without pain at baseline on bone scan or axial imaging or 1 skeletal lesion and bone pain within 28 days prior to the registration.
Subjects must fall into one of the two populations below:
Anti-androgen receptor antagonist therapy must be bicalutamide. Subjects already started on other anti-androgens must be willing to switch over to bicalutamide.
Subjects must consent to bank whole blood, serum, plasma for future unspecified studies.
Prior concomitant therapy with ketoconazole, aminoglutethimide or abiraterone acetate or enzalutamide (MDV3100) or intent to treat with the above. Concurrent megestrol for hot flashes is allowed.
Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188.
No direct evidence of regional or distant metastases after appropriate staging studies;
Pre-existing hearing impairment
Requires total parenteral nutrition and is unable to swallow pills or unable to take a suspension through a gastrostomy tube
Stopped initial treatment with MK-3475 after attaining an investigator-determined confirmed response according to RECIST1.1 response criteria
CLL/SLL cells must demonstrate one or more of the following high-risk genomic features:\r\n* Del17p13.1(tumor protein p53 [TP53]) as detected by fluorescence in-situ hybridization (FISH)\r\n* Del11q22.3(ataxia telangiectasia mutated [ATM]) as detected by FISH\r\n* Complex karyotype (>= 3 cytogenetic abnormalities on stimulated karyotype)\r\n* Unmutated immunoglobulin variable region heavy chain (IgVH) ( >= 98% sequence homology compared with germline sequence)\r\n* Zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) gene promoter hypomethylation < 20%
Consented to genome sequencing and database of genotypes and phenotypes (dbGaP)-based data sharing and has provided or will provide germline (peripheral blood mononuclear cell [PBMC]) and tumor DNA/ribonucleic acid (RNA) samples of adequate quality for sequencing; (acquisition of specimens for sequencing and the sequencing itself may be done under this study or as part of routine care or another research project)
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids
Inadequate tissue acquisition to allow for neoantigen screening
No candidate neoantigen identified during screening
ANC ?1500/?L
NYHA ? Class 2.
Participants must meet protocol specified hematology and chemistry lab parameters criteria
Glycosylated hemoglobin (HbA1c) >=7.5 percent (%)
Prior irradiation to lung fields
Requirement for any excluded medication as specified in protocol
A pathologically confirmed (histology or cytology) malignant neoplasm with at least one target lesion that is confirmed by conventional imaging and is determined to express somatostatin receptors by 68Ga-DOTATOC (TATE) PET within 120 days prior to treatment with 90Y-DOTATOC
Completion of Norfolk Quality of Life Questionnaire
Urinalysis with no greater than 1+ hematuria or proteinuria
Prior PRRT with 90Y-DOTATOC (tyr3-octreotate [TATE]) or 177Lu-DOTATOC (TATE) or 131I-metaiodobenzylguanidine (MIBG) therapy for this malignancy
Any subject for whom, in the opinion of their physician, a 12-hour discontinuation of somatostatin analogue therapy represents a health risk; also subjects who have received long-acting somatostatin analogue in the past 28 days or long-acting lanreotide within the past 16 weeks are excluded; subjects may be maintained on short acting octreotide during the time from last injection of long-acting somatostatin analogue until 12 hours (hrs) prior to injection of study drug; known antibodies to octreotide, lanreotide, or DOTATOC or history of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTATOC
Subject weighs more than 450 pounds; (subjects who weigh more than 450 pounds will not be able to fit inside the imaging machines)
KPS ?70.
ER/PgR negativity to follow local guidelines
Candidate for first-line therapy with sunitinib initiated 5-8 weeks after nephrectomy
Adequate hematological parameters, i.e:
B-Leukocyte count ?4.5 x10e9/L
Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening disqualifying the patient from nephrectomy and from subsequent sunitinib treatment
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
Abnormal and clinical significant coagulation parameters at the discretion of the Investigator, i.e.:
Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction)
A signed Patient Authorization Form (HIPAA) has been obtained prior to registration
Complete Metabolic Profile (CMP) within normal limits
Normal carcinoembryonic antigen (CEA) prior to study entry
Any congenital or acquired condition leading to compromised ability to generate an immune response
Requirement for continual immune suppression
Presence of meningeal carcinomatosis
Participation in any other clinical trial
Those have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
Previously treated with ruxolitinib (unless not a good candidate for ruxolitinib therapy in the judgment of treating physician)
Patients must have high grade upper tract urothelial carcinoma proven by one of the following:\r\n* Biopsy;\r\n* Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or\r\n* Urinary cytology and a mass visualized during upper urinary tract endoscopy
Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
Hematocrit >= 30%
Unwilling to undergo two leukapheresis procedures; if patients are unable to undergo the leukapheresis procedures, then a 200-cc blood draw (green heparinized tubes) is permitted in place of the leukapheresis
HBV viral load (VL) <200 IU/mL (approximately 1000 cps/mL)
Subjects HCV-positive after successful treatment (defined as sustained virologic response [SVR] 12 or SVR 24) are allowed as long as 4 weeks have passed between completion of HCV therapy and start of study drug
Are currently enrolled in another clinical trial.
Have clinical evidence of concomitant infectious conditions.
Patients can have either failed BCG induction therapy within a six-month period or have been successfully treated with BCG, but subsequently found to have recurrence. The first standard course of intravesical BCG therapy must include at least six weekly treatments (allowable range of instillations per course is 4-9). The second course of BCG therapy must include at least two weekly treatments.
Radical cystectomy has been declined by the patient in a signed special section of the informed consent, whereby there is a clear explanation by the investigator to the subject that a delay of cystectomy may increase his/her chance of disease progression, the results of which may lead to serious and life threatening consequences.
PT/INR, PTT, and fibrinogen within institutional acceptable limits
Previous lung or mediastinal radiotherapy
Cannot achieve acceptable stereotactic ablative radiation therapy (SABR) planning to meet minimal requirement of target coverage and dose-volume constraints of critical structures
Epithelial type
Prior systemic therapy or radiotherapy for MPM; local radiotherapy of noncurative intent (ie, for prevention of instrument-tract recurrence and/or symptom control) is permitted
Currently have mesothelioma of the sarcomatous type, mixed histologic disease, or have malignant peritoneal mesothelioma
Patients with refractory cancer pain who are seen by the supportive care or pain medicine teams, and who either (1) are on appropriate opioid therapy at the time of consultation, or (2) who undergo an initial consultation and at least 2 clinical follow-up evaluations by these services
Waldenström macroglobulinemia
Amyloidosis
Willing to adhere to medically accepted form of birth control to prevent pregnancy (includes: complete abstention from intercourse, condoms, diaphragms, cervical cap, intra-uterine device, history of surgical sterility – tubal ligation or vasectomy in patient or partner, or oral contraceptive)
Requirement for active immunosuppression to treat GVHD
Eastern Cooperative Oncology Group (ECOG) performance status =< 1; ECOG 0 indicates that the patient is fully active and able to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature
DONOR: Positive or reactive test results for Food and Drug Administration (FDA)-mandated relevant communicable diseases (HIV, hepatitis B [hep B], hepatitis C, human T-cell lymphotropic virus [HTLV], Syphilis, Trypanosoma [T.] cruzi)
Primary systemic AL (immunoglobulin light chain) amyloidosis
Participants with adenocarcinoma of the esophagus are excluded.
Has anaplastic oligodendroglioma
The tumor must be unifocal, confined to the supratentorial compartment and have undergone a gross total or near gross total resection; this will increase the likelihood that the patient will not require corticosteroids or develop pseudoprogression
Blood urea nitrogen (BUN) =< 30 mg/dl
Prior placement of Gliadel wafer or local brachytherapy
Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable)
Have unresectable malignant mesothelioma (any histology)
Requirement for constant administration of proton pump inhibitor, histamine 2 (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
Prior administration of an aurora A kinase-targeted agent, including alisertib
Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become incarcerated during the study
Identified deleterious mutation in BRCA 1 or 2 genes (this does not include variants of uncertain significance)
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
Not consenting to participate in LAB00-099
Patient is premenopausal or perimenopausal at the time of study entry
Patient is postmenopausal
Patient is currently using other antineoplastic agents
Haemoglobin ? 9 g/dL
Hereditary complement deficiency
No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.
The diagnosis of mCRC will be based on histologic or cytologic confirmation
Serum bicarbonate >= 20 mEq/L
Has known renal tubular acidosis with serum bicarbonate < 20 mEq/L
In the phase II portion, patients must be newly diagnosed or imatinib treatment naive in the advanced/metastatic setting; prior adjuvant imatinib therapy is allowed as long as disease recurrence was documented >= 90 days after last dose of imatinib and imatinib has not yet been restarted
Active corneal disorder or keratopathy (e.g. corneal abrasion, bullous keratopathy)
Concomitant malignancies
ECG abnormalities as defined by the protocol
Allergies or hypersensitivities to monoclonal antibodies, BMS-986012 or related compounds, including fucosyl-GM1 vaccine and Nivolumab
Have postmenopausal status
Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis
African American adults who are interested in quitting and whose smoking patterns meet criteria for non-daily smoking as determined by eligibility screening
Contraindications to behavioral counseling, nicotine gum, patch, or lozenge and unable to complete study procedures as determined by eligibility screening
Caution should be taken with the use of hydroxychloroquine and any drugs known to interact with it; it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians’ Desk Reference may also provide this information
Lipid panel:
Total abstinence or;
Use caution when co-administered with moderate CYP3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem).
Grapefruit, grapefruit juice, and other foods known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment.
St. John's Wort may decrease everolimus exposure unpredictably and should be avoided.
current or prior dialysis,
household contact with hepatitis B infected patient(s),
body piercing or tattoos,
history suggestive of hepatitis B infection, e.g., dark urine, jaundice, right upper quadrant pain.
blood transfusions prior to 1990,
current or prior dialysis,
household contact of hepatitis C infected patient(s),
For patient with LM, inability to undergo collection of CSF
Known intracranial haemorrhage which is unrelated to tumour
Clinical stages T1b – T3a
Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (GCP) guidelines and to the local legislation
Any form of active primary or secondary immunodeficiency
All metastases not resected must be amenable to SBRT
The patient must meet ONE of the three following criteria:\r\n* 3-4 radiographically distinct metastases of any distribution in the allowed anatomical sites OR\r\n* 2 radiographically distinct metastases that must be anatomically close (i.e., with less than or equal to 5 cm of normal tissue between them) OR\r\n* 3 or 4 distinct metastasis, 2 or 3 to be treated with SBRT and the other (s) having been surgically removed
Metastases with indistinct borders making targeting not feasible
Metastases located within 3 cm of the previously irradiated structures:\r\n* Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)\r\n* Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)\r\n* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)\r\n* Brain stem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)\r\n* Whole lung previously irradiated with prior volume 20 Gy (V20Gy) > 30% (delivered in =< 3 Gy/fraction)\r\n* Primary tumor irradiated with SBRT\r\n* Metastasis irradiated with SBRT
Haemoglobin >=9 g/dL.
Archive tumour tissue is available prior to recruitment for pharmacogenomic tests
Prior therapy with agents targeting Insulin Growth Factor (IGF) and/or Insulin Growth Factor Receptor (IGFR) pathway.
Inability to receive a port or peripherally inserted central catheter (PICC) line
Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower
Satisfactory completion of dosing & efficacy assessments in ISIS 420915-CS2
Known KRAS or NRAS mutations:\r\n* All patients must have molecular testing performed in a clinical lab which includes codon 12 and 13 of KRAS; patients with any mutation in codon 12 and 13 of KRAS are not eligible for the protocol\r\n* Testing for additional codons in KRAS or testing for NRAS is not required; however, if such testing has been performed in a clinical lab and any mutation in codons 61 or 146 in KRAS, or codons 12, 13, 61, or 146 in NRAS is detected, the patient is not eligible for the protocol
SPECIMEN SUBMISSION CRITERIA:
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Sarcomatoid malignant pleural mesothelioma (MPM) histology which is known in the literature to not express mesothelin; biphasic MPM is also excluded
Previous experimental therapy with SS1 moiety, murine or chimeric antibodies (human and humanized antibodies are allowed)
Agree to follow a low lycopene and phytoene diet
Potassium 3.4 – 5.0 mmol/L
Inability to assess BRAF or NRAS mutation status; hypersensitivity to digoxin
Wolff-Parkinson White syndrome or first/second/third degree atrioventricular (AV) block or sinus node dysfunction or the presence of an intra-cardiac defibrillator
Must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past
Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom.
Concurrent corneal disorder or ophthalmologic condition making subject unsuitable
Uveal or ocular MEL
Participants with intracardiac defibrillators.
Radiographically documented evidence of major vessel invasion or encasement by cancer.
Good candidate for treatment per protocol in the judgement of the principle investigator (PI) and/or treating physician follow stimulation
Postmenopausal status
Premenopausal status
Diagnosis of systemic lupus erythematosus, scleroderma, or dermatomyositis
Unsatisfactory breast for HG-PBI as determined by the treating physician; for example, if there is little breast tissue remaining between the skin and pectoralis muscle after surgery, treatment with HG-PBI is technically problematic
Partial mastectomy so extensive that the cosmetic result is fair or poor prior to HG-PBI as determined by the treating physician
Time between final definitive breast procedure to HG-PBI simulation is greater than 8 weeks
Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia
NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies
No restriction based on prior treatments
Histological confirmation of glioblastoma
Proteinuria level =< 2+
Deteriorating neurological symptoms, or need for increasing doses of corticosteroids or new onset of seizures between the screening assessment and cycle 1 day 1
Target Population
Subjects with carcinomatous meningitis
Subjects with coagulopathies, including thrombocytopenia
International prognostic index (IPI) score must be 2-5
Treatment-related mortality (TRM) score =< 6.9 as calculated with simplified model
Concomitant illness associated with a likely survival of < 1 year
Deleterious or pathogenic germline BRCA 1 or BRCA 2 mutation
Prisoners or subjects who are involuntarily incarcerated
Has a known DPD deficiency
Certain serious illnesses or medical conditions
Has had prior gastrectomy
Has known sensitivity to capecitabine or metabolites
Acceptable coagulation status
Known past or current coagulation defects.
Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B
Presence of an index lesion between 1 and 5 cm
Ability to tolerate stereotactic body radiation therapy (e.g. lie flat and hold position for treatment)
Palpable splenomegaly at least 5 cm below the left costal margin
Confirmed diagnosis of PMF or post-PV/ET MF
Peripheral blood blast count < 10%
Prior splenectomy
Any menopausal status
On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization.
Circulating human anti-mouse antibody (HAMA), to be determined before each infusion
Southwestern Oncology Group (SWOG) performance status >= 2.0
Radiographic evidence of cavitary or necrotic tumours or local invasion of major blood vessels by MPM
Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
Patients must have one of the following: elevated beta (b)2-microglobulin levels (defined as 2 times compared to normal), carry a Janus kinase 2 (JAK2) mutation, or presence of phosphorylated p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) component in at least 5% of bone marrow cells
Serum magnesium >= the institutional lower limit of normal (supplementation of electrolytes prior to screening is allowed)
Serum potassium >= the institutional lower limit of normal (supplementation of electrolytes prior to screening is allowed)
Adjusted (or ionized) calcium >= the institutional lower limit of normal (supplementation of electrolytes prior to screening is allowed)
Patients currently taking one or more of the following drugs that are generally accepted to have a risk of causing Torsades de Pointes:\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, sotalol, ibutilide, dofetilide\r\n* Erythromycins, clarithromycin\r\n* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Tolerate one test dose (15 g) of ascorbate
G6PD (glucose-6-phosphate dehydrogenase) deficiency
Two or more breast cancers not resectable through a single lumpectomy incision
Neoplastic mast cells must express CD30 by immunohistochemistry or flow cytometry
Any other significant medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the PI
Blood urea nitrogen (BUN) < 1.5 times ULN
Sodium (Na), potassium chloride (K Cl), carbon dioxide (CO2), calcium (Ca), phosphate (PO4) within institutional limits
Platelets >= 100 x 10^9 (SI units 10^9/L)
Prior splenectomy
Concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin) during the study
The lesion is suitable for repeat measurement
Clear invasion into the bile duct
Portal vein invasion at the main portal branch (Vp4)
Meningeal carcinomatosis
Surgical arterial-portal venous shunt or arterial-venous shunt
Known intolerance to lenvatinib or sorafenib (or any of the excipients)
Ongoing diarrhea defined as more than 1 watery stools/day.
Primary uveal or mucosal melanoma
Active herpetic skin lesions or prior complications of herpes simplex type-1 virus (HSV-1) infection (eg, herpetic keratitis or encephalitis).
COHORT 3 (RARE HISTOLOGIES)
ALL COHORTS
Metabolic acidosis, acute or chronic, including ketoacidosis
Negative tuberculosis quantiferon test for anakinra arm.
Negative serology for histoplasma, blastomycosis, and coccidiomycosis for anakinra arm.
Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER, RR)
Cardiovascular dysfunction or Respiratory Failure due to sepsis.
Coagulopathy characterized by an INR >1.40 without other known causes.
Subject has an advance directive to withhold life-sustaining treatment.
Platelets < 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is not due to sepsis.
History of head trauma, spinal trauma, or other acute trauma with an increased risk of bleeding within 3 months prior to consent.
History of congenital bleeding diathesesor anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia).
Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture or gram stain consistent with bacterial infection.
Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine output < 0.3 ml/kg/hr) > 48 hours prior to first dose of study drug whether receiving RRT or not
Confirmed or suspected endocarditis
Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but with one log BCR-ABL reduction (BCR-ABL level >10% IS) 3 months of imatinib 400mg treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within the 3 month period before randomization). Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)
Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement
Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening)
Radiographic progression on bevacizumab by Revised Assessment in Neuro-Oncology (RANO) criteria
Persons with positive sentinel nodes must have a complete lymphadenectomy
Diagnosis of non-cutaneous melanoma or melanoma with unknown primary origin
ANC ? 1500 /?L
Subjects who desire to enroll in this study and for whom anti-HER-2 therapy is not available or contraindicated, may be eligible to enroll in this trial.
During the study period, subjects using hormonal therapy and bisphosphonates should maintain a constant dose and should not change existing regimen.
However, if a change in hormonal therapy is indicated, e.g. due to intolerable adverse effects, the regimen may be modified but change should be minimized thereafter.
Subjects with splenectomy.
e.g. Type 1 juvenile onset diabetes mellitus, antibody positive for rheumatoid arthritis, Grave's disease, Hashimoto's thyroiditis, lupus, scleroderma, systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, etc
Autoimmune disorders confined to the skin (e.g. psoriasis) are eligible, and topical steroids are allowed for the treatment of such skin disorders.
Anti-neoplastic agents
Immunotherapy [mAbs, Interferons, Cytokines (except GCSF)]
Subjects with bladder inflammation and urinary outflow obstruction.
Circulating antibody against mouse immunoglobulin (HAMA)
Plasmacytomas > 1 cm in marrow areas measured by magnetic resonance imaging (MRI) or extramedullary plasmacytomas (radiated lesions are exempt from this criteria); patients may receive cytoreductive therapy, including allogeneic stem cell transplant (ASCT) (if high risk) or second ASCT (if failed a prior ASCT) to achieve disease control, but may not receive any cytoreductive therapy within 30 days of the dosimetry infusion and must have bone marrow cellularity meeting inclusion criteria obtained at least 21 days after any cytoreductive/myelosuppressive chemotherapy was last administered
Part I: Subjects must have relapsed or refractory B cell NHL
SCREENING
SCREENING
Hemoglobin >= 9.0 grams/deciliter
Mantle cell lymphoma International Prognostic Index (IPI) (MIPI) score must be calculated and entered in Oncology Patient Enrollment Network (OPEN)\r\n* NOTE: for this calculation white blood cell (WBC) 7,500/mm^3 = 7,500/uL = 7.5 x 10^9/L should be entered as 7500
Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing pro-thrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips)
Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing pro-thrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g uninterrupted long car or plane trips)
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Subject is know to have active tuberculosis, leishmaniasis, or listeriosis
Newly diagnosed previously untreated ALL or lymphoblastic lymphoma; allow urgent administration of cytarabine/hydroxyurea (hydrea)/all-trans retinoic acid (atra) prior to starting treatment on protocol; allow previous administration of up to one course of hyper-CVAD and/or Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI)
Diagnosis of recurrent CD30+ HL or CD30+ NHL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and stem cell transplantation
Available autologous T cells with >= 15% expression of CD30CAR determined by flow-cytometry
Patient with low-intermediate risk, early-stage organ-confined prostate cancer (cT1c and cT2a, N0, M0), diagnosed with TRUS guided transperineal biopsy (TPBx) and voluntarily chooses MRgFUS as the non-invasive treatment, who may currently be on watchful waiting or active surveillance and not in need of imminent radical therapy.
Gleason score 6 or 7 (no 5 grades), based on TRUS guided Transperineal Mapping Biopsy, as defined in the protocol.
Positive TRUS-guided transperineal biopsy (TPBx) cores, detected in a maximum of four (4) sectors, (2 for each cancerous focus) out of 16 sectors (or out of 12 sectors in prostates with volume <20 cc)
Patient eligible for epidural anesthesia, and general anesthesia (in case of complication, requiring intervention).
ASA status > 2
Severely abnormal coagulation (INR>1.5)
Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (approximately 3 hrs.)
Any rectal pathology, anomaly or previous treatment, which can change acoustic properties of rectal wall or prevent safe probe insertion (e.g., fistula, stenosis, fibrosis).
Any spinal pathology which can prevent safe administration of epidural anesthesia
Identified calcification of 2 mm or more in largest diameter neighboring the rectal wall (in a distance of less than 5 mm) and interfering with the acoustic beam path.
Lower limb musculo-skeletal fixed deformities.
Patient that had TURP procedure before
Patient with baseline symptoms of incontinence defined as urine leak in any of the following circumstances: 20.1. Before the patient can get to the toilet 20.2. When coughing or sneezing 20.3. While being asleep 20.4. While being physically active/exercising 20.5. After finishing urinating and being dressed 20.6. Leaking for no obvious reason
Patient with baseline impotence scoring 17 or below in the IIEF-5 (SHIM) questionnaire
Active UTI
Prostatitis NIH categories I, II and III
Interest in future fertility
Granulocytes >= 1,500/ml
Participants must have agreed to and signed an authorization for the release of their protected health information
Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary
Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption
Patient with electrolyte abnormality deemed clinically significant by the investigator (e.g., hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hypocalcemia, hyponatremia) unless the level can be corrected to normal levels prior to initiating study drug
The following medications within four weeks prior to start of study treatment (week 1): systemically administered radiopharmaceuticals such as bone seeking isotopes (e.g., samarium-153 lexidronam); hematopoietic growth factors other than erythropoietin; medroxyprogesterone as an appetite stimulant; or alternative medicine treatments for prostate cancer, including Prostasol (formerly: PC-Plus), saw palmetto, or Zyflamend
Administration of subunit or killed vaccines, such as influenza or pneumococcal vaccine, within two weeks prior to study treatment (day-1) and throughout the study; EXCEPTION - Vaccination for influenza is permitted between week 12 through week 16 and after week 20
Positive stool guaiac, excluding hemorrhoids or documented radiation-induced proctitis, if test is performed at the discretion of the treating physician (stool guaiac test is not required to screen for eligibility)
Must consent to collection of blood samples for PK analysis.
The participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy\r\n* Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances:\r\n** Anatomic or mechanical compromise of critical organ function by tumor (eg, respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc)\r\n** Uncorrectable coagulopathy\r\n* For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur:\r\n** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment\r\n** Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment\r\n** If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
For patients with stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 eligibility case report form (CRF)
MART-1 positive melanoma by reverse transcription (RT)-polymerase chain reaction (PCR) or immunohistochemistry (IHC)
No restriction based on prior treatments
Human anti-mouse antibody (HAMA) titer < 1000 enzyme-linked immunosorbent assay (Elisa) units/ml if applicable
HAMA titer > 1000 Elisa units/ml
Adult Women (? 18 years old).
Pre-anesthetic medical evaluation and clearance for anesthesia
Willingness to provide the biologic specimens and participate in imaging studies as required by the protocol
Absence of rectum or other anatomic features which would preclude transperineal needle insertion into the prostate
American Urologic Association Obstructive Symptom Index Score > 24
Coagulopathy which contraindicates transperineal and intraprostatic needle insertion
Subjects with > 1 renal/genitourinary toxicity: \r\n* Bladder spasms\r\n* Creatine > 1.5 x UNL\r\n* Dysuria (painful urination)\r\n* Genitourinary fistula\r\n* Hemoglobinuria (> 1+)\r\n* Operative injury to bladder and/or ureter\r\n* Proteinuria\r\n* Renal failure\r\n* Ureteral obstruction\r\n* Urinary retention\r\n* Urine color change (not related to other dietary or physiologic cause e.g. bilirubin, concentrated urine, hematuria)
Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival
Pathologically proven diagnosis of NSCLC
ANC ? 1500 cells/µL
WBC counts > 2500/µL
Lymphocyte count ? 300/µL
Involved contralateral hilar nodes
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, HIV testing is required for entry into this protocol due to the immunologic basis for induction treatment.
Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alcometasone dipropionate 0.05%)
Clinical and definitive histologic diagnosis of WM
Prior exposure to a pyrrolobenzodiazepine (PBD)- or indolinobenzodiazepine-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity or other contraindications to rovalpituzumab tesirine or excipient contained in the drug formulation.
NEOADJUVANT COHORT
Medically appropriate candidate for radical cystectomy, as per Memorial Sloan-Kettering (MSK) or participating site attending urologic oncologist
Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1; abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows >= 100,000 colonies of bacteria; patients with an ileal conduit and a urinalysis and/or culture that are abnormal are eligible unless they have peripheral blood white blood cell (WBC) > ULN, fever, or other symptoms suggestive of a urinary tract infection
Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before cycle 1, day 1
Have a deleterious mutation in a BRCA1/2 or ATM gene
Measurable disease defined by: \r\n* Lugano classification for systemic lymphoma or\r\n* Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood or bone marrow or \r\n* Modified severity-weighted assessment tool (mSWAT) > 0 or Sezary count >= 1000 cells/uL for CTCL
Androgen receptor positive (AR+)\r\n* Defined as >= 10% nuclear AR staining by immunohistochemistry (IHC) in either the primary or metastatic lesion\r\n* NOTE: Research testing of AR status is available at City of Hope (COH) Pathology
Currently on bisphosphonate or denosumab with elevated serum calcium levels corrected for albumin/ionized calcium levels outside of institutional normal limits
Therapeutic-dose anticoagulation must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and fulvestrant.
Subjects with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including subjects with massive uncontrolled effusions, pulmonary lymphangitis, and over 50% of liver involvement in metastases.
Lymphocytes ? 0.5 x 109/L
(* = without ongoing growth factor or transfusion support)
NSCLC
Gastric, Esophageal, and G-E Junction Adenocarcinoma
SCCHN
?18 years old.
Normal LVEF per institutional criteria as determined by either ECHO or MUGA scanning.
Cataract of Grade ?2 for posterior subcapsular cataract, cortical cataract, nuclear opalescence, or nuclear color based on the LOCS III.
The patient requires treatment with a medication that is a strong inhibitor of CYP3A4 (boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, or voriconazole).
The patient has uveal melanoma.
Absolute lymphocyte count (ALC) ? 1 × 10e3/µL
Pregnant women are excluded from this study because nivolumab, personalized neoantigen peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.
Nursing women are excluded from this study because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with nivolumab, personalized neoantigen peptides, and Poly-ICLC.
Mucosal melanoma and uvueal melanoma.
Women using any form of hormonal contraception (oral, injected, implanted, transdermal) will be excluded (unless they are willing to switch to another effective form of contraception under their physician's guidance) Additional exclusion criteria for PDR001/HDM201-
Prior treatment with compounds with the same mode of action as proposed for HDM201, i.e. an inhibition of the interaction of TP53 with HDM2, e.g. RG7112 or CGM097
No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
Previous enrollment in the present study.
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Not a woman of childbearing potential as defined in Appendix VIII OR
Receive only RIC regimen (i.e. Regimen A)
Be willing to comply with effective antiretroviral therapy (ARV)
Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may pose an excessive risk for transplantation-related morbidity as determined by the Treatment Review Committee (see Appendix D).
May not be currently prescribed ritonavir, cobacistat and/or zidovudine
Prior allogeneic HCT
Phase 2: activated B-cell or unclassifiable subtypes confirmed by immunohistochemistry using the Hans algorithm
Subject is positive for FLT3 mutation (internal tandem duplication [ITD] or tyrosine kinase domain [TKD] [D835/I836] mutation) in bone marrow or whole blood as determined by central laboratory. Note: Only applicable to the randomization portion.
Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of another anthracycline).
Serum magnesium ? Institutional LLN
Female subject must either:
Be of nonchildbearing potential:
Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
Emergency leukapheresis
Growth factor or cytokine support
Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but activating somatic mutations of HER2 gene identified through genomic sequencing including but not limited to the following (Clinical Laboratory Improvement Act [CLIA] certified lab test): missense substitutions (G309A, G309E, S310F, S310Y, S653C, V659E, R678Q, V697L, T733I, L755S, L755P, E757A, D769H, D769Y, D769N, G776V, G776C, V777L, L841V, V842I, R849W, L869R, R896C); insertions/deletions (A775_G776insYVMA aka Y772_A755dup, G776VinsC, G776AinsVGC, G776 insertions, G778_S779insCPG, P780_781insGSP aka G778_P780dup, L755_T759del) and/or HER3 activating mutations; there is no limitation on the number of prior lines of systemic therapy or HER2-targeted therapies (prior neratinib not allowed)
Have documented CD45 expression by leukemic cells via flow cytometry (a \blast gate\ on CD45 vs. side scatter analysis consistent with AML)
Have a circulating blast count of less than 10,000/mm3 (control with hydroxyurea is allowed)
Have circulating HAMA noted on initial screening
Have abnormal QTcF (>450milliseconds) after electrolytes have been corrected (at least two different ECG readings and at least 15 minutes between readings)
Prior ipilimumab is permitted.
Subject consents to hospitalization for first (Cycle 1 Day 1) dose of CC-90002 and for 72 hours after.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Has a diagnosis of immunodeficiency
Ages 2 to 21 at the time of Assent or Consent per IRB guidelines
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
B-cell hematologic malignancies expected to express the cluster of differentiation 20 (CD20) antigen who have relapsed after or failed to respond to at least one prior treatment regimen and for whom there is no available therapy expected to improve survival
All patients with a diagnosis of complex atypical hyperplasia OR grade 1 endometrioid endometrial carcinoma on endometrial biopsy or dilation and curettage (D & C) within three months of study enrollment
Congenital or acquired uterine anomaly which distorts the uterine cavity
Genital actinomycosis
Part 1: 0 or 1
Part 2 and 3: 0, 1, or 2
Current evidence of corneal disorder/keratopathy
Participants must be planning to receive or have received autologous stem cell transplantation; participants may enroll prior to ASCT, but will not be eligible to begin treatment until after ASCT, and must fulfill all inclusion and exclusion criteria at that time; ASCT will be performed according to institutional standards and is not a part of this study
Participants must begin study treatment no later than 21 days from the post-ASCT discharge; additionally, they must have recovered from ASCT toxicities at the time of first study treatment; recovery from ASCT toxicity is defined using the eligibility criteria in this section, as well as outpatient status, ability to drink and eat normally, without the need for intravenous hydration; participants must be no later than 60 days from stem cell reinfusion; exceptions to these time frames may be made in discussion with the overall principal investigator (PI) and will not constitute study violations
Receipt of > 600 mg/m^2 total dose of carmustine (BCNU) with prior treatments including transplant conditioning regimen
Patients must be willing to receive follow-up care for a minimum of five years after treatment at Massachusetts General Hospital (MGH) and annual visits unless it is too difficult to return to MGH for follow-up care; in that event, the patient or guardian must be willing to have their outside medical information (i.e. imaging studies, laboratory results and doctor or other health professional notes) released in order to track the results of treatment
Timing of radiation may be according to a concurrent protocol (such as a Children’s Oncology Group [COG] study) or according to physician discretion
Primary tumor must be arising in one of the following central chest locations:\r\n* Within or touching the zone of the proximal bronchial tree (a volume 2 cm in all directions around the proximal bronchial tree [carina, right (R) & left (L) main bronchi, R & L upper lobe bronchi, intermedius bronchus, R middle lobe bronchus, lingular bronchus, R & L lower lobe bronchi])\r\n* Adjacent to (within 5 mm) or invading the mediastinal pleura\r\n* Adjacent to (within 5 mm) or invading the parietal pericardium
PRESTUDY REQUIREMENTS: \r\n* History and physical examination, weight, Zubrod performance status (within 4 weeks pre-study entry)\r\n* Evaluation by thoracic cancer clinician (within 8 weeks pre-study entry)\r\n* Pregnancy test, if applicable (serum or urine, within 72 hours prior to treatment start)\r\n* CT (preferably with contrast unless medically contraindicated; both lungs, mediastinum, liver, adrenals)\r\n* PET (using fluorodeoxyglucose [FDG] with visualization of primary tumor and draining lymph node basins in hilar and mediastinal regions)\r\n* Brain and MRI or head CT with contrast\r\n* Pulmonary function tests (PFTs) - include routine spirometry, lung volumes, diffusion capacity\r\n* Signed informed consent
Premenopausal status
Diagnosis of precursor B-cell or precursor T-cell ALL by immunophenotyping
Primary breast cancers must be of clinical and/or radiologic size > 3 cm, and deemed surgically operable
Electrocardiogram showing no acute ischemic changes
Is not eligible or has refused any protocols of higher priority
No active ischemia by electrocardiography (ECG) or clinical symptoms
Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded
No concurrent administration of cimetidine (as it can decrease the clearance of fluorouracil [5-FU]); another histamine-2 receptor (H2)-blocker or proton pump inhibitor may be substituted before study entry
No previous allogeneic HSCT
Medically fit to and willing to donate
No portal invasion or extrahepatic spread
Contraindications for doxorubicin administration
Child’s class C
Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant cause of renal damage
Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) > 500mg/day in a 24-hour urine collection
NT-proBNP < 1800 pg/mL
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis
Patients who have neuromuscular disorders that are associated with elevated creatinine phosphokinase (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Agree to allow the sponsor to collect data on all GBM-related treatments received after the patient comes off the current study, and to collect survival data after the patient comes off the current study.
Patient must be ? 18 years old.
Patient has previously received standard of care chemo-radiation with temozolomide, ± adjuvant temozolomide and bevacizumab and now has radiographic evidence of recurrent/progressive GBM or GS during or after bevacizumab.
Patient must have bi dimensionally measurable disease, per the proposed Response Assessment in NeuroOncology (RANO; Appendix C) (Wen et al., 2010), with measurement of >1 cm in one diameter and ?5 cm diameter in any plane on MRI performed within 2 weeks prior to randomization.
Prior therapy with Laser-Induced Thermal Therapy (LITT) is allowed but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence.
KPS must have been stable during the period from wash-out of prior therapy to randomization. A declining KPS is defined by reduction of 10 points or more over at least a 28-day period.
Presence of hemosiderin.
Eligibility for T-cell infusion (includes cyclophosphamide, T cell, anti-CTLA4 infusions and s.c. IL-2) (Turnstile 2) (Note: evaluate at least 1 week before T-cell infusion): ECOG/Zubrod performance status of 0-1.
Prior to cyclophosphamide and T cell infusions: platelets =< 50,000
Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
Diagnosis of PNH by flow cytometry
Inadequate response to eculizumab defined as having received eculizumab for at least 6 months plus a documented LDH level ? 1.5 x the upper limit of normal (ULN) and/or the presence of a known C5 mutation conferring resistance to eculizumab
Gynecologic Oncology Group (GOG) performance status of 0 to 1.
Subject is willing and able to undergo biopsy.
Investigator considers R-CHOP immunochemotherapy appropriate.
Presence of any condition requiring any form of anticoagulant therapy (heparin flushes for IV catheter are permitted)
Non-pregnant and non-nursing. The effect of nab-paclitaxel and nivolumab on the fetus is unknown.
Presence of T315I mutation by ABL1 sequencing
No evidence of increased calcium levels, renal insufficiency, anemia or bone lesions (CRAB criteria) or new criteria of active MM which including the following:\r\n* Increased calcium levels (corrected serum calcium > 0.25 mmol/dL [> 1mg/dL] above the upper limit of normal or > 2.75 mmol/dL [11mg/dL]) related to MM\r\n* Renal insufficiency (attributable to MM)\r\n** Participants with creatinine levels =< 1.5 mg/dL not attributable to myeloma are eligible\r\n* Anemia (hemoglobin [Hb] 2 g/dL below the lower limit of normal or < 10 g/dL) related to MM\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* Bone marrow plasma cells >= 60%\r\n* Serum involved/uninvolved free light chain (FLC) ratio >= 100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice (light chain smoldering myeloma is not an exclusion criteria)\r\n* MRI with two or more focal lesions that are at least 5 mm or greater in size\r\n* Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible
Known amyloid involvement
Prior cerebrovascular accident (CVA) with persistent neurological deficit
Histological diagnosis of adenocarcinoma of the pancreas
Glucose-6-phosphatase deficiency (G6PD) level of 5-14 units/g hemoglobin (Hgb) or within institutional standard parameters
Prior neoadjuvant FOLFIRINOX
Current dependency on IV hydration or total parenteral nutrition (TPN)
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Vaccination with a live or attenuated vaccine =< 28 days prior to randomization; Note: other types of vaccines, including inactivated/killed, toxoid (inactivated toxoid), and subunit/conjugate are all permitted at any time
No other non-protocol antineoplastic agents will be permitted during this study
May have had intervening therapy since completion of initial UC-961 dosing, but excluding the following:\r\n* Within 7 days of UC-961 restart, or 5 half-lives (if known), whichever is shorter: small molecular tyrosine kinase inhibitor (e.g.: ibrutinib, idelalisib, AVL-292, IPI-145); \r\n* Within 28 days of UC-961 restart: chemotherapy (e.g., purine analogues, alkylating agents), corticosteroids, radiation therapy, or participation in any other investigational drug treatment (besides UC-961) \r\n* Within 56 days UC-961 restart: previous UC-961 dosing\r\n* Within 56 days of UC-961 restart: monoclonal antibody therapy directed against CLL (eg. rituximab, ofatumumab, obinutuzumab, alemtuzumab)
Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia
Recurrent respiratory papillomatosis (RRP) criteria\r\n* Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\r\n* One of the following:\r\n** A Derkay anatomic score of 10 or greater and a history of two or more endoscopic interventions in the last 12 months for control of RRP\r\n** Pulmonary RRP with pulmonary disease that is measurable by computed tomography scan\r\n** Tracheal involvement with RRP that has required either two or more endoscopic interventions in the last 12 months or a tracheostomy
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Be scheduled for a colectomy procedure with a stapled anastomosis
At time of surgery, has a completed anastomosis that is able to be visualized and is accessible to allow for circumferential sealant application with minimal bowel manipulation (?90%)
Completed anastomosis must be at a location where a WCE can be performed to evaluate for a sub-clinical leak
ASA score (American Society of Anesthesiologists) ? 4
Neutropenia ? 800 cells/µl
Has undergone chemotherapy within 4 weeks of the anastomosis procedure and/or radiation within 3 days of the anastomosis procedure
Has an emergent infection related to a previous colectomy procedure
Is scheduled to undergo a Hartmann's procedure
Is scheduled to undergo trans-anal endoscopic microsurgery (TEM)
Is scheduled to undergo procedure using omental wrapping
Circumferential resection margin: CRM+ (Positive)
Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the neurofibromatosis 2 (NF2) gene\r\n* The NIH criteria includes presence of:\r\n** Bilateral vestibular schwannomas, OR\r\n** First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the\r\nfollowing: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity\r\n* The Manchester criteria includes presence of:\r\n** Bilateral vestibular schwannomas, OR\r\n** First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\r\n** Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\r\n** Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract
Participants must have progressive or symptomatic meningioma\r\n* NOTE: Histologic confirmation of target meningioma is not required in the setting of compatible radiographic appearance\r\n* NOTE: Progression is defined as an increase in target meningioma volume >= 20% OR >= 3 mm during the past 2 years
Exposure to sensitive or narrow therapeutic range substrates of the drug metabolizing enzymes CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 within the appropriate wash-out period (a minimum of 5 x reported elimination half-life) before the first dose of study treatment
Detection of one of the following must be present:\r\n* t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics\r\n* Breakpoint cluster region (BCR)-Abelson (ABL) positive status by molecular analysis with qualitative polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)
Have serum albumin that is ?25 grams per liter at the time of enrollment.
nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents).
other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide).
Have radiologically documented evidence of major blood vessel invasion or encasement by cancer.
Participants with a history of poor tolerance to either ibrutinib or idelalisib should not be enrolled on the arm containing that drug, but may be enrolled to the other arm; must agree not to share study medication with another person
Currently enrolled in study 2007-0169 and benefiting from therapy as determined by treating physician
Ability and agreement to attend protocol-specified visits at the study site
Subject has ASA classification of 5;
Subject has religious or other objections to porcine, bovine, or human components;
Subject in whom the investigational or control device will be used at the site of a valve replacement or repair;
Subject in whom the investigational or control device will be used at the site of a synthetic graft or patch implant;
Subject in whom the Investigator is able to identify a TBS for which any applicable conventional means for hemostasis are ineffective or impractical; and
Renal failure requiring hemo-or peritoneal dialysis
Patients who have developed any evidence of clinical or radiologic pneumonitis, cryptogenic organizing pneumonia (COP)/bronchiolitis obliterans organizing pneumonia (BOOP), or other lung injury, during treatment with prior FRalpha-targeting therapy, such as mirvetuximab soravtansine (IMGN853), or with any prior cancer immunotherapy
Patient has a score of >= 12 on the Patient Health Questionnaire (PHQ)-9 questionnaire, selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9), score >= 15 on Generalized Anxiety Disorder (GAD)-7 mood scale
Have a preexisting chronic condition resulting in persistent diarrhea.
Testing of patient’s archived (paraffin embedded, unstained slides) or freshly biopsied tumor nodules must be positive for WT1 protein expression:\r\n* WT1 expression: Immunohistochemical analysis will be performed; WT1 expression will be graded according to an adaptation of the German Immunoreactive Score (IRS); only tumors with moderate to strong IRS scores (4-12) will be considered WT1 positive
The subjects must have at least four BCCs in non-cosmetically sensitive sites
Taking any medication known to affect hedgehog (HH) signaling pathway
Have participated in a previous study of duvelisib, and:
Subjects actively receiving duvelisib are to be excluded from this study if they have any ongoing ? Grade 3 AE considered related to duvelisib treatment at screening
Absence of renal failure attributed to the plasma cell disorder*: calculated creatinine clearance (according to Cockcroft-Gault method, Modification of Diet in Renal Disease [MDRD], or CKD Epidemiology Collaboration [CKD-EPI] formulae) > 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)\r\n* To be determined based on clinical and laboratory assessment by the primary oncologist
Absence of hypercalcemia attributed to the plasma cell disorder*: calcium (Ca) < 10.5 mg/dl or =< 2.5 mmol/L\r\n* To be determined based on clinical and laboratory assessment by the primary oncologist
Absence of involved: uninvolved serum free light chain ratio >= 100
Lymphocytes >= 700/mm^3
Willing to travel to the NIH, MSKCC, DFCI, BIDMC for follow-up visits
Previous serious adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
Lesions that have been radiated previously cannot be considered target lesions
Ability to complete questionnaires by themselves or with assistance
Patient has score of 0 or 1 on the neurotoxicity evaluation, as determined by the healthcare provider
Diagnosis of fibromyalgia
Unfit for chemotherapy based on investigator assessment or patient not willing to receive intensive induction as advised by investigator
For participants previously treated with first generation anti-androgens (ie, flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur greater than (>) 4 weeks (>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (no decline in serum PSA)
History of listeriosis or vaccination with a listeria-based vaccine or prophylactic vaccine (example influenza, pneumococcal, diphtheria, tetanus, and pertussis [dTP/dTAP]) within 28 days of study treatment
Histological documentation of malignant pleural mesothelioma (MPM) overexpressing mesothelin
At least one metastasis must show uptake of 111In-DTPA-octreotide (indium In-111 pentetreotide) on SPECT that is higher than the physiologic radiotracer uptake by the liver
Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia
Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of >= 2 times the upper limit of normal is required
Histological documentation of primary adenocarcinoma of the pancreas
Non ductal adenocarcinomas, neuroendocrine neoplasms, cystic tumors of the pancreas such as cystadenomas, cystadenocarcinomas and solid pseudopapillary neoplasms; in addition, adenocarcinomas arising from duodenum, distal bile duct, and ampulla will also be excluded
Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand disease, or cancer associated disseminated intravascular coagulation [DIC])
Past history of radiotherapy within the projected treatment field of any of the disease sites to be treated by MRI-guided, gated, and/or online adaptive SBRT
Positive urine tetrahydrocannabinol (THC) dipstick test (> 50ng/mL; indicating marijuana use in the past 48-72 hours)
Conditions contraindicated to progesterone treatment (including, but not limited to, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, diabetes, history of stroke, allergy to peanuts, hypersensitive to progesterone and liver dysfunction)
Intent to treat the patient with a leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy regimen containing fluorouracil (5-FU), leucovorin, and oxaliplatin according to clinical standard practice; the intent should be to dose oxaliplatin at 85 mg/m^2 on an every 2 week basis
No radiographic evidence of cavitary or necrotic tumors
Negative hepatitis B serologic tests; if positive results are not indicative of active or chronic infection, the subjects can enter the study at the investigator’s discretion
CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement)
Patient is unable to receive IV contrast
Neuroimaging evidence of midline shift
Patient will have ?4 tumors, none of which exceeds 3.5 cm in diameter.
Patient has or has ever had
Pathology material: hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) slides or a representative formalin-fixed paraffin-embedded (FFPE) tissue block along with the pathology report from initial diagnosis, should be sent to be reviewed, and the diagnosis confirmed by Mayo Clinic department (retrospective diagnostic review: treatment may commence prior to the Mayo Clinic review)
Pregnancy; patient attestation that they are not pregnant will be acceptable as per standard policy for MRIs at Dartmouth Hitchcock Medical Center (DHMC)
Potassium within normal range, or correctable with supplements
Patients who are Human epidermal growth factor 2 +(HER2+) as defined by American Society of Clinical Oncology and College of American Pathologists (ASCO CAP) guidelines must have failed all prior therapy known to confer clinical benefit
have major abnormalities documented by echocardiography (ECHO) with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal). For additional details, refer to ECHO protocol.
have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography (CT) scan with contrast).
B-type Natriuretic Peptide (BNP) above 3 times the baseline value and above the ULN that is sustained consecutive, scheduled blood draws. Troponin I above ULN, high sensitive C-reactive protein (hsCRP) above ULN or Cystatin above ULN.
Pregnant or nursing women, due to the unknown effects ofLY2157299 on the developing fetus or newborn infant.
Any National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) score; a calculated score required for enrollment
Target lesion previously embolized, perfused, or irradiated without objective evidence of progression before start of therapy to be considered for response assessment
Performance status < 3 (unless previous performance status was 0 or 1 and deterioration is due to lymphoma which treating medical doctor [MD] expects to reverse with therapy)
Subjects who are unwilling to take venous thromboembolism (VTE) prophylaxis
Subject's lesions are not amenable to local therapies which may be beneficial, such as transarterial chemoembolization (TACE), radiofrequency ablation, radiotherapy, etc., and the subject is not a candidate for any curative treatments such as resection or liver transplant.
Female subject is either:
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Bradycardia (in the presence of known cardiovascular disease) as indicated by a heart rate of < 50 beats per minute on the Screening electrocardiogram (ECG) recording.
Subject has received an agent that either blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, bicalutamide, enzalutamide, ARN-509 or other investigational AR signaling inhibitors). The exception of spironolactone is allowed after Medical Monitor consultation.
Systemic androgens and estrogens (vaginal estrogen creams are allowed)
Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the enzalutamide capsule components, including caprylocaproyl polyoxylglycerides (Labrasol), butylated hydroxyanisole and butylated hydroxytoluene.
Patients will have the option to enroll on blood collection protocol, LAB09-0983, for serial collections of blood before, during intervals of treatment, and at follow up visits; enrolling on the LAB09-0983 protocol is not required to enroll on the 2014-0722 study
Women are eligible to participate if: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] > 40 MlU/mL and estradiol < 40 pg/mL [< 140 pmol/L] is confirmatory); females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study; otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment; for most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT
Prisoners or subjects who are involuntarily incarcerated
Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
Prior radical prostatectomy or bilateral orchiectomy for any reason
Active infection requiring systemic antibiotic therapy or causing fever (temp > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to dosing with AZD1775
Patient has uveal melanoma
Patient has active infection at time of study entry that require systemic antibiotics and/or with an oral temperature of >= 38.3 degrees C (100.9 degrees Fahrenheit [F]) within 5 days of first treatment
Diagnosis of chronic GVHD according to National Institutes of Health (NIH) Consensus Criteria\r\n* May have either classic chronic GVHD or overlap subtype of chronic GVHD
Has contraindications to cryotherapy of the prostate, including: previous transurethral prostatic resection (TURP) with persistent transurethral resection (TUR) defect, existing peri-anal or recto-urethral fistula, previous external beam radiation therapy or brachytherapy, coagulopathy, inability to tolerate anesthesia (spinal or general), inability to tolerate transrectal ultrasound (i.e. history of previous abdominal perineal resection)
Biliary stents (plastic or metallic) are allowed; however, those patients with metallic stents will not undergo the functional MRI correlative component of this study
Intolerance to dexamethasone
At least one lesion (excluding the brain), not previously irradiated that can be accurately measured per RECIST version 1.1
Active or chronic pancreatitis
Patients with any condition/anomaly that would interfere with the appropriate placement of the IP catheter for study drug administration including: abdominal surgery within 4 weeks of study entry (for reasons other than IP port placement), intestinal dysfunction, or suspected extensive adhesions from prior history or finding at laparoscopy.
Goggle assessment substudy: iodine or seafood allergies
Locally confirmed MMR deficient or MSI-H status.
At least one measureable lesion.
MRI (completed within 96 hours after surgery) documenting gross total resection consisting of no gadolinium enhancement; or subtotal resection consisting of linear enhancement with (or without) nodular gadolinium enhancement measuring no greater than 1 cm x 1 cm x 1 cm total volume or 100 mm^2 in cross sectional area
No evidence of true progressive disease from the postoperative period to the post-chemoradiation period, based on changes in the neurologic exam, steroid use, or evident radiographic progression, according to RANO criteria; patients with increased or new gadolinium enhancement may continue on protocol if in the investigator’s judgment that enhancement is likely due to pseuodoprogression; the use of correlative imaging studies (including perfusion-weighted imaging [PWI]) and repeat or diffusion weighted imaging (DWI), and repeat imaging after an interval of 2-4 weeks is strongly encouraged to help distinguish between pseudoprogression and true progression
Patients must have completed initial radiation therapy (RT) and temozolomide (TMZ) for the treatment of their glioblastoma (i.e., completed 6-week course of RT and, completed >= 75% of 6-week course of induction TMZ chemotherapy)
Ophthalmological conditions
Grade 1-3 invasive ductal, mammary, mucinous, tubular, colloidal, or pure ductal carcinoma in situ (DCIS) measuring =< 2.5 cm on final pathology (the tumor should be clinical stage T1N0M0 in patients electing brachytherapy in whom the catheter will be placed intraoperatively)
Ability to complete questionnaire(s) by themselves or with assistance
Ability to elect radiotherapy care in conjunction with their physician
Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study and collect involved blood specimen prior to the start of radiation therapy, IRB number 15-000136.
Proven multicentric carcinoma (DCIS or invasive) in more than one quadrant or separated by 4 or more centimeters or diffuse (> 1 quadrant) suspicious calcifications
Histologic evidence of angiolymphatic invasion (ALI); Note: Cases termed focally suspicious for ALI but where no definitive ALI is found are eligible
BRCA 1/2 mutation; Note: Patients are not required to undergo BRCA1 and BRCA2 or other genetic mutation tests in order to enroll on the study. However, in the event a patient is tested and is found to be a mutation carrier, she would be excluded from the study
Extensive intraductal component
Reduction mammoplasty if 3DCRT or proton APBI are planned
Creatine phosphokinase (CPK) < 2.5 X ULN
Prior exposure to PM01183
Non-soft tissue sarcomas, such as osteosarcoma and chondrosarcoma are excluded
Known myopathy or persistent CPK elevations > 2.5 ULN in two different determinations performed one week apart
Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESS is unable to complete because of limited literacy or vision
Must be able to avoid direct contact with pregnant women, infants < 3 months of age and immunocompromised individuals while on study and for >= 3 weeks following the last dose of study agent administration; direct contact is defined as household contact, i.e., anyone living with the patient
Absolute neutrophil count 1.5 × 10^9/Liter (L), platelets 100 × 10^9/L, and hemoglobin 9 g/deciliter (dL) (5.58 millimoles/Liter).
Nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents), or
Note: Laboratory assessments used to support the hypercalcemia, renal failure, anemia, bone lesions (CRAB) criteria in the International Myeloma Working Group (IMWG) 2014 diagnostic criteria of MM are performed at the time of diagnosis; these assessments are not required to be performed within the 21 days of initiation of protocol therapy
Has low-grade or non-epithelial cancers, mucinous cancers, and/or borderline low-malignant potential cancers
Patients with a past history of synchronous endometrial cancer are excluded unless all of the following conditions are met: stage not greater than I-A (International Federation of Gynecology and Obstetrics [FIGO] 2010 staging criteria); no more than superficial myometrial invasion (< 50%), without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions, and it has been greater than 3 years since diagnosis and there have been no recurrences
Clinicopathological diagnosis of Waldenstrom macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia or serum immunoglobulin M (IgM) > 6000 mg/dL and measurable disease
Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required
Prior exposure to idelalisib
Grade 2 or higher peripheral ischemia, except for brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit.
Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
Lack of availability for immunological and clinical follow-up assessment.
Patients must have either isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) or isocitrate dehydrogenase 2 (NADP+), mitochondrial (IDH2) mutations (any known mutations) based on the SNaPshot platform or other molecular testing platform from either archived tissue or fresh biopsy (tested in Clinical Laboratory Improvement Amendments [CLIA]-certified lab)
Patients with other biliary tract cancers (extrahepatic or gallbladder cancers) with IDH1 or IDH2 mutations are allowed
Periampullary tumors
Active Richter’s transformation
Subject entering the study will need to consent for mandatory biopsy at study entrance and as an optional procedure at week 11 and at progression for biomarker evaluation; biopsy should be excisional, incisional or core needle; fine needle aspiration is insufficient
Subjects with carcinomatous meningitis
Prisoners or subjects who are involuntarily incarcerated
A back-up graft identified, in case of graft failure, from any of the following sources: an available fraction of autologous marrow; or peripheral blood progenitor cells (PBPCs) harvested and cryopreserved; or family member donor; or a third cord blood unit
Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy; the principal investigator (PI) is the final arbiter of eligibility
Serum potassium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
Sodium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
Magnesium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
Phosphorus (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
Total calcium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted)
The direct bilirubin must be within normal parameters
Administration of the radioisotope, 18-FLT, which is being concurrently investigated on an imaging study within the Pediatric Brain Tumor Consortium (PBTC), is allowed > 72 hours prior to initiation of pomalidomide on this study; any adverse events related to the FLT must have resolved completely
All races and ethnic groups are eligible for this study
Locally advanced tumors at diagnosis (T4), including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid)
Prior exposure to an immunomodulatory agent (IMiD)
Waldenström macroglobulinemia
Known cirrhosis
Arm 2 ONLY: Surgically operable NSCLC or mesothelioma
Pregnant women and nursing mothers will be eligible for screening only to test HLA type by saliva or buccal swab and WT1 expression from previously collected tissue sample
Exclusions for the leukapheresis procedure (this can be performed at a later time of symptoms resolve): \r\n* Infection, with or without antibiotic treatment\r\n* Recent hepatitis exposure (hepatitis B or C antigenemia)\r\n* Pregnancy or nursing\r\n* HIV or human T-lymphotropic virus (HTLV) infection\r\n* Positive result on standard test for syphilis (STS)
Unable to generate antigen-specific WT1-specific CD8+ T cells for infusions; however, the patient will have the option to receive WT1-specific T-cells if a lower than planned number of cells is available
Meets the criteria for post ET/PV myelofibrosis (MF) as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Patients must have a clinicopathological diagnosis of WM (Owen 2003), with symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM (Kyle 2003) or serum immunoglobulin M (IgM) > 6000 mg/dL, and measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of > 2 times the upper limit of normal
Esophagogastroduodenoscopy (EGD) with endoscopic ultrasound (EUS) +/- biopsy at M.D. Anderson are required to confirm staging
Patients must have a primary invasive cutaneous melanoma of Breslow thickness greater than 1 millimetre as determined by diagnostic biopsy (narrow excision, incision or punch biopsy) and subsequent histopathological analysis.
Patients must have had the invasive primary completely excised, including any in situ component but excluding melanocytic atypia, with a narrow margin, either in one stage or more than one stage in the case where an incision or punch biopsy has previously been performed. This information, including measured margins of lateral and deep clearance must be documented on the pathology report.
An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary melanoma.
Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI.
Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown malignant potential'.
Patient has already undergone wide local excision at the site of the primary index lesion.
Desmoplastic or neurotropic melanoma.
Microsatellitosis as per AJCC 2009 definition
Patient has already undergone a local flap reconstruction of the defect after excision of the primary and determination of an accurate excision margin is impossible.
Melanoma located distal to the metacarpophalangeal joint, on the tip of the nose, the eyelids or on the ear, mucous membranes or internal viscera.
Melanoma-related operative procedures not corresponding to criteria described in the protocol.
Screening 99mTc-MDP bone scintigraphy showing a superscan;
Renal failure requiring hemo-or peritoneal dialysis
Other exclusions apply
Is unable to receive a port or peripherally inserted central catheter (PICC).
Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not required)
Subject is considered postmenopausal
Subject has been previously treated with azacitidine (any formulation), decitabine, or any other hypomethylating agent.
A diagnosis of PVNS or GCT-TS (i) that has been histologically confirmed either by a pathologist at the treating institution or a central pathologist, and (ii) where surgical resection would be associated with potentially worsening functional limitation or severe morbidity (locally advanced disease), with morbidity determined consensually by qualified personnel (eg, two surgeons or a multi-disciplinary tumor board).
a worst pain of at least 4 at any time during the week preceding the Screening Visit (based on scale of 0 to 10, with 10 representing \pain as bad as you can imagine\).
a worst stiffness of at least 4 at any time during the week preceding the Screening Visit (based on a scale of 0 to 10, with 10 representing \stiffness as bad as you can imagine\).
During the 2 weeks prior to randomization, at least 4 of 7 consecutive days of BPI Worst Pain NRS items and Worst Stiffness NRS items completed correctly.
Willingness and ability to complete the Worst Pain NRS item, Worst Stiffness NRS item, PROMIS Physical Function Scale, and other self-assessment instruments throughout the study.
Known metastatic PVNS/GCT-TS.
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM).
histological confirmation of transformation, or
Positive cytomegalovirus (CMV) PCR test at baseline
Histological or cytological documentation of adenocarcinoma of the colon or rectum
Ability to complete questionnaire(s) by themselves or with assistance
Renal failure requiring hematological (hemo-) or peritoneal dialysis
Study population:
Primary ocular or mucosal melanoma
Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis)
Visible uptake in at least one lesion on bone scanning prior to radium therapy
Mucosal or ocular melanoma
Unstable hyperthyroidism or hypothyroidism
Diagnosis of immunodeficiency
Patient is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial without prospective Institutional Review Board approval (by chair or designee) is given
Histologic confirmation of advanced (metastatic or unresectable) uveal melanoma; if uveal melanoma has been diagnosed clinically and/or by gene expression profiling, patients may be included following discussion with the principal investigator
Potassium within normal range, or correctable with supplements
Subjects who have significant urinary obstructive symptoms; American Urological Association (AUA) score must be =< 18 (alpha blockers allowed)
Subjects with evidence of extraprostatic extension (T3a) or seminal vesicle involvement (T3b) on clinical evaluation
Must have progressed on, been intolerant to, or refused gemcitabine-based therapy
Baseline troponin I or T > IULN and b-type natriuretic peptide > IULN
Inclusion Criteria:\n\n        Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic\n        leukemia) according to WHO classification.\n\n        Performance status (ECOG) of 0-3. Adults with previously untreated AML except for\n        hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for\n        myelodysplastic syndrome (MDS) is allowed.\n\n        Not considered candidates for intensive remission induction chemotherapy at time of\n        enrollment based on EITHER:\n\n          1. ?75 years of age OR\n\n          2. <75 years of age with at least 1 of the following:\n\n        i. Poor performance status (ECOG) score of 2-3.\n\n        ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:\n\n          1. Left ventricular ejection fraction (LVEF) ?50%.\n\n          2. Lung diffusing capacity for carbon monoxide (DLCO) ?65% of expected.\n\n          3. Forced expiratory volume in 1 second (FEV1) ?65% of expected.\n\n          4. Chronic stable angina or congestive heart failure controlled with medication.\n\n        iii. Liver transaminases >3 × upper limit of normal (ULN).\n\n        iv. Other contraindication(s) to anthracycline therapy (must be documented).\n\n        v. Other comorbidity the investigator judges incompatible with intensive remission\n        induction chemotherapy, which must be documented and approved by the study medical monitor\n        before randomization.\n\n        Creatinine clearance as estimated by the Cockroft-Gault (C-G) or other medically acceptable\n        formulas ?30 mL/min.\n\n        Exclusion Criteria:\n\n        Candidate for intensive remission induction chemotherapy at the time of enrollment.\n\n        Candidate for best supportive care only, ie, not a candidate for any active therapy with\n        the TC comparators.\n\n        Known extramedullary central nervous system (CNS) AML.\n\n        Second malignancy currently requiring active therapy except breast or prostate cancer\n        stable on or responding to endocrine therapy.\n\n        Prior treatment with decitabine or azacitidine.\n\n        Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.\n\n        Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C\n        virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on\n        antivirals is allowed.\n\n        Known significant mental illness or other condition such as active alcohol or other\n        substance abuse or addiction that, in the opinion of the investigator, predisposes the\n        subject to high risk of noncompliance with the protocol.\n\n        Refractory congestive heart failure unresponsive to medical treatment; active infection\n        resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute\n        (LPM) oxygen.
OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
Hemoptysis (defined as > ½ teaspoon of blood)
Participants may not have a dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
Histological or cytological evidence of NSCLC
Must have completed concurrent chemoradiation with a standard chemotherapy regimen (either cisplatin/etoposide or carboplatin/paclitaxel) and a dose of radiation ranging from 59.4-66.6Gy
No active second cancers
The subject has evidence of wound dehiscence
Pregnant females (lactating females must agree not to breast feed while taking carfilzomib, lenalidomide or romidepsin)
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
Active malignant relapse
Has been treated previously with bevacizumab
Has a diagnosis of immunodeficiency
Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery
Has received anti-angiogenic or anti-vascular endothelial growth factor (VEGF) targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc.)
Patient has an ECOG performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), as assessed on C1D1, before the first dose of PBI 05204.
Patient has serum potassium and magnesium levels WNL for the institution and total serum calcium or ionized calcium levels ? the lower limit of normal (LLN). Patients with low potassium, calcium, and/or magnesium levels may receive supplementation to meet the protocol entry criteria. (Calcium supplementation is prohibited after starting PBI-05204; see Appendix 2.)
Heart rate <50 bpm during screening.
Patient has evidence of uncontrolled malabsorptive diarrhea that would prevent adequate absorption of PBI 05204.
Patient was previously exposed to PBI 05204.
ANC ? 1.5 x 10?/L
Other conditions which could jeopardize the subject's ability to comply with the protocol including but not limited to dementia, psychosis, or other major psychiatric disorder.
Subjects who require therapeutic doses of anticoagulants.
Ability to take pills by mouth
Participants must satisfy one of the criteria for treatment initiation, as outlined in the iwCLL NCI-WG guidelines. The criteria include: (a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia, (b) Massive (i.e., greater than or equal to [>=] 6 centimeters [cm] below the left costal margin) or progressive or symptomatic splenomegaly, (c) Massive nodes (i.e., >= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy, (d) Progressive lymphocytosis with an increase of greater than (>) 50 percent (%) over a 2-month period or lymphocyte doubling time (LDT) of less than (<) 6 months, (e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, (f) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of >=10% within the previous 6 months, significant fatigue (i.e., Eastern Cooperative Oncology Group Performance Status [ECOG PS] of 2 or worse or the inability to work or perform usual activities), fevers higher than 100.5 degrees Fahrenheit (°F)/38.0 degrees Celsius (°C) for >= 2 weeks without other evidence of infection, or night sweats for >1 month without evidence of infection
Central pathology review submission; Note: this review for MART-1 positivity is mandatory prior to randomization to confirm eligibility
Requirement for constant administration of proton pump inhibitor, histamine (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed as described
Platelets >= 100,000/mcL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
Participant with post-transplant exposure to donor lymphocyte infusion (DLI), or T-cell or IL-2 targeted medication (e.g. anti-thymocyte globulin [ATG], alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior
Participants with active malignant relapse or recrudescence of their prior hematologic disorder
History of thrombotic microangiopathy, hemolytic-uremic syndrome, or thrombotic thrombocytopenic purpura
No clinical evidence of pancreatitis
Grade II or greater peripheral vascular disease based on National Cancer Institute (NCI) Common Toxicity Criteria (CTC); e.g. ischemic rest pain, minor tissue loss, and ulceration or gangrene
WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product
All HIV+ patients will be under the care of an infectious diseases specialist; if a relationship with an infectious diseases specialist is not established, infectious disease specialist will be consulted; records of all viral counts and peripheral T-cell counts must be sent to the study coordinator in order to follow these values over the course of treatment
Endorse persistent CRCI subjective complaints
Previous treatment with a camptothecin derivative (eg., irinotecan, topotecan, and investigational agents including but not limited to exatecan, rubitecan, gimatecan, karenitecan, SN38 investigational agents, EZN 2208, SN 2310, and AR 67) is not allowed
Histologically documented PCNSL or SCNSL; patients with SCNSL need to have cytology or tissue biopsy documenting lymphomatous involvement of the central nervous system (CNS)
Patient has a score >= 12 on the Patient Health Questionnaire (PHQ)-9 questionnaire
Patient selects a response of \1, 2 or 3\ to question number 9 on the PHQ-9-questionaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
Patient has a Generalized Anxiety Disorder (GAD)-7 mood scale score >= 15
Previous therapy with ibrutinib, or any drug that specifically inhibits Bruton's tyrosine kinase (BTK)
Premenopausal or peri-menopausal women.
HER2-positive as determined using ASCO-CAP Guidelines.
Diagnosis by fine needle aspiration (FNA) alone or excisional biopsy or lumpectomy performed prior to study entry.
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Presence of a RAS mutation in exons 2, 3, or 4 of KRAS or NRAS (patients with mutations in exons 2, 3, or 4 of KRAS and/or NRAS are excluded)
Prior intolerance to irinotecan and/or bevacizumab despite dose reduction
Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 loose stools daily in subjects without a colostomy or ileostomy; subjects with a colostomy or ileostomy may be entered at investigator discretion
Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the study medical monitor before study enrollment
Subject must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
If female, subject must be either:
Patients must have one of the following: somatic mutations or deletions in BRCA1 or BRCA2; genomic alterations in other BRCA pathway genes (subcohorts: a. ATM, b. PALB2, c. other genes, e.g. Fanconi Anemia genes, ARID1A, MER11, RAD50, NBS1, ATR; amplification of EMSY); or germline mutation in BRCA1 or BRCA 2 (not breast or ovarian cancer)
Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g. gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)
Patient has disease amenable to biopsy and is agreeable to undergo a biopsy; note: under unusual circumstances, submission of ascites material may be acceptable if a biopsy is not possible; this will require approval by one of the study principal investigators
Participants must have a baseline mammographic density >= 25% based upon the Breast Imaging Reporting and Data System (BIRADS) density score of 2, 3, or 4 (2 = 25-50%, “scattered fibroglandular densities”; 3 = 51-75%, “heterogeneously dense breasts”; 4 = > 75%, “extremely dense breasts”); women with a baseline mammographic density of < 25% (1 = 0.-24%, “breasts are almost entirely fat”) will not be eligible
MRI demonstration of a stereotactically accessible enhancing mass of less than 40 cm^3 that does not require resection to relieve clinically significant mass effect
Patient is mentally or legally incapacitated at the time of the study
Tumors involving the cerebellum
Unexplained febrile illness
In the dose-finding phase, patients may be cetuximab-exposed or cetuximab-naïve; if the most recent line of therapy included cetuximab, a two-week washout period without cetuximab dosing is required
Nasopharyngeal primary site, if WHO type II or III (non-keratinizing)
Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings.
Active connective tissue disorders, such as lupus or scleroderma
Pathologically proven diagnosis of adenocarcinoma of the rectum (located below the peritoneal reflection or begins within 15 cm of the anal verge on flexible endoscopy) within 90 days of registration; diagnosis of rectal adenocarcinoma must be obtained by biopsy technique that does not completely excise the lesion (eg, fine needle aspiration, core needle biopsy)
Patients requiring drainage gastrostomy (e.g., drainage percutaneous endoscopic gastrostomy [PEG] tube) and/or parenteral hydration and/or nutrition
Diagnosed with CML in chronic phase and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR-ABL protein
Currently taking imatinib, dasatinib, nilotinib or bosutinib
Documented BCR-ABL <0.01% (>MR4 i.e. >4 log reduction) or undetectable BCR-ABL by PCR for at least 2 years according to the patient's local lab
Documented BCR-ABL <0.01% (>MR4 i.e. >4 log reduction) or undetectable BCR-ABL at least 3 times prior to screening according to the patient's local lab
Two (2) Screening PCRs have been completed and both results are < 0.01% (>MR4 i.e > 4 log reduction) by central lab
Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed)
Poor compliance with taking TKI
Unable to comply with lab appointments schedule and PRO assessments
Participants must be candidates for RP and considered surgically resectable by urologic evaluation
Serum potassium >= 3.5 mmol/L
Ability to complete questionnaire(s) by themselves or with assistance
HPV testing must follow the following criteria\r\n* HPV testing using an E6/E7 based assay is preferred, and does not require any validation (e.g. HPV in situ hybridization [ISH] or HPV E6/E7 polymerase chain reaction [PCR])\r\n* For oropharyngeal tumors p16 immunohistochemistry (IHC) positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan/Lingen et al 2012); it is recommended that p16 IHC positivity is validated at a later point (during or after treatment) using an E6/E7 based test at the University of Chicago and provided slides will be used\r\n* For non-operative (OP) tumors accurate HPV testing (i.e. ISH, or E6/E7 based testing) is required for enrollment and treatment initiation
Availability of >= 10 unstained 5 micron slides
The primary and nodal involvement must have been defined bi- or uni-dimensional measurements measurable by RECIST
History of severe hypersensitivity reaction to paclitaxel, docetaxel, or to other drugs formulated with polysorbate 80 or polyoxyethylated castor oil, or to vinflunine or other vinca alkaloids
A diagnosis of active hepatitis B or C as defined by detectable viral load assays in the blood
The development of erythema nodosum if characterized by a desquamating rash while taking lenalidomide
Immunosuppression including primary, secondary, iatrogenic and idiopathic
History of abdominoperineal resection for rectal cancer, rectal stenosis, or other major rectal pathology
Non-AL amyloidosis
Renal failure (on dialysis)
Cluster of differentiation (CD)4 count >= 200/mcL
Patients who have received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal vaccinations within 28 days of study treatment; examples include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 flu, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine
Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine or CRS-207 (e.g., glycerol)
Patient is unable to avoid intimate contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) ) for at least 7 days after receiving CRS-207 infusion
Total Cumulative Illness Rating Scale (CIRS score) greater than (>) 6
An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
A platelet count of at least 100,000/mm^3 on at least 2 consecutive blood draws at least 1 week apart with results stable or trending upward is required
Patients must not eat grapefruit or drink grapefruit juice or plan to eat or drink them during study therapy
Patients must not be taking hepatic enzyme inducing anti-epileptic drug (EIAED) defined as:\r\n* EIAEDs (not allowed):\r\n** Carbamazepine (Tegretol, Tegretol XR, Carbatrol)\r\n** Oxcarbazepine (Trileptal)\r\n** Phenytoin (Dilantin, Phenytek)\r\n** Fosphenytoin (Cerebyx)\r\n** Phenobarbital\r\n** Primidone (Mysoline)\r\n* If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment
Baseline Oncotype Dx recurrence score =< 25
In patients with multicentric or bilateral invasive breast cancers, all sampled lesions must be hormone receptor-positive and HER2-negative and have an Oncotype Dx recurrence score =< 25; one lesion (typically the largest) should be designated as the target lesion for which response to the neoadjuvant therapy will be judged
Known T315I or V299L mutation.
Subjects must have at least 1 lesion
Adequate organ function as determined by: i. Absolute neutrophil count ? 1.5 x 109/L (1,500/mm3) ii.Platelet count ? 100 x 109/L (100,000/mm3) iii.Hemoglobin ? 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min v.Total bilirubin ? 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ? 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ? 2.5× ULN vii.Serum Electrolytes within normal limits
Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) .
Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
Histological confirmation of thymoma
Hemoglobin A1c (HbA1c) =< 8 %
Capable of swallowing tablets
Requirement for constant administration of proton pump inhibitor, histamine-2 (H2) antagonist, or pancreatic enzymes; histamine-2 (H2) receptor antagonists are not permitted from the day prior (day -1) through to the end of alisertib dosing (e.g., day 7), except as required for premedication for a protocol-specific agent (e.g., taxane); neutralizing antacids and calcium-containing supplements cannot be taken from 2 hours prior to alisertib dosing until up to 2 hours after dosing
Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
Histological confirmation of CTCL; a documented verifiable biopsy report is required
CTCL with histologic evidence of folliculotropic variant or large cell transformed CTCL
Circulating atypical cells of clinical significance
Note: Biopsied lesions should not be used as target lesions.
HER2/neu gene amplification by fluorescence, chromogenic, or silver in situ hybridization [FISH, CISH or SISH;>=6 HER2/neu gene copies per nucleus or a FISH, CISH, or SISH test ratio (HER2 gene copies to chromosome 17 signals) of >=2.0 OR HER2/chromosome 17 ratio <=2.0 with average HER2 copy number >=6 signals/cell nucleus]
Centrally determined HER2-positive, hormone receptor status, breast molecular subtype by Prediction Analysis of Microarray 50 (PAM50) on the pre-treatment biopsy of metastatic lesion obtained during screening
Note: Biopsied lesions should not be used as target lesions.
Note: Discontinuation of Trastuzumab is not necessary.
The QTc should be based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period.
Completion of screening and baseline assessments
Hematologic(These values must be independent of growth factor support and stable for at least one week post transfusion)
Angina pectoris requiring antianginal medication
Evidence of transmural infarction on ECG
Lack of archival specimens from the time of primary or recurrence diagnosis
Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
Current indwelling urinary stent
Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony metastases
Current, untreated pathologic long-bone fractures or imminent pathologic long-bone fracture (cortical erosion on radiography > 50%)
Lymphadenopathy exceeding 3 cm in short-axis diameter
Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5°F or 38.1°C) within 1 week prior to registration
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Male participants, even if surgically sterilized (ie, status postvasectomy), who:
Tumors with involvement of the mediastinum.
No more than 3 previous treatments for cGVHD.
Participants with known or suspected COPD must have a FEV1 test during screening
Prior cumulative exposure to doxorubicin (including liposomal preparation) > 350 mg/m^2
Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
Female participants who:
Double (tandem) ASCT.
AGS67E
L-Histidine
?-trehalose dihydrate or
polysorbate 20
Prior radiotherapy to the thorax
Serum alkaline phosphatase less than 2.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
History of oxalate nephrolithiasis or urine oxalate > 60 mg/dL
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Simultaneous participation in other therapeutic clinical trials will not be allowed
Centrally confirmed clinicopathological diagnosis of WM
Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment
Hematology and biochemical values within protocol-defined limits
Subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in declining platelet or hemoglobin levels within the 4 weeks prior to first dose of study drug are not eligible
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
Prior splenectomy
The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact):\r\n* Persons with active or a history of eczema or other eczematoid skin disorders\r\n* Those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves\r\n* Pregnant or nursing women; children under 3 years of age\r\n* Patients should have no evidence, as listed below, of being immunocompromised:\r\n** HIV positivity \r\n** Hepatitis B or C positivity\r\n** Concurrent use of topical steroids (including steroid eye drops) or systemic steroids; nasal or inhaled steroid use is permitted
Central confirmation of T790M+ mutation status
At least one lesion, not previously irradiated.
The patient has pain that is persistent and distinguishably associated with the target sites to be treated; the patient’s average Brief Pain Inventory (BPI) pain score (0-10 scale) for last 72 hours at specified location is > 3
Patients may have additional non-painful or minimally painful osseous metastases (if patient has pain from additional sites, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the BPI compared to the site[s] treated)
Long bone target lesions with a Mirels fracture score > 7
RAI-refractory disease on structural imaging, defined as any one of the following: \r\n* A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed up to 2 years prior to enrollment in the current study, or \r\n* A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to entry in the study; there are no size limitations for the index lesion used to satisfy this entry criterion\r\n* The presence of at least one fluorodeoxyglucose (FDG) avid lesion with a maximum standardized uptake value (SUVmax) >= 5
Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration; those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration
Subject has developed Richter's transformation confirmed by biopsy
Medical, social, or psychological factors that would prevent the patient from receiving or cooperating with the full course of therapy
Plasma creatine phosphokinase (CK) less than 1.5 x ULN
No eating disorders, food allergies or intolerances
Willing to allow blood collections; and capable of performing a simple test for assessing cardiopulmonary fitness
Plans to relocate from area within the next year
Positive serology for hepatitis C (HC) defined as a positive test for HC antibody (HepC Ab), in which case reflexively perform an HC recombinant immunoblot assay (RIBA) or hepatitis C viral load to confirm the result; if the confirmatory test is negative the subject will be eligible
Plasma creatine phosphokinase (CK) < 1.5 x ULN
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 5 half lives prior to starting LDE225 treatment; NOTE: if it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
At least one lesion, not previously irradiated, and not chosen for a biopsy if performed during the screening period that can be accurately measured at baseline and which is suitable for accurate repeated measurements.
Haemoglobin ?9 g/dL
Subjects must be entered no more than 12 weeks postoperatively
Subjects must agree to undergo genetic counseling and breast cancer (BRCA) testing; patients in the expansion cohort must have a germline BRCA 1 or 2 mutation
Patients must have an intraperitoneal (IP) port in place; if a patient does not have an IP port, she must be willing to undergo surgical placement of one
Prior therapy with a combination regimen containing pomalidomide except the 2 drug combination of pomalidomide and dexamethasone
Known immunodeficiency disorders
Other active malignancies
For unilateral retinoblastoma\r\n* Group A eye that has failed local therapy\r\n* Group B eye that has failed local therapy\r\n* Group C eye that has failed local therapy\r\n* Group D eye\r\n* Group E eye that is not buphthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age
For bilateral retinoblastoma\r\n* Group A and Group A eyes that have failed local therapy\r\n* Group A and Group B eyes that have failed local therapy\r\n* Group A and Group C eyes\r\n* Group A and Group D eyes\r\n* Group A and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy\r\n* Group B and Group B eyes that have failed local therapy\r\n* Group B and Group C eyes\r\n* Group B and Group D eyes\r\n* Group B and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy\r\n* Group C and Group C eyes\r\n* Group C and Group D eyes\r\n* Group C and Group E eyes even if early enucleation is planned for the Group E eye\r\n* Group D and Group D eyes\r\n* Group D and Group E eyes even if early enucleation is planned for the Group E eye\r\n* Group E and Group E eyes if at least one eye is not planned for enucleation
Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision
Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast)
Abnormal cerebral vasculature noted on magnetic resonance (MR) angiography that would increase the risk of the procedure, including but not limited to an incomplete circle of Willis; other abnormalities that are less severe than an incomplete circle of Willis will be reviewed by the study chair in consultation with a neuro-interventional radiologist
Renal failure requiring hemo-or peritoneal dialysis
Asymptomatic or minimally symptomatic
Other malignancies requiring active therapy or known to be associated with altered immune response
Pathologically confirmed de novo ABC DLBCL
Lymphocytes >= 0.3 x 10^9/L
Monocytes >= 0.25 x 10^9/L
Willingness to undergo a tetanus vaccination
Persistent fever (> 24 hours) documented by repeated measurement =< 4 weeks prior to registration
Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
Histologic diagnosis of melanoma with metastatic disease to a visceral organ (lung, liver, brain, adrenal, nodal station outside the regional lymph drainage of the primary, vertebral bodies)
Electrolytes (including potassium, sodium, and serum calcium corrected for albumin or ionized calcium) must be within normal limits
Serious underlying lung function abnormality due to the risk of fatal pneumonitis that was caused by the combination of Abraxane and gemcitabine
Palpable splenomegaly at least 5 cm below left costal margin
Confirmed diagnosis of PMF in accordance, or Post-PV/ET MF
Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by
Peripheral blood blast count < 10%
Prior splenectomy
Subjects with a past or current diagnosis of another malignancy that will interfere with conduct of the trial; patients with past or current cancer diagnoses other than ACC are allowed to enroll if the investigator believes it will not interfere with trial conduct
Renal failure requiring hemo- or peritoneal dialysis
Daily consumption of alcohol exceeding 3 standard drinks a day (defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor)
Women taking drugs associated with a substantial risk of myopathy when co-administered with simvastatin are not eligible
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; subjects with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
For subjects enrolled for a “major deformity” or “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the study chair or co-chair must be contacted to review subject eligibility prior to enrollment
Steroids: subjects with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary
Subjects with glaucoma, intraocular pressure > 21 mmHg, or any other significant abnormality on ophthalmic examination (performed by an ophthalmologist); ophthalmological findings secondary to long-standing optic pathway glioma such as optic nerve pallor or strabismus will NOT be considered significant for the purposes of the study
Histological or cytological documentation of adenocarcinoma of the colon or rectum;
Subject must have received at least oxaliplatin-, and irinotecan-based regimens with bevacizumab and with, cetuximab or panitumumab if KRAS wildtype and are refractory to irinotecan;
Patient should have a normalized or normal uric acid level prior to study entry
Intolerance to previous bendamustine, carfilzomib or dexamethasone or mannitol; subjects who are allergic to bortezomib are not excluded
Subjects with known or likely systemic amyloidosis
Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
Cytologic or histologic proof of adenocarcinoma of the stomach or gastroesophageal junction
Subjects with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacity
Electrolytes (including potassium, sodium, and serum calcium corrected for albumin or ionized calcium) must be within normal limits
Patient's tumour sample must be PD-L1 positive (?25%of tumour cells with membrane staining (Cohort 1 and 2) or PD-L1 positive with ?90% of tumour cells with membrane staining (Cohort 3))
Unable to draw labs for HDMTX serum concentration
Enrollment on a protocol (Children's Oncology Group [COG] or other) which restricts proposed dose modifications
Dose Escalation
Dose Expansion: Cholangiocarcinoma
Subject must have available at least 3 prior full sets of scans (not including screening), each separated by at least 2 months with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR.
Dose Expansion: Solid Tumors Not Otherwise Eligible for the Cholangiocarcinoma, Chondrosarcoma, or Non-enhancing Glioma Cohorts
Subjects must have documented IDH1 gene-mutated disease based on local test evaluation. (Centralized testing will be performed retrospectively.)
Subjects must be amenable to serial peripheral blood sampling, urine sampling, and biopsies during the study.
Chronic daily NSAID use as treatment for controlling desmoid tumors is not allowed, and should be stopped >= 3 days prior to registration; NSAIDS are allowed when used for desmoid tumor-related pain or for symptoms that are unrelated to desmoid disease (eg. headache, arthritis)
Patient has documented evidence of PrR negative endometrial cancer. PrR negativity can be determined by immunohistochemistry. The tumor is considered PrR negative if the number of PrR positive cells is less than 1% determined by immunohistochemistry;
Tumors within a previously irradiated field will be designated as \non-target\ lesions unless progression is documented;
WBC >3000/microliter
Subjects in whom everolimus is contraindicated.
Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas.
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
Radiologic workup must demonstrate that the disease is confined to the abdominal cavity and/or is controlled outside of the abdominal cavity
Radiologic workup or prior abdominal exploration must be consistent with disease which can be debulked to a residual size of less than or equal to 1 cm thickness
Patients must have fully intact mental status and normal neurologic abilities; intact mental status is defined by the capacity to identify and recall one's identity and place in time and space; assessment of mental status and documentation of fully intact mental status will be completed using physical and mental exam by the referring doctor or oncologist
Able to swallow thin liquids or have a feeding tube for delivery of nutrition
Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy; (late induction permitted within 3 months of starting LHRH analogue therapy or antiandrogen); no minimum PSA requirement for patients with measurable disease
Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or agents that block the androgen receptor (e.g., ARN-509)
Presence of documented neuroendocrine differentiation on the original pathology report
Lack of acute renal failure/requirement for dialysis, as evidenced by creatinine < 1.6 mg/dL
Any malabsorption problem
Requirement for hemodialysis or peritoneal dialysis
Requirement for IV alimentation
Any recurrence of a glioblastoma multiforme
blood urea nitrogen (BUN) < 30 mg/dL
Radiosurgery including Gamma Knife, linear accelerator based radiosurgery, CyberKnife and placement of Gliadel wafer
Foreseeable condition which would preclude the reduction of steroids (dexamethasone) to a maximum of 2 mg BID within a week prior to apheresis -
Ability to tolerate FCR based therapy
No deletion of 17p13 on cytogenetic analysis by FISH
Morning cortisol >= institutional normal
Bisphosphonate (e.g. zoledronic acid) and receptor activator of nuclear transcription factor kappa-B (NF-kappaB) ligand (RANKL) inhibitor (e.g. denosumab) use for bone metastasis is permitted
Subjects of all genders and races are eligible
Subjects who received combined androgen blockade with an anti-androgen must have shown PSA(prostate specific antigen) progression after discontinuing the anti-androgen prior to enrollment.
Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
Previous malignancies
Grade 1, 2, or 3a FL without pathologic evidence of transformation
At least one lesion that measures >1.5 cm
Patient who is growth factor or transfusion dependent
Serum phosphorus, calcium and potassium >= lower limit of normal (LLN)
Subjects with recurrent or refractory, metastatic disease (N1 or M1) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading
Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
Multiple skeletal metastases (?2 hot spots) on bone scan
Previously untreated, apparently resectable, adenocarcinoma of the pancreas at registration
Transaminases < 3 x ULN
Neutrophils > 1.5 x 10^9/L
Ongoing toxic manifestations of previous treatments.
Treatment Naive only: and a) do not want to receive chemoimmunotherapy or b) have comorbidities that would preclude chemoimmunotherapy.
Previous use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988); ketoconazole
Melan-A (MART) 1 or solute carrier family 45, member 2 (SLC45A2) (+) staining results; (if patients have not had staining test in the past, the test will be run after patient consent is obtained, but before enrollment)
No single lesion larger than 1 cm
No more than 5 lesions
Ongoing participation in a Phase 2 (LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 (LX1606.1-301-CS, LX1606.1-303-CS) study
Major protocol violations or tolerability concerns in a Phase 2 (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 (eg, LX1606.1-301-CS, LX1606.1-303-CS) study
Serum or plasma potassium >= 3.5 mmol/L or institutional lower limit of normal (LLN) (independent of potassium supplementation)
Willing to take AA on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose AA is taken
Hepatocellular carcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator.
Pancreatic adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
Cholangiocarcinoma for which treatment with FOLFOX6 or CAPOX would be acceptable as determined by the Investigator.
Gastric, GEJ or esophageal adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Abnormal glucuronidation of bilirubin
Proteinuria at screening as demonstrated by urinalysis with proteinuria ? 2+.
Renal failure requiring hemo- or peritoneal dialysis
Two or more skeletal metastases (? 2 hot spots) on bone scintigraphy within 8 weeks of randomization
Warfarin use is excluded; other anticoagulants are permitted, but for participants enrolled in the RP2D cohort, the investigator must deem it safe to temporarily hold to facilitate pre and on-treatment tumor biopsies; participants where this is not feasible are excluded from participation
No primary amyloidosis
Heart rate 45-100 beats per minute
No evidence of second- or third-degree atrioventricular block
COHORT A: The subject must be deemed medically fit for radical prostatectomy by the attending urologic surgeon at the selected study site
COHORT B: More than 3 cycles of intermittent hormones (for the treatment of biochemical recurrence or castration sensitive metastatic disease), with a cycle defined as a period of consistent androgen deprivation therapy (generally 3-12 months) followed by intentional cessation of androgen deprivation therapy (ADT) without reinitiation of ADT until PSA rises
First recurrence of GBM (Cohorts 1, 1b and 2 only)
First diagnosis of unmethylated MGMT GBM (Cohort 1d and Cohort 1c Part B only)
More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
Any recurrence of GBM (Cohorts 1c and 1d only)
Participants should have normal blood pressure according to age; participants 18 years of age and younger should have a blood pressure =< 95th percentile for age, height and gender, and should not be receiving medication for treatment of hypertension; preexisting hypertension in adults should be controlled (either with pharmacological or non-pharmacological methods) at the time of enrollment
Participants who are >= 18 years of age or Legally Authorized Representative (LAR) of participants who are younger than 18 years must sign an informed consent for the Pediatric Oncology Branch (POB) Screening Protocol (01-C-0157: Eligibility Screening and Tissue Procurement for the National Cancer Institute [NCI], Pediatric Oncology Branch [POB] Clinical Research Protocols) prior to participating in studies required to determine eligibility for this trial; after confirmation of eligibility, participants who are >= 18 years of age or LAR of minor participants must sign an informed consent document for this trial, indicating that they are aware of the investigational nature of the proposed treatment, the risks and benefits of participating and the alternatives to participating, prior to the conduct of any study procedures
Previous enrollment in the present study
Have some types of eye problems or impairments
With historically documented Ph+ cells
Currently progressing, resistance to or with a suboptimal response to their most recent therapy
Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)
Subjects with any prior exposure to a thrombopoietin-receptor agonist
Grade 2 or higher diarrhea at baseline unless deemed by the investigator to be caused by laxatives prescribed for symptomatic partial obstruction (e.g. MiraLAX)
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Prior splenectomy
Severely impaired lung function
Willingness by subject to be randomized to receive either ofatumumab or duvelisib at the dose and schedule defined in the protocol
Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)
Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
Zometa or denosumab can be continued as per standard of care as long as started before the study treatment is started
HER2 positive breast cancer (3+ by immunohistochemistry or Her2 gene amplification by in situ hybridization with a ratio of HER2 gene signals to centromere 17 signals > 2.0 or average HER2 copy number > 6.0 signals/cell)
Prior exposure to oprozomib
ANC < 1,000/µL
Pituitary or adrenal dysfunction
Neutrophils >= 1.5 x 10^9 cells/L
Have a plan by treating physician to receive FOLFOX or FOLFOX-Avastin standard therapy for colorectal cancer as a first-line chemotherapy treatment
Patients with collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or active skin rash, systemic lupus erythematosus, or scleroderma
Must have target or non-target lesions as per RECIST 1.1.
INR and aPTT < 1.5 X ULN unless on medication known to alter INR and aPTT.
Modified KPS of < 80%
> 5 comorbidity points on the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI)
Anti-thymocyte globulin (ATG) level of >= 2 ugm/ml
Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan
Prior exposure to plerixafor
Prior sensitivity to plerixafor
For subjects who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the study.
Subject must have failed at least one course of androgen deprivation therapy (ADT), i.e., treatment with GnRH analogues.
Subject has been evaluated by a local neurologist prior to study entry who has determined the subject has at least one risk factor for seizure including:
Subject is currently being treated with anti-epileptics.
Subject's absolute neutrophil count is < 1500/microliter (µL), platelet count is < 100,000/µL) or hemoglobin is < 5.6 millimoles(mmol)/liter (L) (9 grams (g)/deciliter (dL) at Screening.
Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
at least 4 weeks since craniotomy and resection or stereotactic radiosurgery
Lack of availability for immunological and clinical follow-up assessments.
Candidate for primary chemoradiation as decided by an interdisciplinary team including otolaryngology, medical oncology, and radiation oncology
Uric acid within University of Iowa Hospital and Clinics (UIHC) normal institutional limits; medical therapy may be used to achieve this targeted range; must be within limits (2.4 – 7.0 mg/dL) prior to starting diet
Known/established G6PD (glucose-6-phosphate dehydrogenase) deficiency
Previous exposure to any 2nd generation anti-hormonal including abiraterone and enzalutamide
Substrates of CYP2D6 with a narrow therapeutic index (eg, thioridazine);
Haemoglobin (Hb) <100 g/L
Patient must be scheduled to undergo either a single or bilateral elective nipple-areola skin sparing mastectomy (NASSM) procedure with planned immediate reconstruction
Cognitive impairment
Adults with a confirmed pathologic diagnosis of pheochromocytoma/paraganglioma by the Laboratory of Pathology, National Cancer Institute (NCI) when such tissue is available to confirm or in the event that outside tissue is not available:\r\n* An outside pathology report confirms the diagnosis of pheochromocytoma (Pheo)/paraganglioma (PGL), AND\r\n* The patient has nuclear medicine imaging studies that would only be positive in an adult patient with a diagnosis of Pheo/PGL (fluorordopa [F-DOPA], Dotatate, fluorodopamine [F-Dopamine] or metaiodobenzylguanidine [MIBG])
Information available or pending regarding possible genetic alterations that can explain the patient’s pheochromocytoma/paraganglioma (mutations in succinate dehydrogenase subunit B [SDHB], SDHV or von Hippel-Lindau [VHL] genes)
Prior therapeutic MIBG is allowed
Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety
Minimum weight 20 kilograms is required to be eligible for the study since the minimum injection volume of SYLATRON is 0.05 ml, 20 mcg, subcutaneously (SQ) as suggested by Merck
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Have a baseline serum potassium >= 3.5 mmol/L
Previous anti-androgen therapy and progression after withdrawal; patients who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (>= 4 weeks since last flutamide, >= 6 weeks since last bicalutamide or nilutamide)
Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of cycle 1 day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to cycle 1, day 1)
Total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of biliary stent (7 French or greater) or percutaneous transhepatic drainage are acceptable; once biliary drainage has been established, institution of gemcitabine therapy may proceed when the total bilirubin falls to =< 4.0 mg/dL; patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
Patients receiving the following drugs that are contraindicated with nelfinavir (NFV) (VIRACEPT) will be excluded if they cannot be change or discontinued; drugs that should not be coadministered with Viracept:\r\n* Antiarrhythmics: amiodarone, quinidine\r\n* Antimycobacterial: rifampin\r\n* Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine\r\n* Herbal products: St. John's wort (hypericum perforatum)\r\n* 3-hydroxy-3-methyl-glutaryl (HMG)-acetyl coenzyme A (CoA) reductase inhibitors: lovastatin, simvastatin\r\n* Neuroleptic: pimozide\r\n* Sedative/hypnotics: midazolam, triazolam
Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: \r\n* Anti-convulsants: carbamazepine, phenobarbital\r\n* Anti-convulsant: phenytoin; phenytoin plasma/serum concentrations should be monitored; phenytoin dose may require adjustment to compensate for altered phenytoin concentration\r\n* Anti-mycobacterial: rifabutin; it is recommended that the dose of rifabutin be reduced to one-half the usual dose when administered with VIRACEPT; 1250 mg BID is the preferred dose of VIRACEPT when coadministered with rifabutin\r\n* Erectile dysfunction agent: sildenafil; sildenafil shall not exceed a maximum single dose of 25 mg in a 48 hour period\r\n* HMG-CoA reductase inhibitor: atorvastatin; use lowest possible dose of atorvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as pravastatin or fluvastatin in combination with VIRACEPT\r\n* Immunosuppressants: cyclosporine, tacrolimus, sirolimus\r\n* Narcotic analgesic: methadone; dosage of methadone may need to be increased when coadministered with VIRACEPT\r\n* Oral contraceptive: ethinyl estradiol; alternative or additional contraceptive measures should be used when oral contraceptives and VIRACEPT are coadministered\r\n* Macrolide antibiotic: azithromycin; dose adjustment of azithromycin is not recommended, but close monitoring for known side effects such as liver enzyme abnormalities and hearing impairment is warranted
Patient is postmenopausal. Postmenopausal status is defined either by:
Documented cardiomyopathy
That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.
Willing and capable of undergoing apheresis for collection of mononuclear cells
Creatinine =< 1 x UNL
Patient must be at least 18 years old.
The target index tumor(s) is determined (by CT images) to be in a location where cryoablation is technically achievable based on the proximity of adjacent organs/ structures and is greater than 0.5 cm from any critical organ/structure (possibly achieved with additional maneuvers such as iatrogenic pneumothorax or hydrodissection).
Patient is unable to lie flat or has respiratory distress at rest.
Patient is currently participating in other experimental studies that could affect the primary endpoint (e.g. experimental chemotherapy regimen).
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage\r\n* Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed\r\n* Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
Part B2 Arm 1 only:
Left ventricular fractional shortening < 30%
Hb level ?9 g/dL
Female subject must be either:
post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
Emergency leukapheresis;
Growth factor or cytokine support;
Subject has disseminated intravascular coagulation abnormality (DIC).
Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Subject has hypokalemia and hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]).
Patients must have pathological Gleason (pG) sum 8-10; or pG sum 7 and either pT3 or R1 disease (i.e. positive margins)
The patient was informed about the positive survival results of the RTOG 96-01 clinical trial, and has elected to forgo treatment with high-dose bicalutamide
BCC/SCC that was previously treated (i.e., recurrent BCC/SCC)
BCC/SCC in region adjacent to or overlapping with region of prior radiotherapy
BCC/SCC on irregular surface (i.e., target area not flat)
BCC/SCC adjacent to or overlapping with burn or scar
BCC/SCC in area prone to trauma (including, but not limited to the skin overlying the tibia, dorsum of hands and elbow)
BCC/SCC in area with compromised lymphatic drainage or vascular supply
BCC/SCC within 3 cm of another treated or untreated BCC/SCC
Inflammatory process in target area
Genetic disorder predisposing patient to skin cancers or radiation sensitivity (basal cell nevus syndrome, xeroderma pigmentosum, ataxia telangiectasia mutans)
Receipt of drug that will affect biologic response to radiation (radiosensitizer or radioprotector)
Must consent to collection of whole blood samples for genomic analysis
Subjects must be able to discontinue any drug treatment aimed at lowering disease burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs that have more long-lasting effects on the marrow, such as thalidomide and its analogs, and interferon, subjects should discontinue these no later than day -28
Subjects must be willing to accept/continue transfusions to treat low hemoglobin levels
Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies (aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below 50,000 on two different laboratory evaluations, separated by minimum of two weeks
Having smoked at least 1 cigarette within 4 weeks of study enrollment
Columbia Suicide Severity Rating Scale (C-SRSS) baseline/screening: patient response of “yes” to any question except question 1
Currently taking bupropion (bupropion hydrochloride) for depression
Active widespread skin disorders such as psoriasis, chronic urticarial or dermatitis
Currently enrolled in other professional tobacco cessation therapeutic intervention
Enrollment in a concurrent cancer therapeutic trial will require prior review and approval by the study site principal investigator (PI) to determine that there are no drug interactions concerns
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
History of malignancy with confirmed activating RAS mutation at any time. Prospective RAS testing is not required. However, if the results of previous RAS testing are known, then those results must be used in assessing eligibility.
Patient must have a medical oncology consult with the recommendation of chemotherapy; recommended regimens are as follows: cyclophosphamide and doxorubicin (AC); Taxotere, doxorubicin and cyclophosphamide (TAC); Taxotere and cyclophosphamide (TC); or Taxotere, carboplatin and trastuzumab (TCH) prior to registration; the use of additional chemotherapy, hormonal therapy or trastuzumab after the initial regimen is at the discretion of the medical oncologist; other primary regimens are possible but the principal investigator (PI) must be notified prior to enrollment
Previously received trastuzumab as part of a regimen in the perioperative or metastatic setting with evidence of progression; 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted
All patients with disease technically amenable to biopsy will be asked to undergo a biopsy; patient must agree to allow 2 biopsies of any malignant lesion that can be accessed by endoscopy or with the aid or radiology (i.e. CT guided)
Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating esophagogastric cancer; 89Zr-trastuzumab uses as imaging agent for 89Zr-trastuzumab PET permitted
International Federation of Gynecology and Obstetrics (FIGO) stage IA2 or IB1 disease
No lymphovascular space invasion (LVSI) present on biopsy or previous cone
Less than 10 mm of cervical stromal invasion
Cone margins and endocervical curettage (ECC) specimen negative for invasive cancer, cervical intraepithelial neoplasia (CIN) II, CIN III or adenocarcinoma-in-situ; (a negative margin is defined as no invasive cancer within 1.0 mm of both the endocervical and ectocervical margins and no adenocarcinoma in situ [AIS] or CIN II or CIN III at the inked or cauterized margin; one repeat cone and ECC permitted)
Presence of LVSI
Cone margins or ECC specimen positive for invasive cancer, CIN II, CIN III or adenocarcinoma-in-situ (one repeat cone permitted)
More than 2 x 10^6 autologous CD34+ cells/kg cryopreserved. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center
Pregnant or lactating females. Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study
Prior dose limiting toxicity from carfilzomib or lenalidomide
Patient is not a candidate for or declines consolidative thoracic radiotherapy.
Previous enrollment in the present study.
Prior grade 3 hypersensitivity to cetuximab requiring discontinuation\r\n* An exception is for a patient who could subsequently receive cetuximab without a reaction.
Prior lenvatinib
Locally advanced, unresectable pancreatic cancer defined on post-induction chemotherapy computed tomography (CT) as having tumor involvement of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or pemphigus vulgaris (PV) involvement
Completion of at least 3 months of standard induction chemotherapy for locally advanced pancreatic carcinoma (LAPC), which may include fluorouracil/irinotecan/leucovorin calcium/oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel, within 6 weeks of enrollment
Patient with multiple, serious major neurologic deficits including encephalopathy.
Platelet count >= 75 x 10^9/L. No transfusion or growth factor support for one week prior to labs.
International Prostate Symptom Score (IPSS) < 18 (and < 10 if on medication for benign prostatic hypertrophy such as tamsulosin) at time of enrollment
Androgen deprivation therapy based on clinician judgment is permitted on study
Prior prostatectomy
At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Lugano Classification\r\n* Site of disease deemed amenable to low-dose, local radiotherapy (2 x 2Gy) should not be counted as target lesions\r\n* Previously irradiated lesions should not be counted as target lesions\r\n* Lesions that are intended to be used to collect tissue samples for biopsy should not be counted as target lesions\r\n* Bone lesions should not be counted as target lesions
For men: agreement to remain abstinent
Recipient of an allogeneic HSCT.
Diagnosed with cGVHD per the 2014 cGVHD NIH Consensus Criteria(Jagasia, 2015; Appendix 8) within the past 2 years prior to screening.
Moderate to severe cGVHD (in accordance with 2014 cGVHD NIH Consensus Criteria [Jagasia, 2015; Appendix 9]) at screening with involvement of at least one of the following organs at the screening and baseline visits: skin, mouth, eyes, gastrointestinal (GI) tract, liver, lungs, and joint and fascia.
No more than 3 previous treatments for cGVHD, excluding topical agents.
Key
Treatment with T-cell depleting, B-cell depleting or IL-2 signaling targeted medication (eg, ATG, alemtuzumab, basiliximab, denileukin diftitox, IL-2, rituximab within 12wks prior to starting AMG 592.
Treatment with T regulatory cell expanding therapies (ie ECP, PUVA, UVB, adoptively transferred T regulatory cells) within 4 wks prior to starting dose of AMG 592.
History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
Hep B and Hep C
Undergoing a laparotomy procedure via a vertical midline incision for any indication with the gynecology service at Memorial Sloan Kettering (MSK)
Hepatic dysfunction as evidenced by elevated transaminases
Laparotomy incisions unable to be closed primarily due to tissue or fascial damage
Transverse laparotomy incisions
Laparotomy incisions left open due to a case classification as “contaminated” or “dirty”
At least one targetable lesion appropriate for palliative SBRT and one non-target lesion
Known contraindications to radiotherapy
Active infection or unexplained fever > 38.5 degrees Celsius (C) (> 101.3 degrees Fahrenheit [F]) within 2 weeks prior to enrollment
Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn’s disease, malabsorption, or grade >= 2 diarrhea of any etiology screening)
Known dihydropyrimidine dehydrogenase deficiency
Participants for Cohort A:
Has been previously treated with fluoropyrimidine, irinotecan, and oxaliplatin
Participants for Cohorts B and C:
Participants for Cohorts D and E:
Must have been previously treated with 1 line of therapy including a fluoropyrimidine plus an oxaliplatin-based regimen
Participants for Cohorts A, C, and E:
Has neuromuscular disorders associated with an elevated creatine kinase
Potential Participants for Cohorts A, C or E who are to Receive Binimetinib:
Potential Participants for Cohorts A, C, D or E:
Potential Participants for Cohorts D or E:
Prior exposure to selected immune cell-modulating antibody regimens
Diagnosis of:
SLL (lymphadenopathy and/or splenomegaly and < 5×10^9 CD19+ CD5+ clonal B lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL)
Subjects in the ibrutinib + JCAR017 combination therapy cohort must be either:
receiving ibrutinib and progressing at the time of study enrollment
Subjects with Richter's transformation
Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
Lenalidomide within 1 day prior to leukapheresis
Subjects with simultaneous primary cancers outside of the oropharynx
Are postmenopausal for at least 1 year before the screening visit, OR
COHORT I: Patients must have MM that harbors an NF2 mutation believed to cause functional loss of the NF2 protein as determined by any Clinical Laboratory Improvement Act (CLIA) lab certified next generation sequencing (NGS) platform or NF2 loss must be documented by CLIA certified immunohistochemistry (IHC)
Is the age of majority in country of residence
Has a diagnosis of:
tenosynovial giant cell tumor (TGCT), which is associated with severe morbidity or functional limitations and for whom surgery is not an option (prior pexidartinib is permitted for TGCT patients unless ineffective or not tolerated and there has been a washout period of at least 4 weeks)
intra-uterine device (nonhormonal or hormonal)
sexual abstinence (only if this is in line with the patient's current lifestyle)
analysis of results
Amyloidosis
Participants must have documented HER2+ disease by overexpression and/or gene amplification on the most recent biopsy, per current ASCO-CAP (American Society of Clinical Oncology – College of American Pathologists) 2013 guidelines; central confirmation of HER2 status is not required
Recurrent or refractory solid tumors
Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ?21 days after the completion of interleukins, interferons or cytokines (other than hematopoietic growth factors)
Cellular Therapy: ?42 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer cells, dendritic cells, etc)
Adequate coagulation
Radiographic evidence of major blood vessel invasion/infiltration.
Participants who are currently receiving enzyme-inducing anticonvulsants
Prisoners or subjects who are involuntarily incarcerated
Mayo Clinic Arizona only: Willing to participate in associated biobanking study, 919-04; the patient must sign consent to enroll onto the mandatory companion biobanking study in order to participate in this treatment study
Mayo Clinic Rochester and Florida only: Willing to participate in associated biobanking study, 521-93; the patient must sign consent to enroll onto the mandatory companion biobanking study in order to participate in this treatment study
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
No structurally unstable bone lesions suggesting impending fracture
Asymptomatic or mildly symptomatic from prostate cancer\r\n* A score of 0-1 on Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours) will be considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic
Radiotherapy to >= 3 sites at the same time within 1 week prior to signing consent
Subjects with known or likely systemic amyloidosis
For expansion part:
No clinical ileus or subileus
Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
Legal incapacity or limited legal capacity
CRPC with metastatic disease with at least one site of metastatic disease must be amenable to needle biopsy; soft tissue biopsy sites include: lymph node or visceral metastases; bone sites include lumbar vertebrae, pelvic bones and long bones; excluded sites are thoracic, cervical vertebrae, skull and rib lesions; biopsy site will be selected with guidance of interventional radiologist determining best site to optimize balance of obtaining useful tissue for analysis and minimizing risk
Written authorization for use and release of health and research study information (Health Insurance Portability and Accountability Act [HIPAA] authorization per institutional requirements)
Serum potassium >= 3.5 mEq/L
Self-reported race of either African American or Caucasian
Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable; limited and resectable multi- focal disease (less than 4 tumors technically resectable)
Diagnosis of sclerosing cholangitis
Patients with occlusion of the main portal vein or of the right and left portal branches
PART B: Patients must be proven to meet marker criteria (FGFR1 SISH+ ISH+, FGFR1 SISH+ ISH negative [-ve], FGFR1 SISH-ve ISH+, FGFR1 SISH-ve ISH-ve [FGFR1 double negative cohort] or ret proto-oncogene [RET] FISH+) prior to enrollment into Part B (treatment); adenocarcinoma patients must be known to not possess either an EGFR mutation or an ALK rearrangement in their tumor (if positive for one, testing for both is not required)
PRE-REGISTRATION
Ability to complete questionnaire(s) by themselves or with assistance
Bilirubin =< 1.5 x UNL
Patient must have failed prior chemoradiation with temozolomide and any other therapies except BEV (group A), or must have failed primary chemoradiation and a BEV-incorporating treatment (group B)
Serum potassium >= 3.5 mmol/L
Requirement for constant administration of proton pump inhibitor or H2 antagonist; intermittent uses of antacids or H2 antagonists are allowed
PSA value that is undetectable can be enrolled if pathology from prostatectomy demonstrates one or more of the following: positive margin, extracapsular extension, or seminal vesicle invasion
A history of known Gilbert’s syndrome or homozygous presence of the uridine diphosphate (UDP)-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele on pre-treatment testing
New or progressive CNS lesions, as assessed by the patient’s treating physician, with at least one of the following clinical scenarios:\r\n* It is anticipated that some participants may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Participants who have had prior cranial surgery are eligible, provided that there is evidence of measurable residual or progressive lesions; if a patient has surgical resection followed by whole brain radiation therapy (WBRT) and/or SRS, then there must be evidence of progressive CNS disease after the completion of WBRT and/or SRS\r\n* Participants who have had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS\r\n* Participants who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids
CD30 negative HL
Subjects in second or later relapse;
Enrolled in Human Research Protection Office (HRPO) # 201011766 (“Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Malignancies”)
Normal functioning of daily living activities
Uveal and mucosal melanoma
Patients with unknown BRAF^600X status: histologically confirmed melanoma, papillary thyroid, cholangiocarcinoma or testicular cancer that is metastatic or unresectable and for which the investigator feels a BRAF^600X targeted agent is a reasonable treatment\r\n* NOTE: patient must be screened by central BRAF testing and must demonstrate a V600 mutation prior to start of study agent\r\n* Note: other tumor types without known BRAF^600X mutations will not be eligible for central testing
Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gray (Gy) with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy)
Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide
Willing to remain abstinent from consuming alcohol while on disulfiram
Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram; of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram
Patients must be willing to submit blood for pharmacokinetics; sites must order S1221 pharmacokinetic (PK) kit immediately after registration; the Southwest Oncology Group (SWOG) patient identification (ID) number must be provided on the S1221 PK Kit request form
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Main portal vein thrombosis (PVT)
Contraindications to angiography and selective visceral arterial catheterization
Any prior intervention for, or ongoing compromise of, the ampulla of Vater or biliary-enteric anastomosis
Subjects must be>/= 18 years of age at the time of informed consent, because no dosing or adverse event data are currently available on the use of eltrombopag in children.
Subjects with any prior exposure to a thrombopoietin-receptor agonist
Pregnant or breast-feeding because there are no adequate and well-controlled studies of eltrombopag use in pregnancy and it is unknown whether eltrombopag is excreted in human milk.
Infratentorial meningioma (patients may have infratentorial meningioma if there is concurrent growing supratentorial meningioma that serves as the target lesion)
Skull defect with missing bone
Ventricular shunt/catheter
Presence of a foreign body intracranially such as a bullet fragment
Patients must have confirmed expression of NY-ESO-1 and/or LAGE-1 by RT-PCR, immunohistochemistry or quantigene analysis. (This determination will be made under a pre-enrollment screening ICF)
Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study. The specific type of stress test will be selected at the PI's discretion.
Active, uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)
VS or meningioma surgery determined clinically necessary by the treating physician; similar cerebellopontine (CP) angle schwannomas, such as facial nerve schwannomas and “collision tumors”, i.e. tumors arising from multiple cranial nerves, are eligible
Patients cannot receive cytochrome P450 3A (CYP3A4) inhibiting drugs including antibiotics (clarithromycin, erythromycin, troleandomycin), anti-HIV agents (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir), antifungals (itraconazole, ketoconazole, fluconazole at doses > 200 mg/day, voriconazole), antidepressants (nefazodone, fluvoxamine), calcium channel blockers (verapamil, diltiazem) or amiodarone
Subject must be known to be RET positive (known KIF5B-RET translocation, or other confirmed RET translocations (e.g., CCDC6-RET)) or have an available tumor sample for local or central testing obtained prior to consent (Screen 1). Subjects whose samples need to be submitted for central laboratory testing must be current non-smokers and not known to have mutation in EGFR, KRAS, or ALK.
Previously treated SCLC with only one prior treatment regimen (cyclophosphamide/doxorubicin/vincristine [CAV] alternating with etoposide/cisplatin [EP] is acceptable)
Previous serious adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., \Variants of uncertain clinical significance\ or \Variant of unknown significance\ or \Variant, favor polymorphism\ or \benign polymorphism\ etc.)
Patients must have completed all planned/elective surgeries > 4 weeks and must have recovered from surgery before registration; participants should try to avoid any additional elective surgeries during the study period; particular instances may be discussed with Protocol Chair/designee
To ensure compliance with the POWER-remote and PatientViewpoint programs, patients must meet the following:\r\n* Prior experience with web forms and feels able to use the POWER-remote web program and PatientViewpoint\r\n* Has or is able to download Internet Explorer 8+, Firefox 3.0+, Safari 4.0+, Chrome 4.0+, and Adobe Flash Player 10\r\n* Familiarity with and access to internet at least 4 days per week\r\n* Use of an email program or willing and able to establish one for this study\r\n* Able to read and write the English language without assistance\r\nNOTE: participants who are unable to receive email or to complete the PatientViewpoint questionnaires for any reason will not be allowed to continue on the study
History of toxicity to the most recent AI (letrozole or exemestane) that warrants cessation of the AI
Previous adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV)
Medical oncologist agrees that four day window on curcumin alone is appropriate/safe prior to start of irinotecan for trial candidate
The subject is capable of understanding and complying with parameters as outlined in the protocol
Any prior allergies to curcumin or turmeric
Prior intolerance of irinotecan or necessity for dose reduction greater than 20%
DONOR: Donors who fail eligibility requirements for donation of cells or tissue per section 21 Code of Federal Regulations (CFR) 1271 for donation of a HCT/product (P) will be excluded unless use of the cells complies with 21 CFR 1271.65(b)(iii) (urgent medical need) or with 21 CFR 1271.65(b)(i) (allogeneic use in a first-degree or second-degree relative)
Revised International Prognostic Index score of >=1
Minimum Karnofsky Scale
Blood urea nitrogen (BUN) =< 35 mg/dl
Magnesium > lower limit of normal (LLN) or correctable with supplements
Calcium (after correction for albumin level) > LLN or correctable with supplements
Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
Re-Induction Criteria (if applicable):
Scheduled for MLA
Hemoglobin >= 9 (packed red blood cells [pRBC] transfusion +/- erythropoiesis-stimulating agents [ESA] are allowed) (must be within 7 days of MLA)
More than 2 prior relapses
Meet the clinical laboratories criteria as specified in the protocol
Suitable for treatment with at least one of the physician's choice chemotherapy options (liposomal doxorubicin, paclitaxel or topotecan) as determined by the Investigator.
Additional criteria exist.
Additional criteria exist.
Platelet count < 30 x 10^9/L, unless myeloma-related; if MM-related (hypercellular marrow biopsy of > 80% and packed with at least 80% plasma cells) the enrolling investigator must document this
Participants must not have life-threatening co-morbidities
Detectable HCV RNA with anti-HCV-positivity
Bicarbonate within the normal range of the hospital lab (24-32 mmol/L)
Heart rate > 60 beats per minute (bpm)
Agree to participate in research blood collection at 4 different time periods (20 ml = 4 teaspoons)
First degree atrioventricular (AV) block on ECG in which PR interval lengthened > 200 milliseconds; second degree; or third degree
Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
BRCA1 and/or BRCA2 mutations that are considered to be non detrimental (e.g. \Variants of uncertain clinical significance\ or \Variant of unknown significance\ or \Variant, favor polymorphism\ or \benign polymorphism\ etc).
Ocular melanoma
Diagnosis of symptomatic MM
Granulocytes >= 1,500/mcL
Prior loco-regional therapy including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded) is allowed
Prior exposure to systemic intravenously given doxorubicin
No evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN)
Bilirubin =< 1.5 x UNL
Dyspnea with moderate exertion
T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen; acceptable conditioning regimens include but are not limited to fludarabine/melphalan/alemtuzumab; fludarabine/busulfan/alemtuzumab; fludarabine/melphalan/ATG; fludarabine/busulfan/ATG
Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
Human immune deficiency virus
Screen labs of Hemoglobin, platelets, absolute neutrophil count (ANC), bilirubin, AST, ALT, serum creatinine, serum albumin, PT/INR, and PTT within specified values/criteria per protocol prior to dosing.
Inclusion Criteria:\n\n        Subjects eligible for enrollment in the study must meet all the following criteria:\n\n          1. Male or female ?18 years of age\n\n          2. Able to provide written informed consent prior to any study procedures being\n             performed; eligible subjects must be able to understand the informed consent form\n             prior to inclusion into the study.\n\n          3. Confirmed diagnosis of newly diagnosed, persistent or recurrent CD if subjects are not\n             candidates for surgery or radiotherapy CD is defined according to the criteria in the\n             Endocrine Society Clinical Practice Guideline for diagnosis of CD (Nieman 2008).\n             Previous medical records will be collected and used to support the diagnosis of CD.\n\n             Specifically, CD is defined as\n\n               -  Mean 24-hour UFC level of ?1.5X ULN on repeated determination\n\n               -  Morning plasma corticotropin (ACTH) level of 5 ng/L (1.1 nmol /L) or more\n\n               -  Either MRI confirmation of pituitary macroadenoma, or inferior petrosal sinus\n                  gradient >3 after corticotropin-releasing hormone (CRH) stimulation for those\n                  patients with a microadenoma, or for subjects who have had prior pituitary\n                  surgery, histopathology confirming and ACTH-staining adenoma. If inferior\n                  petrosal sampling had been performed without CRH, then a central to peripheral\n                  pre-stimulation gradient >2 is required\n\n          4. Confirmed diagnosis of newly diagnosed, persistent or recurrent endogenous CS of other\n             etiology if subjects are not candidates for surgery or radiotherapy. CS will be\n             defined according to the criteria in the Endocrine Society Clinical Practice Guideline\n             for diagnosis of CS (Nieman 2008). Previous medical records will be collected and used\n             to support the diagnosis, and the differentiation of the cause of CS, specifically\n\n               -  Mean 24-hour UFC level of ?1.5X ULN on repeated determination\n\n               -  Ectopic ACTH secretion, not of pituitary origin\n\n               -  Ectopic CRH secretion\n\n               -  Adrenal-dependent CS (adrenal adenoma, adrenal autonomy)\n\n               -  Etiology unknown\n\n          5. Subjects MUST have elevated mean 24-hour UFC levels ?1.5X ULN of assay based on a\n             minimum of four measurements from adequately collected urine. Urine may be collected\n             on sequential days.\n\n          6. In addition to elevated mean UFC, presence of abnormal values from one of the\n             following tests:\n\n               -  Abnormal DST: Elevated 8 AM serum cortisol ?1.8 ug/dL (50 nmol/L) after 1 mg\n                  dexamethasone orally at 11 PM the evening prior (if not conducted already in the\n                  diagnostic workup of the subject within the previous 2 months before start of\n                  Screening Phase; in that case previous test results and details of conduct will\n                  need to be available by the Baseline visit)\n\n               -  Elevated late night salivary cortisol concentrations (at least two measurements)\n                  >ULN NOTE: For subjects with estimated glomerular filtration rate (eGFR as\n                  determined by Modified Diet in Renal Disease MDRD equation) >40 and <60\n                  mL/min/1.73 m2 in addition to meeting the UFC criteria, late night salivary\n                  cortisol test results (?2 measurements) MUST also demonstrate evidence of CS.\n\n          7. Previously irradiated subjects with CD or CS of other etiology will be allowed as long\n             as the radiation treatment occurred > 4 years ago and subjects have not exhibited\n             evidence for improvement in their underlying Cushing's disease for 6 months. The total\n             number of previously irradiated subjects enrolled in this study will not exceed 10.\n\n          8. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse\n             surgery, or in whom surgery will be delayed for >6 months. Subjects may be allowed to\n             participate in the trial while awaiting surgery, but must agree to complete this study\n             prior to surgery. For subjects who have already undergone surgery, a minimum of 3\n             months should have elapsed before the subject can be deemed a surgical failure.\n\n          9. Subjects on treatment for CD or endogenous CS of other etiology for whom treatment has\n             been inadequate or not well tolerated must agree to the following minimum washout\n             periods prior to the Baseline Visit:\n\n               -  Inhibitors of steroidogenesis (including ketoconazole): 2 weeks\n\n               -  Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks)\n\n               -  Octreotide acetate LAR and lanreotide Autogel®: 12 weeks\n\n               -  Lanreotide SR/long-acting pasireotide: 8 weeks\n\n               -  Octreotide acetate (immediate release formulation) or short-acting pasireotide: 1\n                  week\n\n               -  Mifepristone (RU 486): 4 weeks\n\n         10. Subjects on megesterol acetate (medroxyprogesterone acetate) must agree to a washout\n             period of at least 6 weeks prior to the Baseline Visit\n\n         11. A female is eligible to enter and participate in the study if she is of:\n\n             Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,\n             including any female who is post-menopausal or surgically sterile). Surgically sterile\n             females are defined as those with a documented hysterectomy and/or bilateral\n             oophorectomy or tubal ligation.\n\n             Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with\n             an appropriate clinical profile, e.g. age > 45 years, in the absence of hormone\n             replacement therapy. However in questionable cases, a blood sample with FSH > 40MIU/ml\n             and estradiol < 40pg/ml (<140 pmol/L) is confirmatory.\n\n             OR Child bearing potential and agrees to use highly effective methods of birth control\n             while participating in the study and for 2 weeks after the study is completed.\n\n         12. Fertile men must also agree to use a medically acceptable form of birth control while\n             on study drug and up to 2 weeks after the study is completed.\n\n         13. Able to comprehend and comply with procedures.\n\n        Exclusion Criteria\n\n        Subjects will be excluded from the study if any of the following criteria are met:\n\n          1. Subjects with Pseudo-Cushing's syndrome based on assessment of the investigator.\n\n          2. Subjects with cyclic Cushing's syndrome based on assessment of the investigator\n\n          3. Subjects with a non-endogenous source of hypercortisolism such as exogenous source of\n             glucocorticoids or therapeutic use of ACTH.\n\n          4. Known inherited syndrome as the cause of hypercortisolism, including but not limited\n             to multiple endocrine neoplasia Type 1, McCune Albright Syndrome and Carney Complex\n\n          5. Subjects with adrenal carcinoma\n\n          6. History of malignancy, other than thyroid, early stage prostate, squamous cell and\n             basal cell carcinoma, within 3 years prior to the Screening Phase. Subjects with\n             history of such allowed carcinoma must have a life expectancy of >1 year and must be\n             on stable doses of their specific therapies. Subjects with early stage prostate cancer\n             undergoing no treatment due to low grade potential may be enrolled.\n\n          7. Clinical or radiological signs of compression of the optic chiasm.\n\n          8. Major surgery within 1 month prior to enrollment (ICF signing)\n\n          9. Subjects with clinically significant abnormality in 12-lead ECGs during the Screening\n             Phase needing medical intervention.\n\n         10. Subjects with QTc interval of >470 msec during the Screening Phase.\n\n         11. Subjects with a history of Torsades des Pointes, or ventricular tachycardia, or\n             ventricular fibrillation, or history of prolonged QT syndrome (including family\n             history), or use of medications resulting in QT/QTc prolongation, or hypokalemia <3.0\n             meq/L.\n\n         12. Preexisting hepatic disease; subjects with mild to moderate hepatic steatosis\n             consistent with fatty infiltration (non-alcoholic fatty liver disease [NAFLD] are\n             allowed).\n\n         13. Positive for hepatitis B surface antigen (HbsAg) or positive hepatitis C test.\n\n         14. History or symptoms of recurrent symptomatic cholelithiasis or pancreatitis.\n\n         15. Liver function tests (LFT) must not be above the following cut-offs during the\n             Screening Phase:\n\n               -  ALT and/or AST >3 X ULN\n\n               -  Total bilirubin >2 X ULN If all LFTs are within normal limits (WNL) and total\n                  bilirubin (TBN) is elevated, examination of direct and indirect bilirubin may be\n                  conducted. Subjects with isolated indirect TBN up to 3X ULN are presumed to have\n                  Gilbert's syndrome and may be enrolled if all other LFTs are within normal\n                  levels.\n\n         16. History of documented or suspected drug-induced liver injury requiring drug\n             discontinuation of ketoconazole or any azole antifungals.\n\n         17. Pregnant or lactating women\n\n         18. HIV-positive.\n\n         19. History of persistent uncontrolled hypertension (>180/120 mmHg) despite medical\n             intervention.\n\n         20. Subjects with hypercholesterolemia who are currently treated with atorvastatin,\n             lovastatin or simvastatin and not willing or unable to change to alternative therapies\n             with pravastatin, fluvastatin, and rosuvastatin within 2 weeks of start of the\n             Screening Phase.\n\n         21. Body habitus preventing repeated venipuncture as required by protocol.\n\n         22. Subject is currently in another study or has received any investigational treatment\n             (drug, biological agent or device) within 30 days or 5 half-lives of treatment,\n             whichever is longer.\n\n         23. Repeated hospitalization for hyperglycemia or any complication of hyperglycemia and\n             diabetes during the last 12 months\n\n         24. Subjects with decreased renal function as defined by eGFR <40 mL/min/1.73 m2, using\n             MDRD equation for estimating renal function (eGFR).\n\n         25. Any other clinically significant medical condition, as determined by the Investigator\n             that precludes enrollment and participation in the study through completion, including\n             conditions that would preclude the subject from being able to follow instructions or\n             to perform the necessary procedures (for example, psychiatric instability or severe\n             disability).\n\n         26. Abnormal free T4. Subjects with TSH <LLN and normal free T4 are permitted to\n             participate in the study.\n\n         27. Subjects who have a history of alcohol or drug abuse in the 6 month period prior to\n             enrollment.\n\n         28. Subjects who have been treated with mitotane within 6 months of the Screening Phase.\n\n         29. Subjects who are currently taking any H2 receptor antagonists, proton-pump inhibitors,\n             or sucralfate (all of which inhibit absorption of COR-003). A list of orally\n             acceptable antacids (for example, Mylanta and Maalox) will be provided, and can only\n             be taken a minimum of 2 hours after dosing of COR-003.\n\n         30. Subjects who receive any prohibited concomitant medication:\n\n               -  Weight loss medications (prescription or over the counter)\n\n               -  Acetaminophen >3 g total daily dose (due to increased hepatotoxicity)\n\n               -  Co-administration of strong inducers or inhibitors of CYP3A4 enzyme system that\n                  may interfere with the metabolism of COR-003 and cannot be discontinued prior to\n                  first dose\n\n               -  The following herbal medicines are prohibited: St John's Wort, echinacea, gingko,\n                  goldenseal, yohimbe, red rice yeast, danshen, silybum marianum, Asian ginseng,\n                  schissandra sphenanther, shankhapushi, and Asian herb mixture (Xiao chai hu tang\n                  and Salboku-to).\n\n               -  Topical or inhaled steroids\n\n               -  Carbamazipine, fenofibrate, carbenoxolone.\n\n               -  Ingestion of genuine licorice.
Borderline resectable- Tumors considered borderline resectable are defined as follows:
Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery without extension to the celiac axis.
Tumors considered to be unresectable due to local advancement include an absence of distant metastases as well as:
Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
Tail: SMA or celiac encasement greater than 180 degrees.
Nasopharyngeal, salivary gland, lip or sinonasal carcinoma
Prior serious infusion reaction to cetuximab
Bilirubin =< 1.5 x UNL
Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with no standard curative options available with at least one indicator lesion avid on 99mTc-MDP scan or a Sodium Fluoride (Na F) Bone PET scan will be eligible. In addition, subjects with extremely rare bone forming osteosarcoma-like tumors that behave like osteosarcoma phenotypically and are clinically treated like osteosarcoma (eg. Malignant Fibrous Histiocytoma of Bone or malignant transformation of giant cell tumor of bone) may be included if they satisfy all of the inclusion criteria.
Indicator lesion that has uptake of 99mTc-MDP on bone scan or a Sodium Fluoride ( Na F) Bone PET scan and can be subjected to quantitative assessment by this scans and possibly other means.
ECOG=2 or better
Diagnosis other than osteosarcoma.
Prior carfizolmib is not required but is allowed if a patient had at least 2 cycles of carfilzomib alone or in combination with a dose of at least 20/27 mg/m2, as long as the patient :
Was not removed from carfilzomib therapy due to toxicity, unless approved by the medical monitor
Prior oprozomib exposure
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage\r\n* Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (computed tomography [CT] with contrast is strongly recommended to evaluate such lesions)\r\n** Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.\r\n** Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
Patient may not be receiving any other antineoplastic agents (hydroxyurea is allowed)
Must meet one of the following three criteria\r\n* < 100 cigarettes smoked lifetime\r\n* Known to harbor a RET rearrangement; importantly, at least 3 patients out of the first 18 and 6 patients overall must harbor RET rearrangements in their lung cancers (note that screening for RET rearrangements will not be done as part of this study and must be done separately, prior to screening)\r\n* Known to harbor another potentially targetable genomic alteration in RET, cKIT, PDGFRa, or PDGFRb; eligible genomic alterations include rearrangements, high level amplifications, insertions or deletions in the kinase domain, or point mutations that are known to be oncogenic
Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
Malabsorption problem that may limit or inhibit the absorption of MEK162
Subjects with a hypersensitivity to halichondrin B or halichondrin B chemical derivative
Patient must NOT have absorption issues that would limit the ability to absorb study agents
Subjects must not have received any chemotherapeutic agents for the AML (except hydroxyurea); intrathecal cytarabine (ARA-C) and intrathecal methotrexate are permissible
Subjects must not be receiving growth factors, except for erythropoietin
Subjects with bacteremia must have documented negative blood cultures prior to study entry
Patients with locally advanced, unresectable disease will be included; locally advanced unresectable disease is defined by the National Comprehensive Cancer Network (NCCN) as:\r\n* Tumors of the head that have greater than 180 degrees of superior mesenteric artery (SMA) encasement or any celiac abutment, unreconstructable superior mesenteric vein (SMV) or portal occlusion, or aortic invasion or encasement\r\n* Tumors of the body with SMA or celiac encasement of greater than 180 degrees, unreconstructable SMV or portal occlusion, or aortic invasion\r\n* Tumors of the tail with SMA or celiac encasement of greater than 180 degrees\r\n* Irrespective of location, all tumors with evidence of nodal metastasis outside of the resection field are deemed unresectable
Patients cannot be already treated on angiotensin-converting enzyme inhibitor (ACE) or angiotensin II receptor blocker (ARB) therapy for hypertension or renal protection (with diabetes) at the time of enrollment
Plasma calcium > 8.5 and < 10.5
Current treatment with lenalidomide, thalidomide, imiquimod, interferon, cytokines (filgrastim [G-CSF], sargramostim [GM-CSF], interleukin 1 receptor alpha [IL-1Ra]), tumor necrosis factor alpha [TNFa] antagonists, or lithium
Clinical stage IIA (T2N0), IIB (T2N1, T3N0) or stage IIIA (T1N2, T2N2, T3N1, T3N2), IIIB, or IIIC breast cancer with no prior treatment
Known hypersensitivity to doxorubicin, cyclophosphamide, paclitaxel, Cremophor or medications containing Cremophor (miconazole, docetaxel, Sandimmune, nelfinavir mesylate, propofol, diazepam injection, vitamin K injection, ixabepilone, Aci-Jel) or carboplatin
T0 tumors
Inability to swallow BKM120 capsules; (in the future a different formulation of BKM120 may become available and may be approved by Novartis for other routes of administration, which would then supersede this exclusion criteria)
Patients with any history of hyperglycemia (elevated blood glucose level on blood chemistries) should be considered for initiation of Metformin treatment (500mg, PO, twice daily) prior to starting BKM120
Suitable and interested to proceed to ASCT
Male subjects must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant
Male subjects must agree not to donate semen or sperm while taking lenalidomide and/or carfilzomib and 28 days after the last lenalidomide/carfilzomib dose
The ability to take aspirin or other appropriate venous thromboembolism (VTE) prophylaxis
Waldenstrom's macroglobulinemia or immunoglobulin (Ig)M myeloma
Subjects with known or suspected amyloidosis of any organ
For subjected enrolled in the United States, no coverage or not-acceptable by patient co-pay for lenalidomide
Willing to return to consenting Mayo Clinic (Mayo Clinic’s campus in Rochester, Mayo Clinic’s campus in Arizona, or Mayo Clinic’s campus in Florida) institution for follow-up during the active monitoring phase of the study
AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study).
Gynecologic Oncology Group (GOG) performance status =< 2
Patients with acute or chronic metabolic acidosis, lactic acidosis, or ketoacidosis; Note: during the study, metformin must be discontinued for 24 hours before and 48 hours after imaging involving intravenous (IV) contrast to minimize risk of lactic acidosis
Pregnant women are excluded from this study because indoximod is an immunoregulatory agent with the potential for abortifacient effects due to fetal rejection by the maternal immune system. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with indoximod, breastfeeding should be discontinued if the mother is treated with indoximod. Also, docetaxel and paclitaxel are category D cytotoxic agents and are not administered to pregnant females.
Obtained within 2 weeks from study entry: Hemoglobin A1c (HgBA1c) =< 8%
Evidence of recurrent GBM or metastases detected outside of the cranial vault.
Rising PSA after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy with curative intent
Prior bilateral orchiectomy
Expansion cohort: a final expansion cohort for this study in a subset of interest utilizing the recommended dosing of combination; this cohort will include patients harboring characteristics that may predict response of combination or with clinical features that proved to derive most benefit of the study combination during preclinical studies; cancers with positive BRAF (V600) mutation detected by a CLIA-certified laboratory
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Significant co-morbidity that could affect the safety or evaluability of participants as assessed by the treating physician and or principal investigator
Recovery from any major or minor surgeries
Granulocytes >= 1,500/mcL
Phosphorus at or above lower limit of normal (correction with supplements is fine as long as the resultant level is at or above the lower limit of normal)
Intolerance of vitamin B12, folic acid or dexamethasone
REGISTRATION EXCLUSION CRITERIA: Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation
Current diagnosis of primary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas or mycosis fungoides
Uncontrolled ascites defined as not easily controlled by stable doses of diuretics
Major surgery within 30 days prior to start of study drug; for patients who had port-a-cath placement, they should have the port-a-cath placement at least one week prior the initiation of leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX)
Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation, chemoembolization or systemic sorafenib.
Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
Cardiopulmonary dysfunction as defined by protocol
Colon wall involvement
Presence of bowel fistula
Gastric or duodenal ulcer (at least 10 mm in size) within 10 mm of expected endoscopy puncture site(s) for photodynamic therapy (PDT)
Esophageal or gastric varices
Bulky celiac adenopathy (i.e., >= 2.5 cm in diameter)
Unable to receive or previously intolerant of moderate and/or deep sedation
Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for at least 30 days
Porphyria
Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene\r\n* The NIH criteria includes presence of:\r\n** Bilateral vestibular schwannomas, OR\r\n** First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.\r\n* The Manchester criteria includes presence of:\r\n** Bilateral vestibular schwannomas, OR\r\n** First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\r\n** Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR\r\n** Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract
Must have established relationship with primary care physician and provide contact information
Previous therapy with GS-1101 (CAL-101), IPI-145 or any drug that specifically inhibits the PI3K or mTOR pathway;
Normal functioning of daily living activities
Uveal or mucosal melanoma
Diagnosis of acute or chronic pancreatitis
Total serum bilirubin < 1.5, unless there is congenital benign hyperbilirubinemia
Pregnant females; (lactating females must agree not to breastfeed while taking lenalidomide or romidepsin)
Individuals seropositive for hepatitis B or C are ineligible
Tolerate one test dose (15 g) of ascorbate
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
Treating physician must deem that SRS is appropriate treatment for the metastatic spinal lesion(s)
Each SRS target must be the equivalent of =< 3 vertebral levels
Serum potassium >= 3.5 mEq/L
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Willingness to participate in the RevAssist program
EXPANSION PHASE ONLY: Evaluable or measurable disease with the largest nodule measuring less than 5 cm in greatest dimension by radiographic imaging after debulking procedure
Metastatic disease outside the intraperitoneal cavity and retroperitoneum, intrahepatic lesions, or pleural effusions; significant ascites precluding catheter placement; exception: intrahepatic lesions removed or planning to be removed during the debulking procedure
Successful test expansion of T-cells
No contraindications for leukapheresis
A known hypercoagulable disorder such as activated protein C (APC) resistance (factor V Leiden), protein S deficiency, protein C deficiency, antithrombin III deficiency, hyperhomocystinemia, dysplasminogenemia, high plasminogen activator inhibitor, dysfibrinogenemia, antiphospholipid syndrome, thrombocythemia, or dysproteinemia
Patient must be determined fit to undergo auto-SCT procedure by a study physician
Diagnosis of CML
Treated with at least 1 year of imatinib
T315I mutation
Reporting being bothered by vulvovaginal symptoms of estrogen deprivation (i.e., vulvovaginal dryness or discomfort [pain with intercourse or examination])
Refractory to prior Bortezomib-containing therapy under the 1.3 mg/m2 dose twice weekly dosing schedule.
post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-ET/PV MF) per the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria
Females of childbearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study; permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed
Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up; permitted methods for preventing pregnancy should be communicated to the subjects and their understanding confirmed
More than three relapses
Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy; metronidazole and mebendazole have been reported to be associated with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
Patients with severe bradycardia (heart rate < 40 beats per minute [bpm], hypotension, light-headedness, syncope)
Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible provided their CD4+ cell counts are ? 200/mm3
Subjects with mycosis fungoides (MF) and a known history of non-complicated staphylococcus infection/colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics
Large cell transformation. However, subjects with a history of LCT but without current aggressive disease and no current evidence of LCT on pathology in skin and lymph nodes would be eligible.
Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, and have no active signs of active infection, and whose last active infection was more than 6 months ago, may enter the study, and should continue to take the prescribed medication for the duration of the study.
Patient is taking concurrent drugs that are contraindicated with nelfinavir, including any of the following:\r\n* Alfuzosin\r\n* Cisapride\r\n* Sildenafil (Revatio)\r\n* Amiodarone\r\n* Quinidine\r\n* Rifampin\r\n* Dihydroergotamine\r\n* Ergonovine\r\n* Ergotamine\r\n* Methylergonovine\r\n* Hypericum perforatum (St. John's wort)\r\n* Lovastatin\r\n* Simvastatin\r\n* Pimozide\r\n* Midazolam\r\n* Triazolam\r\n* Oral Midazolam
N-Terminal ProB-type natriuretic peptide (NTproBNP) < 8500 pg/mL
Patients with a history of hypertension MUST have hypertension adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet prior to study entry; Note: To be eligible a subject must have an average of BP below 140/90 based on 3 separate measures; if the subject has a record of BP recordings taken at home, =< 20% of BPs taken should have numbers > 140/90
History of malignancy with confirmed activating RAS mutation at any time; Note: prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility
STEPS 1 AND 2 AND RANDOMIZATION
Presence of significant third space fluid which cannot be controlled by drainage
Inclusion Criteria:\n\n          1. Randomized in the parent study, PCYC-1115-CA\n\n          2. Informed consent for Study PCYC-1116-CA\n\n          3. IRC-confirmed PD in the parent study PCYC-1115-CA or closure of the parent study\n\n        Exclusion Criteria:
Investigator considers patient ineligible for intensive remission induction therapy based on documented medical reasons (e.g. disease characteristics like AML genetics, type of AML (de novo or secondary), and patient characteristics like performance score, concomitant diagnoses, organ dysfunctions).
Unknown BRAF status
Ocular melanoma
Acute or chronic pancreatitis
Creatinine equal or less than 1.4 mg/dl based on University of Iowa Hospitals and Clinics (UIHC) values/tests
Patient must not experience hemoptysis in excess of 2.5 mL within 8 weeks prior to the first dose of pazopanib
Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
Histologically confirmed classical HCL with one of the following:\r\n* Intolerance to purine analogs or considered to be poor candidates for purine analog-based therapy\r\n* Failure to achieve any response (CR or PR) to the initial purine analog-based therapy\r\n* Relapse =< 2 years of purine analog-based therapy\r\n* >= 2 Relapses\r\n* Histological confirmation of diagnosis will be performed at Memorial Sloan Kettering Cancer Center (MSKCC) or a participating site
Patients with HCL variant (as defined by absence of expression of cluster of differentiation [CD]25 or absence of BRAF V600E mutation)
Demonstration of progression while on androgen blockade
Diagnosis of systemic AL amyloidosis (subjects with non-AL amyloidosis are not eligible);
Secondary or familial amyloidosis;
Hypersensitivities to other monoclonal antibodies;
Karnofsky score of 60% or better (requires occasional assistance, but is able to care for most of his/her needs)
New or active infection as determined by fever, unexplained pulmonary infiltrate or sinusitis on radiographic assessment; infections diagnosed within 4 weeks of registration must be determined to be controlled or resolving prior to treatment
DONOR: Donors must meet the selection criteria prior to the start of the recipient’s pre-transplant conditioning regimen as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened according to the American Association of Blood Banks (AABB) guidelines and UW Bone Marrow Transplant (BMT) program standard operating procedure (SOP)
Creatinine within normal range for age (per institutional defined lab value ranges)
Patient with diagnosis of BCR-ABL positive CML CP
Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Potassium
Magnesium
Prior AP, BC or allo-transplant
Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)
Patient ever attempted to permanently discontinue imatinib or nilotinib treatment
Complete left bundle branch block
Disease location amenable to biopsy in outpatient clinical setting or operative biopsy within routine accepted schedule and practice of clinical care
Prior adverse reaction to diphtheria vaccine
Confirmation of:
De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.
Total serum calcium [corrected for serum albumin] or ionized calcium >= LLN
Serum magnesium >= LLN
Serum phosphorus >= LLN
Willingness to provide consent for biopsy sample (dose-expansion only)
Lansky (< 16 years old) >= 60
Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)
Potassium =< 3.5 mEq/L
Systemic immune suppression or systemic therapy for cGvHD started within preceding 4 weeks including extracorporeal photopheresis
NIH lung score 3
Patient must have undergone transoral resection of their T1-4a oropharynx primary to a negative margin, and a neck dissection(s)
Patient must not have a true unknown primary in which permanent section results are negative for malignancy in completely excised ipsilateral oropharyngeal tissue (palatine and lingual tonsil)
An adverse risk karyotype defined by:\r\n* Complex karyotype by cytogenetics, or\r\n* Deletion of all or part of chromosome 5, 7, 12, or 17 defined by fluorescence in situ hybridization (FISH) or cytogenetics, or\r\n* Somatic TP53 mutation
Patient must have undergone =< 2 cycles of prior hypomethylating agent (decitabine or azacitidine)
Patient must be enrolled in Human Research Protections Office (HRPO) # 201011766 (\Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases\)
Have a confirmed diagnosis of endometrial hyperplasia without atypia based upon endometrial biopsy
Have a random glucose of =< 65 or >= 200
Are currently taking insulin
FL
DLBCL
Other indolent NHL (eg, MZL/MALT)
Haemoglobin ? 8.0 g/dL (may have been transfused)
Calcium >= LLN
Magnesium >= LLN
Potassium >= LLN
Graft:\r\n* Cryopreserved dose will be >= 1.5 x 10^7 total nucleated cells (TNC)/kilogram in each unit for double unit CB grafts; this will be the CB graft for the majority of patients\r\n* In select patients with access to CB units that have high TNC (> 5.0 x 10^7/kg), and are from good quality CB banks a single unit could be considered with a back-up CB unit on standby\r\n* In select patients who have a very poor search and only have one suitable CB unit available, this unit could be given as a single unit; this unit must have a TNC >= 2.0 x 10^7 TNC/kilogram and a cluster of differentiation (CD)34+ cell dose >= 1.5 x 10^5 CD34+/kilogram\r\n* Haplo-identical donors who are 5/10 or better but not HLA-identical will be used
Prior radiation therapy with 400 cGy or more of TBI; if 200 cGy of prior TBI then only 400 cGy of TBI on this protocol is permitted
Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
Uncontrolled infectious complications not responsive to appropriate antimicrobial therapy
Neutrophils < 1.0 x 10^9/L (neutrophil count should be > 1000 without growth factor support, unless neutropenia is caused by anti-neutrophil antibodies or other manifestation of chronic GVHD)
For Cohort 3, participants must have WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma that is histologically confirmed either by the previous biopsy or resection, or at the time of re-operation (re-operation before entry to the current study is allowed; however participants must be off post-surgery dexamethasone for at least 4 weeks before administration of the first vaccine)
Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
Participants with known addiction to any drugs
Patient must have disease that is easily accessible for a core biopsy as determined by the treating physician or study principal investigator (PI), patient must agree to the mandatory biopsies at baseline and end of cycle 2 (MTD expansion cohort only, and at the discretion of the PI/PI optional)
Patient must not require constant administration of a proton pump inhibitor, histamine receptor 2 (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
Have a clinical diagnosis of cutaneous T cell lymphoma CTCL, including documentation of a skin biopsy within the prior 3 years with histological findings consistent with CTCL (atypical epidermotropic or folliculocentric T-cells)
Previous treatment with at least one standard therapy used to treat stage IA, IB or IIA CTCL including but not limited to oral corticosteroids, high-potency topical corticosteroids, topical mechlorethamine, topical bexarotene, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB), total body electron beam radiation, biological response or oral methotrexate
Have measurable skin disease with 1 to 4 eligible baseline target lesions with a total area >= 25 cm^2 but =< 100 cm^2; eligible lesions must be below the neck and may not involve the genitalia, intertriginous areas, internally, or to frankly ulcerated or infected skin
Generally healthy other than for CTCL, or with other stable diseases/conditions that are adequately controlled
Willing to abstain from therapeutic sunbathing, tanning beds, etc. for the duration of the study
Have histologically confirmed epithelial or biphasic MPM not amenable to potentially curative surgical resection (subjects with biphasic tumors that have a predominantly (?50%) sarcomatoid component will be excluded)
An artificial (prosthetic) joint or other artificial implant or device that cannot be easily removed (with some exceptions for dental and breast implants and biliary stents and mediports)
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Subjects with carcinomatous meningitis
Contraindications to administration of bortezomib
No prior treatment with bortezomib for cGVHD; participants may have received bortezomib for other reasons besides cGVHD (such as leukemia or solid tumor); any other previous treatments for cGVHD are allowed
Osteoporosis complicated by pathologic fracture
Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)
Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of white blood cells [WBCs], red blood cells [RBCs], and platelets)
Unresectable or metastatic sporadic or NF1 associated high-grade MPNST
Patients using Seville orange, star fruit, grapefruit and their juices, and St. John's Wort
Histologic or cytologic diagnosis of adenocarcinoma of the pancreas.
A patent superior mesenteric (SMV)- portal vein (PV) confluence (assuming the technical ability to resect and reconstruct this venous confluence if needed)
Presentation at a multidisciplinary conference at either University of Chicago or NorthShore University
Short removable metal stents rather than plastic stents are preferred but not required for palliation of initial obstructive jaundice
Indolent NHL:
Aggressive NHL:
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
For Part B:
Absence of a FLT3 activating mutation
If brentuximab vedotin or bendamustine was previously received, had disease progression during the first 3 cycles of either brentuximab vedotin or bendamustine
Potassium levels < 3.5 mmol/L or > 5.1 mmol/L
Spinal metastatic lesion being treated must be =< 6cm in greatest dimension
Patients must be able to fit into either the Civco stereotactic immobilization or the Elekta Stereotactic BodyFix immobilization device
Patients with evidence of spinal instability OR neurologic deficit resulting from bony compression of neurologic structures
GROUP A MONOTHERAPY
Participants with gross hematuria are ineligible
Participants must consent to collection of blood, ascites fluid and tumor tissue samples prior to first dose of CRLX101 and at least one additional sample collection after the second dose (archived material is acceptable for collection prior to first dose of CRLX101)
FOR COHORT 2 (BEVACIZUMAB INELIGIBLE):
FOR ALL (COHORT 1 AND COHORT 2):
Both men and women and members of all races and ethnic groups are eligible for this trial
Known acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or other acquired or congenital disorder of the immune system
Diagnosis of recurrent or progressive HGG or DIPG
Growth factors: interval >= 1 week and >= 2 weeks before study enrollment for standard and long-acting growth factors (e.g., pegfilgrastim), respectively
Completion of local RT with or without concomitant chemotherapy including temozolomide and radiosensitizing agents (e.g., carboplatin, vorinostat) outside the context of a clinical trial; any agent administered during RT should have a short half-life so that it should already be completely eliminated by the start of this therapy; if other agents were used concurrently with RT, they will need to be discussed with the principal investigator to assess eligibility
Presence of LGL clone prior to enrollment will not be an exclusion criterion if the LGL clone is < 25% of T cell population
Recipient of mismatched (allele or antigen level) graft in more than one loci of HLAA, -B, -C or –DR loci will not be eligible, i.e. recipients of 2-antigen or 2-allelele mismatched graft
Prohibited treatments and or therapies:\r\n* Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (patients must discontinue drug 7 days prior to starting dasatinib)\r\n** Quinidine, procainamide, disopyramide\r\n** Amiodarone, sotalol, ibutilide, dofetilide\r\n** Erythromycin, clarithromycin\r\n** Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n** Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine\r\n* Patient agrees to discontinue St. Johns wort while receiving dasatinib therapy (discontinue St. Johns wort at least 5 days before starting dasatinib)\r\n* Patient agrees that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Prisoners or subjects who are involuntarily incarcerated
Subjects may be of any ethnic background
Subjects who failed at least one prior therapy (BT062/Len/dex)
Subjects who failed at least two prior therapy (BT062/Pom/dex)
Acute or relevant abnormalities in electrocardiogram (ECG)
Patients with normal renal function according to MD Anderson testing standards and no prior renal disease [screening cut off for serum creatinine < 1.5 times ULN]
Concurrent estrogens, anti-estrogens or progesterone compounds
DONOR: Able and willing to undergo an apheresis procedure (unmobilized) for iTreg production and have up to 3 separate mobilized apheresis collections performed for PBSC transplant
Willing to schedule definitive resection of DCIS 2-5 weeks after study enrollment
Original breast core biopsy specimen available for pathologic review and staining by Yale School of Medicine Department of Pathology
Spinal hardware at either a) the vertebral body to be treated or b) one vertebra (VB) above and below
Prior kyphoplasty at either a) the vertebral body to be treated or b) one VB above and below
Inability to tolerate lying flat on treatment table for greater than 30 minutes
Prior irradiation of the spine site and level to be treated
Granulocytes >= 2,500/mm^3
Lymphocytes >= 1000/mm^3
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), alkaline phosphatase (Alk phos) =< 2.5 X the ULN
Subjects with acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk
Hematology and biochemical values within protocol-defined limits
The presence of deletion of the short arm of chromosome 17
Hepatic: < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
Candidate for a protocol of higher priority; for the purpose of this study, the following protocols will be considered of higher priority: 10-051
Tumor cell negative for cluster of differentiation (CD)20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria)
Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of registration
Cytologic or histologic proof pancreatic ductal carcinoma is required prior to study entry; diagnosis must be confirmed by the Massachusetts General Hospital (MGH) pathology department
Relapsed or refractory TCL status including diagnoses of peripheral TCL-NOS, angioimmunoblastic TCL, anaplastic large cell lymphoma, hepatosplenic TCL, enteropathy-associated TCL, or mycosis fungoides(MF)/cutaneous TCL with transformation to systemic TCL.
Grade 3 infection within 2 weeks of first dose romidepsin plus ICE.
Willing to comply with protocol therapy and required safety monitoring (self-report, pulse oximetry, remote spirometry, labs)
Currently being treated with bronchodilators or corticosteroids
Medically appropriate candidate for radical cystectomy, as per MSKCC or participating site attending urologic oncologist
Calcium (Ca), magnesium (Mg), potassium (K) within normal
Corrected serum calcium ? ULN
Agreement to participate in RevAssist® Program
Histological confirmed diagnosis of relapsed intracranial GB
Serious concomitant systemic disorder
Previously untreated stage I or II non-bulky Hodgkin lymphoma\r\n* No mediastinal mass > 0.33 maximum intrathoracic diameter on chest x-ray, if available; chest x-ray is not required\r\n* No adenopathy > 7.5 cm in its largest diameter
Information available for calculation of International Prognostic Score (IPS): age, gender; albumin, white blood cell (WBC) count, hemoglobin, lymphocyte count, and stage of disease according to Ann Arbor classification
Achieved at least a PR (and not progressed) after ABVD therapy
A 3-week washout period is required from previous treatments (with the exception of a 12-week washout for antibody-directed or immunoglobulin-based immune therapy, or other monoclonal antibody therapies), unless it is not in the best interest of the patient in the opinion of the investigator. Individual cases should be discussed with the project clinician before enrollment.
Participants with cardiovascular conditions specified in protocols
Ki67 index ? 20% (to be centrally confirmed).
Patients must have progressive disease based on RECIST Criteria, Version 1.1 while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained.
Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan.
The tumour uptake observed in each target lesion (for target/non-target/measurable lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1) using OctreoScan® must be ? normal liver uptake observed on planar imaging (to be centrally confirmed) (§Appendices 5 and 6).
Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.
Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as normal liver uptake observed by planar imaging.
Current spontaneous urinary incontinence.
Lack of availability of a patient for immunological and clinical follow-up assessment
Serum free light chain (FLC) assay: involved FLC level ? 10 mg/dL (? 100 mg/L), provided that the serum FLC ratio was abnormal.
Female participants who:
The patient is a candidate for definitive external beam radiotherapy; the patient has had no prior radiotherapy to the region of study; the patient has no inflammatory bowel disease, active collagen vascular or connective tissue disorders, and no other medical or social contraindications to radiotherapy, as determined by a participating radiation oncologist
Patient must be consented to the study prior to salvage assessment
CRIZOTINIB PLUS PAZOPANIB ARM A:
CRIZOTINIB PLUS PEMETREXED ARM B, PAXOPANIB PLUS PEMETREXED ARM C, CRIZOTINIB PLUS PAZOPANIB PLUS PEMETREXED ARM D:
The ability to take folic acid, vitamin B12, and dexamethasone according to protocol for all pemetrexed arms
Expansion cohort only for arms containing crizotinib: arm A (crizotinib plus pazopanib) and arm B (crizotinib plus pemetrexed) and arm D (crizotinib plus pazopanib plus pemetrexed) but not arm C (pazopanib plus pemetrexed); patients must have anaplastic lymphoma receptor tyrosine kinase (ALK) abnormality including: translocation, ALK amplification, mutation and overexpression as determined by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC),quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription (qRT)-PCR, array comparative genomic hybridization or direct sequencing (aCGH); or patients must have a macrophage stimulating 1 receptor (c-met-related tyrosine kinase) (c-Met) abnormality, either c-Met amplification or c-Met mutation or patients must have the c-ros oncogene 1, receptor tyrosine kinase (ROS1) translocation as determined by FISH
Patient has any signs of intestinal obstruction
Pemetrexed arms only: presence of third space fluid which cannot be controlled by drainage
Therapy with supplements or complementary is excluded with the following exceptions; all other supplements must be discontinued prior to initiation of study drug\r\n* Conventional multivitamin supplements\r\n* Selenium\r\n* Lycopene\r\n* Soy supplements
Tumors must be CD20+ on prior pathologic analysis
Persistent neurotoxicity from intraventricular methotrexate, cytarabine, thiotepa
Planning to have or have had a radical prostatectomy (RP) at MSKCC
Two pretreatment CA125 values (documented on two occasions taken at least one week apart) must be at least twice the upper limit of normal, or twice the nadir value if pretreatment CA125 values never normalized
Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the trial
If radiotherapy is required in a given patient, that patient should be withdrawn from the study
Histologically documented classical or nodular lymphocyte predominant Hodgkin’s lymphoma that is recurrent or refractory after standard chemotherapy; core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable
Is currently participating in a GSK2110183 study (monotherapy or in combination with an approved anti-cancer agent) sponsored by GSK or by another research organization working on behalf of GSK.
QTcF interval greater than 500 msecs at the time of transition to this study.
Patients must have histologically confirmed pancreatic neuroendocrine tumors that are considered low or intermediate grade as defined by Klimstra et al (to include proliferation-related Ki-67 antigen [Ki-67] and mitotic index)
Platelets (PLT) >= 100 x 10^9/L (>= 100,000/mm^3) may be supported by transfusion and/or hematopoetic growth factors
Poorly differentiated or high grade pancreatic neuroendocrine tumors
GENERAL MEDICAL EXCLUSIONS:
BEVACIZUMAB-SPECIFIC EXCLUSIONS:
Individuals with a known t(9;22)/breakpoint cluster region-Abelson (BCR-ABL) fusion based on testing at either initial diagnosis or at relapse
Individuals whose lymphoblasts have surface immunoglobulin by flow cytometry and/or known t(8;14), t(2;8), or t(8;22); absence of surface immunoglobulin by flow cytometry at time of initial diagnosis or relapse is sufficient to rule out mature B-cell leukemia; karyotype or fluorescent in situ hybridization (FISH) results documenting absence of t(8;14), t(2;8), or t(8;22) are not necessary prior to enrollment if absence of surface of immunoglobulin is documented by flow cytometry
Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of PEG asparaginase; participants with a history of allergy to PEG asparaginase are allowed on study but should receive Erwinia asparaginase instead of PEG asparaginase; individuals with a history of allergy to both PEG and Erwinia asparaginase are excluded from the study
Antecedent hematological disorder (AHD)
Currently participating in an abiraterone acetate clinical study considered complete and had received at least 3 months of treatment with abiraterone acetate tablets.
Medical conditions that require hospitalization.
Serum calcium (corrected for albumin level) =< 1x institutional ULN
Patient is capable of swallowing.
Known Glucose-6-phosphate-dehydrogenase deficiency (G6PD).
AST (GOT) ? 100 IU/L
ALT (GPT) ? 100 IU/L
Subject must not be pregnant or plan to conceive a child.
Pulse >= 60 beat per minute (bpm)
Normotensive individuals not already on beta blockers (may be on other anti hypertensives): SBP =< 140, DBP =< 90
Cardiogenic shock
Severe sinus bradycardia; heart block, second or third degree or sick sinus syndrome (if no artificial pacemaker present)
Enrollment will be restricted to patients demonstrating NAD(P)H dehydrogenase, quinone 1 (NQO1) immunohistochemistry (IHC) overexpression; demonstration of NQO1 overexpression by IHC should be confirmed prior to conducting other study procedures (e.g., laboratory and imaging studies)
If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results
Presence of an index lesion between 1 and 5 cm
Ability to tolerate stereotactic body radiation therapy (e.g. lie flat and hold position for treatment)
Positive serology for hepatitis C (HC) defined as a positive test for HBcAb, in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
Have one or more symptoms that the Investigator believes to be related to the patient's MTC.
Lesions must be amenable to accurate and repeat measurement.
Abnormal electrolytes such as potassium, magnesium and calcium, or abnormal organ functions such as decreased creatinine clearance.
Over-expression by immunohistochemistry (IHC) with score of 3+ (in > 30% of invasive tumor cells) AND/OR HER2 gene amplification (average of > 6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene copies to chromosome 17 signals] of >= 2.0), according to guidelines and in keeping with past eligibility for ratio of >= 2.0 rather than the ratio of > 2.2 required by new guidelines
Any predisposing chronic condition resulting in baseline grade 2 or higher diarrhea
Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to study entry; diagnosis must be confirmed by the Massachusetts General Hospital (MGH) pathology department prior to registration
Total bilirubin =< 5 x upper limit of normal if patient is s/p biliary stenting AND decreasing at least two time points after stenting
Tumors in the body or tail of the pancreas (to the left of the portal-SMV confluence) are not eligible; location at the portal–SMV confluence is allowed
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Positive serum anti-poliovirus titer prior to biopsy (except for retreatment)
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Post-menopausal status over 1 year
Primary systemic amyloid light (AL) chain amyloidosis (a build-up of amyloid light chain proteins in the blood)
Prior exposure to agents targeting interleukin 6 (IL 6) or the IL 6 receptor
Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
Classical FAP Phenotype: 100's to 1,000's of colorectal adenomatous polyps, usually appearing in teenage years
UGI endoscopy/LGI endoscopy (proctoscopy/colonoscopy) performed within 30 days of randomization.
Rectal/pouch polyposis as a stratification site as follows:
For all subjects, any rectal/pouch polyps > 5 mm must be excised at \baseline\.
Current Spigelman Stage 3 or 4. (Refer to Appendix A for Modified Spigelman Score and Classification table).
Absence of gross blood in stool; red blood on toilet paper only acceptable.
No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated with antibiotics.
No concurrent warfarin, fluconazole, lithium, Pradaxa® or other direct thrombin inhibitors, Plavix®, cyclosporine, other NSAIDs (such as ibuprofen, aspirin, diflunisal), diuretics (furosemide and thiazides), DMSO, methotrexate, probenecid, propoxyphene hydrochloride, Tylenol® (acetaminophen) preparations containing aspirin or cytotoxic chemotherapy drugs.
Colon/rectum/pouch with high grade dysplasia or cancer on biopsy or a large polyp (>1 cm) not amenable to complete removal.
Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local laboratory that has received an international or country-specific, quality standards certification)
obscured by other structures or artifacts on the images)
Definitive pathologic diagnosis by needle core biopsy
Cluster of microcalcifications that do not exceed 10 mm in diameter and measures at least 5mm away from the skin and chest wall
Subjects with less than 25% intraductal component
Tumors poorly visualized by x-ray mammography or ultrasound imaging
Women who are morbidly obese (>300 lbs)
Tumors measuring greater than 20mm in diameter
Subjects with benign lesions such as fibroadenoma, atypical ductal hyperplasia, sclerosing adenosis, Papilloma, fibrocystic disease of breast
Subjects with DCIS with microinvasion
Subjects with a cluster of microcalcifications whose diameter is larger than 10 mm.
Subjects with extensive intraductal component and other characteristics not well visualized by imaging studies
Subjects who are BRCA positive.
Inability to lie prone or supine for one hour
Willing to follow pregnancy precautions
Both men and women and members of all races and ethnic groups are eligible for this trial
Significant shunting to the lung (> 20%) identified on macroaggregated albumin (MAA) scan
Unsuccessful closure of collateral blood flows from the hepatic artery to non-targeted organs such as the gastrointestinal (GI) tract
Occlusion of the main portal vein, or inadequate collateral flow around an occluded branch of the portal vein as determined by angiography
Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with cyclin D1 overexpression by immunohistochemistry, and a characteristic immunophenotypic profile with CD5(+), CD23(-), CD20(+), and CD10(-). In tumor tissues with negative cyclin D1, evidence of cyclin D2 or D3 overexpression by immunohistochemistry will be acceptable.
Subjects with histological confirmation of RCC
Able and willing to swallow and absorb orally administered medications and maintain a fast as required before and after MLN8237 administration
Lack of care-giver for the early (100-day) post-transplant period
Premenopausal levels of estradiol, or ongoing menses
Meningeal carcinomatosis.
High grade or poorly differentiated neuroendocrine tumors
Ongoing immunosuppression with systemic steroids or other immune modulator
Severely impaired lung function
Total serum calcium (corrected for serum albumin) or ionized calcium >= LLN
Serum magnesium >= LLN
Cumulative anthracycline exposure greater than 200 mg/m^2 doxorubicin isotoxic equivalents
Right bundle branch block + left anterior hemiblock (bifascicular block)
Unwilling to accept blood product transfusions
Cytologic or histologically diagnosed NSCLC in stages IIIA (non-resectable) or IIIB or IV (TNM).
Imaging studies documenting the response to first-line therapy must be available for evaluation by the investigator.
Recurrent NSCLC, who relapse less than one year after completing curative intent therapy
Autoimmune diseases or chronic decompensated diseases
Radioimmunotherapy (i.e. Zevalin) within 8 weeks of enrollment
Known leptomeningeal or parenchymal brain involvement with lymphoma unless in complete remission after treatment for at least 12 weeks with negative cerebrospinal fluid (CSF) cytology within 2 weeks; prophylaxis of central nervous system (CNS) disease using intrathecal or intraventricular dosing of cytotoxic regimens is permitted and should be performed according to the discretion of the treating physician
Positive serology for hepatitis C (HC) defined as a positive test for HC antibody (Ab) if confirmed by HC recombinant immunoblot assay (RIBA) immunoblot assay (for positive HCAb reflexively perform a HC RIBA immunoblot assay on the same sample)
Serum free light chain (FLC) > 100 mg/L of involved FLC
No evidence of cerebral edema
Primary ocular and mucosal melanomas are allowed
Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab
Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s)
Prisoners or subjects who are involuntarily incarcerated
Any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks before or after any dose of ipilimumab
Chronic systemic corticosteroids (unless required for treating treatment emergent AEs or required for management of signs or symptoms due to brain metastases, upon discussion with Bristol-Myers Squibb [BMS] medical monitor)
Postmenopausal
Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >= 38 degree Celsius)
Genetically confirmed diagnosis of VHL or measurable disease consistent with the clinical diagnosis of VHL
(2. continued) f) Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. g) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
Perioperative anticonvulsants should be tapered as indicated in the protocol.
Patients must have borderline resectable pancreatic adenocarcinoma defined by one of the following criteria: \r\n* Tumor associated deformity of the superior mesenteric vein (SMV) or portal vein (PV) \r\n* Abutment of the SMV or PV =< 180 degrees \r\n* Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction \r\n* Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction or \r\n* Abutment of the superior mesenteric artery (SMA) =< 180 degrees
Plasma creatinine phosphokinase (CK) < 1.5 x ULN
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment; if it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
? 5 x PK half-life of a small molecule therapeutic not otherwise defined above
For mefloquine arm, patients must not be on enzyme inducing anticonvulsants (EIAED); if the treating physician elects to change the medication to a non-enzyme inducing agent, a 2-week wash out period will be required after stopping EIAED prior to initiation of treatment
Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy
?18 years old
Histological or cytological proof of colorectal or pancreatic adenocarcinoma
Southwest Oncology Group (SWOG) performance status 0 or 1
Patients should be proteasome inhibitor naive (including bortezomib and carfilzomib) OR have received less than 6 cycles of therapy with a bortezomib or carfilzomib containing regimen and were not refractory to the bortezomib or carfilzomib based regimen (less than a PR or progression on or within 60 days of discontinuation)
Hematological malignancy associated with a poor prognosis with medical therapy alone. Diagnoses to be included:
Active Cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction.
AIDS related syndromes or symptoms that pose a perceived excessive risk for transplantation-related morbidity as determined by the principal investigator.
Prior allogeneic HCT.
T-cell depletion (including ATG or alemtuzumab) is not allowed.
Magnesium (1.2 - ULN)
Patients must have the following laboratory values (WNL = within normal limits at the local institution lab) or corrected to within normal limits with supplements prior to the first dose of study medication:\r\n* Potassium (WNL)\r\n* Phosphorus (WNL)\r\n* Calcium (WNL)
Previously untreated patients with a morphologic diagnosis of APL, confirmed by demonstration of t(15;17) using conventional cytogenetics OR fluorescence in situ hybridization (FISH), OR a positive reverse transcriptase (RT)-polymerase chain reaction (PCR) assay for promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RAR-alpha) at the subject's local institution
Other serious or life-threatening conditions deemed unacceptable by the principal investigator
Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes; the following must be discontinued at least 7 days prior to enrollment to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
For patients with MPN: Tolerating ruxolitinib but with persistent manifestations of disease (i.e. persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms residual fibrosis in bone marrow [2+ or greater], or measurable allele burden as evidenced of clonal JAK2 or MPL mutation)
RELATED DONORS:
Craniotomy wound that has not sufficiently healed
Suspected or documented radionecrosis
Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-tumor necrosis factor receptor superfamily, member 11a, NFKB activator [RANK] ligand denosumab) is allowed
Subjects enrolled in France: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system
Willing and able to complete neurocognitive examination without assistance from family and companions; Note: because neurocognitive testing is one of the primary goals of this study, patients must be able to utilize English language booklets (and/or French booklets if enrolled in Canada)
Willing and able to complete quality-of-life (QOL) questionnaires by themselves or with assistance
Primary amyloidosis
Requires agents other than hydroxyurea to control blast count
Women with neuroendocrine histologies, or histologies other than squamous, adenosquamous or adenocarcinoma
Women who have undergone simple or radical hysterectomy prior to radiotherapy
Philadelphia chromosome (Ph)+ ALL
Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a HC radioimmunoblotting assay (RIBA) immunoblot assay on the same sample to confirm the result
Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN not permitted
Ability to read and follow instructions
Blood and urine samples must be provided from all subjects for biomarker analysis before and during treatment with pazopanib
Active infection with HIV, HBV or HCV as defined below, due to the immunosuppressive effects of cyclophosphamide used and the unknown risks associated with viral replication.
Pathological diagnosis of chondrosarcoma of the spine or sacrum or chordoma of the spine, or sacrum
Hematocrit >= 30%
Inability or refusal to practice contraception during therapy (as physiologically relevant)
Patient with cognitive impairment
Subjects who received a tetanus- diphtheria (Td) or diphtheria toxoid/tetanus toxoid vaccine adsorbed (Tdap) immunization in the previous 5 years
At NIH: age >= 15 years old and/or >= 9 years old and pubertal and =< 55 years for recipient; pubertal is defined by: prior menses at any time (females), documentation of clinical Tanner stage greater than 2 at some point pre-chemotherapy or at the current visit; (at this point, sex steroids have been produced for a few years which has driven initial pubertal development); Tanner 2 is defined as: breast buds for females with coarse pubic hair, and coarse pubic hair and testes > 2.5 cm for males
At Children’s National Medical Center only: age > 4 years old and < 24
Myelodysplastic syndrome refractory anemia with excess blasts (RAEB) 1 or 2; cytogenetics showing complex karyotype (3 or more abnormalities), monosomy 7/del(7q), or inv(3)/t(3q)/del(3q); or transfusion dependent
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Symptomatic OR
Asymptomatic and untreated but >1 cm in the longest dimension
For participants with follicular lymphoma: requirement for treatment according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
Subject must have either:
Bronchiolitis obliterans as the sole indication of ECP
Mechanical ventilation, renal replacement therapy, admitted in intensive care until at time of enrollment
At least 1 target lesion, as defined by RECIST, that has not been irradiated; new lesions that have developed in a previously irradiated field may be used as sites of measurable disease assuming all other criteria are met; all target lesions must have a unidimensional diameter of at least 1 cm for spiral computed tomography (CT) scans if the reconstruction algorithm is 0.5 cm, or a standard uptake value (SUV) >= 2.5; baseline measurements/evaluations must be completed within 4 weeks prior to treatment
No active serious infection or other comorbid illness which would impair ability to participate in the trial
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Patients currently receiving chronic systemic treatment with steroids or another immunosuppressive agent; NOTE: this restriction regarding choice of glucocorticoid does not apply should patient need < 2 week course of glucocorticoid for treatment of noninfectious pneumonitis during study, or if ARM C patient with brain metastases treated with glucocorticoid is enrolled; topical applications (e.g., rash), inhaled sprays, eye drops or local injections of steroids are allowed
Known coagulopathies, and those who require therapeutic anticoagulation with coumarin-derivative anticoagulants
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pomelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study due to potential cytochrome P450 3A4 (CYP3A4) interaction with the study medication; orange juice is allowed
Circulating human anti-mouse antibody (HAMA)
Histological or cytological documentation of adenocarcinoma of the colon or rectum
The subject is capable of understanding and complying with parameters as outlined in the protocol
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Pernicious anemia or other anemias due to vitamin B12 deficiency (due to potential masking of deficiency with leucovorin)
Renal failure requiring hemo- or peritoneal dialysis
Hematopoietic stem cell transplant (HSCT) patients with symptomatic hemorrhagic cystitis (minimal grade 1 symptoms of HC per NCI criteria) and positive BKV in urine > 1 x 10^3 deoxyribonucleic acid (DNA) copies/ml
Splenic enlargement extending > 8 cm below the left costal margin
History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
Evidence of transmural infarction on electrocardiogram (ECG)
Histologic or cytologic confirmation of thyroid cancer (papillary, follicular, medullary); histologic variants such as Hurthle and tall cell variants are allowed
Serum transaminases activity =< 3 x ULN
Patients with symptomatic cholelithiasis (asymptomatic gall stone discovered on screening ultrasound [US] should be reviewed by the principal investigator [PI] but will not lead to automatic exclusion)
Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (enzyme-linked immunosorbent assay [ELISA] and western blot)
Patients with active infection requiring systemic therapy or who are dependent on or currently receiving antibiotics that cannot be discontinued before dosing; (Note: subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any ADXS11-001 infusion)
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
Significant co-morbidity that could affect the safety or evaluability of participants, specifically including: \r\n* Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 140 or diastolic pressures above 90 despite therapy; note that this may be better established with home blood pressure (BP) readings than with clinic visit results; note further that this is NOT a criterion related to particular BP results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes; the intent is to exclude patients that may have unrecognized renal damage from chronic, uncontrolled hypertension, NOT to exclude patients who may be hypertensive acutely; there are no absolute criteria for BP readings with respect to eligibility (as determined by treating physician)\r\n* Uncontrolled diabetes mellitus, defined as: hemoglobin (Hgb) A1c > 8.5%; or symptomatic hypoglycemic episodes > 1 per week during the two months prior to eligibility evaluation; or more than 1 glucose excursion to > 300 mg/dL in prior two months--unless clearly iatrogenic and the cause has been eliminated \r\n* Lung disease requiring supplemental oxygen \r\n* Known chronic liver disease causing either fibrosis or synthetic dysfunction \r\n* Known human immunodeficiency virus (HIV) infection \r\n* Overt psychosis, mental disability or being otherwise incompetent to grant informed consent or a history of non-compliance with medical care
Hydronephrosis (either bilateral or involving a solitary kidney) that has not been addressed by means of a nephrostomy or indwelling stent; EXCEPTION: non-obstructive hydronephrosis in setting of prior urinary diversion is consistent with eligibility
Unwillingness to maintain adequate contraception measures for the entire course of the study
Total serum calcium (corrected for serum albumin) or ionized calcium >= LLN
Right bundle branch block + left anterior hemiblock (bifascicular block)
Pheochromocytoma
Concurrent therapy with a Selective Serotonin Reuptake Inhibitor (SSRI), tricyclic antidepressant, or Monoamine Oxidase Inhibitor (MAOi); clinical judgment should be used in a decision to discontinue antidepressants; a minimum of a 1 week washout period is required for any tricyclic or related antidepressant, or any SSRI (2 weeks for paroxetine or sertraline, 5 weeks for fluoxetine); minimum 2 week washout for any MAOi
Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia purpura (ITP)
Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion
Have major abnormalities documented by echocardiography with Doppler
Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress
At least 1 of the following high-risk features for previously untreated patients:\r\n* Rai stage II disease\r\n* Rai stage 0-I with disease-related fatigue\r\n* Serum beta 2 microglobulin (beta2M) >= 3 mg/L\r\n* Absolute lymphocyte count >= 25,000/uL\r\n* Unmutated immunoglobulin heavy variable cluster (IGHV) gene or IGHV3-21\r\n* Zeta-chain-associated protein kinase 70kDa (ZAP70) positive (>= 20% by flow cytometry or positive by immunohistochemistry)\r\n* CD38 positive (>= 30% by flow cytometry); OR\r\n* Deletion 11q or 17p by fluorescent in situ hybridization (FISH)
Patient was not refractory
Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma
Successful completion of three 24-hour dietary recalls during the run-in period
Is currently participating in a GSK-sponsored study of GSK2118436
For Cohort C only: Subjects must have a calcium phosphate product (CPP) of <4.4 mmol^2/L^2 (55 mg^2/dL^2) if they are to continue treatment with GSK1120212
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Presence of rheumatoid arthritis
Ages > 50 years with hematologic malignancies treatable by unrelated hematopoietic cell transplant (HCT)
Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by the principal investigators at the collaborating centers and at FHCRC
Surgery must be planned to be performed by a pre-approved, study-specific credentialed surgeon; the registering physician MUST be the pre-approved, credentialed surgeon intended to perform the assigned procedure
As part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Prior radiotherapy delivered to the target region
Lesions which comprise > 70% of the width of weight bearing bones, such as the femur
Existing cortical bone destruction, where orthopedic stabilization would be required
Histopathology of amyloidosis or light chain deposition disease based on detection by polarizing microscopy of green bi-refringent material in Congo red-stained tissue specimens or characteristic electron microscopy appearance or immunohistochemical stain with anti-light chain anti-sera
Total serum calcium (corrected for serum albumin) or ionized calcium below ULN
Patients with N-terminal (NT)-proB-type Natriuretic Peptide (BNP) >= 1800 ng/L or BNP >= 400 ng/L, abnormal troponin T, cardiac muscle (cTnT) or troponin I, cardiac muscle (cTnI) can only be included after evaluation by cardiology to determine of the risk associate with the treatment; this evaluation needs to be discussed with the principal investigator (PI)
Any form of secondary / familial amyloidosis
Has taken commercially available enzalutamide (Xtandi);
Tissue diagnosis of lymphoplasmacytic lymphoma with surface immunoglobulin G (IgG), immunoglobulin A (IgA) or immunoglobulin M (IgM) phenotype with a monoclonal heavy and light chain as determined by flow cytometry; all primary diagnostic lymph node and/or bone marrow biopsies will be reviewed at the University of Texas M.D. Anderson Cancer Center (UTMDACC)
?18 years old
Previously treated with ponatinib
Diagnosis of chronic lymphocytic leukemia:\r\n* Lymphocytosis of >= 5,000 cells/ul; AND\r\n* Marrow aspirate with >= 30% of mononuclear cells being lymphocytes; AND\r\n* Flow cytometry demonstrating monoclonal B-cells co-expressing >= one B cell marker (cluster of differentiation [CD]19, CD20, or CD23) and CD5
CARBOPLATIN AND PACLITAXEL ARMS: platelets >= 100,000/mL
Any contraindications to irradiation
Must be able to anticipate achieving SBRT/RT dosimetry guidelines
ADRENAL GLAND:
Treatment of any bone lesion is permissible if it is anticipated that the dosimetry guidelines can be met
SPINE AND PARASPINAL LESIONS:
Patients cannot have more than 3 vertebrae or paraspinal sites involved (each involved vertebral body or paraspinal site is scored as 1 site of disease)
UNTREATED PRIMARY:
Untreated T1-2N0 primary lesions may also be treated with SBRT
Untreated T1-4 and N1-2 disease will be treated with radiation therapy using 5 to 7 weeks of daily radiotherapy per standard practice; must be able to anticipate meeting lung dosimetry guidelines
Retreatment of previously irradiated tumor will be excluded; this will in general be described as an anticipated overlap of a region that has previously received >= 50 Gy and would now be included within the D90 region of the SBRT plan; there is no restriction on prior stage as long as dosimetry guidelines can be met
Other prohibited medications: \r\n* Oral hypoglycemics: tolbutamide, chlorpropamide; \r\n* Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine; \r\n* Neuroleptics: pimozide; \r\n* Antiarrhythmics: amiodarone, bepridil, flecainide, lidocaine, mexiletine, quinidine, propafenone; \r\n* Immune modulators: cyclosporine, tacrolimus, sirolimus; \r\n* Miscellaneous: theophylline, quetiapine, risperidone, tacrine, clozapine, atomoxetine
EXPANSION COHORT ONLY: Karnofsky >= 70% or ECOG =< 1
EXPANSION COHORT ONLY: Other prohibited medications: \r\n* Oral hypoglycemics: tolbutamide, chlorpropamide; \r\n* Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine; \r\n* Neuroleptics: pimozide; \r\n* Antiarrhythmics: amiodarone, bepridil, flecainide, lidocaine, mexiletine, quinidine, propafenone; \r\n* Immune modulators: cyclosporine, tacrolimus, sirolimus; \r\n* Miscellaneous: theophylline, quetiapine, risperidone, tacrine, clozapine, atomoxetine
Advanced/poorly differentiated thyroid cancers of follicular cell origin that have no uptake (< 1%) on radioiodine scan or are unresponsive to radioiodine therapy; unresponsiveness to radioiodine therapy is defined as a patient’s thyroglobulin not falling to less than 2 ng/ml within 6 months after previous radioiodine ablative treatment
Thyroglobulin (Tg) levels greater than or equal to 100 ng/ml in the absence of Tg antibodies; patients who are Tg-antibody (Tg-Ab) positive may be included despite a lower Tg level if they have detectable disease on cross sectional imaging; (the presence of Tg-Ab may lead to falsely low Tg levels and therefore render the Tg a less sensitive marker of disease; however, Tg-Ab has been shown to also act as a tumor marker, and will be used as an endpoint for the study in patients who are Tg-Ab positive)
Within 18 months of enrollment, patients must have had a radioactive iodine (RAI) scan, showing no or therapeutically insignificant RAI uptake (=< 1%)
Ammonia < 1.5 times ULN
There are other criteria--please discuss with your doctor.
There are other criteria--please discuss with your doctor.
Subjects, who participated in previous ARQ 197 studies that have reached their designated end-dates, who did not meet discontinuation criteria in their original study, and who may, in the opinion of the Investigator and the Sponsor, benefit from treatment
Ductal carcinoma in situ (DCIS) or invasive ductal, medullary, papillary, mucinous (colloid), or tubular histologies
Negative margins after lumpectomy (re-excision for initial positive margins is allowed-negative margins defined as >= 2 mm clear of tumor in all directions); histological negative margins closer than 2 mm are permitted in the circumstance where the margin of excision is limited by adjacent tissues such as pectoral muscle or skin, but in the opinion of the surgeon and radiation oncologist an oncologically adequate excision was achieved
Negative post-lumpectomy mammography if malignancy-associated microcalcifications were initially present
The target lumpectomy cavity must be clearly delineated
Patients must complete appropriate pretreatment evaluation including post-lumpectomy mammogram if microcalcifications were initially present to confirm complete removal
Patients with history of collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or active skin rash, systemic lupus erythematosus, or scleroderma
PB or BM basophils ?20%
Serious intercurrent medical illnesses which would interfere with the ability of the patient to carry out the treatment program
SGOT < 2.5 times ULN
Lysate must meet release criteria
Subjects who screen fails can be re?enrolled if the causation of the screen fail has been corrected
Subject has a positive serum Yo antibody
Subject whose groins are not accessible
Human T-lymphotropic virus (HTLV)-1/2
Subject requires or is likely to require more than a two week course of corticosteroids for intercurrent illness; subject must complete the course of corticosteroids 2 weeks before screening to meet eligibility
Subject has proteinuria > 3.5 gm over 24 hrs. are not eligible for the study
Hematocrit < 30%
Subject has clinical symptoms or signs of partial or complete gastrointestinal obstruction or who require parenteral hydration and/or nutrition (For cohort 3 only)
Hepatic: < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
positive for translocation or inversion event involving the ALK gene locus
positive for ALK amplification events
mutations of amplifications involving the c-Met gene but not the ALK gene
Blood urea nitrogen (BUN) =< 30 mg/dL
Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing posterior-anterior chest x-ray or mass measuring > 10 cm in its largest diameter
FGFR2 gene fusion status confirmed by NGS or FISH testing
Hematological
Current evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination
Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of ARQ 087)
TP53 sequencing by NGS performed by central pathology lab
NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
Expansion Cohort 2: Subjects with UC with transitional cell histology (including renal pelvis, ureter, bladder, urethra) who have progressed on or after platinum-containing chemotherapy
Histologically confirmed diagnosis of GCT (nonseminoma or seminoma in men; non-dysgerminomas, dysgerminomas, or germinomas in women or patients with pineal gland GCT) at Memorial Sloan-Kettering Cancer Center (MSKCC) of any primary site (includes female GCT and intracranial GCT)
Previous enrollment in the present study
Hydroxyurea for cytoreduction
Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ? 1 lesion that measures > 1.5 cm in the longest transverse diameter and ? 1.0 cm in the longest perpendicular diameter.
Presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of hydroxyurea.
Hydroxyurea-related fever.
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
Any unresolved toxicity (CTCAE grade > 1) from previous anti-cancer systemic therapy unless approved by one of the principal investigators (Drs. Lee or Sherman); rare exceptions that would not affect the study (e.g., radiation induced dysphagia) allowed with the consent of either principal investigators (Drs. Lee or Sherman)
Safety Cohort (Dose Escalation)
Safety and Expansion Cohorts
Legal incapacity or limited legal capacity.
Histologically confirmed diagnosis of grade 2 or 3 out of 3 UPS or dedifferentiated/pleomorphic LPS of the extremity (including limb girdle, i.e. shoulder or hip) that measures greater than 5 cm in any direction as assessed by imaging; Alternative terms for UPS meeting inclusion criteria include but are not limited to the following
Diagnosis of scleroderma.
Confirmation of MET-driven PRCC without co-occurring Fumarate Hydratase or Von Hippel Lindau mutations from a tumour sample using the sponsor-designated central laboratory validated MET Next Generational Sequencing assay
Final criteria for eligibility established after simulation: the tumor bed can be readily visualized on simulation computed tomography (CT) and is localized to one quadrant or region of the breast that is amenable to partial breast irradiation
Calcium >= lower limit of normal (=< 48 hours prior to enrollment/randomization)
Prior transarterial chemoembolization (TACE)
IPSS =< 20
Study subjects should be post-menopausal women (premenopausal women are eligible if they are on or willing to be on mandatory ovarian function suppression)
T1c, N1-N2
T2, N0-N2
T3, N0-N2
T4a-d, N0-N2
Cavitary tumors or tumors invading or abutting large blood vessels.
e. Renal failure needing hemodialysis or peritoneal dialysis
i. Untreated psychiatric disorders
Documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, based on standard diagnostic cytogenetic evaluation performed locally, before signing informed consent for this study.
History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, except calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications.
Current evidence of corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis, as confirmed by ophthalmologic examination.
For patients previously treated with first generation anti-androgens (i.e., flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur >4 weeks (>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).
Enrollment in another interventional study.
Previous enrollment in the present study;
Had previous exposure to Betafectin® or Imprime PGG
Follicular lymphoma with histology documented by the participating institution (grades 1, 2 or 3a)\r\n* For subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening disease, or frequent B-symptoms, a pre-treatment biopsy is required to rule out large cell transformation
Prior exposure to radio- or toxin-immunoconjugates
Meets one or more Groupe d'Etude des Lymphomes Folliculaire (GELF) criteria.
Amyloidosis
Age ?18 years. A patient may be of either sex and of any race/ethnicity.
Patient must not have curative options available (e.g. a single metastatic focus in the liver in a patient with MCRC eligible for metastasectomy).
Chemo-refractory is defined as:
Ability to adhere to dose and visit schedules.
A female subject is eligible to enter the study if she is:
combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
vasectomized partner (if vasectomized is the sole sexual partner and has received medical confirmation of surgical success)
Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer)
Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer
Subjects with carcinomatous meningitis
Subjects with known SCLC transformation
The patient's treating physician states that one of the lesions can be treated with SBRT
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology)
Previous enrollment in the present study
Mucinous or tubal histology or other good prognosis histology
Current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
Triglyceride level of no more than 400 mg/dL
Incompletely healed wound
Hematocrit >= 29%
Proton pump inhibitors, such as rabeprazole, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, and pantoprazole are prohibited; short acting antacids such as Maalox Maximum Strength are allowed
Suitable candidates are patients with classic chronic GVHD or overlap syndrome (classic chronic plus acute GVHD)that is: a)Previously untreated (newly diagnosed) as defined by having received < 14 days of prednisone (or equivalent) before enrollment/randomization to study therapy; b)Previously treated but inadequately responding after ? 16 weeks of initial therapy with prednisone and/or calcineurin inhibitor (CNI) ± additional non-sirolimus agent (started at the time of chronic GVHD diagnosis).
Requirement for platelet transfusions.
Adequately functioning bladder, defined as continent and without the need for an indwelling catheter
Patients with a tracheoesophageal (TE) fistula or direct invasion into the mucosa of the trachea or major bronchi; bronchoscopy is encouraged if a TE fistula is suspected; the presence of a fistula will exclude a patient from this study
Patients who are pregnant (positive pregnancy test) or nursing. Use of effective means of contraception (men and women) in subjects of child-bearing potential. To date, no fetal studies in animals or humans have been performed. The possibility of harm to a fetus is likely. Bevacizumab specifically inhibits VEGF, which is responsible for formation of new blood vessels during development, and antibodies can cross the placenta. Therefore, bevacizumab should not be administered to pregnant women.
(continued from no. 22) Subjects will be apprised of the large potential risk to a developing fetus. It is not known whether bevacizumab is excreted in human milk. Because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women. Patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy.
At least 2 doses of fusion vaccine were produced
Normal serum calcium (or normal corrected serum calcium)
Patient is judged to be mentally reliable to follow instructions and to keep appointments (Please note that mental reliability is not determined through any specific test rather it is ascertained by the treating physician through conversation at the time of consult)
Absence of macroscopic disease after upfront surgery (i.e., TxNx and TxN0; TxN+ and T1-3Nx are eligible if the T/N stage categories meet the criteria above)
Serum creatinine > 1.3 or upper limit or normal (ULN), CCL < 60 cc/min, peripheral neuropathy > grade 1 and/or frequency hearing loss that interferes with activities of daily living are contraindications to cisplatin but not to carboplatin
Current participation in other clinical study
Prior sorafenib is allowed as long as toxicity from ongoing is =< grade 2 and prior intolerance of 400 mg sorafenib PO daily is felt amenable, by the principal investigator, to supportive care measures or dose modifications
Known intolerance of vorinostat
PRIOR TO POST-TRANSPLANT IMMUNOTHERAPY: WBC >= 2.0 X 10^3/uL
PRIOR TO POST-TRANSPLANT IMMUNOTHERAPY: AST/ALT < 3.0 x ULN
PRIOR TO POST-TRANSPLANT IMMUNOTHERAPY (COHORT 2): Able to produce at least 2 doses of fusion vaccine to be considered evaluable; patients who are unable to produce at least 2 doses of fusion vaccine, but otherwise meet eligibility criteria for post-transplant immunotherapy, will be treated with pidilizumab (MDV9300) alone and will be replaced
Coagulation
Prisoners and other vulnerable populations
Participants may have had a gross total resection, sub-total resection or biopsy\r\nonly
Large tumors > 8 cm
Clinically (medically) indicated procedure (i.e. biopsy of lesions of recurrent disease, palliative management via resection, thoracentesis, etc.) to collect tumor in sufficient quantity (\golf ball size\ estimated weight 10-30 grams, pleural, and/or ascites fluid estimated volume ? 500 mL) for vaccine processing.
Patients with tracheal/esophageal involvement. High mitotic activity or necrosis in pathology does not exclude from the study. Note: in Categories a and b, patients can be followed using US locally in addition to standard diagnostic followup menu but, if US only is positive, a FDG-PET or MRI will be obtained. If negative, a rising thyroglobulin titer is required in which case response will be monitored by continued US and suppressed and/or stimulated thyroglobulin. Thyroglobulin titer cannot be used if anti-thyroglobulin antibodies are present).
Prior splenectomy unless Howell-Jolly bodies are absent.
Participants with seronegative occult HBV infection or past HBV infection (defined as anti-HBc positive and HBV DNA negative) could be eligible if they were willing to be followed according to the protocol for HBV DNA testing
Positive test results for human T-lymphotropic virus type I (HTLV 1) virus in endemic countries
Erythropoietin stimulating agents (ESA) and blood transfusions are allowed as medically indicated, ESA use should be consistent with American Society of Clinical Oncology (ASCO) guidelines
Cytology and tumor markers: serum and lumbar CSF must be obtained to evaluate for alpha fetoprotein (AFP) and beta human chorionic gonadotropin (HCG); any patient with elevated AFP (serum > 10 IU/L and CSF > than institutional norm) or elevated B-HCG (serum or CSF > 100 IU/dL) will be considered to have a nongerminomatous germ cell tumors (NGGCT) regardless of histology; lumbar CSF will also be evaluated for dissemination of tumor cells; if elevated, serum and CSF should be repeated after chemotherapy until these values are within normal range; all patients with elevation of AFP or HCG at any time prior to RT will have serum HCG and AFP repeated within 14 days before radiation therapy (RT) or within 14 days of initiation of RT
Lactate dehydrogenase (LDH) within normal limits (WNL)
Histological confirmation of breast carcinoma; pathologic evidence of dermal lymphatic invasion should be noted but not required
Clinical diagnosis of IBC (presence of inflammatory changes in the involved breast, including diffuse erythema, heat, ridging, and peau d'orange)
Subjects that relapse within one year of diagnosis
Consent to participate in Data Bank and BioRepository (DBBR) (Roswell Park Cancer Institute [RPCI] only)
Women currently on tamoxifen and raloxefene for prevention are not eligible
CT scans showing involvement of ? 1clearly demarcated lesions measuring ? 1.5 cm
Arm A:
Females or female partners not of childbearing potential must have been surgically sterilized or postmenopausal (as defined above in inclusion criterion #12). Sterilized males must be at least 1 year post vasectomy
Previous therapy directed against CD19, such as MAbs or MAb conjugates
Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given
Employees of the clinical study site who are directly involved with the conduct of the study, or immediate family members of such individuals. These subjects may be treated at another site participating in the study
Tumors must be supratentorially located
Hematocrit >= 30%
Patients must not have active eczema, atopic dermatitis, or other exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne, contact dermatitis, psoriasis, herpes or other open rashes or wounds)
Any form of active primary or secondary immunodeficiency
The resection cavity must have a maximum diameter of less than or equal to 4 cm; this criteria will be determined by the study radiologist)
Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
Ferritin> 1000 mcg/L at screening
Anticipated to be transfused at least 8 times annually during the study
More than 6 months of cumulative iron-chelation therapy (such as daily deferasirox (Exjade) or deferiprone or 5x/week deferosamine). intermittent deferoxamine doses in association with blood transfusions are not exclusionary regardless of duration of such treatment. -- More than 3 years since patient began receiving regular transfusions (2 units per 8 weeks or 4 units received in a 3 month period).
Treating physician assesses tumor to be sufficiently distant from sensitive structures to be able to achieve greater than or equal to 66 Gray (Gy) (i.e., spinal cord tolerance respected in vertebral body metastisis
Confirmation of diagnosis of B cell malignancy and positivity for CD19 confirmed by the Laboratory of Pathology of the National Cancer Institute (NCI); the choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient; immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood, fine needle aspirates and bone marrow samples
Willing to sign a durable power of attorney
Evaluable KS involving the skin and/or viscera, including at least one of the following:\r\n* KS of the skin with >= 5 KS lesions that are evaluable by non-invasive methods that have not been treated with local therapeutic modalities\r\n* Pulmonary KS evaluable by computed tomography (CT) scan\r\n* Gastrointestinal KS evaluable by direct visualization or fiberoptic instrumentation\r\n* Biopsy proven lymph node involvement measurable by CT scan
Inclusion of women and minorities: both men and women and members of all races and ethnic groups are eligible for this trial
Supraphysiologic doses of corticosteroids within 3 weeks
Proteinuria > 500 mg/24hrs
Patients with any other abnormality that would be scored as a grade 3 or greater toxicity, except:\r\n* Lymphopenia\r\n* Direct manifestations of KS\r\n* Direct manifestation of HIV\r\n* Direct manifestation of HIV therapy (i.e. hyperbilirubinemia associated with protease inhibitors)\r\n* Asymptomatic hyperuricemia\r\n* Hypophosphatemia
Must agree to follow pregnancy precautions as required by the protocol.
Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
Must agree not to donate blood or semen as defined by the protocol
Evidence of TLS at screening
Presence of specific hematology and/or chemistry abnormalities
Venous thromboembolism within one year
Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
Chronic diarrhea
Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes or prolonged QT interval including: (Patients must discontinue drug 7 days prior to starting dasatinib)\r\n* Quinidine, procainamide, disopyramide\r\n* Amiodarone, sotalol, ibutilide, dofetilide\r\n* Erythromycin, clarithromycin\r\n* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide\r\n* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Prisoners, or subjects who are involuntarily incarcerated
Could have been treated neoadjuvantly but have not reached pathologic complete response.
Diagnosis of SSc as defined by American College of Rheumatology and at high-risk for fatal outcome based on the following prognostic factors; patients must have (1) both a and b below and (2) at least one of c, d, e, or f\r\n* a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to the elbows or knees and/or torso, in addition to distal extremity involvement\r\n* b) Duration of systemic sclerosis =< 5 years from the onset of first non-Raynaud’s symptom\r\n* c) Presence of interstitial or pulmonary vascular lung involvement (forced vital capacity [FVC] or DLCO < 70% of predicted) especially with evidence of alveolitis (abnormal bronchoalveolar lavage or high-resolution chest CT scan)\r\n* d) Presence of SSc-related pulmonary disease and alveolitis (abnormal bronchoalveolar lavage or high-resolution chest CT scan) with FVC or DLCO between 70% and 80% predicted, AND a drop in FVC > 15% predicted within the preceding 18 months\r\n* e) Presence of myocardial disease (arrhythmia needing therapy, cardiomegaly, presence of moderate or large pericardial effusion, or left axis deviation on electrocardiogram [EKG])\r\n* f) History of SSc renal crisis
Failure of 2 of the following drugs: interferon-beta1b, interferon beta 1a, and glatiramer acetate; failure is defined by new or progressive physical signs and symptoms that impair activities of daily living; such changes include cognitive decline, vision loss, swallowing dysfunction, limb weakness, limb plasticity, bowel or bladder dysfunction, and coordination or gait dysfunction; these clinical changes should be supported by new or expanding lesions on MRI scanning consistent with disease progression
A Kurtzke extended disability status scale (EDSS) of 2.0 to 6.0
Available allogeneic CD19CAR transduced tri-virus-specific cytotoxic T lymphocytes with >=15% expression of CD19CAR determined by flow cytometry and greater than 10% killing of one or more viral antigen pulsed targets in a cytotoxicity assay at an effector:target ratio of 20:1
Chronic lymphocytic leukemia (CLL) must have either \r\n * 1) Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing FLU (fludarabine phosphate) (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog) \r\n * 2) Failed FLU- CY (cyclophosphamide)-rituximab (FCR) combination chemotherapy at any time point; or \r\n * 3) Have \17p deletion\ cytogenetic abnormality and relapsed at any time point after any initial chemotherapy
Waldenstrom's macroglobulinemia must have failed 2 courses of therapy
Women of any racial or ethnic group
Diagnosis of grade 2 endometrioid endometrial carcinoma or higher on endometrial biopsy or on dilation and curettage specimen
Congenital or acquired uterine anomaly which distorts the uterine cavity
Conditions associated with increased susceptibility to infections with microorganisms; such conditions include, but are not limited to, acquired immune deficiency syndrome (AIDS), leukemia and intravenous (IV) drug abuse
Genital actinomycosis
Confirmed diagnosis of aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) according to WHO criteria for SM and established criteria for ASM and MCL (Valent et al 2003), presenting with at least one measurable C-Finding.
CP-CML who prove resistant or intolerant to imatinib (Cohort 1)
Ph+ ALL, AP-CML, or BP-CML who are resistant or intolerant to or who relapse after imatinib therapy (Cohort 2)
a purine analog-containing regimen
a bendamustine-containing regimen
an anti-CD20 antibody-containing regimen
a chlorambucil-containing regimen
an alemtuzumab-containing regimen (for those subjects with a 17p deletion)
All subjects must:
All subjects must be counseled about pregnancy precautions and risks of fetal exposure.
Central nervous system involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to randomization.
Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
Venous thromboembolism within one year
Prisoners.
American Society of Anesthesiologists (ASA) criteria of IV or higher;
intra-prostatic calcifications >1.0 cm (single or continuous grouping) on 2 or more consecutive images along the same plane by either the TRUS or Sonablate 500 measurement will not be enrolled;
interest in future fertility;
inability to visualize the prostatic tissue adequately on transrectal ultrasound imaging;
history of urethral stent or urethral surgery (urethral dilation, urethroplasty); a Uroflow exam may be conducted at the investigators discretion;
functional bladder problems defined as IPSS > 19;
current bladder cancer, urethral stricture, or bladder neck contracture; a cystoscopy my be performed at the investigator's discretion to rule out these conditions;
urinary tract or rectal fistula;
rectal fibrosis/stenosis; anoscopy or proctoscopy may be performed at the investigator's discretion;
anomaly of the rectal anatomy or mucus membrane; anoscopy or proctoscopy may be performed at the investigator's discretion;
participation in other investigational studies, unless approved in writing by the study sponsor.
fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
current participation in other clinical study
Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
Fanconi anemia (FA)
PRE-REGISTRATION
The melanoma must harbor a c-KIT mutation determined by PCR and sequencing
Serum potassium and magnesium levels within institutional normal limits; patients with low potassium and magnesium levels may be repleted to allow for protocol entry
Total serum calcium or ionized calcium level >= institutional lower limit of normal
Serum electrolyte values (sodium, potassium, magnesium, calcium) must be checked prior to enrollment and clinically significant abnormalities corrected prior to surgery/AdV-tk injection
Tumor material available for central 1p/19q assessment, central O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase promoter methylation status assessment, isocitrate dehydrogenase mutation analysis, and central pathology review
Curran Group status of I-IV at the time of enrollment
Platelets =< 125,000 cells/ul (blood work will be repeated within 2 weeks and if still abnormal, patient will be excluded)
The patient's hematopoietic cell transplant donor must consent to a 2 volume leukapheresis or whole blood donations obtained at one phlebotomy which will total approximately 250 ml from which the WT-1 specific T cells to be used for adoptive transfer will be generated
In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines; if day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day
Patient compliance and geographic proximity that do not allow adequate follow-up
Histologic diagnosis has been verified by institutional pathologist and classified according to the WHO (2007) system
No evidence of CNS metastasis as indicated by MR images of the brain and spine and by cytologic examination of lumbar CSF 7 to 28 days after surgery; if lumbar puncture is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease; if CSF sampling is not possible and the patient has no other evidence of metastasis, the patient should be assigned to the intermediate risk arm
No evidence of CNS metastasis as indicated by MR images of the brain and spine and by cytologic examination of lumbar CSF 7 to 28 days after surgery; if lumbar puncture is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease; if CSF sampling is not possible and the patient has no other evidence of metastasis, the patient will be assigned to the low risk arm
Histologic diagnosis of nodular desmoplastic medulloblastoma with less than gross total resection, but with no evidence of metastasis
Circulating antibody against mouse immunoglobulin (HAMA)
Prior radiation to maximally tolerated levels to any critical normal organ
(2. continued) Patients with prior therapy that included interstitial brachytherapy, Gliadel wafers or stereotactic radiosurgical procedures must have confirmation of true progressive disease rather than radiation necrosis. Such confirmation may be using advanced imaging studies (e.g. PET scans, diffusion-perfusion MRI, SPECT etc) or if available, surgical sampling and histological confirmation (surgery is not required).
(10. continued) (such as presurgically for obtaining pharmacology data for the agent) will be eligible to enter the study provided they have recovered from the toxic effects of the agent if any. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
Group A: Pathologic fracture or impending pathologic fracture of the femur;
Group A: Intramedullary rod, plating, cementation, hip arthroplasty, or knee arthroplasty.
Group B: T2 tu;mor (>5 cm buty < 20 cm);
Presence of DVT on pre-operative screening ultrasound study
Surgical drain output > 500 cc of bloody fluid during first 8 hours
I.N.R. > 1.3 pre-operatively or > 1.5 post-operatively
Platelet count < 100,000 either pre-operatively or post-operatively
Indwelling post-operative epidural catheter for pain control
Treatment with warfarin, clopidogrel, aspirin, NSAIDs, LMWH or other anti-coagulants for conditions
Hodgkin’s lymphoma\r\n* Primary treatment failure ineligible for autologous HSCT; relapse/progression after autologous HSCT
Myeloproliferative disorders (idiopathic myelofibrosis, polycythemia vera, essential thrombocytosis, chronic myelomonocytic leukemia, agnogenic myeloid metaplasia)\r\n* Agnogenic myeloid metaplasia with adverse-risk features \r\n* Polycythemia vera or essential thrombocythemia in transformation to secondary AML
Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal (myeloablative regimen 4, reduced intensity regimen 3) or =< 4.0 x normal (nonmyeloablative regimen 2)
Bilirubin =< to 2.0 x normal (myeloablative regimen 4, reduced intensity regimen 3) or =< 4.0 x normal (nonmyeloablative regimen 2)
Have identified a back-up cell source in case of engraftment failure; the source can be autologous, related, or unrelated
Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation; (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
Anticancer chemotherapy or immunotherapy: Anticancer therapy is defined as any agent or combination of agents with clinically proven anticancer activity administered by any route with the purpose of affecting the cancer, either directly or indirectly, including palliative and therapeutic endpoints
Any malabsorption conditions
TIER II SUBJECTS: Patients with follicular lymphoma who have achieved at least a partial response with an initial chemotherapy and/or immunotherapy regimen; response from pre-study regimen may be either a clinically determined response by the principal investigator or physician co-investigator member of the study team, or a measured response as per the response criteria of this protocol
Persistent, unexplained increases in absolute eosinophil count prior to initiation of vaccine
Patient has hypersensitivity to bortezomib, boron, mannitol, gemcitabine, or doxorubicin. Gemcitabine skin rash that be controlled by short course steroids is allowed.
Willingness to provide all biological specimens as required by the protocol
Measles antibody titer on the BioRad Multiplex assay less than or equal to 1.0
Previous exposure to heat inactivated measles virus vaccine (this vaccine was given to some individuals between the years of 1963-1967)
Patients with neurofibromatosis type 1 (NF1) and an inoperable plexiform neurofibroma that has the potential to cause significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings; however, if any clinical observation or scan suggests possible malignant transformation, the tumor should be biopsied prior to therapy; patients without biopsy-proof of a plexiform neurofibroma must have at least one other diagnostic criteria for NF1 as defined by the National Institutes of Health (NIH) Consensus Conference:\t\r\n* Six or more café-au-lait spots (> 0.5 cm in prepubertal subjects or > 1.5 cm in postpubertal subjects)\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first degree relative with NF1
Prior administration of interferon alfa-2b or PEG-Intron
Women with and without prior therapy are also eligible; priority will be given to those who consent to participating in the pharmacokinetic studies
Prior therapy with E7389 Halichondrin analog (eribulin)
Ph+ CML; the diagnosis of chronic phase CML based on cytogenetic detection of the Ph chromosome and/or detection of the breakpoint cluster region (BCR)-Abelson (ABL) rearrangement by molecular analysis (recombinant deoxyribonucleic acid [DNA] analysis of the BCR-ABL fusion gene, fluorescence in situ hybridization, or polymerase chain reaction detection of the BCR-ABL hybrid messenger ribonucleic acid [mRNA])
Documentation of complete cytogenetic response (CCR) by conventional cytogenetics or fluorescent in situ hybridization (FISH) analysis on a frontline TKI with stable dosing
Over-expression of HER2
Exclusion for fludeoxyglucose F 18 (FDG) scan is anyone exceeding the weight limit of the scanner (350 lb)
UNRELATED DONORS: Only G-CSF mobilized PBMC will be permitted as a HSC source on this protocol
Confirmed diagnosis of AL amyloidosis
Planned first-line chemotherapy contains a proteasome-inhibiting agent administered weekly
Non-AL amyloidosis
Subject is eligible for and plans to undergo ASCT
Female subject must either:
Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile
Serum sodium level is ? 130 mmol/L
No portal invasion or extrahepatic spread on imaging.
Contraindications for doxorubicin administration.
Subject has a known history contraindicating contrast dye or iodine that cannot be safely controlled via antihistamine, steroids, or with any other agent.
Portal vein thrombosis of bland or malignant origin.
Patient declines participation in NANT 2004-05, the NANT Biology Study.
Completed the End of Study Visit in Study NEOD001-201
First degree atrioventricular (AV) block
Second degree AV block Type 1 (Mobitz Type 1/ Wenckebach type)
Right or left bundle branch block
Any experimental imaging agent directed at amyloid within 2 weeks
Subject is under legal custodianship
Progressed or intolerant to at least 1 approved prior anticancer regimen.
Active diverticulitis.
Be undergoing open, or minimally invasive LAR for the treatment of a rectal or rectosigmoid neoplasm (Subjects with rectal or rectosigmoid neoplasm(s) may be treated with or without neoadjuvant therapy. Long-course neoadjuvant therapy must have been completed ?6 weeks prior to LAR surgery (Day 0).
Have a planned low circular stapled or transanally hand sewn anastomosis ?10 cm from the anal verge.
Have a colorectal or coloanal reconstruction with or without reservoir/pouch.
Undergoing ileoanal reconstruction, total colectomy or proctocolectomy, abdominoperineal resection, Hartmann's procedure, Hartmann's reversal or multiple synchronous colon resections (e.g., LAR and concomitant right colectomy).
Has previously undergone a left sided colon resection.
Has previously undergone a rectal resection.
Has a diagnosis of locally advanced rectal or rectosigmoid cancer undergoing extended en bloc operations.
Has a diagnosis of inflammatory bowel disease (IBD). Subjects with rectal or rectosigmoid cancer neoplasms and IBD are excluded.
Recipient of 1 allo-HSCT but not more than 1 allo-HSCT.
Patient must have a histological diagnosis of neuroblastoma or ganglioneuroblastoma and be either newly diagnosed with high risk disease or have failed previous treatment:\r\n* Patients who have failed previous treatment may have had no more than one earlier autologous hematopoietic progenitor cell (HPC) transplant\r\n* High risk is defined as any of the following scenarios:\r\n** Stage 2A/2B, any age , amplified myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) , any ploidy , any International Neuroblastoma Pathology Classification (INPC) histology\r\n** Stage 3, any age , amplified MYCN , any ploidy, any INPA histology\r\n** Stage 3, age >= 547 days , not amplified MYCN, any ploidy , unfavorable INPA histology\r\n** Stage 4, age < 365 days , amplified MYCN, any ploidy, any INPA histology \r\n** Stage 4, age 365 - < 547 days , amplified MYCN, any ploidy , any INPA histology\r\n** Stage 4, age 365 - < 547 days , any MYCN , ploidy (DI) = 1, any INPA histology\r\n** Stage 4, age 365 - < 547 days , any MYCN, any ploidy, unfavorable INPA histology\r\n** Stage 4, age >= 547 days , any MYCN, any ploidy, any INPA histology\r\n** Stage 4S , age < 365 days , amplified MYCN, any ploidy, any INPA histology
Patient is not an eligible candidate for collection by apheresis or HPC transplant
Subjects must have histological or serological proof of metastatic germ cell neoplasm (gonadal or extragonadal primary) with disease not amenable to cure with either surgery or chemotherapy; subjects with seminoma and non-seminoma are eligible, as are women with ovarian GCTs
Subjects must have received initial cisplatin based combination therapy, such as bleomycin-etoposide-cisplatin (BEP), cisplatin-etoposide (EP), etoposide-ifosfamide-cisplatin (VIP), or similar regimens AND demonstrated progression following the administration of at least one ‘salvage’ regimen for advanced germ cell neoplasm, such as high dose chemotherapy, paclitaxel-ifosfamide-cisplatin (TIP), or vinblastine-ifosfamide-cisplatin (VeIP)
Participants in the combination therapy arms must be eligible to receive pomalidomide/dexamethasone, bortezomib/dexamethasone or lenalidomide/dexamethasone or other approved agents per current prescribing information for MM.
Major immunologic reaction to any IgG containing agent or auristatin based agent
Corneal pathology that would limit evaluation of loss in visual acuity associated with corneal deposits.
Prior exposure to pomalidomide for subjects enrolling in the pomalidomide/dexamethasone combination arm.
Confirmation of AR+ (defined as ? 10% nuclear AR staining by immunohistochemistry [IHC]) TNBC in either the primary or metastatic lesion, assessed during the screening period by a local laboratory or by medical history
Estrogens
Megesterol acetate
Current treatment with intravenous bisphosphonate or denosumab with elevated serum calcium corrected for albumin or ionized calcium levels outside institutional normal limits at screening
Integral biomarkers: all patients who are eligible for the study due to a history of positive BRCA1/2 mutation must provide documented evidence of their deleterious germline mutation status, obtained in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory, including but not limited to Myriad Genetics prior to study enrollment; variants of uncertain significance (VUS) of BRCA1/2 and BRCA1/2 somatic mutations are not considered deleterious germline BRCA1/2 mutations; due to the long acceptance of BRCA 1 and BRCA 2 mutation testing through Myriad, Myriad results will be acceptable; if testing for BRCA 1 and BRCA 2 mutation is done by other organizations, a genetic consultation report from a qualified medical professional confirming that the laboratory results showed a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or deleterious BRCA 1 rearrangement is required
Subjects with Stage 1-4 (per the Modified Keystone Grading Schema) acute GVHD of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which developed in the first 180 days following allogeneic hematopoietic cell transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after preplanned donor lymphocyte infusion.
Subjects are willing to undergo or must have had an endoscopy of the upper and/or lower GI tract and biopsy to confirm GI GVHD.
Stage of acute GVHD of the lower GI tract will be determined using the Modified Keystone Grading Schema.
Subjects with signs and symptoms of chronic GVHD.
Subjects who test positive for Clostridium difficile (C. difficile) at Screening.
Glucose-6-phosphate dehydrogenase (G6PD) status normal
Group 3: Have progressive active SSc after prior autologous transplant based on the presence of progressive pulmonary disease; this will be defined by a decrease in the FVC or DLCO adjusted since prior autologous transplant of 15 percent or greater of the pre-transplant percent predicted value, in addition to evidence of alveolitis as defined by chest CT changes or BAL; f patients had prior autologous HCT on the \Scleroderma: Cyclophosphamide Or Transplantation\ (SCOT) clinical trial, they must have failed based on the defined study endpoints and be approved by the protocol principal investigator (PI)
Group 4: Patients who meet group 1 inclusion criteria but may have FVC or DLCO-adjusted less than 70% plus have had an adverse event on cyclophosphamide preventing its further use (specifically hemorrhagic cystitis, leukopenia with white blood cell [WBC]< 2000 or absolute neutrophil count [ANC] < 1000 or platelet count < 100,000)
Patient has either metastatic disease (M1; stage IVB), is medically unable to receive brachytherapy, or refuses brachytherapy
Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Additional criteria apply, please contact the investigator for more information
Additional criteria apply, please contact the investigator for more information
Patient must have either mutation or amplification of c-KIT gene tested by commercially available molecular or gene sequencing techniques
Has known psychiatric disorder that would interfere with fulfilling the requirements of the study
Active grades III or IV acute GVHD
Ongoing drug-induced pneumonitis would be exclusion for idelalisib therapy but ibrutinib would be an option
Mature B cell (Burkitt’s) ALL
Subjects older than 75 years old to be discussed with principal investigator (PI) prior to subject consent; consensus between PI and treating physician is required
Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
Demonstrated progression on abiraterone and/or enzalutamide
Asymptomatic or mildly symptomatic
Normal coagulation panel.
Negative antiviral serology.
Subject must be deemed a suitable candidate for regorafenib as per their treating physician.
Subject should not be receiving any agent for fatigue including steroids, megace or opioids. NOTE: Subjects who have a contrast-induced allergy are allowed to receive steroids for their scans.
Subjects with pheochromocytoma.
Renal failure requiring hemo- or peritoneal dialysis
Relapsed or refractory B-ALL, defined as:
Evidence of CD19 expression
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
History of treatment with a murine-derived biological product other than blinatumomab unless subject has been shown to be negative for human-anti-mouse-antibodies (HAMA) prior to or during screening
Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test.
Macrovascular invasion of lobar portal vein branches or main portal vein.
Assessment of FLT3 mutation status;
Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts:
Cohort C: Subjects without a FLT3 mutation at the time of enrollment
Normal coagulation profile as evidenced by PT and aPTT ? 1.5 x ULN;
Absolute leukemic blast count in peripheral blood >50,000/ microliter;
CYP3A4 or CYP2C19 or P glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrates having a narrow therapeutic index;
Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma according to the American Association for the Study of Liver Diseases Guidelines.A biopsy performed at screening may serve as a diagnostic biopsy for subjects with radiographic diagnosis.
Subject has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1. Evaluable target lesions may not have been treated with local therapy; previously treated lesions may only be evaluated as target lesions if they are the only lesions available and have shown objective definite progression after prior treatment. Local therapy must have been completed at least four weeks prior to baseline tumor evaluation
Potassium within normal range or corrected with supplements
Complete abstinence is only acceptable in cases where this is the preferred and usual lifestyle of the subject.
Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable.
All subjects must:
Other than the subject, Female of Childbearing Potential and males able to father a child should not handle CC-122 or touch the capsules, unless gloves are worn.
Be counseled about pregnancy precautions and risks of fetal exposure
Complete left bundle branch or bifascicular block
Patients with the following TNM stages are eligible: \r\n* pT3aN0-2 (pN0;pN1;pN2) provided less than 10 nodes dissected and/or positive surgical margins\r\n* pT3bN0-2 (pN0;pN1;pN2)\r\n* pT4aN0-2 (pN0;pN1;pN2)\r\n* pT4bN0-2 (pN0;pN1;pN2)
Diagnosis of primary MF (PMF) or secondary MF (PET-MF and PPV-MF) as per WHO 2008 criteria.
Randomized cohort: resistant or intolerant to prior ruxolitinib therapy. Documentation by the Investigator that the patient has exhausted available treatment options (eg, resistant or intolerant to hydroxyurea, etc).
Spleen 5 cm below the inferior left costal margin as measured by manual palpation.
Active symptomatic MF as defined by the screening MPN-SAD patient-reported instrument requiring a severity score of at least 5 on one symptom, or a severity score of ? 3 on at least two of the symptoms (on a 0 to 10 scale).
Evidence of distant metastases (below the clavicle) by clinical or radiographic examination
Evidence of any other primary cancers or metastases; evidence of deep soft-tissue or bony invasion, which would preclude transoral minimally invasive surgery (TMIS) by clinical and/or radiographic exam
Contraindications to general anesthesia
One to two painful vertebrae (T1-L5) with evidence of osteolytic or mixed lytic and blastic metastatic lesion by cross sectional imaging and pathologic fracture (presence of non-painful vertebrae with metastatic lesions in addition to the painful index vertebrae are allowed)
Brief Pain Inventory (BPI) worst pain score of ? 4 (irrespective of medication),
Primary tumors of the bone (e.g., osteosarcoma) at site of index vertebra(e),
Benign tumors of the bone (e.g. osteoid osteoma) at site of index vertebra (e),
Compromise in the posterior column of the vertebral body or walls of pedicles.
Extra-osseous extension of metastatic lesion is >10mm,
Additional non-kyphoplasty/vertebroplasty surgical treatment is required for the index vertebra(e),
Significant clinical morbidities (aside from the index vertebra(e) and recurrent cancer) that may interfere with data collection that affects pain and functional results,
Bedridden due to paralysis or neurological decline,
Resting bradycardia < 55 beats/min
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower.
Subjects with acute or chronic pancreatitis.
Cumulative Illness Rating Scale score > 6, by assessment of the investigator
Must have achieved at least a minor response to any previous regimen according to adapted European Group for Blood and Marrow Transplantation (EBMT) criteria
RAS (KRAS/NRAS) wild type mCRC not previously treated with an anti-EGFR containing regimen (unless contraindicated or not considered standard practice per clinical site or country guidelines).
All sites of metastasis must be measured in 3 planes, in millimeters and stored in Pediatric Oncology Network Database (POND) (a web-based data network, secure, independent and password protected)
All patients to be included in this study must be presented to the principal investigator using Horizon Live Web-conferencing through the Cure4Kids website; eligibility and target CNS sites will be determined, as well as non-target sites
The patient has been exposed to >= 350mg/m^2 of anthracycline
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
Prior anthracycline exposure: Patients must have less than 400 mg/m2 lifetime exposure of anthracycline chemotherapy. (See Appendix II for calculation worksheet)
Evidence of immunodeficiency or immune suppression
Planned invasive dental procedure for the course of the study
Prior or current IV bisphosphonate administration
Prior administration of denosumab
No evidence of dyspnea at rest
No exercise intolerance
Patients with a history of prior veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD, defined as: conjugated serum bilirubin >1.4 mg/dL AND unexplained weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right upper quadrant pain without another explanation, OR reversal of portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.
Positive blood culture within 48 hours of study enrollment.
Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection.
Participants with carcinomatous meningitis
Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Adequate tissue must have been obtained from surgical intervention to satisfy biospecimen requirements of study (collected under biospecimen collection protocols; either AAAO5706 principal investigator [PI]: Yvonne Saenger or AAAR1327 PI: Adrian Sacher)
Pre- or post-operative radiotherapy
Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session
Serum sodium level ? 130 mmol/L
Female subject must either:
Be of nonchildbearing potential:
Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
Subject must be willing to fast for approximately 10 hours predose and 4 hours postdose on day 1 of each period in the pharmacokinetic phase.
Consistent and correct usage of established hormonal contraceptives that inhibit ovulation,
Male subject is sterile due to a bilateral orchiectomy.
Mutation load determined by FoundationOne of >= 13 mutations/MB tested on archival tumor sample; the mutation load metric will be displayed on the FoundationOne report for all participating sites or may be obtained from Foundation Medicine from older reports using the Insights Portal, which will be available to all participating sites, or by emailing Foundation Medicine
Subjects with known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded; if tested, use of an FDA-approved test is strongly encouraged; subjects with unknown or indeterminate ALK status may be enrolled
Prisoners or subjects who are involuntarily incarcerated
Lower GI GvHD manifested by diarrhea must have other causes of diarrhea ruled out (eg, negative for Clostridium difficile or cytomegalovirus [CMV] infection or oral magnesium administration)
Patient with any active or chronic corneal disorders
Patients with monocular vision or have media opacities or any other condition that precludes monitoring of the retina or fundus.
Has squamous NSCLC
Refuses to complete quality of life questionnaires either alone or with assistance from study staff despite adequate fluency
Confirmed new diagnosis of Philadelphia chromosome-positive or BCR-ABL1 positive precursor B cell acute lymphoblastic leukemia (B-ALL) based on >= 20% lymphoblasts in bone marrow or blood; outside specimens will be subject to central review at the Huntsman Cancer Institute (HCI) Department of Pathology; BCR-ABL1 or Philadelphia-chromosome positivity may be determined by polymerase chain reaction (PCR), conventional cytogenetics and/or fluorescence in situ hybridization (FISH)
Elevated lactate dehydrogenase (any elevation above normal range)
Anemia below lower limit of normal or anemia requiring transfusion support as per center standard
Schistocytes on peripheral blood smear (>2 per HPF) OR histologic evidence of microangiopathy
Absence of coagulopathy (no uncompensated disseminated intravascular coagulation, DIC) at screening
Able to receive antibiotic prophylaxis against N. meningitides for the duration of the study.
Meningococcal vaccine(s) prior to LFG316 treatment if prior vaccination cannot be confirmed. The choice of vaccine(s) should take into account the serotypes prevalent in the geographic areas in which study patients will be enrolled. In case vaccination is not possible or will result in an unfavorable risk benefit ratio as judged by the investigator, vaccination can be postponed until deemed likely to be effective.
Patients <18 years old should receive vaccination for the prevention of S. pneumoniae and H. influenzae type b prior to LFG316 administration. In case vaccination is not possible or will result in an unfavorable risk benefit ratio as judged by the investigator, vaccination can be postponed until deemed likely to be effective.
Male sterilization (at least 6 m prior to screening). The vasectomized male partner should be the sole partner for that subject.
Positive HIV (ELISA and Western blot) test result (checked at screening). Historical local data will be acceptable if it the test was done within one month before start of HSCT conditioning and not more than 3 months before study visit 3.
ANC 1000 cells/mL
WBC counts 2500/mL
Lymphocyte count 500/mL
Serum sodium greater than 120 mmol/L
Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
Requires hospitalization for intravenous (IV) empiric antibiotic therapy
Myc positive lymphoma is defined by:\r\n* Positive for Myc gene rearrangement by fluorescence in-situ hybridization (FISH) involving various breakpoints (e.g. 8-14, 8-22 and 2-8) AND concurrent gene rearrangements in bcl-2 and/or bcl-6 by FISH OR\r\n* Myc and Bcl-2 overexpression defined by >= 40% Myc and > 50% Bcl-2 expression by immunohistochemistry (IHC); patients may enroll in the study based on the local laboratory evaluation, but these should be confirmed by the University of North Carolina (UNC) Hematopathology Laboratory retrospectively
Positive for cluster of differentiation (CD)20 via immunophenotyping
Patient agrees to consume no more than 1 standard unit of alcohol per day during the study and for 30 days from the last dose of alisertib; a standard unit of alcohol is defined as a 12 oz beer (350 mL), 1.5 oz (45 mL) of 80-proof alcohol, or one 6-oz (175 mL) glass of wine
Sufficient data to calculate the International Prognostic Index (IPI) score at baseline:\r\n* Age\r\n* Stage of disease\r\n* Lactate dehydrogenase (LDH)\r\n* ECOG performance status\r\n* Number of extranodal sites
Prior administration of an aurora A kinase-targeted agent, including alisertib
Requirement for constant administration of proton pump inhibitor from 5 days prior to D1 of alisertib, and/or requirement for constant administration of histone 2 (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
Tubal litigation in the female partner
Subjects with > Grade 1 (high or low) serum potassium, magnesium, or calcium levels.
Mercury (Hg) > 8 gr/dL
Histologically proven malignant pleural or peritoneal mesothelioma of epithelioid or biphasic histology
Sarcomatoid histology
Patients must have a total bilirubin =< 2.1 mg/dL within 72 hours of initiating the induction cycle, unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert’s syndrome or hemolysis or non-hepatic origin, and not to liver dysfunction
For Post-allo Part B: Active GVHD Grade 2 or higher
Biliary obstruction or presence of a percutaneous biliary drain. Note: Subjects with endobiliary stents may participate as long the enrollment criterion relating to serum bilirubin concentration is met.
Diagnosis of AA
Duration and extent of current episode of AA
Evidence of diffuse, spontaneous terminal hair regrowth
Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) < 5 for age < 65, HCT-CI < 4 for age > 65
Participants who have an indwelling draining IP catheter (to be drained only under medical supervision)
Active joint inflammation or other immune disorder involving joints (osteoarthritis is not exclusionary)
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrolimus
Female subject must either:
Be of nonchildbearing potential:
Subject has hypokalemia or hypomagnesemia at screening.
Disease progression: FDG avid malignancy that is classified as an FDG PET non-responder\r\n* PET non-responders are defined as having < 35% reduction in the FDG uptake of the primary tumor when compared to baseline
Patient must have received only one cycle of the following regimens (with or without epirubicin) during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:\r\n* Oxaliplatin, and capecitabine\r\n* Oxaliplatin, and fluorouracil\r\n* Cisplatin, and capecitabine\r\n* Cisplatin, and fluorouracil
Carcinomatous meningitis
Serious concomitant conditions
Known sensitivity to ferumoxytol
Granulocytes >= 1,000/mm^3
Blood urea nitrogen (BUN) =< 1.5 times normal
LVEF >= 45% at rest (by ECHO)
Minor changes from the required initial laboratory data guidelines will be allowed at the discretion of the attending team under special circumstances; the reasons for exceptions must be documented prior to enrollment
Appropriate slides of the primary lesion will be available for future review; if available, HER2/neu positivity will be recorded
Peritoneal dialysis catheter implantation is identical to that from the Gynecologic Oncology Group (GOG) 252 Protocol and revised from the GOG Surgical Procedures Manual
Subjects with any prior exposure to the hypomethylating agents (5-azacitadine or decitabine) are excluded
Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin
Hepatic: Total bilirubin ? 1.25 x upper limit of normal (ULN) (Arm: idelalisib + nab-paclitaxel ); total bilirubin ?1.5 x ULN (Arm: single agent idelalisib and Arm: idelalisib + mFOLFOX6); aspartate transaminase (AST) (SGOT), alanine transaminase (ALT) (SGPT) < 2.5 x ULN, and albumin > 3.0 g/dL
Currently or previously treated with biologic, or immunotherapy
Currently or previously treated with conventional chemotherapy, or other agents for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + nab-paclitaxel only)
Presence of peripheral neuropathy ? Grade 2 (Arm: idelalisib + nab-paclitaxel and Arm: idelalisib + mFOLFOX6)
Anti-arrhythmic and heart rate lowering drugs.
Cytomegalovirus (CMV) PCR positive at baseline
Tubal ligation in the female partner.
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
Detectable AR-V7 from circulating tumors (CTCs)
No evidence of HCT graft failure or multi-organ failure
CMV PCR > 500 copies/mL or evidence of end-organ damage due to CMV
Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts)
Skull defect (e.g. missing bone with no replacement)
Shunt
Bullet fragments
Sensitivity to conductive hydrogels
Planned to be treated by active surveillance
Any level of CD56 expression will be considered sufficient for enrollment on this study
Histologically confirmed DLBCL, cluster of differentiation (CD)20 positive by flow or immunohistochemistry (IHC); transformed DLBCL is allowed as long as no prior therapy has been given
Patients must be considered ineligible for rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) standard therapy; to be ineligible for R-CHOP, patients must meet at least one of the following criteria are met:\r\n* Prior anthracycline therapy for other malignancies or other disorders whereby if additional anthracyclines are given for DLBCL, the maximum lifetime allowable dose will be exceeded\r\n* Meeting the geriatric criteria of ineligibility for standard R-CHOP if one of the following criteria is present:\r\n** Three or more organ systems with a score of 3 or any 1 organ system with a score of 4 (using the Cumulative Illness Rating Scale for Geriatrics, [CIRS-G])\r\n** Score of 3 or above on the Vulnerable Elders Survey (VES-13)\r\n** Score of =< 9 in the short physical performance battery (SPPB)\r\n** Presence of a significant geriatric syndrome (dementia, delirium, falls, incontinence, malnutrition, and severe osteoporosis) in the past year prior to diagnosis\r\n** Any abnormality in performing activities of daily living (ADLs) or instrumental activities of daily living (IADLs)
Lymphoblasts may have any positive expression of cluster of differentiation (CD)20 for ofatumumab administration
Presence of the Philadelphia chromosome t(9;22)
Inclusion Criteria:\n\n        Phase 1 and 2: Confirmed advanced hematologic malignancies\n\n          -  Confirmed relapsed or refractory AML with a documented FLT3 mutation, or\n\n               -  60 years with newly diagnosed FLT3+ AML and not eligible for standard induction\n                  chemotherapy or FLT3+\n\n          -  high-risk MDS/CMML (defined as ? 10% peripheral blood or marrow blasts and\n             international Prognostic Scoring System [IPSS] score ? 2) and relapsed or refractory\n             to prior therapy\n\n          -  At least 3 weeks beyond the last cancer treatment for the disease under study, major\n             surgery and recovered from all acute toxicities (? Grade 1). Hydroxyurea used to\n             control peripheral blast counts is permitted during the first 2 cycles.\n\n          -  Adequate performance status ECOG ? 2;\n\n          -  Adequate renal and hepatic function:\n\n               -  creatinine ? 1.5 mg/dL OR calculated creatinine clearance ? 45 mL/minute\n\n               -  total bilirubin ? 2 times the upper limit of normal (ULN) unless due to Gilbert's\n                  disease or thought to be due to underlying AML\n\n               -  ALT and AST ? 5 times ULN\n\n          -  Negative serum pregnancy test within 14 days prior to the first dose of study therapy\n             for women of child-bearing potential\n\n          -  Ability to provide written informed consent\n\n        Exclusion Criteria:\n\n          -  History of clinically significant cardiac impairment, congestive heart failure (CHF)\n             New York Heart Association (NYHA) Class III or IV, unstable angina, or myocardial\n             infarction during the previous 6 months, or serious cardiac arrhythmia\n\n          -  QT interval corrected for rate (QTc) ? 450 msec for males and ? 460 msec for females\n             on the ECG obtained at Screening using Fridericia method for QTc calculation (average\n             of 3 readings)\n\n          -  Concomitant medication(s) that may cause QTc prolongation or induce Torsades de\n             Pointes with the exception of anti-microbials used as standard of care to prevent or\n             treat infections and other such drugs that are considered by the investigator to be\n             essential for the care of the patient. However, if such medications are deemed to be\n             necessary during the study, E6201 will be held during the period of their use. of\n             anti-microbials used as standard\n\n          -  Presence of active central nervous system (CNS) leukemia. Subjects adequately treated\n             for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for\n             leukemia cells are eligible. Subjects with no history of CNS leukemia will not be\n             required to undergo cerebrospinal fluid sampling for eligibility.\n\n          -  Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface\n             antigen (HBsAg), or hepatitis C virus HCV)\n\n          -  Active, uncontrolled infection\n\n          -  Known hypersensitivity to any study drug component\n\n          -  History of another malignancy; Exception: Patients disease-free for 2 years or treated\n             in situ carcinoma\n\n          -  Any other medical intervention or other condition which, in the opinion of the\n             Principal Investigator, could compromise adherence to study requirements or confound\n             the interpretation of study results\n\n          -  Pregnancy or lactation
Histologic diagnosis of melanoma.
Ocular Melanoma
Active diverticulitis
Patients with idiopathic myelofibrosis or myelofibrosis secondary to polycythemia vera or essential thrombocythemia
Borderline resectable- Tumors considered borderline resectable are defined as follows:
Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery without extension to the celiac axis.
Tumors considered to be unresectable due to local advancement include an absence of distant metastases as well as:
Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
Tail: SMA or celiac encasement greater than 180 degrees.
Female participants must agree to not donate eggs (ova) during the course of this study and for 30 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
Male participants must agree to not donate sperm during the course of the study and for 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
Male participants who intend to donate sperm during the course of this study or 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
This study will be limited to enrollment of Caucasian males only
Radiographic evidence of cavitary or necrotic tumors
Active diverticulitis.
Human immunodeficiency virus (HIV)-infected persons are eligible if they meet other eligibility criteria including the following:\r\n* No prior acquired immune deficiency syndrome (AIDS)-defining condition other than cluster of differentiation (CD)4+ cells nadir < 200/mm^3\r\n* Pre-leukemia CD4+ cell count >= 250/mm^3\r\n* Willing to adhere to antiretroviral therapy regimen with minimal overlapping toxicity and PK interactions with the experimental agents in this study; no zidovudine- and no ritonavir-containing regimens and no 3-drugs-in-1 pill regimens containing pharmacologic boosters are allowed; recommended regimens are integrase inhibitors combined with tenofovir and emtricitabine
Clinical picture indicative of leukostasis or evidence of disseminated intravascular coagulopathy
Any known UGT1A polymorphism, heterozygous or homozygous
Normal Coagulation profile.
No more than 2 prior regimens for DLBCL.
Previous exposure to PNT2258.
Have had a previous extra pleural pneumonectomy (EPP).
Acute or chronic pancreatitis.
All subjects must be >/= 18 years at the first screening examination / visit
Congenital coagulation abnormalities
Prior radioimmunotherapy
Availability of suitable primary and secondary umbilical cord blood (UCB) units.
Persistent cytopenia requiring growth factors and/or blood products AND evidence of hypocellular BM (< 25%); persistent cytopenia (at least 4 week period) is defined by presence of TWO of the following:\r\n* Absolute neutrophil count (ANC) < 1.0 x 10^9/L without filgrastim support or any ANC value that requires recurrent support by filgrastim (administered at least once a week)\r\n* Platelets (Plt) < 50 x 10^9/L\r\n* Hemoglobin (Hb) < 8 or packed red blood cell (PRBC) transfusion dependent (once every 2 weeks or more) with reticulocyte count of < 40 x 10^9\r\n* This criteria for persistent cytopenia and hypocellular bone marrow does not apply to patients with auto-immune cytopenia ONLY PGF patients
Pulmonary function\r\n* ARM A: Spontaneous breathing, not requiring ventilatory support\r\n* ARM B: No limitation
Patient who underwent TCD boost without counts recovery and are considered for another TCD boost will be treated off protocol
Specific ranges/levels of Screening labs that are acceptable per protocol.
No ongoing requirement for corticosteroids
Intolerance to dexamethasone, as determined by Investigator.
Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
In the opinion of the HCT center will be ready to begin pre-transplant conditioning within 6 weeks of trial enrollment from a medical and psychosocial standpoint
Subjects who are unable to walk because of paralysis, but who are upright in a wheel chair will be considered ambulatory for the purpose of calculating the performance score
Subjects with known 11q23 MLL rearrangement are excluded.
Mesothelin-positive refractory/recurrent solid tumors, other than malignant pleural mesothelioma (MPM) and pancreatic ductal adenocarcinoma (PDA) (Group 1 only)
Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient’s mood assessment questionnaire:\r\n* Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety\r\n* Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of “1, 2, or 3” to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
KPS 3 or worse
Previous exposure to BTKi therapy and meets at least one of the below criteria:
Discontinued a BTKi therapy due to BTKi treatment-related intolerance
Sodium >= lower limit of normal (LLN) after correction of hyperglycemia
Progression on irinotecan containing regimen
Prisoners are excluded from this study
Prior malignancy is acceptable if the subject is considered to be cured; in most cases this will mean a 5-year disease-free period; contact the principal investigator for any specific question regarding this requirement
Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, ulcerative colitis, malabsorption or Common Toxicity Criteria (CTC) grade >= 2 diarrhea of any etiology
Retinal pathology beyond normal age-related processes
Unwilling to be transfused with blood components.
Evidence of leptomeningeal spread of glibolastoma or gliosarcoma.
Active thyroiditis
Current anticoagulant therapy (acetylsalicylic acid [ASA] =< 325 mg per day allowed)
Rapidly doubling white cell count uncontrolled with hydroxyurea
Diagnosis of a nonmalignant disorder considered treatable by HCT.
Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Primary diagnosis of uveal melanoma at least 12 mm in largest basal diameter as clinically determined by the treating investigator; cytologic determination of diagnosis is not required; size is based on clinical assessment (e.g. by ultrasound or direct ophthalmoscopy) prior to enucleation or radiation therapy
Involved FLC assay > 10 mg/dL with abnormal FLC ratio.
Must have a confirmed diagnosis of WM as defined by the Second International Workshop, with a clinical indication for treatment.
Must have measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of ? 2 times the upper limit of each institution's normal value is required.
AST (SGOT) ? 3 × the ULN;
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol
substantially impaired gastrointestinal function
Feeding tube dependence
Adults >/= 18 years old
Diagnosis of CD20-positive FL:
Histology grades 1, 2 or 3a
Biopsy-confirmed histopathological diagnosis of FL. Biopsy specimen should be obtained ?2 years prior to randomization, unless medically contraindicated
CD20 immunophenotyping performed ?2 years prior to randomization
Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other I/E criteria are met
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Prior or concomitant urothelial tumors of the upper urinary tract or urethra
Bladder capacity of less than 200 ml
Untreated urinary-tract infection
Urethral strictures that would prevent endoscopic procedures and repeated catheterization
Upper urinary tract disease (eg, vesicoureteral reflux or urinary-tract stones) that would make multiple transurethral procedures a risk
Previous radiotherapy to the pelvis
Multiple lesions that don’t meet the criteria as satellite lesions
Extrahepatic metastases or malignant nodes beyond the periportal region; celiac, pancreaticoduodenal and para-aortic nodes > 2 cm are ineligible; note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
Maximum diameter exceeding 12 cm (maximum diameter does not include satellite lesion)
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Histological diagnosis of unresectable or metastatic colorectal cancer which is KRAS and NRAS mutation negative (wild type); patients with any known mutation in KRAS or NRAS codons 12, 13, 59, 61, 117, or 146 will be excluded; mutations of KRAS and NRAS codons not listed above are allowed; biopsy of metastatic lesion is not required
Any known mutation in KRAS or NRAS codons 12, 13, 59, 61,117, or 146
Bilirubin =< 1.5 x UNL
Arterial or venous thrombotic or embolic events
Adequate baseline organ function defined by the criteria below: total bilirubin =< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic] bilirubin in the absence of alanine aminotransferase [ALT] abnormality); ALT =< 2.5xULN; creatinine =< 2.5xULN
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
Must have included trastuzumab, pertuzumab, and trastuzumab emtansine. Subjects starting initial systemic therapy for HER2-positive breast cancer prior to June 2012 are not required to have had pertuzumab
CSF cytology positive for malignant cells or symptomatic leptomeningeal carcinomatosis in the Phase 1b portion. In Group 3, subjects are required to have CSF cytology positive for malignant cells
Has an active infectious process
Morphologically confirmed diagnosis of MDS/CMMoL according to FAB or WHO classification, including RAEB-t and MDS/MPN
Previously untreated with hypomethylating agents for MDS/CMMoL
Relapsed or refractory to hypomethylating agents
Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed
Carcinomatous meningitis
Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses
Prolymphocytic transformation
Inability or unwillingness to take supportive medications including a centrally acting appetite stimulant (e.g., mirtazapine or olanzapine) and a peripherally acting appetite stimulant (e.g., low dose glucocorticoids or megesterol acetate).
If a patient is randomized to the RFA arm, but is deemed not to be an anesthesia candidate, he/she will be placed in the non-randomized SBRT cohort
Participants must have cutaneous lesion(s) amenable to four total biopsies (either four lesions > 4 mm or one large lesion measuring 20 mm that can undergo serial biopsy) and at least five additional lesions measurable for assessment with no improvement over the four weeks prior to enrollment
Serologic documentation of HIV infection by any of the Food and Drug Administration (FDA)-approved tests; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior enzyme-linked immunosorbent assay (ELISA) and Western blot, or other approved diagnostic tests
A cluster of differentiation (CD)4+ lymphocyte count > 50/mcL will be required within 2 weeks of study participation
Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry; as study-specific (antiretroviral-based) strata fill, however, only participants who are receiving the therapies eligible for the remaining open strata will be accrued
The participant requires concomitant treatment with the following inhibitors of CYP3A4:\r\n* Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin\r\n* Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole\r\n* Antidepressants: nefazodone\r\n* Antidiuretic: conivaptan\r\n* Gastrointestinal (GI): cimetidine, aprepitant\r\n* Hepatitis C: boceprevir, telaprevir\r\n* Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids); use of any of anti-retrovirals (delavirdine) or protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir, nelfinavir) is permitted; specifically, ritonavir and cobicistat is permitted for participants considered for the CYP3A4-inhibitor based ART regimen arm (Stratum A) of the trial
Participants should not have significant abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren’s syndrome), congenital abnormality (e.g., Fuch’s dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
Prior exposure to ibrutinib
Isolated extramedullary relapse (i.e., testicular or CNS)
An mGPS of 1 or 2 as defined below:
modified Glasgow prognostic score (mGPS) of 1: CRP > 10 mg/L and albumin ? 35 g/L
mGPS of 2: C-reactive protein (CRP) > 10 mg/L and albumin < 35 g/L
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
mGPS of 1: C-reactive protein (CRP) > 10 mg/L and albumin ? 35 g/L
mGPS of 2: CRP > 10 mg/L and albumin < 35 g/L
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
Squamous or mixed histology (eg, adenosquamous) NSCLC
Prior anti-androgens are permitted but not required (2 week washout from anti-androgens)
Prior abiraterone and enzalutamide are permitted (2 week washout for both agents)
ECOG PS equals 2 or less.
Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation; the lesion must be at least 1 cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization =< 7 days)
Willing to sign a durable power of attorney
Prior exposure to ibrutinib
Assessment by the attending thoracic surgeon that radical pleurectomy can be safely achieved in pts with malignant pleural mesothelioma
Pts of all ethnic and gender groups will be included; protocol accrual will be reviewed annually to include a determination of minority and gender representation; if accrual demonstrates under-representation of any group with comparison to disease incidence in that group, then appropriate measures will be undertaken to attempt to increase participation of pts of that minority or gender group
Historical control data will be derived from patient medical records at the Ohio State University Medical Center (OSUMC)
Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin in conjunction with either:
The presence of a mass in the pancreas, OR
External biliary drain
Solid tumors that meet the following criteria: Measurable disease by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST) in at least 1 site. For Castrate Resistant Prostate Cancer (CRPC) measurable disease can also include Prostate Specific Antigen (PSA) level. Disease progression with the last line of therapy and at least one prior standard of care regimens, or tumor for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Mutation Status: Solid tumor types, other than prostate, must have a one of the following EZH2 inhibitor sensitizing mutations as determined via local testing: An activating mutation in EZH2 (Y641F/C/S/H/N, A677V/G, and/or A687V; Loss of a component of the SWI/SNF complex, including, but not limited to, ARID1A, SMARCB1 (aka SNF5/INI1/BAF47), SMARCA4 (aka BRG1), or PBRM1 (aka PB1) as determined by molecular testing (bi-allelic loss or mutation) or immunohistochemistry; Loss of BAP1 (ubiquitin carboxy-terminal hydrolase) as determined by molecular testing (bi-allelic loss or mutation) or immunohistochemistry
Based on the results of the mutation test, lymphoma subjects may be enrolled in one of four cohorts: GCB-DLBCL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. GCB-DLBCL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort. tFL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. tFL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort
Previously undergone metal stent insertion
Porphyria or hypersensitivity to porphyrins (constituents of porfimer sodium), gemcitabine, cisplatin or other platinum-containing compounds
Acute or chronic medical or psychological illnesses that prevent endoscopy procedures
Abnormal blood test results
Decompensated cirrhosis
Pregnant or intend to become pregnant, breastfeeding or intend to breast-feed during this study
KS patients with skin-only disease must have cutaneous lesions amenable to four 3 mm punch biopsies during the course of the study (either four separate lesions measuring >= 4 mm each OR two separate lesions measuring >= 8 mm each)
Chronic diarrhea (loose, watery or frequent stools) at baseline
Patient medication lists will be reviewed by a member of the study team for possible interactions with the nelfinavir; a patient may be deemed ineligible for the study if he/she is taking an essential medication that is known to interact with nelfinavir
Four or more American College of Rheumatology (ACR) criteria as revised by Hochberg for the classification of SLE or 4 or more of the Systemic Lupus International Collaborating Clinics (SLICC) criteria
Willing to sign a durable power of attorney
Total Symptom Score ? 13 on the MPN-SAF TSS 2.0, not including the inactivity question
Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Radiosensitizing doses of 5-fluorouracil;
1st progression of GBM on bevacizumab-containing regimen or within 8 weeks of discontinuing bevacizumab. In either case, must have received a minimum of 8 weeks (4 infusions) of bevacizumab.
1 week for non-cytotoxic agents (e.g., interferon, tamoxifen, & cis-retinoic acid)
Signed & dated ICF prior to Screening evaluations
Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
Previously or currently enrolled in Protocol No. TPI-287-17
Patients with symptomatic bradycardia (heart rate < 50 beats per minute [bpm], hypotension, light-headedness, syncope)
Subject has symptomatic or untreated central nervous system (CNS) metastases; any type of active seizure disorder; febrile neutropenia; ? Grade 2 peripheral neuropathy; peritoneal or pleural effusions requiring a tap more frequently than every 14 days; QT interval corrected (QTc) prolongation or a prior history of serious arrhythmias or significant abnormalities on screening ECG; previously experienced a severe reaction to a liposomal product or a taxane; received IV treatment for bacterial/fungal infection within 7 days of screening.
hyperleukocytosis (blast counts >30 000/mm3).
An intraoperative MRI upon resection will confirm the distance of the planned injection sites from the ventricular system prior to the HSV1716 injection; intra-operatively, the neurosurgeon may decide to not inject the HSV1716 or may revise the sites of HSV1716 injection if injection cannot be guaranteed >= 1 cm from the ventricular system; patient will removed from the study if there are not sufficient areas in the tumor cavity to guarantee injection of HSV1716 >= 1 cm from the ventricular system
Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days; growth factors include: GCSF (filgrastim), PEG-GCSF (Neulasta), GM-CSF (sargramostim) and erythropoietin
There is no available information regarding human fetal or teratogenic toxicities
Able to daily self-administer AMG 337 orally as a whole capsule
Subject has an average score of 6 or higher for average daily overall pain on the Numerical Rating Scale (NRS) based on the 7 day pain diary
Subject has attempted \best\ medical therapy and has tried and failed at least three documented medically supervised treatments (including, but not limited to physical therapy, acupuncture, etc.) and has failed medication treatment from at least two different classes
Subject agrees not to add or increase pain-related medication throughout the 12 week randomized evaluation phase of the study (starting at activation)
Subject has been implanted with a previous neuromodulation system (PNfS, SCS-PNfS or SCS) or participated in a trial for a neuromodulation system
Subject's overall Beck Depression Inventory II Score is > 24 or has a score of 3 on question 9 relating to suicidal thoughts or wishes at the baseline visit
Subject with an infusion pump or any implantable neurostimulator device
Subject has an existing medical condition that is likely to require repetitive MRI evaluation in the future (i.e. epilepsy, stroke, multiple sclerosis, acoustic neuroma, tumor)
Subject is immunocompromised
Gleason score on diagnostic biopsy specimens of >= 6
>= 3 positive cores within diagnostic biopsy specimens
Scheduled to undergo a prostatectomy at Johns Hopkins
Sexual Health Inventory for Men (SHIM) score >= 17
Known intolerance or allergy to medications used for sedation (midazolam), analgesia (fentanyl), and local and regional anesthesia (lidocaine, bupivacaine, and ropivacaine)
Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 5 hours [hrs] of total table time)
Patient not candidate for either regional anesthesia or mild sedation
Southwestern Oncology Group (SWOG) performance status 0 or 1
V20 =< 40% of total lung volume
Clear symptomatic deterioration supported by at least two of the following clinical criteria: ? 10% worsening in KPS or ? 1 worsening in ECOG; increasing weakness or fatigue; progressive weight loss; new/worsening pain requiring increased pain medication; new/worsening jaundice, nausea, or vomiting; new/worsening ascites or pleural effusions; other physical or laboratory findings consistent with disease progression.
KPS >/= 70
Bulky disease (any single mass >10 cm). ->Grade 2 nausea or vomiting, and/or signs of intestinal obstruction.
Absolute lymphocyte count (ALC) >= 0.5 X 10^9/L
Prior to randomization, have histological confirmation that CRC lesions were adenocarcinoma (subtypes of adenocarcinoma, e.g. mucinous adenocarcinoma are allowed). Subjects with CRC lesions of other histological types, including mixed type with predominant adenocarcinoma, will not be eligible to be randomized to study treatment.
Have pathology-proven complete removal of all primary and liver metastatic CRC lesions. Subjects with positive margins will not be eligible for the study.
Carcinoembryonic antigen (CEA)</=3 times the ULN
Have pheochromocytoma.
Prostate biopsy must be positive for cancer: clinically localized T1c or T2a, PSA =< 10, Gleason =< 6 at the time of initial diagnosis; as the intent of serial biopsy is to ensure that the disease has not progressed to the stage or grade of requiring treatment, the presence of a negative biopsy following an initial positive biopsy (coupled with clinically localized T1c or T2a PSA =< 10 and Gleason =< 6 for a patient who has had no treatment) will not render the patient ineligible; if the consecutive biopsy is either negative, or if positive and remains clinically localized T1c or T2a, PSA =< 10 and Gleason =< 6, the patient is eligible
Willing to refrain from drinking any kind of tea (including herbal tea) or using supplements containing green tea for the duration of the study
Subject must be willing to limit alcohol to moderate use which is defined as: up to one drink a day for women or two drinks a day for men; examples of one drink include:\r\n* Beer: 12 fluid ounces (355 milliliters)\r\n* Wine: 5 fluid ounces (148 milliliters)\r\n* Distilled spirits (80 proof): 1.5 fluid ounces (44 milliliters)
Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic oncologist
Serum magnesium =< 1.4 mEq/L
EUS clinically indicated for staging, and/or celiac neurolysis
Prior radioimmunotherapy within 3 years of enrollment
History of microangiopathic hemolysis, thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS)
Patients with laboratory findings consistent with grade equal to greater than 3 disseminated intravascular coagulation (DIC) or any grade 2 DIC that does not correct
Evidence of hepatic vein invasion or caval thrombosis
Contraindications to angiography or selective visceral catheterization
Histologically confirmed solid tumors, including primary brain tumors; in subjects with brain stem or optic gliomas the requirement for histological confirmation may be waived
Lymphopenia, cluster of differentiation 4 (CD4) lymphopenia, leukopenia, and anemia will not render patients ineligible
Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by IHC confirmed by local or central assessment.
Phase II: Documented evidence of c-Met amplification (GCN>5) (fusion transcripts or mutant c-Met may be eligible after discussion with Novartis) or PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by central assessment.
HbA1c > 8%.
6. Have completed baseline quality of life evaluation as assessed by LCSS modified for mesothelioma
Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.
Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).
Acceptable hematologic status (without growth factor support for neutropenia or transfusion dependency):
Normal 12-lead ECG (clinically insignificant abnormalities permitted)
Resting heart rate less than 60 bpm at time of screening
On chronotropic drugs (acetylcholine, digoxin, diltiazem, verapamil, atropine, dopamine, dobutamine, epinephrine, isoproterenol)
Meets the requirements for HD IL-2 therapy per Institutional guidelines
Meets the requirements for ipilimumab therapy per Institutional guidelines
Willing and able to give informed consent and participate in study procedures as described in the 12PLK02 and 10PLK13 protocols. Patients consented for 12PLK02 will also be asked to participate in the 10PLK13 PROCLAIM registry study.
Histology slides and pathology material must be available at the site for each patient before enrollment in order to be sent to the leading institution of the study for central pathology review and pharmacodynamic studies
Prior administration of brentuximab vedotin
Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded due to an inability to administer the antidote for methemoglobinemia, methylene blue; testing for G6PD is not required for study enrollment and optional
Acceptable hematological status:
Atelectasis of the entire lung
Exudative, bloody, or cytologically malignant effusions
Previous diagnosis of bipolar disorder
Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab is indicated as per ipilimumab/Yervoy® package insert (applicable for US sites) or product information (applicable for Australia site).
Tumor expression of NY-ESO-1 or LAGE-1 antigen by IHC or RT-PCR, or evidence of seropositivity to NY-ESO-1 or LAGE-1.
Any contraindications for ipilimumab/Yervoy® as per package insert(applicable for US sites) or product information (applicable for Australia site).
Prior exposure to NY-ESO-1 vaccine.
Lack of availability for immunological and clinical follow-up assessments.
Predominantly squamous, adenosquamous or unclear histologic type
Definition of localized, potentially resectable disease:\r\n* Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or magnetic resonance imaging (MRI) (for patients with an IV contrast allergy) using pancreatic protocol; endoscopic ultrasound is required for tissue acquisition and staging confirmation\r\n* No extension to superior mesenteric artery (SMA) and hepatic artery; patent superior mesenteric vein/portal vein (SMV/PV) with < 180-degree abutment and no evidence of invasion\r\n* Clear fat plane between the SMA and celiac axis\r\n* No extension to celiac axis and hepatic artery\r\n* Patent superior mesenteric vein and portal vein\r\n* No evidence of distant disease
Current analgesic therapies have failed (worst pain of 4 or above as measured by Brief Pain Inventory [BPI], despite analgesic therapy) OR the subject is experiencing intolerable side effects that preclude analgesic use (resulting in pain of 4 or above, as measured by BPI)
Anticipated treatment of the index tumor that would require iceball formation within 1.0 cm of the spinal cord, brain, other critical nerve structure, large abdominal vessel such as the aorta or inferior vena cava (IVC), bowel, or bladder
Evidence of Gilbert's Syndrome or homozygosity for the Uridine 5-diphospho-glucuronosyltransferase (UGT) 1A1*28 allele
Children not in the care or custody of a biological parent, adoptive parent, appointed legal guardian, or legally appointed foster care.
Presence of megakaryocyte proliferation and atypia, usually accompanied by either reticulin and/or collagen fibrosis, or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (ie. prefibrotic cellular-phase disease)
Demonstration of JAK2617V>F or other clonal marker (e.g. MPL515W>L/K), or in the absence of a clonal marker, no evidence of bone marrow fibrosis due to underlying inflammatory or other neoplastic disease Minor Criteria
Leukoerythroblastosis
increase in serum Lactase Dehydrogenase (LDH)
Anemia
Palpable splenomegaly
Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocyte [TIL] or lymphokine-activated killer [LAK] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other agents that target merkel cell carcinoma
Unable to generate antigen-specific MCPyV TAg-specific CD8+ T cells for infusions
First recurrence (based on radiological or histological evidence of recurrence)
MMSE score 25 or above
Deep brain stimulator
Vagus nerve stimulator
Programmable shunt
Skull defect without replacement
Second or subsequent recurrence
Actively participating in another therapeutic clinical trial
Radiological suspicion of pseudoprogression or radionecrosis
Any serious co-morbidity which is expected to affect survival more adversely than GBM
> 60 days after reduced intensity conditioning (RIC) allogeneic transplant for lymphoma
Mixed (5-95%) or complete (> 95%) chimerism
Post-transplant lymphoproliferative disorder
Karnofsky performance status >= 70 (Radiation Therapy Oncology Group [RTOG] recursive partitioning analysis [RPA] class I & II)
Minimum pre-treatment online neurocognitive function (tNCF) score >= 70
Must demonstrate basic tablet skills, defined as the ability to open and close an application on the desktop of the tablet, and to be able to advance the screen by swiping left or right (required for the use of tNCF testing)
Caregiver: Must be considered the patient's primary caregiver
Men and women from all ethnic and racial groups
Known poor metabolizers of CYP2C9 substrates
Known deficiency of dihydropyrimidine dehydrogenase (DPD)
Serum phosphorus, magnesium, calcium and potassium >= lower limit of normal (LLN)
Borderline resectable disease as defined by:\r\n* Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or magnetic resonance imaging (MRI) (for patients with an IV contrast allergy) using pancreatic protocol; endoscopic ultrasound is required for tissue acquisition and staging confirmation:\r\n** American Joint Committee on Cancer (AJCC) stage II\r\n** May have abutment of the superior mesenteric artery (SMA); abutment must be < 180\r\n** Abutment of the celiac axis\r\n** May have abutment or short segment encasement of the common hepatic artery (CHA) \r\n** May have short segment occlusion of the superior mesenteric vein (SMV)-portal vein (PV) confluence if reconstruction is possible\r\n** No evidence of distant disease
Endoscopic ultrasound (EUS) with fine needle aspirate (FNA) for cytology
CHEMORADIATION:
Patient must be sufficiently recovered from any adverse effect of induction chemotherapy as determined by treating investigator; the duration of this recovery period is anticipated to be 1-3 weeks
Patient must not be on full dose Coumadin
Biopsy proven plasmacytoma. Prior biopsy is acceptable.
Ability to understand the purpose and risks of the study.
Serum calcium (ionized or corrected for albumin) ? 2.0 mmol/L (8.0 mg/dL or 1.0 mmol/L ionized calcium) to ? 1.2 x ULN.
HgbA1c of ? 7%
BNP or NT-proBNP within normal limits
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
Willing to administer daily subcutaneous injections at home
Post-menopausal
Previously received rapamycin or rapamycin analogs, including ridaforolimus, temsirolimus, or everolimus
Absolute lymphocyte count (ALC) >= 200/?L
Infected at time of protocol entry, or receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole)
Inclusion Criteria:\n\n        Subjects shall be screened according to the following inclusion criteria. An answer of \no\\n        to any inclusion criterion disqualifies a subject from participating in this study.\n\n          -  Patients age: > 18 years\n\n          -  Subject has documented diagnosis of Barrett's esophagus, maximum endoscopic length of\n             no more than C2M5 (i.e. no more than 2cm of circumferential extent and no more than\n             5cm of tongues) containing HGD/EC as follows:\n\n          -  HGD or EC documented on biopsy within previous 6 months from enrollment\n\n          -  Histology slides reviewed at central pathology service for ERADICATE Trial confirm\n             HGD/EC.\n\n          -  Endoscopically visible lesion/area/pattern in a patient with HGD/EC either by high\n             definition white light endoscopy, narrow band imaging, confocal laser endomicroscopy,\n             or another enhanced imaging tool.\n\n          -  Ability to take oral proton pump inhibitor\n\n          -  For female subjects of childbearing potential, a negative urine pregnancy test within\n             2 weeks of enrollment and any subsequent endoscopy encounter\n\n          -  Subject is eligible for treatment and follow-up endoscopy and biopsy as required by\n             the investigational plan\n\n          -  Ability to discontinue aspirin/NSAIDs/Clopidogrel 7 days before and after all ablation\n             procedures\n\n          -  Ability of provide written, informed consent and understands the responsibilities of\n             trial participation NOTE: At the Kansas City Veterans Hospital, participants must be\n             eligible for care at the VA in order to be enrolled. Other sites listed are able to\n             enroll non-veterans.\n\n        Exclusion Criteria:\n\n        Subjects shall be screened according to the following exclusion criteria. An answer of\n        \yes\ to any exclusion criterion disqualifies a subject from participating in this study.\n\n          -  Extent of BE >C2M5\n\n          -  The subject is pregnant or planning a pregnancy during the study period (12 months\n             after treatment)\n\n          -  Esophageal stricture preventing passage of endoscope or catheter\n\n          -  Active erosive esophagitis\n\n          -  History of malignancy of the esophagus, esophageal varices or coagulopathy\n\n          -  Prior radiation therapy to the esophagus, except head and neck region radiation\n             therapy.\n\n          -  Any previous ablation therapy within the esophagus (photodynamic therapy, multipolar\n             electrocoagulation, argon plasma coagulation, laser treatment, or other)\n\n          -  Any previous EMR in the esophagus\n\n          -  Any previous esophageal surgery, including fundoplication\n\n          -  Evidence of esophageal varices during treatment endoscopy\n\n          -  Subject has a life-expectancy of less than two years due to an underlying medical\n             condition\n\n          -  Subject has a known history of unresolved drug or alcohol dependency that would limit\n             ability to comprehend or follow instructions related to informed consent,\n             post-treatment instructions, or follow-up guidelines\n\n          -  Subject has an implantable pacing device (examples: Implantable cardiac defibrillator,\n             neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in\n             this study by specialist responsible for the pacing device\n\n          -  The subject is currently enrolled in an investigational drug or device trial that\n             clinically interferes with the ERADICATE trial.\n\n          -  Subject suffers from psychiatric or other illness deemed by the investigator as an\n             inability to comply with protocol
Poor-risk (monosomy 5,7) or complex cytogenetics profile (3 or more cytogenetic abnormalities), or deletion of chromosome 5 (-5), or deletion of chromosome 7 (-7), or positive FLT3-ITD mutation
Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation Test)
KPS 60% or higher
Renal insufficiency or serum creatinine above the normal reference range
Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, cobimetinib, and vemurafenib, female participants who are breastfeeding must agree to discontinue nursing prior to Day 1 of the study.
Subjects are receiving ongoing treatment with AGS-003 in protocol AGS- 003-004 or AGS-003-006.
Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine
BMI ? 85th percentile or waist circumference ? 85th percentile for age and gender
Obesity from a genetic cause (e.g., Prader-Willi)
Known systolic or diastolic dysfunction or heart failure
Angioimmunoblastic TCL
PTCL-unspecified
Hepatosplenic TCL
Subcutaneous panniculitis TCL
Transformed mycosis fungoides (tMF)
Primary cutaneous gamma-delta TCL
Primary cutaneous CD8+ aggressive epidermic cytotoxic TCL
Documented completion of at least 6 cycles of CHOP-based therapy:
CHOP 21
CHOP 14
CHOP + etoposide
Patient has:
Precursor T/NK neoplasms
Mycosis fungoides, except tMF
Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis
Prior exposure to pralatrexate.
Patient has:
Patient must have a completed 3D plan and the attending physician must have reviewed and approved the dose volume histograms as follows: total lung volume percentage receiving at least 20 Gy (V20) =< 35%, and mean lung dose =< 20 Gy
Have had previous transplants and/or prior mobilization attempts
Have had prior radioimmunotherapy
Neutrophils ? 1.5x109/L
Total lymphocytes count ? 0.5x10E9/L
Platelets count ? 100x10E9/L
Cervical intra epithelial neoplasia
Total bilirubin: see guidelines for individual cohorts
Serum neutralization antibody assay shows >= 75% neutralization of the SS1 (dsFv) PE38 activity at 200 ng/ml
Known Abl-kinase T315I or T315A mutation
EXPANSION COHORT ONLY:
No patient may be entered onto the study without consultation with the principal investigator or his designee
Currently participating in any other interventional clinical study
Unresected tumour prior to chemo-radiotherapy (CRT)
Concomitant CRT completed prior to randomisation
TREATMENT: NCI Laboratory of Pathology confirmation of diagnosis of sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura must have been obtained
Patients with an active infection (i.e., clinical signs or symptoms, including, but not limited to: bleeding/pustulant skin infections; productive cough associated with fever) on antibiotics or with a fever >= 38.5° Celsius (C) within 3 days prior to registration (i.e. date when the patient signs the consent and/or the patient is registered in CORE)
Aspartate and alanine aminotransferase =< 2.5 x IULN, bilirubin =< 1.5x IULN
Other serious medical problem that in the view of the investigator makes therapy difficult to comply with or difficult to interpret toxicity
Other serious medical problem that in the view of the investigator makes therapy difficult to comply with or difficult to interpret toxicity
Is >18 years old;
Must be KRAS WT;
Has had previous exposure to Betafectin® or Imprime PGG;
INITIAL ENROLLMENT:
AKT INHIBITOR MK2206 ARM: Patients must have one of the following as determined by analysis of the primary tumor or a metastatic site in a CLIA certified laboratory:\r\n* Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) mutation or\r\n* PI3KCA gene amplification by fluorescent in situ hybridization (FISH) (gene to chromosome ration > 2) or\r\n* V-akt murine thymoma viral oncogene homolog 1 (AKT) mutation or\r\n* Phosphatase and tensin homolog (PTEN) mutation
AKT INHIBITOR MK2206 ARM: Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
LAPATINIB DITOSYLATE ARM: Patients must have one of the following as determined by analysis of the primary tumor or a metastatic site in a CLIA certified laboratory:\r\n* Human epidermal growth factor receptor 2 (ERBB2) mutation or\r\n* ERBB2 gene amplification by FISH (gene to chromosome ration > 2)
LAPATINIB DITOSYLATE ARM: Previous lapatinib (lapatinib ditosylate) therapy
LAPATINIB DITOSYLATE ARM: LVEF < 50%
SUNITINIB MALATE ARM: Patients must have one of the following as determined by analysis of the primary tumor or a metastatic site in a CLIA certified laboratory:\r\n* Platelet derived growth factor receptor alpha (PDGFR-A) mutation or\r\n* PDGFR-A gene amplification by FISH (gene to chromosome ratio > 2) or\r\n* V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation
SUNITINIB MALATE ARM: Previous sunitinib (sunitinib malate) therapy
Has given written consent prior to any trial-related activity is performed. (A trial-related activity is defined as any procedure that would not have been performed during the normal management of the patient).
Has completed the CS35 trial.
Has been withdrawn from the CS35 trial.
Has had end of trial visit in CS35 prior to approval of the CS35A protocol.
Documented progression on (a) at least one prior hormone treatment, which must have incorporated LH-RH agonist therapy AND (b) at least one chemotherapy regimen, which must have been taxane based; progression may be demonstrated by ) or radiologic criteria (defined by radiologic documentation of a new lesion or a >= 20% increase in the sum of the diameters of previously noted measurable lesions) or by PSA (defined by a 25% increase in the PSA from its most recent treatment nadir, confirmed with a second measurement at least 4 weeks later) only if accompanied by new or worsening symptoms (pain progression)
Willingness to discontinue LHRH analogue therapy and for the duration of the study
Patients who received treatment with strontium-89 or samarium-153 are excluded, except prior samarium will be allowed provided it was administered > 1 year ago and/or the patient has demonstrated the ability to\r\nreceive cytotoxic chemotherapy without excess myelosuppression after receiving samarium.
Prior exposure to anthracyclines or anthracenediones including doxorubicin, daunorubicin, and mitoxantrone
Patient must have at least 2 measurable lesions that are >= 1.5 cm in one dimension; one of the lesions, must meet additional criteria a or b depending on the treatment arm:\r\n* For Arm A patient must have at least one lesion that is >= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by Interventional Radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)\r\n* For Arm B patient must have one lesion that can be excised for in vitro vaccine preparation
Willing to sign a durable power of attorney
Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder
Participants must have biopsy-proven KS involving skin with or without visceral involvement
Participants must have cutaneous lesion(s) amenable to four (4) 5-mm tumor biopsies during the study (either 4 separate lesions measuring >= 5 mm each OR 2 separate lesions measuring >= 10 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month
Participants for whom front-line cytotoxic therapy is indicated (i.e. symptomatic visceral or pulmonary KS or symptomatic KS impairing functional status)
Participants with a QTcF (Fridericia correction formula) > 480 ms on 2 out of 3 electrocardiograms (EKGs) (if first EKG is < 480, no need to repeat, if first EKG is > 480 repeat twice for a total of 3 EKGs)
Participants with a recent history (< 6 months) of a major bleed which will be defined as a symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level 2 grams/dL or more, or leading to transfusion of two or more units of whole blood or packed red cells
Subjects enrolled in Part B must have at least 1 lesion that may qualify as a target lesion
Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and neuropathy
For BCG-unresponsive and BCG-relapsing NMIBC, participants must have received an adequate course of BCG
Concurrent febrile illness, urinary tract infection, or gross hematuria
Expression of mesothelin must be confirmed by meeting 1 of the following criteria:\r\n* Mesothelin expression (> 10% of the tumor expressing mesothelin) by immunohistochemistry (IHC) \r\n* Elevated serum SMRP levels (> 0.4 nM/L)
Patients scheduled for elective thoracic surgery (segmentectomy, lobectomy or bi-lobectomy, pneumonectomy or esophagectomy) and meeting one of the four following risk criteria:\r\n* Female and B-type natriuretic peptide (BNP) >= 25 pg/ml (no age limit) \r\n* Male gender < 75 and BNP >= 25 pg/ml\r\n* Male- age >= 75 (No BNP limit)\r\n* History of prior AF
Adequate coagulation status
Sufficient physiological reserves
Prior allogeneic HSCT
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Platelets >= 100,000/mm^3 (unsupported, defined as no platelet transfusion within 7 days, and recovery from post-transfusion nadir)
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Potassium >= lower limit of normal (LLN)
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Serum total calcium (correct for serum albumin) or ionized calcium >= LLN
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Female patient is breastfeeding
NON-PROGRESSED DIPG (STRATUM 2): Platelets >= 100,000/ mm^3 (unsupported, defined as no platelet transfusion within 7 days, and recovery from post-transfusion nadir)
NON-PROGRESSED DIPG (STRATUM 2): Potassium >= LLN
NON-PROGRESSED DIPG (STRATUM 2): Serum total calcium (correct for serum albumin) or ionized calcium >= LLN
NON-PROGRESSED DIPG (STRATUM 2): Female patient is breastfeeding
Deemed surgically resectable by a thoracic surgeon
For oropharynx or nasopharynx primary lesions, documentation of viral status is required (e.g. high risk human papilloma virus [HPV] sub-type polymerase chain reaction [PCR], p16 IHC, HPV in situ hybridization [ISH], Epstein-Barr virus-encoded small ribonucleic acid [EBER], etc); tests done on primary tumor specimens from date of initial diagnosis at outside institutions are sufficient to meet this criterion
Subjects with initial magnesium < 0.5 mmol/liter (1.2 mg/deciliter) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation
Insurance approval for SBRT should be obtained prior to randomization
Children are excluded from this study
Have on CT imaging done within 28 days of Day 1 findings consistent with advanced ccRCC, including at least one extra-renal measurable target lesion meeting the criteria of RECIST version 1.1.
Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on computed tomography (CT) as having tumor abutment of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement
Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to =< 5 mm
Known CD20-negative status at relapse or progression
Patient may receive bisphosphonates/denosumab for the palliation of bone metastases
Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
Metastatic or locally recurrent EBV-positive, non-keratinizing and/ or undifferentiated NPC* who do not have curative options such as chemo-radiation or surgery *Subjects will be enrolled based on confirmed histology diagnosis of the NPC
Normal corrected calcium levels
Prior chemo-radiotherapy with curative intent
Treated with ado-trastuzumab emtansine (T-DM1) Part 2b:
Treated with trastuzumab Part 2c:
Patients tumors must have known PI3K pathway activation defined as EITHER of the following on a Clinical Laboratory Improvement Amendments (CLIA)-approved molecular diagnostics test:\r\n* Genomic alteration resulting in loss of phosphatase and tensin homolog (PTEN) function including a whole or partial gene deletion, frame shift mutations, or non-sense mutations; missense mutations in PTEN will not be considered qualifying\r\n* A previously characterized activating mutation in any component of the pathway including: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2), mTOR
Patients previously treated with an mTOR, AKT, or PI3K inhibitor (including but not limited to GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101, everolimus, temsirolimus, and ridaforolimus); for agents not listed, the study principal investigator (PI) or Co-PI will make a determination
Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib
FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent
Treatment with proton pump inhibitors within 3 days prior to study entry; if treatment with an histamine (H2)-receptor antagonist such as ranitidine is required, erlotinib must be taken 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of the H2-receptor antagonist; although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the erlotinib dose should be separated by several hours, if an antacid is necessary
Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren’s syndrome), congenital abnormality (e.g., Fuch’s dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
Simultaneous participation in other therapeutic clinical trials will not be allowed
If a subject is receiving allopurinol/cimetidine/antivirals they must be discontinued prior to starting this protocol
Lesions that have had radiotherapy must show subsequent radiographic evidence of increased size to be deemed a target lesion.
For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.
Subjects must have at least 1 lesion that is measureable using RECIST guidelines
Prior treatment with tumor necrosis factor receptor superfamily agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, anti PDL-1 and anti PDL-1.
Platelets >= 100,000/microliters
Must have undergone first-line treatment with a high-dose methotrexate-based chemotherapy regimen with or without brain radiotherapy; high-dose methotrexate is defined as >= 3 grams/m^2; methotrexate dose reduction for creatinine clearance < 100 ml/min is permitted
Serum phosphorus >= lower limit of normal (LLN) (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
Serum calcium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
Serum magnesium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
Serum potassium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
Hemoglobin A1C (HBA1C) < 7.0%
Expression of mesothelin must be confirmed by meeting one of the following criteria\r\n* Mesothelin expression (> 10% of the tumor expressing mesothelin) by immunohistochemical (IHC) analysis\r\n* Elevated serum SMRP levels (> 0.4 nM/L)
Any major thoracic (thoracotomy with lung or esophageal resection) or abdominal (laparotomy with organ resection) operation must have occurred at least 28 days before study enrollment; patients who have undergone diagnostic video assisted thoracoscopy (VATS) or laparoscopy can be included in the study
Breast cancer metastatic to the pleura that extends outside of the pleura requiring immediate therapy
Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter.
Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL guidelines). In addition: a. Presence of at least one clinically measurable lesion: i. nodal lesion that measures ? 1.5 cm in longest dimension (LD) and ? 1.0 cm in longest perpendicular dimension (LPD), or ii. spleen that measures ? 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement, or iii. liver that measures ? 20 cm in LVD with a minimum of 2 cm enlargement, or iv. peripheral blood B lymphocyte count > 5000/uL.
has 17p- and/or TP53 mutation; or
No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
Complete abstinence is only acceptable in cases where this is the preferred and usual lifestyle of the subject.
Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable.
Males (including those who have had a vasectomy) must practice complete abstinence or use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in the PPRMP.
All subjects must:
Agree not to share IP with another person.
Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn.
Be counseled about pregnancy precautions and risks of fetal exposure. ARM B ONLY:
Subject must be either resistant to or intolerant of (ie., treatment failures) the last BCR PI and/or venetoclax. Resistant is defined as relapsed or refractory per
Complete left bundle branch, or bifasicular, block.
Troponin-T value >0.4 ng/mL or BNP >300 pg/mL. Subjects with baseline troponin-T >ULN or BNP >100 pg/mL are eligible but must have cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy.
Known acute or chronic pancreatitis 17. Pregnant or lactating females Arm B only (CC-122 in combination with ibrutinib):
Part 2d: Patients with non GIST solid tumors with KIT mutations, who are TKI naïve or have been previously treated with KIT directed TKI therapy who are appropriate for KIT directed TKI therapy
Known or demonstrated wild type KIT or PDGF-R, or known or demonstrated mutations of PDGF R, SDH, or NF 1 that are causative for the observed malignancy.
All subjects or legally appointed representatives/caregivers, must personally sign and date the IRB/IEC approved consent form before initiating any study specific procedures or activities.
Neutrophils >= 1.5 x 10^9/L
Corrected calcium =< institutional ULN (corrected calcium = (4- Albumin) x 0.8 + calcium)
Evidence of nephrectomy
Unwillingness to stop calcium supplementation (during the first cycle of treatment) or vitamin D supplementation throughout the study
Thiazide (e.g HCTZ, Hydrochoirthiazide) or digoxin therapy (e.g Lanoxicaps, Lanoxin)
Total serum calcium (corrected for serum albumin) or ionized calcium >= LLN
Serum magnesium >= LLN
Serum phosphorus >= LLN
Right bundle branch block + left anterior hemiblock (bifascicular block)
NHL SUBJECTS:
ALL SUBJECTS:
Evidence of aggressive or highly aggressive lymphoma or Richter’s transformation based on WHO/REAL classification criteria(1)
NOTE: If both serum and urine m-components are present, both must be followed in order to evaluate response.
Able to take required prophylactic anticoagulation.
Prior total body irradiation (TBI) making TMI not feasible
Diagnosed with relapsed or refractory NHL limited to subtypes listed below; the subject must have histologic confirmation of diagnosis according to review at the Cleveland Clinic Foundation, either at initial diagnosis or at any subsequent relapse; (biopsy is not required at relapse, but is suggested; biopsy at outside institution, reviewed at the Cleveland Clinic, is acceptable)
Men of all ethnic groups are eligible for this trial; efforts will be made to include minority groups and all representative ethnicities and races in the community serviced by Roswell Park Cancer Institute (RPCI)
Unwillingness to stop calcium supplementation
Presence of carcinomatous meningitis.
Hematocrit >= 30%, may be reached by transfusion
Histologic sections for all patients must be submitted for pathology review; failure to submit pathology materials will render the patient non-evaluable for response but evaluable for toxicities
Subjects with radiographic signs of excessive intra-cranial mass effect with associated rapid neurologic deterioration, and/or spinal block, are unsafe to undergo blood-brain barrier disruption (BBBD) chemotherapy and are not eligible
Non-epithelial ovarian carcinomas or ovarian tumors with low malignant potential (i.e., borderline tumors)
Moderate to severe cGVHD as assessed by NIH cGVHD Diagnosis and Staging Criteria (NCDSC) with at least three organ systems involved OR one organ system with a score of 2 OR lung organ score = 1
Have either a normal ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor
B cell depleting biologic agents
Phototherapy-unless administered for acute GVHD
Adults (aged ? 18 years)
Serum cardiac troponin (cTn) level ? 99% percentile of the upper reference limit
Patient must have a palpable femoral/radial pulse in the affected extremity
Patient must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to United States (US) Health Insurance Portability and Accountability Act (HIPAA) regulations
Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
Lytic lesion requiring an impending orthopedic intervention
Fasting ?-CTX of >1000 pg/mL
Diagnosis of PMF or Post PV/ET-MF
Transfusion dependent at baseline, defined as ? 4 U red blood cell (RBC) transfusion in the 8 weeks prior to first dose of MMB
Lactating females must agree to discontinue nursing before MMB administration
Prior splenectomy
Unwilling to consent to genomics sampling
Patient was diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The subject may have Grade C or D aGVHD involving the skin, liver, and/or gastrointestinal (GI) tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.
Patients who have had persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/day in the absence of nausea or vomiting may be deemed as having Grade B GVHD if other causes of diarrhea have been ruled out (e.g., C. difficile or cytomegalovirus (CMV) infection, oral magnesium administration) and if the low stool volume reflects the effects of fasting or administration of narcotics or antidiarrheal medications.
Patient has Grade B aGvHD with skin-only involvement.
Patient shows evidence of diffuse alveolar hemorrhage or other active pulmonary disease, which is likely to require more than 2L of oxygen via face mask or an estimated FiO(2) of 28% via other delivery methods in order to sustain an O(2) saturation of 92%.
Patient shows evidence of encephalopathy as defined by a change in mental status since the onset of aGVHD.
Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed).
Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after doing.
Glasgow Coma Score (GCS) of less than 15.
Asplenia.
Antibiotic allergies that would preclude treatment for a C. novyi-NT infection.
Patient is postmenopausal.
Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
Men and members of all ethnic groups are eligible for this trial
Melanoma of uveal origin
Confirmed diagnosis of systemic AL amyloidosis
NT-proBNP ?650
Non-AL amyloidosis
NT-proBNP >5000
Clinical diagnosis of acquired TTP (initial or recurrent), which includes thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g., schistocytes).
Others as defined in the protocol
Known other causes of thrombocytopenia
Congenital TTP (known at the time of study entry).
Others as defined in the protocol
Symptomatic pericarditis.
Patient who does not apply highly effective contraception during the study from screening until 90 days after discontinuing study treatment Protocol No. PQR309-003 Protocol Amendment 3, 23 September 2015 PIQUR Therapeutics AG - Confidential Page 16 of 108 (see section 11.3).
Patients have any of the following mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ? 12 the PHQ-9 or a cut-off of ? 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) see Appendix 4.
Premenopausal or postmenopausal women
Prisoners
Documentation of mucin 16 (MUC16) expression by either serum carcinoma antigen 125 (CA125) >=2 x Upper limit of normal (ULN) or by immunohistochemistry [IHC] by central review
Part B1: Gastric or Gastroesophageal Junction (GEJ) adenocarcinoma
UGT1A1 genotype of TA 7 in both alleles (homozygous UGT1A1*28) or TA 8 in either one or both alleles (hetero- or homozygous for UGT1A1*37)
Chronic or acute GI disorders resulting in diarrhea
Serum phosphorus > 2.5; electrolyte repletion is allowed to reach these values
Serum calcium > 8.4; electrolyte repletion is allowed to reach these values
Serum magnesium > 1.3; electrolyte repletion is allowed to reach these values
Serum potassium > 3.3; electrolyte repletion is allowed to reach these values
Subjects with osteonecrosis of the jaw
Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug
Histological diagnosis of GIST.
Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country
Signed informed screening consent form with Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information\r\n* Research personnel will review medical records of subjects consenting to screening to ensure no obvious factors would exclude them from the treatment portion of the study (e.g., history of cirrhosis of the liver) and to confirm diagnosis and staging
Active or chronic corneal disorder, including but not limited to the following:\r\n* Sjogren’s syndrome\r\n* Fuchs corneal dystrophy (requiring treatment)\r\n* History of corneal transplantation\r\n* Active herpetic keratitis\r\n* Active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
Required used of folate-containing supplements (e.g. for folate deficiency)
TURBT successfully completed
Verification received from Argos Therapeutics that ribonucleic acid (RNA) successfully collected from TURBT procedure
Be a candidate for radical cystectomy
Participants with leptomeningeal disease; metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeters (mm) of the optic apparatus (optic nerves and chiasm)
AML relapsed or refractory to at least one attempt at induction or subjects not candidates for aggressive induction regimens
Leukocyte count <3000/µL,
Lymphocyte count <1000/µL,
Non-healed wound;
Previous whole brain radiotherapy (WBRT)
Part B
Hematological and biochemical indices within acceptable ranges shown at screening.
For Part B only:
Subjects with uterine carcinosarcoma
Primary lesions may be acceptable for enrollment
Basal cell carcinomas of aggressive subtypes (infiltrative, morpheaform, micronodular)
Subjects with known photosensitivity diseases
Acceptable blood test results.
Part B: Have alterations of FGFR3.
Have preexisting Grade ?2 skin disorder (for example, erythema, dermatitis).
Patients who have previously received CDX-011 (CR011-vc monomethyl auristatin E [MMAE]; CDX-011) or other MMAE-containing agents
Lactating females are not eligible unless they have agreed not to breastfeed their infants
LVEF
Have postmenopausal status.
Neoadjuvant endocrine monotherapy is deemed to be a suitable therapy.
Patients must have histologically or cytologically confirmed metastatic or locally recurrent uveal melanoma; because histologic or cytologic confirmation of primary uveal melanoma is not always possible, confirmation of the clinical diagnosis of uveal melanoma by the treating investigator is allowed; clinical diagnosis of uveal melanoma is often made by an ophthalmologist, not by tissue diagnosis; if an ophthalmologist diagnosed and treated a patient for uveal melanoma in the past, it is sufficient for a clinical diagnosis
Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin (e.g. Auristatin PHE, Auristatin PE, and symplostatin)
Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym-C infusion
Available Viralym-C T cell line
RR-AML
Relapsed/refractory MDS
Known clinically important respiratory impairment
Pathologic evidence of malignant transformation
Subjects must have HER2-positive tumors and written clinical pathology report documentation of HER2 status available for Sponsor's Medical Monitor review.
Assessment of HER2 status in subjects with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (Wolff et al, 2013) as practicable.
Assessment of HER2 status in subjects with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Rüschoff et al (2012) as practicable.
Assessment of HER2 status in subjects with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
All subjects with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using an assay kit/methodology specifically FDA-approved for their cancer type as practicable.
Subjects for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without a written report of ISH determined HER2 copy number, provided the investigative site confirms that archival tissue is available.
Serum magnesium, calcium, and phosphorus must be within normal reference ranges as per local tests. [If initial screening results are outside of normal reference range, the Investigator may initiate appropriate measures to correct. However administration of FS102 may not proceed until the specified electrolytes have normalized.]
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing as described in this section.
13.9 mmol/L]).
Receipt of trastuzumab, pertuzumab, or ado-trastuzumab emtansine within 4 weeks of scheduled dosing day 1.
History of absolute decrease in LVEF of ? 16 absolute percentage points, or ? 10 absolute percentage points and crossing from > LLN to < LLN on prior anti-HER2 therapy, even if asymptomatic and the LVEF decrease recovered;
Hypersensitivity/infusion reaction to monoclonal antibodies, other therapeutic proteins, or allergy to any component/excipient of FS102 finished drug product (arginine, glycine, phosphoric acid, or polysorbate 80) and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as anti-histamines, 5-HT3 antagonists, or corticosteroids.
Female participants
Postmenopausal status
At least 2 sites of measurable disease per Cheson criteria (must measure at least 1.5 cm in any diameter or 1.0 cm in the shortest diameter if one of the diameters is not ? 1.5 cm), one of which must be palpable and easily accessible in a low-risk site (eg, inguinal, axillary, cervical, subcutaneous) for intratumoral injection (denoted as \Lesion A\ in Treatment Cycle 1) and at least one additional untreated lesion that is located outside the radiation field of the treated lesion (Lesion A) and is accessible for an FNA aspirate.
Is taking systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication
Current bowel obstruction
Patients must have resectable pancreatic cancer OR must be deemed borderline resectable; potentially resectable is defined as a) no extrapancreatic disease, b) no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery (SMA),and c) no evidence (CT or MRI) of occlusion of the superior mesenteric vein (SMV) or superior mesentericportal vein (SMPV) confluence; borderline resectable is defined by the National Comprehensive Cancer Network (NCCN) as tumors with venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall; tumors involving retroperitoneal structures that can be surgically removed (ie. kidney), will also be included
AST and ALT < 10 x ULN AND decreasing at two timepoints if patient is status/post (s/p) biliary stenting
Subjects with negative nodal status (N0)
Hepatic dysfunction defined as MELD Score > 12.
During time of study period, subjects must agree not to take any new vitamin supplementation or herbal remedy
Able to begin extension study within 8 weeks of receiving 6th cycle of DI-Leu16-IL2
Previously collected autologous stem cell product met the minimum collection target and minimum infusion target
Has autoimmune cytopenia (anemia, thrombocytopenia, leukopenia).
Has sensory or motor neuropathy limiting daily activities.
To the best of his or her (or parent/guardian) knowledge, willing and able to participate in all required study activities for the duration of the study.
Patients with a history of excessive alcohol intake which is defined in accordance with Centers for Disease Control and Prevention (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men
Peripheral blood blast count must be ? 30,000 cells/µL.
Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
Lytic lesion requiring an impending orthopedic intervention
Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitazone)
Fasting ?-CTX of >1000 pg/mL
? 18 years old
Complex/combined procedures (coronary artery bypass graft [CABG] plus valve), double/triple valve repair/replacements, ascending aorta/aortic arch surgeries (without baseline AT level restriction or preoperative heparin requirement). OR
Infective endocarditis.
Liver dysfunction: aspartate transaminase, alanine aminotransferase increase ?2-fold above the upper-limit of local lab normal ranges.
FL with evidence of large cell transformation
There are no known contra-indications to any of the planned agents used in this protocol; etoposide may be substituted by etoposide phosphate (Etopophos) if the patient has a history of hypersensitivity reaction to etoposide
ALK-rearrangement confirmed by FDA approved test
Endogenous erythropoietin levels < 500 units/L
Wash-out period:
Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled before the patient enters the trial (glycosylated hemoglobin [Hba1c] < 7.5)
Primary Ocular Melanoma
Haematological parameters:
Platelet count ? 10.0x10(to the 4th power)/?l (? 5.0 x 10(to 4th power)/?l after stem cell transplant)
Biochemical Parameters:
Platelet count ? 10.0 x 1(to the 4th power)/?l (? 5.0 x 10(to the 4th power)/?l after stem cell transplant)
Patient with an extensively disseminated primary glioblastoma.
Patient has an extensively disseminated primary glioblastoma.
Written patient assent (as appropriate).
Scheduled to receive 2 or more cycles* of emetogenic chemotherapy requiring 5-HT3 antagonist treatment.
Clinical or laboratory signs and symptoms of significant cerebral, cardiovascular, respiratory, renal, hepatobiliary, pancreatic or infectious disease, which in the Investigator's judgment may interfere with the study assessment or completion of the study.
Hematocrit >= 27.0%
have not been treated with weekly paclitaxel after first-line treatment in which weekly paclitaxel plus a platinum is permitted
Treated with local radiotherapy
Have identified a back-up cells source in case of engraftment failure; the source can be autologous, related or unrelated
Patients with uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent
Inclusion:\n\n          1. Received prior treatment with NKTR-102\n\n          2. Free of disease progression since receiving NKTR-102\n\n          3. Adequate bone marrow and organ function\n\n          4. Treatment with NKTR-102 in the extension study to begin within 8 weeks after receipt\n             of their of last dose of NKTR-102\n\n          5. Agree to use adequate contraception\n\n        Exclusion:\n\n          1. Treatment with other anti-cancer therapy between the last dose of NKTR-102 in the\n             prior study and before first dose of NKTR-102 in the extension study\n\n          2. A toxicity that requires a 3rd dose reduction after taking NKTR-102 or are scheduled\n             to receive a dose < 70 mg/m2 upon entry into this study\n\n          3. Pregnancy or lactation
Right bundle branch block + left anterior hemiblock (bifascicular block).
Documented hypercoagulable disorders or vasculopathies
Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
Untreated SCCHN of oral cavity/soft palate, categories T1N1-2M0,T2N1-2M0,T3N0-2M0,T4N0-2M0 (T4 allowed only if invasion of mandible is negligible) scheduled for SOC
no immunosuppressives with 1 year
KPS>70
Subjects to be treated with other than SOC
Tumor classifications T1N0, T2N0, T4N3, any TN classification with M1
Active peptic ulcer
Subjects on hemodialysis or peritoneal dialysis
Concomitant diseases/conditions
HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH HER2 gene copies to chromosome 17 signal ratio of ?2.0]
Completion of screening assessments (Refer to protocol for further details)
Postmenopausal status.
Inclusion Criteria:\n\n        Entry criteria include the following:\n\n          1. Clinical diagnosis of VOD, made by Baltimore Criteria, Modified Seattle Criteria, or\n             biopsy proven:\n\n             1.1 Baltimore Criteria- Bilirubin ?2 mg/dL and at least 2 of the following clinical\n             findings:\n\n               -  Ascites (radiographic or physical exam)\n\n               -  Weight gain of ?5% compared to the day of conditioning-- if this value is not\n                  available, the weight on the date of admission to the SCT unit may be used)\n\n               -  Hepatomegaly; increased over baseline.\n\n             1.2 Modified Seattle Criteria: At least two of the following\n\n               -  Bilirubin ?2 mg/dL\n\n               -  Ascites (radiographic or physical exam) and/or weight gain ?5% above baseline\n                  weight (defined as weight on the first day of conditioning- if this value is not\n                  available, the weight on the date of admission to the SCT unit may be used)\n\n               -  hepatomegaly increased over baseline\n\n             1.3 Patients that do not meet the Baltimore Criteria or Modified Seattle Criteria and\n             have biopsy proven VOD are eligible.\n\n          2. Patient must also provide written informed consent.\n\n        Exclusion Criteria:\n\n          -  Use of any medication which increases the risk of hemorrhage is disallowed. Use of\n             heparin or other anticoagulants is disallowed within 12 hours unless being used for\n             routine central venous line management, fibrinolytic instillation for central venous\n             line occlusion, intermittent dialysis or ultrafiltration of CVVH.\n\n          -  Clinically significant uncontrolled acute bleeding, defined as hemorrhage requiring >\n             15 cc/kg of packed red blood cells (e.g., a pediatric patient weighing 20 kg and\n             requiring > 300cc of packed red blood cells/24 hours, or an adult patient weighing 70\n             kg and requiring >3 units of packed red blood cells/24 hours) to replace blood loss,\n             OR bleeding from a site which in the Investigator's opinion constitutes a potential\n             life-threatening source (e.g. pulmonary hemorrhage or CNS bleeding), irrespective of\n             amount of blood loss, at any point from the date of SCT through the date of severe VOD\n             diagnosis.\n\n          -  Hemodynamic instability as defined by a requirement for multiple pressors, or\n             inability to maintain mean arterial pressure (for children: to maintain mean arterial\n             pressure within 1 standard deviation of age-adjusted levels) with single pressor\n             support.\n\n          -  Woman who are pregnant.
Presence of non-target lesions that have not previously been irradiated or biopsied; to allow for collection of needle-biopsies at Screening and after completion of Kevetrin treatment
Electrocardiogram (ECG) obtained at Screening which shows QTc prolongation or other medically relevant abnormalities which may affect subject safety or interpretation of study results
Previous participation in a clinical study of Kevetrin
Malignancies other than UC within 5 years prior to Cycle 1, Day 1
All races and ethnic groups are eligible for this study
Prisoner
All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
Neutrophils ? 1500/µL
Patient Re-enrollment: This study permits the re-enrollment of a patient that has discontinued the study as a screen failure (ie, patient has not been dosed/has not been treated). If re-enrolled, the patient must be re-consented.
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.
Treatment directed against the melanoma (eg, chemotherapy, targeted agents, biotherapy, limb perfusion) that is administered after a prior complete resection other than adjuvant radiation after neurosurgical resection and IFN for resected melanoma.
ANC < 1,500/µL
Participants medicated with anti-depressants reported to have lysine-specific histone demethylase 1A (KDM1A)/lysine (K)-specific demethylase 1A (LSD1) inhibitory activity (such as tranylcypromine or phenelzine) within 28 days of treatment start
Participants with evidence of electrolyte imbalance
Clinical diagnosis of primary uveal melanoma involving the posterior uveal tract in the study eye
Planned enucleation or brachytherapy of the study eye due to uveal melanoma
Uveal melanoma in the study eye originating in the anterior uveal tract (iris)
Hereditary or chronic hemorrhagic or coagulopathy conditions (i.e., hemophilia)
Failure to enroll and comply with Alliance A031201
Prior progression on one or more androgen-receptor/androgen-synthesis inhibitor therapies (e.g. abiraterone, enzalutamide, apalutamide, TAK-700 and/or galeterone) by Prostate Cancer Working Group 2 (PCWG2) criteria. Prior progression on bicalutamide/nilutamide/flutamide/ketoconazole alone is not allowed.
American Society of Anesthesiologists (ASA) score </= 3;
Ejection fraction equal or > 50% before admission for transplant as per institutional standards; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months or arrhythmia) need to be cleared by cardiology as per Emory bone marrow transplant (BMT) standards
Intention or plans for cyclophosphamide mobilization
Enrollment on any other transplant related protocols
Diagnosis of recurrent or metastatic SCCHN on any site except lip, thyroid, salivary gland, or nasopharynx
Tumors with at least one of the following known mutations in the PI-3K signaling pathway, via assays performed in a Clinical Laboratory Improvement Act (CLIA)-approved setting (Foundation Medicine FoundationOne test will be used; this assay uses a cut-off of 5% allele fraction for mutations; allele fraction will be requested on each sample):\r\n* PIK3CA,\r\n* PIK3CG, \r\n* PIK3R1, PIK3R5 and PIK3AP1 (regulatory subunits), \r\n* AKT and mTOR, or\r\n* PTEN \r\n** Note: PIK3CA amplification is not eligible
Blood pressure greater than 170/90 or two standard deviations from normal based on age and weight nomogram on three separate measurements
Greater than 20% aberrant intraepithelial lymphocytes (IEL) as assessed by flow cytometry
Immune suppression
Other agents used strictly with palliative intent might be allowed during this period after discussing with principal investigator
Patients can have previous brain metastasis that was completely surgically resected if the previously resected lesion is at least 1 cm from target lesion(s) for this study; the location of the previous resection cavity is determined by the post-resection MRI
Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least 1 cm from the target lesion(s) for this study; the location of the previous SRS treatment location is determined by the SRS MRI
Neutrophils >= 1,500
No history of lumbar surgery or other pre-existing spinal conditions that would preclude frequent, safe, reliable lumbar punctures
Tumors with HER2 activating or other mutations including G309A, D769H, D769Y, V777L, P780ins, V842I, R896C, HER2 in-frame deletion 755–759, L755S, G309A, S310F, S310Y, V659E, R678Q, L755S, L755P, E757A, D769H, D769Y, A775_G776insYVMA, G776V, G776C, G776 insertions, V777L, G778_S779insCPG, P780_781insGSP, L841V, V842I, L869R, R896C, and any others identified where there is reported activity with neratinib
Potassium within normal range, or correctable with supplements;
Serum calcium and magnesium within the normal range (or corrected with supplements)
Resting bradycardia < 55 beats/min
Doxorubicin or liposomal doxorubicin >350 mg/m².
B) Dose Expansion Cohorts:
Acceptable coagulation status
Known past or current coagulation defects.
No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium.
Prior therapy with a conjugated or unconjugated auristatin derivative.
Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B
CBC (except platelets and hemoglobin), serum chemistry, liver panel, and CPK values ? Grade 1 abnormality as defined in CTCAE v 4.03 dated June 14, 2010
No desire or plans to father new children during the study and/or have a prior vasectomy
Documentation by magnetic resonance (MR) of a gadolinium-enhancing intraparenchymal mass consistent with malignant glioma
Contraindication to placement of endorectal MRI coil, biopsy device or ultrasound probe (e.g., severe hemorrhoids, anal fissure, recent rectal surgery, or prior abdominoperineal resection)
Member of vulnerable population including prisoners or mentally disabled patients, in accordance with U.S. Department of Health and Human Services (DHHS) definitions
Positive NY-ESO-1 expression by reverse transcription (RT)-polymerase chain reaction (PCR) and/or immunohistochemistry (IHC) will be required for entry, as determined by analysis at the trial central laboratory
Generalized dermatologic conditions (such as allergic reactions, infection, edema, or scarring) that will not allow for study drug administration at a site of normal skin or evaluation of localized adverse events
Previous administration of vaccine therapy targeting NY-ESO-1
Volume difference of at least 300 mL between the normal and lymphedematous limb based on perometry evaluation
Palbociclib can be started at week 4, if indicated
Transaminases =< 2 x ULN
Neutrophils >= 1250
Histologically documented diagnosis of myelofibrosis (MF) (idiopathic or post polycythemia vera [PV]/essential thrombocythemia [ET])
Clinical evidence of cirrhosis
Lung lesion size is greater than 1 cm
Patient is cleared to undergo paralytic anesthesia
Female subject must either:
Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile
be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs).
Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the subject.
Haemoglobin 9.0 g/dL
Evidence of QT prolongation and/or torsades de pointes (TdP) on electrocardiogram (EKG)
HBsAG positive
Female subject must be either:
post-menopausal (defined as at least 1 year without any menses) prior to Screening,
or, documented surgically sterile or status post hysterectomy
Subject has a known elevation in serum lactate at screening ? 2x institutional ULN
Subject has difficulty swallowing large pills.
Potassium <3.5 mmol/L.
Concomitant vaccination with yellow fever vaccine.
Pain with a focus at the involved vertebral body that is not adequately controlled by medical management
Osteolysis of a vertebral body(ies) with or without fracture at a site of metastatic infiltration/multiple myeloma, that poses risk of impending vertebral collapse; this is detected by the following cross-sectional imaging (MRI or CT) conditions:\r\n* In the thoracic spine: \r\n** A >= 50% involvement of the vertebral body with no destruction of other structures or;\r\n** A >= 25% involvement of the vertebral body associated with costovertebral joint destruction or posterior elements involvement\r\n* In the lumbar spine: \r\n** A >= 35% involvement of the vertebral body with no destruction of other structures or;\r\n** A >= 20% involvement of the vertebral body associated with involvement of posterior elements
Asymptomatic vertebral fracture and low risk for biomechanical instability and collapse
Pain not localized to the region of metastatic disease; this may include:\r\n* Diffuse non-focal back pain\r\n* Radiculopathy
Inappropriate risk to the patient such as cardiorespiratory compromise such that safe conscious sedation or prone decubitus cannot be obtained
Unable to obtain diagnostic imaging
Subjects with documented diagnosis of a type of sickle cell disorder who require RBC Exchange or RBC Depletion/Exchange treatment.
Medically stable subjects who have been previously treated for sickle cell disease with RBC Exchange or RBC Depletion/Exchange.
Subjects who are able and agree to report adverse events (AEs) during the required reporting period.
Procedures that occur during acute hospitalization.
Procedures prescribed within one week of discharge of a hospitalization.
Subjects who have experienced a serious adverse event associated with an RBCx procedure in the past.
Subjects who fail to comply with site requirements for cessation of medication that interfere or increase procedure risk.
Willing and able to undergo a post-dose core needle biopsy.
Experienced a Grade 3 or higher hypersensitivity reaction to monoclonal antibodies or other therapeutic proteins, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-hydroxytryptamine (5-HT3) receptor antagonists, or corticosteroids;
Prior systemically administered nitrosoureas or vascular endothelial growth factor (VEGF) targeted therapy
Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts), a skull defect (such as missing bone with no replacement), a shunt, or bullet fragments
Known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
Impending or actual pathological fracture of the humerus, secondary to metastatic bone disease.
Postmenopausal for at least 1 year OR
Fracture is closed, Gustilo Type I or II.
Distant foci of infection that may spread to the implant site.
In the investigator's judgment, functional deficit in the target humerus with an etiology other than bone metastases (e.g. due to vascular insufficiency).
Mirels Score < 8 (specific to target humeral lesion).
Destruction of cortical bone at impending fracture site < 50%.
Extremely comminuted fractures where insufficient holding power of the balloon on the intramedullary canal is probable.
Determined by treating urologist to be a good candidate for BCG induction therapy
Temperature =< 38° Celsius (C) (=< 100.4° Fahrenheit [F])
Hematocrit (HCT) >= 30%
Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take mocetinostat with water and recommendation to avoid agents that increase gastric pH
Subjects with sensory neuropathy, ascites, or plastic biliary stent.
Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders (including but not limited to connective tissue disorders, lung disease, and cardiac or seizure disorders)
General and Demographics
Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.
Patient compliance and geographic proximity that allow adequate follow-up
Serious concomitant systemic disorders
Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in situ hybridization [ISH] or a polymerase chain reaction [PCR]-based test)
Willing to sign durable power of attorney
Subjects with NSCLC of predominantly squamous histology documented by histology or cytology from brushing, washing or needle aspiration of a defined lesion but not from sputum cytology alone
Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion
Acute or chronic pancreatitis
Pathologic mediastinal staging to include endobronchial ultrasound with or without endoscopic ultrasound (endobronchial ultrasound [EBUS] +/- endoscopic ultrasound [EUS]) including evaluation of N3 nodes
International Association for the Study of Lung Cancer (IASLC) version 7, subset of stage IIIA single station (N2) disease; specifically T1a-T3, N2(+) with no invasion of key structures (e.g., chest wall or diaphragm)
Secondary immune thrombocytopenia
Mediastinoscopy and/or endoscopic bronchial ultrasound (EBUS) and/or endoscopic ultrasound (EUS) for complete surgical staging when clinically indicated
Aspartate amino transferase (AST) or alanine amino transferase (ALT) >= three (3) times the upper limit of normal
Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom for example Crohn's disease, malabsorption or Common Terminology Criteria (CTC) grade >= 2 diarrhea of any etiology
Lymphocyte count ? 0.8 x 103 cells/µL
Has recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia, and/or other hereditary congenital immunodeficiencies
Willingness to follow pregnancy precautions.
Normal serum potassium magnesium levels
Embryonal or alveolar rhabdomyosarcoma
Dermatofibrosarcoma protuberans
Extraskeletal myxoid chondrosarcoma
Sarcomas arising from bone or cartilage, e.g. chondrosarcoma, osteosarcoma, chordoma.
Must be deemed medically fit for SBRT to the abdomen or thorax by the treating physician
aPTT ? 1.5 x ULN
Glycated haemoglobin (HbA1c) < 8%
Acute or chronic pancreatitis
Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc.
DLBCL of GCB subtype
Has a known human T-lymphotropic virus type 1 (HTLV) infection
Disease is confined to locoregional site as confirmed by the CT and/or diagnostic staging laparoscopy to avoid occult peritoneal deposits; diagnostic laparoscopy will be only if absolutely required
Screening endoscopic ultrasound if done prior to consent but within 6 weeks of expected randomization date it may be used
Estimated life expectance >= 12 weeks
Patient has no evidence of jaundice at the time of enrollment; if stent is required to alleviate jaundice, it should be metallic; if patient has a previously placed stent and this is plastic, this should be changed to metallic
Evidence of distant metastasis on upright chest X-ray (CXR), CT or other staging studies
Rhythm abnormalities (other than sinus bradycardia with HR < 50 bpm)
AV block (other than 1o AV Block with PR > 200 msec)
Bundle branch block or QRS ? 120 msec
Abnormal T wave morphology (other than slight flattening)
Pathological U waves
Other QRS or T/U morphology preventing accurate determination of QT interval
Prior Treatments:
Must not have a serious preexisting medical conditions or concomitant disorders.
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
Sequenced therapy, including any of the following:\r\n* Abiraterone acetate followed by enzalutamide\r\n** Primary resistance will be defined per criteria for abiraterone monotherapy primary resistance\r\n* Enzalutamide followed by abiraterone acetate\r\n** Primary resistance will be defined per criteria for enzalutamide monotherapy primary resistance\r\n* Other second-generation investigational anti-androgen/androgen- receptor targeted therapies, including ARN-509\r\n** Primary resistance will be defined per criteria for other investigational anti-androgen monotherapy primary resistance
Discontinuation of prior therapy for mCRPC: a washout period of 28 days for the following therapies is required: abiraterone, enzalutamide, fluconazole, itraconazole, flutamide, bicalutamide, nilutamide, and other experimental hormonal agents (ARN509, orteronel [TAK-700], etc.), sipuleucel-T (Provenge), other experimental vaccines (PROSTVAC-V/F, etc.), strontium-89, samarium, and radium-223 chloride
Female participants who:
Are post-menopausal for at least 1 year before the screening visit, OR
Male participants, even if surgically sterilized (ie, status postvasectomy), who:
Participants with biliary obstruction for which a stent had been placed are eligible provided that the stent has been in place for more than 14 days before the first dose of alisertib and liver function has stabilized.
Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be excluded.
Must be without neurologic dysfunction that would confound the evaluation of neurologic or other adverse events (AEs).
Has a partially HLA-matched single UCB unit (>= 4 of 6) with adequate cell dose; UCB units must fulfill eligibility as outlined in 21 Code of Federal Regulations (CFR) 1271 and agency guidance
At least single haplotype matched (>= 3 of 6) family member
Meningeal carcinomatosis.
Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
Other active malignancies
Patient must have been pre-identified as having a tumor with an ALK or ROS1 positive mutation, translocation, rearrangement or amplification. The qualifying alteration must be assessed and reported by a CLIA-certified laboratory. ALK positivity as assessed by IHC or FISH are allowed.
Paclitaxel therapy is appropriate for the patient and is recommended by the Investigator.
Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
Cohort 1
Cohort 2
Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White);
Patient has a malignant stricture of the distal esophagus or gastric cardia requiring stent placement across the gastroesophageal junction.
Patient is contraindicated for endoscopic procedure for any reason
Patient presents with esophagorespiratory fistula
Patient has previously undergone esophageal stenting or esophagectomy
Patient has trouble swallowing or experiences regurgitation for reasons which are not related to his/her esophageal cancer
Any other factor identified by the Investigator that would disqualify the prospective patient from participation in the study including but not limited to coagulative disorders and anesthetic risk.
Subjects receiving Coumadin anticoagulants
- fluoropyrimidine
- irinotecan
- bevacizumab or aflibercept
- cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
Serum free light chain (FLC) > 100 mg/L of involved FLC
Narrow therapeutic index substrates of CYP2C8, CYP2C9, CYP2C19 and CYP2D6
Patients must have rearrangement involving the MLL gene, including reciprocal chromosomal translocations involving 11q23 by FISH, cytogenetic analysis, polymerase chain reaction (PCR) or next-generation sequencing (NGS) OR partial tandem duplication (PTD) of MLL by PCR or NGS.
ALT and AST < 3 x ULN (unless attributed to leukemic involvement)
Colonic prosthesis (stent) implant in place
Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-FU toxicity
Patients must have documented ALK positivity at the time of initial crizotinib monotherapy using the Vysis Break-Apart FISH assay (or other Food and Drug Administration [FDA]-approved diagnostic test); samples are deemed to be FISH-positive if greater than or equal to 15% of scored tumor cells had split ALK 5? and 3? probe signals or had isolated 3? signal; FISH status must be documented on the Onstudy Form and a copy of the pathology report from the Vysis Break-Apart FISH assay (or other FDA-approved diagnostic test) must be submitted
Patients must be offered participation in the translational medicine studies; additionally if patient has biopsy accessible disease they must be offered participation in the translational medicine studies
REGULATORY CRITERIA: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Biopsy-proven well-differentiated, low-to-intermediate-grade PNET or GI-NET with elevated (> ULN) biomarkers (serotonin, 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A (CgA), neurokinin A, and neuron-specific enolase (NSE))
High grade or poorly differentiated NET
No elevated biomarker (>ULN) that can be followed
Subjects who fail to meet the above criteria
Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
Participants who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male participants) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924.
Implantable cardioverter defibrillator.
Participants with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension (example, high-dose beta blocker).
chronic insomnia
Other preexisting sleep disorders
Unstable medical illnesses
Treatment related mortality (TRM) score < 22.9; patients with TRM scores > 13.1, in whom the risk of death within 28 days of beginning induction therapy has averaged 41%, will preferentially be placed on protocol 2642
Note, unlike pharmaceutical company sponsored protocols eligibility is not conditioned on bilirubin, creatinine, or absence of other malignancy within the past 2-3 years; the TRM score incorporates creatinine and thus a high creatinine can in principle be offset by favorable values for the other covariates in the TRM score; bilirubin was not a covariate in the TRM; furthermore, in the doses we are using, dose adjustment of decitabine or ara-C is not indicated in the presence of renal or hepatic abnormalities; our broad eligibility criteria may increase the likelihood that our results will be generalizable; the inability to reproduce results of early phase AML studies has been a problem in the past
patient was currently enrolled in Novartis sponsored study, which had met its endpoint and was receiving single agent oral dovitinib or dovitinib and fulvestrant coadministration
patient was currently benefiting from treatment with single agent oral dovitinib or dovitinib and fulvestrant coadministration as determined by the guidelines of the parent protocol and according to the investigator's clinical judgment.
Must be a candidate for radical prostatectomy
Plasma creatine phosphokinase (CK) < 1.5 x ULN, if known
Other concomitant malignancies (with some exceptions per protocol)
Any of the following tumor tissue based genetic alterations: FGFR1, FGFR2, FGFR3, VEGFA, or PDGFR? amplification; Any FGFR1, FGFR2, or FGFR3 gene fusion; FGFR1, FGFR2, or FGFR3 activating mutation
Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
Rapid central review confirmation of group D disease based on RetCam images from diagnostic EUA must be obtained before starting treatment
Unilateral retinoblastoma with group A, B, C, or E eyes
AML blasts must express CD30 (>= 10% expression as assessed by flow-cytometry or 2+ expression by immunohistochemistry) (whenever possible CD30 expression will be assessed by both methods)
Patient has disease that tests positive for BRAF V600 mutations based on the results of a CLIA certified assay
Any patient requiring chronic maintenance of red blood cell, white blood cell or granulocyte counts through the use of blood transfusions or growth factor support (e.g. Neulasta®, Neupogen®)
Received at least 2 cycles of a bortezomib-containing regimen and 2 cycles of a lenalidomide-containing regimen, unless intolerant to these agents (defined as requiring discontinuation due to toxicity).
Additional criteria exist.
Additional criteria exist.
Failure of or intolerance to 5-FU, Oxaliplatin, and Irinotecan
Pretreatment with regorafenib.
Magnesium less than 0.9 milligram per deciliter (mg/dL)
Capable of compliance with the requirements and restrictions listed in the consent form;
Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
Subjects with narrow angle glaucoma
No later than 96 hours (h) in the immediate post-operative period; or
At least 56 of the approximately 76 patients treated must have measurable disease, defined as at least one, contrast-enhancing lesion measuring at least 1 cm in 2 planes (axial, coronal, or sagittal).
Multi-focal (defined as two separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid-attenuated inversion recovery (FLAIR) or T2 sequences);
Associated with either diffuse subependymal or leptomeningeal dissemination; or
? 4 cm in any dimension.
Man or woman >= 18 years old.
Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis
Risk for varices, based on known history of esophageal or gastric varices, evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices
Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
Lytic lesion requiring an impending orthopedic intervention
Fasting ?-CTX of >1000 pg/mL
Subjects >=18 years old.
Histologically or cytologically confirmed diagnosis of advanced or metastatic cutaneous melanoma that is determined to be BRAFV600 wild type and either NRAS wild type or NRAS mutation type. Note: Subjects with a melanoma of unknown primary origin may be allowed to enrol if all other types of melanoma (e.g., uveal, mucosal, or acral) can be reasonably ruled out.
BRAFV600 mutation positive.
History of intolerance or hypersensitivity to paclitaxel and/or adverse events related to paclitaxel that resulted in paclitaxel being permanently discontinued
Serum potassium, magnesium, and calcium levels (corrected for albumin) outside the laboratory’s reference range despite correction
Inclusion Criteria:\n\n        Patient must be at least 1 year of age.\n\n        Patient or the patient's legally authorized guardian must be fully informed about their\n        illness and the investigational nature of the study protocol (including foreseeable risks\n        and possible side effects), and must sign an informed consent in accordance with the\n        institutional policies approved by the U.S. Department of Health and Human Services.\n\n        Patients should have been off other investigational therapy for one month prior to entry in\n        this study.\n\n        Patient must have adequate organ function as below:\n\n        Adequate renal function defined as:\n\n          -  Serum creatinine <2.0 x normal, or\n\n          -  Creatinine clearance or radioisotope GFR > 40 ml/min/m2 or >60 ml/min/1.73 m2 or an\n             equivalent GFR as determined by the institutional normal range\n\n        Adequate liver function defined as:\n\n          -  Total bilirubin <2.0 x normal; and\n\n          -  SGOT (AST) or SGPT (ALT) <5.0 x normal\n\n        Adequate pulmonary function defined as:\n\n        - Pulse oximetry >94% in room air. Lansky (< 16yr) or Karnofsky (> 16 yrs) performance\n        status ? 50% Life expenctancy ? 6 weeks. Women of child bearing age require a negative\n        urine pregnancy test. Clinical status at enrollment to allow tapering of steroids to less\n        than 0.5mg/kg/day prednisone at time of treatment.\n\n        4.5 Disease Status (Eligibility) 4.5.1 Any patient, with one or more of the following\n        EBV-positive type II latency or associated disorders, regardless of the histological\n        subtype: Hodgkin lymphoma Non-Hodgkin lymphoma Lymphoproliferative disorder Severe chronic\n        active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (>\n        4000 genomes per ?g PBMC DNA) and/or biopsy tissue positive for EBV\n\n        The disease needs to be in one of the following stages:\n\n        At diagnosis who would be unable to receive conventional chemotherapy or in first relapse\n        AND the patient is not a candidate for HSCT Partial response after conventional therapy.\n        Refractory to conventional therapy for his/her condition. In second or subsequent relapse.\n        Residual disease after autologous, syngeneic or allogeneic HSCT.\n\n        All patients entered into the study ideally will have tumor tissue from the original\n        diagnostic specimen and/or relapse reviewed centrally for confirmation of EBV positive\n        disease. If no specimen is available, local pathology report documenting EBV positivity is\n        acceptable. Appropriate immunophenotyping to confirm the diagnosis will be performed. In\n        addition, in situ hybridization for EBV (LMP1, and/or EBER positivity) will be performed.\n        All central morphologic analysis and immunohistochemical/insitu hybridization staining will\n        be performed in the laboratory of Sherrie Perkins and Rodney Miles at the University of\n        Utah.\n\n        Donor Eligibility for LMP-CTL Third Party Banking (Aim 2.1.2)\n\n          -  Donor must be HIV negative.\n\n          -  Donors must have adequate hematopoietic function defined as absolute neutrophil count\n             > 1000/mm3, hemoglobin > 10 g/dl, and platelet count >50,000/mm3 and be EBV IgG\n             seropositive.\n\n          -  Donors will have peripheral blood collected for LMP specific CTL production. A minimum\n             of 60 cc of peripheral blood x 2 for a total maximum amount of blood of 120cc, will be\n             collected from the donor (subjects must be at least 12 kg or 24 pounds). (See Appendix\n             B) For donors <18 years a maximum of 3cc/kg blood will be taken in an 8 week period.\n\n          -  For donors that are to undergo stem cell collection, the peripheral blood for LMP\n             specific CTL production will be collected prior to the stem cell collection and\n             without a specific day specification.\n\n          -  Donor eligibility must meet criteria as per 21 CFR 1271.\n\n        Exclusion Criteria:\n\n        Currently receiving any investigational agents or have received any tumor vaccines within\n        previous 4 weeks.\n\n        Active acute grade III-IV graft-versus-host disease. Severe refractory intercurrent\n        infection other than EBV. Received alemtuzumab or other anti-Tcell antibody within 28 days.\n        HIV seropositivity. Pregnancy (due to unknown effects of this therapy on a fetus) or\n        lactation. Patients with PTLD post solid organ transplantation eligible for the COG PTLD\n        LMP/CTL protocol.
Inclusion Criteria:\n\n          -  Subject must currently be participating in an Astellas sponsored linsitinib trial that\n             has ended with respect to the overall study analysis.\n\n          -  Subject must not have met criteria for discontinuation or have progressed on the\n             current linsitinib study in which they are participating.\n\n          -  Subject must be deriving benefit from continued treatment.
Accessibility to the site that optimizes the subject's ability to keep all study-related appointments.
Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin.
Patient is deemed by the investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Patients must have at least one injectable lesion, defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable IT injection.
Adequate neutrophil and platelet counts
Members of all genders, races and ethnic groups are eligible for this trial
Patient had a resection and/or completed a course of cranial irradiation; and
Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil);
Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin), OCT1 transporter (e.g., metformin), OAT1 transporter (e.g., captopril, furosemide, methotrexate), and OATP1B3 transporter (e.g., atorvastatin, rosuvastatin, valsartan);
Single solid organ recipients (kidney only)
Donor-specific antibodies (DSA) will be assessed by the local laboratory 30 days or less prior to transplant using solid phase micro particle technology (by Luminex phenotype panel or Luminex single antigen bead test); the following criteria apply:\r\n* Participants without detectable DSA will be deemed eligible if they meet other entry criteria\r\n* Participants with detectable DSA and a positive flow cytometric crossmatch may undergo de-sensitization per standard of care if they are cytotoxic crossmatch negative; such participants must demonstrate a negative flow cytometric crossmatch by day -9 in order to receive the first dose of study therapy (ATG); participants who do not demonstrate an acceptable response to de-sensitization by day -9 will be considered screen failures and will be terminated from the study\r\n* Participants with a positive cytotoxicity crossmatch will be excluded
Serological evidence of prior Epstein-Barr virus (EBV) infection as documented by positive immunoglobulin G (IgG) and negative immunoglobulin M (IgM) antibodies against EBV
All participants must demonstrate a negative QuantiFERON (QFT) assay result within 52 weeks of transplant regardless of purified protein derivative (PPD) status; participants with a positive QFT assay must complete treatment for latent tuberculosis (TB) and have a negative chest x-ray; QFT testing done within 52 weeks before transplant is acceptable as long as there is documentation of the results; prior recipients of a bacillus calmette-guerin (BCG) vaccination are not exempt
DONOR: Serologic evidence of prior EBV infection as documented by positive IgG and negative IgM antibodies against EBV
Clinically important genital/urinary tract dysfunction
Positive cytotoxic crossmatch
Calculated panel reactive antibody (PRA) greater than 90%
Adults >/= 18 years old
Radiographic progression by RANO Working Group Criteria will be confirmed by Imaging Endpoints, a central imaging vendor.
Geographically accessible to site, i.e. the ability to come to the study site for each scheduled appointment and evaluation.
Prior exposure to the an anthracycline.
Laboratory values: screening serum creatinine > 1.5xULN, ALT > 2.5xULN, total bilirubin > 1.5xULN, ANC < 1500/mm3, platelet concentrations < 100,000/mm3, absolute lymphocyte count < 1000/mm3, hematocrit level < 27% for females or < 30% for males, serum albumin ? 2.5 g/dL, PT/INR 1.5xULN or >3xULN on anticoagulant with no evidence of active bleeding.
Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
Subject has disseminated intravascular coagulation abnormality (DIC)
Subject required treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
? 18 years old Part 2, dose expansion:
Any other significant co-morbid conditions that would impair study participation or cooperation
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
Current mucositis.
Tumors of the lips, sinuses, salivary glands or nasopharynx.
2nd line, 3rd line or greater
Have prosthetic heart valves, major implant or device placed in the last 12 months or history of infection with implant/device that cannot be easily removed
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
An individual with an adrenal neoplasm less than 5 cm in size with biochemically confirmed evidence of hypercortisolism (2 out of 3: dexamethasone suppression test [DST] > 3 mcg/dL, elevated urine free cortisol, and/or morning adrenocorticotropic hormone [ACTH] < 2.2 pmol/l) without overt clinical signs and symptoms
Biochemically and/or radiologically confirmed pheochromocytoma, hyperaldosteronoma, or adrenocortical carcinoma
Nonfunctioning adrenal neoplasm
Lack of metabolic complications
OR intolerant to second generation TKI and intolerant or refractory to imatinib mesylate
Cavitary tumors or tumors invading or abutting large blood vessels
For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+).
Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement,
Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm,
Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry
Presence of primary (light chain) amyloidosis.
Additional criteria exist.
Additional criteria exist.
No more than 10 treatable lesions as evaluated by an experienced interventional oncologic radiologist for eligibility and lesion accessibility as the ablation of more than 10 lesions becomes technically infeasible; these lesions must be treated in a two- to three-week time period from initial interventional radiology evaluation; lung and liver lesions can range from 1 cm to 7 cm for a single lesion and no greater than 5 cm for multiple lesions; there are no size criteria for the osseous lesions
The lesions will be amenable to a safe, ultrasound/computed tomographic/fluoroscopic guided percutaneous approach; the targeted metastases must be sufficiently separable from the central nervous system, major peripheral motor nerves, bowel, and bladder; all lesions must be amenable to treatment
Is the subject between 18 years old and 80 years old inclusive?
Does the subject have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.
Evidence of life-threatening or fulminant CDAD.
Likelihood of death within 72 hours from any cause.
Histologically documented marginal zone lymphoma including splenic, nodal, and extranodal sub-types; subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criteria 5
Patients must have metastatic histologically or cytologically confirmed uveal melanoma; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of metastatic disease will be performed at Memorial Sloan Kettering (MSK) or at a participating site
Not removed from trametinib treatment due to the development of unacceptable toxicity that is not manageable with dose reduction
experienced no dose limiting toxicity (DLT)
Known immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia; and/or other hereditary or congenital immunodeficiencies
Administration of any vaccine ? 4 weeks prior to first maintenance or retreatment cohort dose of ONT-10 with the exception of influenza, pneumococcus, and Tdap
Histologically-confirmed metastatic melanoma (Stage IV), carrying BRAF V600E or V600K mutation as determined by testing certified for clinical diagnostic purposes. Previously performed certified BRAF testing is acceptable. If no prior BRAF mutation testing results are available, testing of a distant metastasis is preferred, but testing of a regional metastasis or primary tumor is also acceptable
Coronary angioplasty or stenting within the past 12 weeks
Prior extensive anthracycline exposure
UGT1A1 genotype of TA 7 in both alleles (homozygous UGT1A1*28) or TA 8 in either one or both alleles (hetero- or homozygous for UGT1A1*37)
Chronic or acute GI disorders resulting in diarrhea
Serious non-healing wounds or ulcers at the time of registration
Have a diagnosis of FAP
Neuropathy Impairment Score requirement of 5-130
Has untreated hypo- or hyperthyroidism;
Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid
Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
Lytic lesion requiring an impending orthopedic intervention
Fasting ?-CTX of >1000 pg/mL
Unequivocal evidence of recurrent or progressive GBM before or after bevacizumab treatment first based on radiographic appearances then confirmed by histologic confirmation through biopsy or resection
Prior therapy with weekly paclitaxel for recurrent disease (administration of weekly paclitaxel as part of an upfront treatment strategy is acceptable as long as the patient had not progressed while receiving weekly paclitaxel or recurred within 4 months of receiving weekly paclitaxel)
Prior radiotherapy to the pelvis or abdomen
Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination with cisplatin or carboplatin • For subjects to receive pemetrexed, planned to receive vitamin B12 and folate per pemetrexed approved labeling
Planned to receive bevacizumab
Planned invasive dental procedures for the course of the study.
Histological features of neuroendocrine or bronchioalveolar differentiation.
Paraneoplastic syndromes
ASS deficiency (defined as <50% ASS expression) demonstrated on tissue specimen by Immunohistochemistry (IHC). Cytology and fine need aspirate specimens are not acceptable for ASS testing.
Prior epirubicin exposure of > 600 mg/m2.
Subjects who had been treated with ADI-PEG 20 previously.
Willingness to provide the blood specimens as required by the protocol; please note that the willingness to participate pertains only to the patient and does not factor in the institution’s ability to participate in any part of the translational component
Baseline hemoptysis, per clinician/investigator evaluation
Received antithymocyte globulin (ATG), or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment
Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection; persisting fever without other signs or symptoms will not be interpreted as progressing infection
Platelets >= 100,000/mm^3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
Recent percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) – defined as within 24 weeks prior to screening
Serum magnesium > 1.2mEq/L
Serum potassium >= 3.8 mmol/L
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
An EKG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
The subject is at least 18 years old.
HbA1c ? 8%
Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
Patients with symptomatic relapse, including those with new bone lesions, soft tissue plasmacytomas, an increase in the size of existing bone lesions or soft tissue plasmacytomas, decrease in hemoglobin, rise in serum creatinine or hypercalcemia
Sorror’s co-morbidity factors with total score > 4
Waldenstrom's macroglobulinemia
Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
Has had either partial or total gastrectomy
Subjects undergoing renal dialysis
Prior treatment with an investigational or approved agent for the purpose of inhibiting human epidermal growth factor receptor (HER) family members. This includes, but is not limited to, cetuximab, panitumumab, erlotinib, gefitinib, and lapatinib
Need for antiarrhythmic medical therapy for a ventricular arrhythmia
Psychiatric disorder or social or geographic situation that would preclude study participation.
No prior brentuximab vedotin
Sickle Cell Disease (HbSS, HbSC, HbS??-thalassemia, or HbS??-thalassemia)
On a chronic transfusion program or planning on exchange transfusion during the study
Planned initiation, termination, or dose alteration of hydroxyurea during the study
WBC >3000/microliter.
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
Eligible for induction by daunorubicin + cytarabine.
Waldenstrom macroglobulinemia
Prior exposure to agents targeting either the Hepatocyte Growth Factor (HGF) or MET pathway
Adequate baseline functions:
Sodium, potassium, and phosphorus levels no worse than grade 1
Cardiac stress test (e.g., stress thallium scan, stress echocardiography) with normal results if patient is suspected to have coronary artery disease.
Legal incapacity or limited legal capacity
Patients who present for EGD with dilation for dysphagia symptoms thought secondary to either radiation-induced stricture or anastomotic stricture based on history
Endoscopic finding of a stricture that is not caused by either radiation or anastomotic narrowing
Nasopharyngeal strictures
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Patients currently taking statins who are unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration
Grade >=2 hypercholesterolemia or hypertriglyceridemia
Unwillingness to be transfused with blood components.
total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable;
vasectomized partner(s);
Subjects that have previously been treated with a veliparib.
The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured. Questions regarding the inclusion of individual subject should be directed to the Medical Monitor.
Current enrollment in another clinical study.
Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive veliparib.
Pheochromocytoma
Renal failure requiring hemo- or peritoneal dialysis
Acute renal failure
Acute nephritis
Adequate potassium level > 3.5 mEq/dL
Willing to take abiraterone acetate on empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Previous extensive radiotherapy except limited field RT for locally advanced nasal NK PTCL or for pain palliation
Adult men and women subjects aged 18 to 75, inclusive.
Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse.
Part 2 only: Patients with a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80 (for example, drugs formulated with polysorbate 80 include, but are not limited to: Aranesp, Eprex, Cordarone, some vaccines).
No prior allogeneic HSCT; and
Azacitidine, decitabine or other demethylating agents
Lenalidomide, thalidomide and pomalidomide
PART I: Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
PART I: History of oxalate renal calculi; urine oxalate level > 60 mg/d at baseline
PART I: Subjects with evidence of cardiac toxicity and Q wave abnormalities at baseline electrocardiography (ECG) will not be allowed to participate
PART II: The oncology participants must have study approved by oncologist responsible for management of care or follow up
PART II: ECOG performance status 0-2\r\n* Eastern Cooperative Oncology Group performance status\r\n* Grade 0 = Fully active, able to carry on all pre-disease activities without restriction\r\n* Grade 1 = Restricted in physical strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light housework, office work\r\n* Grade 2 = Ambulatory and capable of all self care but unable to carry out any work activities; up and about more than 50% of waking hours
PART II: Utilizing the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4, values for the following laboratory tests should be no more than grade two levels: ANC, hemoglobin, platelet count, total bilirubin, creatinine, transaminase (AST/ALT), PT, PTT, urine uric acid, urine pH, urine oxalate
PART II: Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
PART II: History of oxalate renal calculi; urine oxalate level > 60 mg/d at baseline
PART II: ECOG performance status of 3-4\r\n* Grade 3 = Capable of only limited self care, confined to bed or chair more than 50% of waking hours\r\n* Grade 4 = Completely disabled; cannot carry on any self care; totally confined to bed or chair and in terminal stages of disease
Hematocrit > 25%
At least moderate dyspnea defined by a BDI score of 6 or less in the self-administered computerized versions of the baseline and transition dyspnea indexes (SAC-BDI/TDI); (this cutoff score is close to the score of 5.7 used to define \moderate dyspnea\ in the publication that validated the instrument and is selected by attending physicians in the pulmonary service as a good indication of \ moderate dyspnea\ in clinical practice; a typical person with BDI of 6, for example, would be a 52 year old woman who has to pause when walking because of dyspnea and/or has eliminated doing an activity because of dyspnea)
Able to safely complete the six minute walk test (6MWT) as per attending physician's clinical judgement
Hypersensitivity to 4-aminoquinoline compounds, including hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine
Known glucose-6-phosphate dehydrogenase (G-6PDH) deficiency
Retinal or visual field changes from prior 4-aminoquinoline compound use such as hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine
Have previously been exposed to MGAH22 in this or any other trial
Non-smoker
Undergoing unilateral or bilateral, two-stage, tissue expander-assisted breast reconstruction
Transplant ineligibility
Waldenström macroglobulinemia (WM)
Known amyloidosis
Any prior ado-trastuzumab emtansine
CARDIOPULMONARY FUNCTION CRITERIA
Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least 6 clinically evident basal cell carcinomas at the time of randomization, of which 3 measure 5 mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions
One of the following known rare hereditary conditions: galactose intolerance, primary hypolactasia or glucose-galactose malabsorption
DOSE ESCALATION COHORT:
Because of the potential risk of QTc changes, serum magnesium and phosphorous levels must be >= the institutional lower limit of normal
Patients must have histologically confirmed HR+ breast cancer; HR+ is defined as either ERa or PgR being positive, or both; positivity is defined for the purposes of this protocol as:\r\n* Allred >= 4\r\n* IHC 1+, 2+, 3+\r\n* Percentage of positive staining > 10%\r\n** When there is discrepancy between the metastatic and primary tumor results with respect to ERA or PgR status, the metastatic results will hold precedence; when there is discrepancy between the local and University of Wisconsin (UW) pathology results with respect to ER? or PgR status, the UW results will hold precedence
DOSE EXPANSION COHORT:
Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model
Bilirubin < 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver
Concomitant illness associated with a likely survival of < 1 year
As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Documented ALK rearrangement based on FDA approved test
Recurrent GBM per RANO criteria
Allergies to temozolomide, dacarbazine, IgG containing agents
Intubated and mechanically-ventilated
Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph
Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions, or suspected Gram-negative pathogen
Impaired oxygenation
Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms
Known or suspected bacteremia secondary to Staphylococcus aureus
Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10
Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed (see section 5.5)
?2 prior doses of fulvestrant are not eligible
Must be female and postmenopausal.
Bisphosphonates or Zometa for bone metastases
Relapsed myeloma that previously became refractory to lenalidomide, after initial response of partial response or better to the drug; refractory is defined as progression on treatment with a dose of at least 10 mg daily for lenalidomide; greater than or equal to 180 days must have elapsed since previous lenalidomide therapy was stopped
Histologically-proven AL amyloidosis, confirmed by positive Congo red stain with green birefringence on polarized light microscopy with evidence of measurable clonal disease that requires active treatment as defined below:
For the dose-escalation cohort: this is defined as having any elevation in the amyloidogenic (i.e. clonal) light chain with an abnormal free kappa:lambda ratio
For the dose expansion cohorts: in addition to the above, there must be a difference between the amyloidogenic (i.e. clonal) and non-amyloidogenic light chain (dFLC) of at least 50mg/L (5mg/dL)
GI Tract: biopsy showing amyloid deposition along with symptoms such as GI bleeding or persistent diarrhea (> 4 loose stools/day) Autonomic or Peripheral Nervous System: defined as orthostasis, symptoms of nausea or dysgeusia, recurrent diarrhea or constipation, abnormal sensory and/or motor findings on neurologic exam, or gastric atony by gastric emptying scan
Amyloid cardiac biomarker stage I or II disease Staging defined by NT-proBNP and troponin T cut-offs of < 332 pg/mL and <0.035 ng/mL, respectively, as thresholds: Stage I, both under threshold; and Stage II, either troponin or NT-proBNP (but not both) over threshold. If troponin T is not available at local institution, troponin I may be used, but threshold is <0.1 ng/mL.23
CrCl ? 30 mL/min as measured by 24-hour urine
Amyloid cardiac biomarker stage III disease, defined as both NT-proBNP ? 332 pg/mL and troponin T ? 0.035 ng/mL. If troponin T is not available at local institution, troponin I may be used, but cut-off is ? 0.1 ng/mL
Grade 2 or 3 atrioventricular (AV) block (Mobitz type I is permitted) or sick sinus syndrome, unless subject has a pacemaker
Known allergies to carfilzomib or Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
Prior bilateral orchiectomy
Complete left bundle branch block
Right bundle branch block and left anterior hemi block (bifascicular block)
Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or elevated baseline CK levels (? Grade 2)
Participants must be ?18 years since no dosing or adverse event data are currently available on the use of OGX-427 in participants <18 years of age.
Pregnant women and breast feeding women are excluded from this study because of the risk to a fetus due to docetaxel chemotherapy and OGX-427 systemic treatment (fertility toxicology studies have not been completed for OGX-427).
Other concomitant malignancies (with some exceptions per protocol)
Adults
Patients who have neuromuscular disorders that are associated with elevated CK (Creatine phosphokinase) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Subjects will be adult allogeneic HSCT recipients aged ? 18 years-old (or as applicable, per local law) who were CMV seropositive before transplantation and are CMV viremia negative posttransplant.
Subjects who have a positive CMV viremia test at any time between transplant and the First Dose Day (FDD).
Subjects who have had any anti-CMV vaccine at any time.
LVEF < LLN for the institution
Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study
Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
Contraindications to general anesthesia
ANC > 1000 /ml
Plt > 75 K/ml (without transfusion)
Subject with CNS metastases with active neurologic dysfunction. These patients are excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse event.
Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to: a.Cardiac disease i. Unstable angina ii. Myocardial infarction < 3 months prior to study initiation b. Ongoing serious infection i. Bacteremia or sepsis requiring intravenous antibiotics ii. HIV with AIDS defining illness c.Inadequate oral nutritional intake i. Requirement for daily intravenous fluids or total parenteral nutrition. d. Psychiatric illness/social situations that would limit compliance with study requirement
Pregnant (positive pregnancy test) and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
Require elective (non-emergency), open (non-laparoscopic), hepatic resection (anatomic or non-anatomic resections of at least one anatomical hepatic segment, or equivalent tissue volume).
Target bleeding site is identified on the cut raw liver surface (resection area).
Require hepatic resection due to trauma.
Previous known sensitivity to any Fibrin Sealant Grifols component or any Surgicel® component.
Diagnosis of ?-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ?8 transfusions of pRBCs per year for the prior 2 years.
Subject has a confirmed diagnosis of HbSS, HbSC, HbS?+thal, or HbS?0thal
Subject is experiencing acute pain typical of vaso-occlusive crisis requiring treatment with parenteral analgesia
Subject requires hospitalization
Subject has complications related to SCD
No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or erythropoetin (EPO) > 500 mU/ml
Chromosome 5q deletion
Prior Exposure to Sotatercept (ACE-011)
18-39 years old
Low-density lipoprotein (LDL) -cholesterol ?130 mg/dL (individuals with elevated LDL-cholesterol will be referred for clinical management of dyslipidemia)
Colorectal adenocarcinoma patients must be known to have CpG island methylator phenotype; CIMP-high phenotype will be defined as hypermethylation at 2 or more of the 6 methylation-specific polymerase chain reaction (PCR) markers (mutL homolog 1, colon cancer, nonpolyposis type 2 [hMLH1], cyclin-dependent kinase inhibitor 2A [P16], cyclin-dependent kinase 2 associated protein 2 [P14], amyloid beta (A4) precursor protein-binding, family A, member 1 [MINT1], amyloid beta (A4) precursor protein-binding, family A, member 2 [MINT2], and amyloid beta (A4) precursor protein-binding, family A, member 3 [MINT3])
Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model
Concomitant illness associated with a likely survival of < 1 year
Previously treated, histologically confirmed cluster of differentiation (CD)20+ B cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies or extra nodal biopsies; fine needle aspirates are not acceptable
Submission of original biopsy for review and verification by participating center hematopathologist
Platelet count of =< 50 x 10^9/L less than 7 days before enrollment; platelet transfusions are permitted to reach entry criteria but should be discussed on a case-by-case basis with the study principal investigator (PI) and permission will depend on etiology of the thrombocytopenia, if not felt to be due to MM
Absolute neutrophil count of =< 1.0 x 10^9/L less than 7 days before enrollment; use of growth factors is permitted to fulfill this criterion, but should be discussed on a case-by-case basis with the study PI and permission will depend on etiology of the neutropenia, if not felt to be due to MM
No blood modifiers while enrolled in the study (i.e., growth factors such as erythropoiesis-stimulating agent [ESA] or filgrastim [G-CSF]); NOTE: blood transfusions are allowed per institutional guidelines
Patient must not have known proteinuria >= 500mg/24 hours
Acceptable coagulation status:
History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are considered clinically significant or may have an impact on the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary
Serum CK ?1.5 ULN
Patients who have neuromuscular disorders that are associated with elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Fevers >100.5º F or night sweats for more than 2 weeks without evidence of infection.
Expected to receive ondansetron as part of antiemetic regimen (Cycle 1); Expected to receive a 5-HT3 antagonist as part of antiemetic regimen (Cycles 2-6)
Pre-existing functioning central venous catheter
Scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
Allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist
Mentally incapacitated or has a significant emotional or psychiatric disorder
Candidate for radical prostatectomy
Following mood disorders as judged by the investigator and/or symptom management service co-investigator, or as a result of patient’s mood assessment questionnaire:\r\n* Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)\r\n* Current >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety\r\n* Meets the cut-off score of >= 10 in the Patient Health Questionnaire-9 (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of “1, 2, or 3” to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study
Patient has a score ? 12 on the PHQ-9 questionnaire.
Patient has a GAD-7 mood scale score ? 15.
Patients must have been previously treated:\r\n* >= 3rd line if bone marrow transplant (BMT) candidate OR\r\n* >= 2nd line if not BMT candidate OR\r\n* >= 2nd relapse for BMT candidate OR\r\n* >= 1st relapse for non- BMT candidate
Prior radioimmunotherapy
PT or aPTT < 1.5 times the ULN
Participants must meet the inclusion criteria outlined in the respective parent protocols: NO21279 (NCT00623870), NO21280 (NCT00559533), NP25299 (NCT01164033), NP28021 (NCT01605526) or NP28023 (NCT01635296)
Participants must have completed one of the following clinical study protocols and have been determined to have clinical benefit on treatment at the conclusion of required study analyses as defined in the respective parent protocols: NO21279 (NCT00623870), NO21280 (NCT00559533), NP25299 (NCT01164033), NP28021 (NCT01605526) or NP28023 (NCT01635296)
Participants must meet the exclusion criteria outlined in the respective parent protocols: NO21279 (NCT00623870), NO21280 (NCT00559533), NP25299 (NCT01164033), NP28021 (NCT01605526) or NP28023 (NCT01635296)
Participants continuing to require dose modifications
Participants with worsening adverse events
The immediate prior treatment regimen must have included an anti-VEGF agent; acceptable anti-VEGF therapy includes bevacizumab, ziv-aflibercept, sunitinib, or sorafenib; for other anti-VEGF therapies, contact the principal investigator
Tumors with clear cell histology: subject must have progressed after at least one anti-vascular endothelial growth factor receptor (anti-VEGFR) therapy
Tumors with non-clear cell histology must be ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3) positive at pre-screening. This sub-group does not have any prior therapy requirement.
Tumors with papillary histology: includes unclassified histology with papillary features and must be ENPP3 positive at pre-screening. This sub-group does not have any prior therapy requirement.
Known sensitivity to any of the ingredients of the investigational product AGS-16C3F
No clinical indication for a peritoneal port
Subjects who had been treated with ADI-PEG 20 previously.
Coagulation status:
Patients must have histologically confirmed thyroid carcinoma with the PAX8-PPARgamma translocation; refractory to radioactive iodine (RAI) as defined by: the tumor does not concentrate RAI; or the patient has had RAI within the last 16 months and has had progression despite that RAI; or the last RAI treatment was > 16 months ago and the patient progressed after at least two RAI treatments; or the patient has received RAI treatments with a cumulative RAI dose of >= 22.2 GBq (600 mCi) \r\n* Not a candidate for surgery or RAI therapy with curative intent \r\n* Lesions that would be treated by external beam radiation therapy (EBRT) based on standard of care can be so treated, but then cannot be used as target lesions unless there has been progression of the lesion since treatment
Total serum calcium [corrected for serum albumin] or ionized calcium >= LLN
Serum magnesium >= LLN
Serum phosphorus >= LLN
Structurally unstable bone lesions suggesting impending fracture
History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
Prior use of ketoconazole, abiraterone acetate or enzalutamide, or participation in a previous clinical trial of ketoconazole, abiraterone acetate or enzalutamide
Additional criteria exist.
Additional criteria exist.
Ability to complete questionnaire(s) by themselves or with assistance
Currently on invasive mechanical ventilation or noninvasive positive pressure ventilation (CPAP or bilevel positive airway pressure) or requiring > 2LPM supplemental oxygen therapy to maintain O2 saturation > 90% due to hypoxemia
Confirmed parainfluenza at screening by one of the following methods using any sample type: Respiratory Virus Panel, Direct fluorescent antibody (DFA), Qualitative/quantitative RT-PCR test for parainfluenza virus performed at the local laboratory (a confirmatory PCR test will be done at the central lab but is not required to start the patient on study).
Confirmed PIV lower tract disease for subjects on mechanical ventilation will be defined as PIV detection in bronchoalveolar lavage (BAL) or biopsy within last 7 days of screening
Confirmed PIV lower tract disease for subjects on non-invasive positive pressure ventilation or supplemental oxygen will be defined as all of the following within the last 7 days of screening: New pulmonary infiltrate on chest imaging and at least one PIV sign and/or symptom as defined in section 10.3.6
Subjects taking any other investigational drug used to research or treat PIV.
Subjects may not have ongoing chronic diarrhea
Subjects may not have other active malignancies other than indolent malignancies not requiring active therapy which the investigator determines are unlikely to interfere with treatment and safety analysis
Require therapeutic doses of any anti-coagulant.
2. If patient is in irPD (unconfirmed) status, they must not have had a decrease in their Karnofsky Performances Scale (KPS) score > 10 points and to be judged to not have \rapid clinical deterioration\ by the investigator since the subject's last tumor measurement leading to irPD assessment.
Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
2. If lesions are too small to be visualized or palpable for accurate injection.
3. Currently in status of irPD (confirmed) or irPD (unconfirmed) without evidence of tumor inflammatory response, or with rapid clinical deterioration, or with a decrease of 10 points or more on their KPS score since their last assessment before irPD (unconfirmed) assessment.
At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-• Chronic diarrhea.
At least one MIBG avid bone site or diffuse MIBG uptake.
For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR a Curie core of 1 - 2, then biopsy confirmation of neuroblastoma and/or ganglioneuroma in at least one site present at the time of enrollment (bone marrow, bone or soft tissue) is required to be obtained at any time point prior to enrollment and two weeks subsequent to most recent prior therapy. If a patient has 3 or more MIBG avid lesions OR a Curie Score of ? 3 then no biopsy is required for eligibility.
In addition to size, a site needs to meet one of the following criteria: MIBG avid. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions OR a Curie Score of 1 - 2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at time of enrollment (either bone marrow, bone and/or soft tissue) is required to be obtained at any time point prior to enrollment and at least two weeks subsequent to most recent prior therapy. If a patient has 3 or more MIBG avid lesions OR a Curie Score of ? 3 then no biopsy is required for eligibility.
FDG-PET avid (only if tumor known to be MIBG non-avid). These patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy.
Non-avid lesion (both MIBG and FDG-PET non-avid). These patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one non-avid lesion present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy.
Hematuria ? 1+ on urinalysis
Patient must have blood pressure ? 95th percentile for age, height, and gender
Subjects with calculated BSA < 0.40 m2 are not eligible for study participation as Sorafenib dosing for this study cannot accommodate subjects of this size utilizing commercially available drug formulation.
Patient declines participation in NANT 04-05. (Neuroblastoma Biology Study)
Clinical Laboratories:
Subjects must be candidates for at least one of the designated comparator drugs
Presence of more than 50 melanoma lesions
Subjects with contraindications to all of the designated comparator drugs
The patient is ?18 years old.
Creatine phosphokinase (CPK) ?2.5 × the ULN.
The patient has a diagnosis of AML associated with karyotype t(15;17).
Prior allogeneic SCT
Suspected or latent tuberculosis
To define DHL, patients must have evidence of C-myc (defined as: cytogenetic evidence [fluorescence in situ hybridization (FISH) or karyotype] of C-myc breaks [increased copy number in itself is not considered positivity for C-myc] OR positive IHC defined as >= 40% of the lymphoma cells staining for C-myc) PLUS either:\r\n* Breaks in BCL-2 via cytogenetic studies or\r\n* BCL-2 immunopositivity in >= 70% of lymphoma cells during phase I portion of the trial and >= 50% of lymphoma cells during the phase II portion of the trial
Prior pomalidomide exposure
Contraindications to general anesthesia
All subjects must be ? 18 years at the first screening examination / visit
Skin toxicity including but not limited to erythema, rash, ulceration, and open wound that is still clinically present and considered as acute or chronic.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Measurable or evaluable tumors. Subjects with neuroblastoma that is only detectable by Meta-iodobenzylguanidine (MIBG) scan are eligible. Subjects with neuroblastoma that is only detected by bone marrow aspirate/biopsy or elevated homovanillic acid / vanillylmandelic acid (HVA/VMA) are not eligible.
B1: Refractory or relapsed neuroblastoma
B2: Recurrent or unresectable low grade gliomas with BRAF tandem duplication with fusion
B3: Neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) that are unresectable and medically significant.
B4: BRAF V600 mutant tumors.
Recurrent or refractory BRAFV600 mutant LGG or LCH tumors
Subjects with NF-1 and only PN lesions that cannot be evaluated by volumetric analysis (only applicable to Part B).
For dose escalation and dose expansion in combination with BMS-936558: HL and DLBCL
NOTE: subjects may not have had a transfusion within 7 days of screening assessment; NOTE: patients who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until PT/INR is stable based on a measurement that is pre-dose as defined by the local standard of care
Renal failure requiring hemo-or peritoneal dialysis
< 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
Prior use of or participation in a clinical trial evaluating and agent that either blocks androgen synthesis (e.g. abiraterone acetate, TAK-700, TAK-683, TAK-44) or targets the AR (e.g., bicalutamide, BMS-641988) (patients who are known to have only received placebo in these studies are eligible)
Cohort B: T2a-4N0M0 who are not candidates for cohort A or who will not be treated with chemotherapy (due to patient preference or at the recommendation of the treating physician)
Patients meeting the following exclusion criteria will be excluded from the functional MRI portion only:\r\n* Metallic implant exclusions will be determined per institutional policies\r\n** Pacemakers and defibrillators are excluded\r\n** Stents etc. will be evaluated according to Memorial Sloan Kettering Cancer Center (MSKCC) policy\r\n* Unmanageable claustrophobia\r\n* High risk for nephrogenic systemic fibrosis
Karnofsky performance status (KPS) >= 60% and be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement
Diagnosis of sclerosing cholangitis
Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis; surgically related ascites does not exclude the patient)
Must have recovered from the immediate post-operative period
Serum phosphorus calcium, magnesium and potassium >= lower limit of normal (LLN)
Contraindications to sorafenib
Prior treatment with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors (VEGFR) (licensed or investigational including sorafenib), except bevacizumab
At least one evaluable lesion.
Has leukaemia.
Subjects with abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (NOTE: subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).
Subjects with moderate valvular thickening.
Documented presence\r\n* GROUP A: kinesin family member 5B (KIF5B)-RET or related variant RET fusions\r\n* GROUP B: any of the following aberrations\r\n** NTRK fusion\r\n** MET overexpression, amplification, or mutation\r\n** AXL overexpression, amplification, or mutation\r\n* GROUP C: ROS1 fusion
Serum phosphorus, magnesium, and potassium >= lower limit of normal (LLN) after adequate supplementation if necessary
Patients with NF1 and inoperable PN defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN has to cause (stratum 1) or have the potential to cause (stratum 2) significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients will be enrolled into stratum 1 or 2 based on PN related morbidity; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF1 or have at least one other diagnostic criterion for NF1 listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more café-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
PHASE II: Measurability and suitability for volumetric MRI analysis of the target PN must be confirmed with the NCI Pediatric Oncology Branch (POB) prior to enrolling a patient; the target PN will be defined as the clinically most relevant PN, which has to be amenable to volumetric MRI analysis; PN will be classified as “typical PN” versus “nodular PN” versus “solitary nodular PN prior to enrollment
Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated
Supplementation with vitamin E greater than 100% of the daily recommended dose; any multivitamin containing vitamin E must be stopped prior to initiation of therapy
Ophthalmologic conditions:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
A bad reaction to AZD5363 or any drugs similar to it in structure or class.
Patients must have an Oncotype DX recurrence score < 18\r\n* If the patient does not already have Oncotype DX recurrence score, specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory in Redwood City, California; please see MA.39 trial specific website for instructions on ordering Oncotype DX test
Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements; each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate\r\n* A similar process must be followed for sites outside of Canada as per their respective cooperative group’s procedures
NET and GIST tumors must be unresectable
NET subjects must have progressed on or been ineligible for treatment with somatostatin analogues (SSA) and at least one other FDA-approved targeted therapy (everolimus or sunitinib).
Absence of available therapy with reasonable likelihood of cure or significant clinical benefit
Circulating hepatitis C virus on qPCR
A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
Active adenovirus viremia
Need for vasopressor or ventilatory support
Treatment with Epstein-Barr virus cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-T cells directed against B cells, or unselected donor lymphocyte infusion (DLI) within 8 weeks of Cycle 1 Day 1
Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm.
Have KPS of ?60%
Valid results from central molecular analysis confirming PIK3CA/AKT1/PTEN-altered status in tumor tissue by next-generation sequencing (NGS)
Participants with HR+/HER2- breast cancer for whom endocrine-based therapy is considered an appropriate option per local clinical guidelines (i.e. participants should not be considered eligible for endocrine-based treatment)
Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
Patients must have adequate organ function, defined as (Note: Complete Blood Count (CBC) test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining screening blood sample):
Previous splenectomy
All immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) must have resolved completely to baseline
Hematocrit at screening and at initiation of idasanutlin > 40%
Resistance to/intolerance to hydroxyurea according to modified European Leukemia Net (ELN) criteria
Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Neutrophil count < 1.5 × 10^9/liter (L) prior to dosing on Cycle 1 Day 1
Lateral pelvic separation greater than 50 cm and/or anterior-posterior separation greater than 35 cm which are incompatible with MR for Calculating Attenuation (MRCAT) reconstruction
Contra-indications to receiving gadolinium contrast
KPS < 80
Unable to complete quality of life questionnaires
?18 years old
For the fifth cohort during Part 2 Cohort Expansion, participants with solid tumors must have evidence of BCL-2 expression.
Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose)
Certain scores on an anxiety and depression mood questionnaire given at screening
Phosphorus >= institutional lower limit of normal (repletion allowed)
Use with caution:\r\n* CYP2C19 non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study\r\n* CYP3A4/5 sensitive substrates and any non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study\r\n* CYP2D6 inducers, moderate/strong inhibitors or sensitive substrates are permitted if no acceptable alternatives are available; however, caution should be used; other non-sensitive substrates or weak inhibitors of CYP2D6 are allowed on study
Does not have active acute bronchiolitis obliterans or bronchiolitis obliterans organizing pneumonia
DONOR: Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271
Participants must have histological or cytological confirmed melanoma that is metastatic or unresectable and clearly progressive
Macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity.
Preoperative eGFR >= 45 cc/min/1.73 m^2 as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation
Part III:
Previously received and are continuing to derive clinical benefit from iniparib, as monotherapy or in combination with chemotherapy, as determined by the treating physician.
Ongoing treatment with iniparib at time of parental study completion/closure and meet criteria to initiate a subsequent cycle of therapy, as described in the parental study protocol.
Patient has not previously participated in any clinical trial of iniparib.
Participants with circumstances that will not permit completion of the study or required follow-up; for instance, if travel to and from treatment site is an issue
Willing to sign a durable power of attorney
Serum phosphorous >= LLN
Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN
Serum magnesium >= LLN
SCLC pathologically confirmed at MSKCC
Untreated extensive stage (ES)-SCLC, defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular lymphadenopathy, or contralateral hilar adenopathy
Plasma creatine phosphokinase (CK) < 1.5 x ULN
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy)
Patients who are planning on embarking on a new strenuous exercise regimen that can result in significant increases in plasma creatine kinase (CK) levels
Mentally, physically, and geographically able to undergo treatment and follow up
This includes but is not limited to cetuximab, panitumumab, erlotinib, geftinib, and lapatinib
For immunoglobulin (Ig) A patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ? 750 mg/dL (0.75 g/dL).
Waldenstrom's Macroglobulinemia.
Requirement for constant administration of proton pump inhibitor, histamine (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
CD22 expression
Currently or previously treated with AMG 386, or other molecules that primarily inhibit the angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor
Treatment within 30 days prior to enrollment with the following: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab
Relapsed or refractory AML with poor prognostic features
Breast feeding must be discontinued for the duration of therapy with vorinostat and the concomitantly used chemotherapy, if applicable
Anaplastic histology will be excluded
The participant’s NSCLC must be considered medically inoperable for a standard lobectomy and mediastinal lymph node dissection/sampling procedure; the participant may have underlying physiological medical problems that would prohibit a surgery due to a low probability of tolerating general anesthesia, the operation, the postoperative recovery period, or the removal of adjacent functioning lung; these types of patients with severe underlying health problems are generally deemed “medically inoperable;\ standard justification for deeming a patient medically inoperable based on pulmonary function for surgical resection of NSCLC may include baseline forced expiratory volume in one second (FEV1) < 40% predicted, postoperative FEV1 < 30% predicted, severely reduced diffusion capacity, baseline hypoxemia and/or hypercapnia, severe pulmonary hypertension, severe cerebral, cardiac, or peripheral vascular disease; if the participant has medically operable disease but declines surgery after consulting with a thoracic surgeon, he/she will be considered eligible
No histological or cytological diagnosis of NSCLC; this includes failure to make an intraoperative diagnosis of malignancy at the time of ENB
The primary tumor of any T-stage\r\n* Is within or touching the zone of the “proximal bronchial tree” defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi), or\r\n* Within 1 cm of the mediastinal pleura but outside the proximal bronchial tree
Zubrod Performance Status (PS) of </= 2; or 3 if of recent onset (i.e. < 2 weeks) and if the compromised performance status is related to uncontrolled pain which is expected to come under control by means of improved pain management.
Unstable angina defined as angina (or anginal equivalent) 2 or more times per week despite medical therapy.
Diastolic dysfunction felt to contribute to any clinical sign or symptom.
Requirement for anticoagulant therapy other than low intensity treatment to maintain patency of central venous catheters.
Desire to quit smoking, with at least one prior failed quit attempt and willingness to participate in a treatment study
Current substance dependence, other than nicotine
Current unstable major medical disorder
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Maintenance of Lupron or antagonist unless previously treated with orchiectomy
Serum potassium of >= 3.5 mEq/L
Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study enrollment
Radioembolization within 8 weeks of day 1 dosing of sorafenib
Ability to receive intravenous contrast for the purpose of imaging
Medical conditions that would contraindicate bevacizumab therapy in non-squamous NSCLC (Arms C, D, E, and F)
Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)
Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either or both are contraindicated.
Must have known MGMT methylation and IDH1 mutation status to be screened for study entry.
Patient with histologically demonstrated, previously untreated glioblastoma
Patient has any of the following baseline mood disorders (not attributable to GBM) as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ? 12 in the PHQ- 9 or a cut-off of ? 15 in the GAD-7 mood scale for reasons not attributable to GBM; or selects a positive response of '1, 2, 3' to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9)
Grade 2 or worse hypercholesterolemia or hypertriglyceridemia or >8% glycated Hb (HbA1C)
Target Population
Prisoners or subjects who are involuntarily incarcerated
Inclusion Criteria (must all be answered \Yes\):\n\n          -  Has the patient given written informed consent?\n\n          -  Is the patient between 18 years old and 80 years old inclusive?\n\n          -  Has the patient had histologically proven HGG with recurrence or progression following\n             initial definitive therapy(s) such as surgery with or without adjuvant radiation\n             therapy and/or chemotherapy (confirmed by diagnostic biopsy or contrast-enhanced MRI\n             and evaluable by Macdonald criteria)? Note if first recurrence of GBM is documented by\n             MRI, an interval of at least 12 weeks after the end of prior radiation therapy is\n             required unless there is either: i) histopathologic confirmation of recurrent tumor,\n             or ii) new enhancement on MRI outside of the radiotherapy treatment field.\n\n          -  Does the patient have a single, HGG tumor recurrence/progression that is ? 5 cm in its\n             greatest dimension?\n\n          -  Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate\n             for ? 80% resection?\n\n          -  Has the patient elected not to undergo treatment with the Gliadel® wafer?\n\n          -  Does the patient have a Karnofsky performance status ? 70?\n\n          -  Does the patient have an absolute neutrophil count (ANC) ? 1500/mm3?\n\n          -  Does the patient have an absolute lymphocyte count ? 500/mm3?\n\n          -  Does the patient have a platelet count ? 100,000/mm3?\n\n          -  Does the patient have a Hgb ? 10 g/dL?\n\n          -  Does the patient have a normal PT/PTT? (subnormal PT/PTT acceptable)\n\n          -  Does the patient have an estimated glomerular filtration rate of at least 50 mL/min\n             (inclusive) by the Cockcroft-Gault formula?\n\n          -  Does the patient have an ALT < 3 times the upper limit of the laboratory reference\n             range and total bilirubin < 1.5 mg/dL?\n\n          -  If the patient is a female of childbearing potential, has she had a negative serum\n             pregnancy test within the past 21 days?\n\n          -  Is the patient willing to use condoms for contraception for 6 months after receiving\n             Toca 511 or until there is no evidence of the virus in his/her blood, whichever is\n             longer. If the patient is a fertile female, is she willing to use contraception for at\n             least 12 months?\n\n          -  Is the patient willing and able to abide by the protocol?\n\n        Exclusion Criteria (must all be answered \No\):\n\n          -  Has the patient received cytotoxic chemotherapy within the past 3 weeks (6 weeks for\n             nitrosoureas) of the planned surgery date?\n\n          -  Does the patient have, or has the subject had, within the past 4 weeks any infection\n             requiring antibiotic, antifungal or antiviral therapy?\n\n          -  Has the patient had a surgical procedure in the last 28 days or a surgical wound that\n             is not healed?\n\n          -  Does the patient have any bleeding diathesis, or must the subject take any\n             anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for\n             surgery?\n\n          -  Does the patient have a history of allergy or intolerance to flucytosine?\n\n          -  Is the patient HIV positive?\n\n          -  Does the patient have any gastrointestinal disease that would prevent him or her from\n             being able to ingest or absorb flucytosine?\n\n          -  Has the patient received any investigational treatment within the past 30 days?\n\n          -  Is the patient breast feeding?\n\n          -  Has the patient received Avastin® (bevacizumab) for this recurrence/progression, or\n             within the past 5 weeks?\n\n          -  Does the patient have a history of prior malignancy, excluding basal or squamous cell\n             carcinoma of the skin, with an expected survival of less than five years?
Histologically confirmed classical or lymphocyte predominant Hodgkin's lymphoma that is relapsed or refractory after at least one prior chemotherapy\r\n* Core-needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping\r\n* Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be used in conjunction with nodal biopsies\r\n* Fine-needle aspirates are not acceptable\r\n* If the original diagnostic specimen is not available, specimens obtained at relapse may be utilized
Any inflammatory changes of the surface of the eye
Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL
Eligible for ASCT
Subjects have had their PIK3CA gene mutation status assessed prior to enrolling into the study
Malabsorption ;
Immunocompromised status
Symptomatic hypercalcemia
No prior bortezomib is allowed
Greater than three prior recurrences
Requires therapeutic anti-coagulation
Candidate for primary chemoradiation as decided by both medical and radiation oncology
Hypertensive medication should be initiated or increased for optimal blood pressure control according to standard public health guidelines prior to starting the ketogenic diet
Known G6PD (glucose-6-phosphate dehydrogenase) deficiency
Hypertensive medication should be initiated or increased for optimal blood pressure control according to standard public health guidelines prior to starting the ketogenic diet
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 5 X institutional upper limit of normal OR a stable or a decreasing test value in patients who have undergone placement of an intrabiliary stent; both the treating radiation oncologist and medical oncologist must agree that the potential subject’s test value is acceptable for study accrual
Known G6PD (glucose-6-phosphate dehydrogenase) deficiency
Prosthetic joint or other artificial implant or device that cannot be easily removed (there are some exceptions)
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Acute or chronic skin disorders that will interfere with subcutaneous injection of the vaccine or subsequent assessment of potential skin reactions
Allergies to any component of the vaccine
Recipient must have available the successful collection of a POL62326 mobilized product.
Myeloproliferative disorder (MPD)
Recipient must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed test.
Recipient must demonstrate ability to be compliant with medical regimen.
Recipient must have no evidence of active infection at the time of the transplant preparative regimen or at time of transplantation.
Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures
Subject has completed a prior study utilizing ABT-806 or 111ln ABT-806 (ABT 806i) and the Investigator believes that continued treatment with ABT-806 is in the best interest of the subject.
Subject discontinued ABT-806 or111ln ABT-806 (ABT-806i) administration before completing the prior study (due to disease progression, toxicity, withdrawn consent, other).
Adequate bone marrow, renal, hepatic, and metabolic function (tests within normal limits or only minimally altered as assessed ? 7 days before inclusion in the study)Recovery to asymptomatic or minimally altered or to baseline from any adverse event (AE) derived from previous treatment (mild alteration for alopecia, skin toxicity or fatigue are allowed).
Recursive partitioning analysis (RPA) class I (Karnofsky performance status [KPS] >= 70%, primary cancer controlled, age < 65, metastases in brain only) or class II
Mini Mental Status Exam (MMSE) >= 18 prior to study entry
Resection cavity volume on planning scan of =< 35 cc
RPA class III (KPS < 70%)
Resection cavity volume > 35 cc
No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm)
Scheduled for an open thoracotomy for lung resection
Had previous open thoracotomy procedures
Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma
Acute renal failure
Patients must have platelets (Plt) >= 50,000/uL; platelet transfusion can be given prior to the start of SGN-35 and during SGN-35 treatment to achieve a target plt >= 50,000/uL
In addition to the inclusion/exclusion criteria outlined, to be eligible for treatment with the higher 2.4 mg/kg dose of brentuximab vedotin in the new cohort of 20 additional patients, best response after 2 cycles of brentuximab vedotin administered at the 1.8 mg/kg dose, must be partial remission (PR) or stable disease (SD) as determined by radiographic imaging
The subject must have received tivozanib while enrolled in another protocol, must be tolerating study drug and must currently display clinical benefit. The length of time that a subject must be on the parent protocol before rolling over to this protocol will be dictated by the parent protocol.
Unhealed wounds (including active peptic ulcers)
Life-threatening illness or organ system dysfunction compromising safety evaluation
Performance status (PS) 0-1 (a measure of the ability to carry out activities of daily living); subjects with PS 2 are eligible if due to disease related symptoms
Elevated triglycerides
Positive for Flt3-ITD activating mutations during Screening. Local laboratory results must be received prior to enrollment. Patients with a history of Flt3-ITD positive disease may be considered after discussion with the Medical Monitor.
Have been postmenopausal for ?1 year
Have FSH levels indicative of postmenopausal state (i.e., 30-120 IU/L) documented within 21 days of C1D1.
Documentation for inclusion criteria histologically proven, unresectable, locally advanced or metastatic liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Participants must have a pathology report indicating the diagnosis of liposarcoma or leiomyosarcoma that has been reviewed by the sponsor before randomization may occur and treated in any order with at least: an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen do not need to be reviewed by the Sponsor
Eligible diagnoses:
No previous allogeneic BMT (syngeneic BMT permissible)
Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
Willingness to take everolimus orally, once daily at the same time every day either consistently with food or consistently without food
Mesenchymal, dedifferentiated, and extraskeletal myxoid chondrosarcoma subtypes.
Dedifferentiated
Myxoid
Round Cell
Pleomorphic - Leiomyosarcoma
Vasectomized partner with confirmed azoospermia.
Subjects that have previously been treated with dacarbazine or its analogue temozolomide or eribulin.
Serious and potentially life-threatening arrhythmia.
Patient has a corrected serum calcium ?ULN.
Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study
Previously treated relapsed or refractory B-cell iNHL
Patients with a history of bleeding varices in previous 1 year are excluded (unless patient has subsequently had a liver transplant); those with gastric varices or varices that are deemed as high risk by the endoscopist should be placed on appropriate medical therapy as advised by the gastroenterologist
Glycated hemoglobin (HbA1c) =< 8%
EXPANSION COHORT B ONLY: documented genetic alteration (mutation or homozygous deletion) in the PTEN gene, identified by the MSKCC Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay platform or other Clinical Laboratory Improvement Amendments (CLIA)-approved test
Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:\r\n* Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety\r\n* At screening, mood rating scores of >= 10 on Patient Health Questionnaire (PHQ)-9 and/or >= 15 on Generalized Anxiety Disorder Scale (GAD)-7, unless overruled by psychiatrist's assessment\r\n* Patient selects a response of \1, 2, or 3\ for question 9 on PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)\r\n* NOTE: the psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment; if mood rating scores do not meet eligibility criteria and/or the investigator deems that a patient has mood disorder that renders the patient ineligible, that patient may not be registered to the study unless there is a subsequent psychiatric clinic consultation in which the psychiatrist overrules the mood assessment questionnaire result/investigator judgment
Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living)
Absolute lymphocyte count lower than 200 x 10^9/l .
Cytomegalovirus (CMV) viremia.
CT imaging in screening (based on local evaluation) showing 2 or more clearly demarcated lesions with a largest diameter > 1.5 cm, or 1 clearly demarcated lesion with a largest diameter > 2.0 cm.
Elevated triglycerides
Serious preexisting medical conditions
Part B Expansion Cohort 1 (CRPC):
Part B Expansion Cohort 6 (LY2875358 plus trametinib in participants with uveal melanoma with liver metastasis): Contra-indications for trametinib
In patients with diseases other than NSCLC, ALK translocation is not required and overexpression of ALK protein may be considered indicative of a genetic abnormality in ALK.
Any drug that results in hepatic enzyme induction such as anti-convulsants (phenytoin, valproic acid, carbamazepine, phenobarbital); Keppra (levetiracetam) is allowed
Any malabsorption problem
Subjects must be CMV seropositive prior to transplant by CMV immune screen or CMV immunoglobulin G (IgG) or develop detectable disease by polymerase chain reaction (PCR) in the post-transplant setting
Subjects who had histopathologically confirmed overall grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible
DONOR: Adult donors must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG positive
Histologic confirmation not required if other diagnostic criteria are met;
Palliative radiotherapy is not permitted throughout the study period;
Active hemoptysis
Pathologic diagnosis of malignant pleural mesothelioma (MPM) confirmed at participating institution
Positive immunohistochemical staining for WT-1 (greater than 10% of cells)
Underwent resection, radiofrequency ablation, radiation or chemoembolization within 4 weeks before enrollment or not recovered from such treatments.
Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease.
Hepatic encephalopathy, per the investigator's evaluation.
History of clinically significant gastrointestinal bleeding requiring procedural intervention (e.g., variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 4 weeks before enrollment.
Acute or chronic severe renal insufficiency (glomoerular filtration rate <30 milliliters [mL]/minute/1.73 square meters) or acute renal insufficiency of any severity due to the hepato-renal syndrome.
A cluster of differentiation (CD) 4 count > 100/mcL will be required within 2 weeks of study participation
Ability to understand and the willingness to sign a written informed consent document; as the correlative studies are critical to the clinical and scientific value of the trial, CD4 count/HIV viral load determinations will be required, and participation in the tumor-based correlative studies will be strongly recommended; additionally, investigators MUST request sample donation to the AIDS Cancer Specimen Resource (ACSR); however, the patient may refuse sample donation; patients accrued to the expansion phase of the study will be required to undergo pharmacokinetic sampling
Since zidovudine and stavudine have potential for severe hematological toxicity potentially overlapping with toxicities of the study therapy, treatment with these agents will be disallowed
Waldenstrom macroglobulinemia
Prior history of a hypersensitivity reaction to PLD, doxorubicin, bortezomib, carfilzomib, or liposomal drug formulations other than PLD
History of reactions to liposomal drug formulations other than PLD should be evaluated individually and if their reactions were felt to have been due to the encapsulated agent, rather than the liposomal component itself they should be excluded at the discretion of the investigators
Serum calcium below the CTCAE grade 1 upper limit (11.5 mg/dL or 2.9 mmol/L); in cases where the serum calcium is below the normal range, the calcium adjusted for albumin is calculated and substituted for the measured value
Serum potassium greater than the lower limit of normal (LLN) and < 5.5 mmol/L
Presence of left bundle branch block (LBBB)
Complete left bundle branch block
Right bundle branch block and left anterior hemiblock (bifascicular block)
Does not have:
Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
Has a known sensitivity to 5-FU
Has a known dihydropyrimidine dehydrogenase deficiency
Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or IMC-18F1, or other agents that specifically target VEGF
Participants who have squamous histology.
The participant is unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or,
Presence of fever [oral temperature of 38°C or equivalent] at Baseline. However, this requirement is waived if the subject has a history of fever within in the 24 hours prior to Baseline; or, if the subject reported symptoms of feverishness at some time during the 48 hours prior to Baseline. AND at least 2 out of the following 4:
Respiration rate >24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived.
Heart rate >100 beats per minute.
Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting.
Clinical symptoms of influenza with positive influenza diagnostic test result or strong suspicion of influenza illness based on clinical symptoms and local surveillance information.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline
Subjects who require routine/intermittent hemodialysis or continuous peritoneal dialysis (due to inability to provide appropriate dosing schedule for oseltamivir) at Baseline. CRRT modalities are allowed.
ALT or AST 3xULN and bilirubin 2xULN
ALT 5xULN
French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
Have serious preexisting medical conditions
Relapsed AML, ALL, CML in blast crisis, or MDS
Involved FLC ?10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
Involved FLC level ?10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
ANC of >1000/mm3 independent of G-CSF
Involved FLC level ?10 mg/dL and an abnormal FLC ratio in serum (<0.26 or >1.65)
a. bortezomib
b. an IMiD
ANC of >1000/mm3 independent of G-CSF
Previous chemo within 2 wks
Hx of ventricular arrhythmia or symptomatic conduction abnormality within 12m
Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
Primary AL amyloidosis
Previous chemo within 2 wks
Hx ventricular arrhythmia or symptomatic conduction abnormality within 12m
Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
Primary AL amyloidosis
Cytopenias
Night sweats without signs of infection
Recurrent, unexplained fever of greater than 100.5F (38C) without signs of infection
Fatigue which interferes with the patient's quality of life
Progressive or massive lymphadenopathy OR
Progressive or massive organomegaly French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Any malabsorption problem
Resectable pancreatic adenocarcinoma
Pathologic diagnosis of pancreatic adenocarcinoma
No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Patients are not eligible if they have received local radiation which includes any of the following: 1200 centigray (cGy) to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria
Patients must have failed (relapsed or refractory) front-line standard anthracycline-containing regimen, such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD), vinblastine, doxorubicin hydrochloride, vincristine sulfate, bleomycin sulfate, mechlorethamine hydrochloride, etoposide, and prednisone (Stanford V), or bleomycin sulfate, etoposide, doxorubicin hydrochloride, cyclophosphamide, procarbazine hydrochloride, and prednisone (BEACOPP)
Normal serum potassium (K+), magnesium (Mg+), phosphates (PO4), and total Ca++ (calcium) (pre-treatment abnormal values may be therapeutically corrected before starting therapy and must be documented as normal or if abnormal values persist must be documented as clinically insignificant)
Lymphocyte predominant histology
Subjects must have failed at least two prior courses of BCG with or without recombinant interferon alpha administration or be BCG intolerant. This includes either two six week induction courses of BCG or a 6 week induction course followed by a 3 week mini-induction course of maintenance BCG.
Subjects with organ transplants
f. Immunologically mediated disease (eg, rheumatoid arthritis, autoimmune hepatitis, immune mediated glomerulonephritis).
Has radiologically documented evidence of major blood vessel invasion or encasement by cancer
Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions)
for intratumoral cohorts, supratentorial HGG (WHO grade III or IV)
technically unresectable HGG
KPS: at least 70
more than 2 recurrences including present recurrence
Gliadel wafer or wafers implanted within the past 8 weeks
any infection requiring antibiotic, anticoagulant, or antiplatelet agents within the past 4 weeks
g.i. condition that would prevent ingestion or absorption of 5-FC
Hematocrit > 21%
Normal serum electrolytes, magnesium and phosphorus on the day of therapy; correction of abnormalities is permitted
Unable to attend to 2nd study visit at Stanford for Mohs surgical excision
Any female that is trying to get pregnant
Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L); subjects must discontinue HRT prior to study enrollment; for most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT; if a female subject is determined not to be post-menopausal, they must use adequate contraception
Melanoma of ocular origin
Achieved a response to at least one prior regimen
If previously treated with a lenalidomide and dexamethasone (len/dex) combination:
Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded
Must have one of the following: newly diagnosed CP Ph+CML, CP or AP resistant/ intolerant to imatinib and/or dasatinib, or Ph+ ALL either relapsed after or refractory to standard therapy
Calcium phosphorus product less than 4.0mmol2/L2.
Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered on study with approval from the medical monitor.
Subjects with known glucose 6 phosphate dehydrogenase deficiency.
Using a consistent and daily amount of ST with specific nicotine and tobacco-specific nitrosamine (TSNA) levels for the past year;
Stable, good mental health (e.g., no recent unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria).
The patient's blasts cells show expression of WT1 transcript, detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR).The patient received the following therapy according to the Institution's standard of care.
The first ASCI administration should be given within one year after the last chemotherapy administration. All screening procedures should be completed within seven weeks before the first ASCI administration.
Serum ALT < 2.5 times the ULN.
The patient has hypercalcemia.
Tumor within or touching the zone of the proximal bronchial tree defined as a volume of 2 cm in all directions around the proximal bronchial tree (carina, right and left mainstem bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
Patient must be considered medically inoperable as determined by the principal investigator
Age initiated after limitation - 18 years or older. A separate pediatric study is proposed to evaluate tolerance to the drug in children.
Gender is not a criterion.
Hypotension requiring vasopressor support
Endotoxin Activity Assay ? 0.60 EAA units
Evidence of at least 1 new onset organ dysfunction
Inability to achieve or maintain a minimum mean arterial pressure (MAP) of 65mmHg
There is clinical support for non-septic shock
Subject has had chest compressions as part of CPR
Major trauma within 36 hours of screening
Subject has sustained extensive third-degree burns
No collecting duct, medullary or sarcomatoid histology.
Normal WBC (3.5-10.8 x 103µL), PLT (140-400 x 103µL), and HCT (37-52%)
Potassium within the normal range of 3.5-5.3 mEq/L
No medically documented preexisting auditory damage.
Patient desires not to participate in the study.
Adults >/=18 years
Any malabsorption problem
Known glucose-6-phosphate (G-6-P) deficiency
Intubated, mechanically ventilated, with respiratory failure secondary to diffuse, bilateral parenchymal lung disease (as judged by chest x-ray).
Oxygenation index (OI) > 13, but < 37, for two consecutive blood gases which should be separated by at least one hour within 48 hours of the initiation of mechanical ventilation.
Arterial catheter placement
Glasgow Coma Score < 8 (prior to respiratory failure).
Pre-existing limitations on care options, (Do Not Attempt Resuscitation Orders, etc).
hypotension unresponsive to treatment (mean BP < 60 or < 5th % for age),
persistent cardiac tachyarrhythmia >150/minute, or persistent bradyarrythmia < 50/minute, or age appropriate criteria for younger children,
metabolic acidosis > - 10 milliequivalent (mEq)/L for more than 2 hours,
hyperkalemia, serum K+ > 6.5 plus widening of QRS complex on EKG (QRS complex corresponds to the depolarization of the right and left ventricles of the heart).
Willingness to participate in Patient-Reported Outcomes assessments
Subjects must agree to receive counseling related to pregnancy precautions, teratogenic and other risks of lenalidomide
Refrain from donating blood or semen as defined by protocol
Paraplegia
The subject has a resectable tumor or cyst arising from the pancreatic exocrine gland (pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm of the pancreas, or mucinous cystic neoplasm of the pancreas) and is undergoing surgical resection of the neoplasm
Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy
Approval for allogenic regimen given at Patient Care Conference
DONOR: History of prior malignancy; however, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis; the risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient
Patients may receive transfusion if necessary to reach the pre-apheresis hematology parameters; if elevated PT is concluded to be due to a circulating anticoagulant then patient may enroll despite the abnormal laboratory finding
Patients must be judged as being in a state of “no evidence of disease” at the time of enrollment; there is sometimes difficulty in definitively determining whether previously irradiated or surgerized sites are truly sterile, but the judgement should be based on standard imaging using the best judgment of the referring physician and Principal Investigator or her designee
ANC > 750 cells/mcl
Life-threatening, visceral metastases
Emotional limitations
Any malabsorption problem
immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
fever (>38ºC) of unclear etiology
night sweats
Normal organ function tests including blood urea nitrogen (BUN)
AST, ALT, and alkaline phosphatase (AP) must meet one of the following criteria:\r\n* AST or ALT =< 5 times ULN AND AP =< normal\r\n* AST or ALT =< 1.5 times ULN AND AP =< 2.5 times ULN\r\n* AST or ALT =< normal AND AP =< 5 times ULN
Baseline laboratories (repeat labs can be evaluated at baseline to establish eligibility):
ANC Granulocytes < 1,500/ microliter
Has a medical or psychiatric condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations.
The recurrence to be treated needs to be the 1st or 2nd recurrence of the AG or GBM
Patients can only be on non-enzyme inducing anti-convulsants; if they are on an enzyme inducing anti-convulsant, they may be converted to a non-enzyme inducing anticonvulsants
Known sensitivity to bendamustine
Known sensitivity to mannitol
Baseline LVEF ? 50% and not lower than the institutional lower limit of normal;
Known DPD deficiency;
Radiographic evidence of cavitary or necrotic tumors
Inadequate blood count
A female subject is eligible to participate if she is of:
Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods stated in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least two to four weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
Diagnosis of MDS or CMML
Patient had recurrence of osteosarcoma, localized to the lungs, had complete surgical removal of all lung nodules are eligible for enrollment.
Patient had histological confirmed diagnosis of osteosarcoma of the recurrent sample.
Serum bilirubin levels =< 1.5 mg/dL; higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis
Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
Treatment with nitrosoureas, such as carmustine (BiCNU), nitrogen mustard agents, or melphalan, within 6 weeks of first dose of elotuzumab.
The patient has hypercalcemia.
Previous radiotherapy delivered to the upper abdomen.
MM diagnostic criteria (all 3 required):
Renal failure requiring hemodialysis or peritoneal dialysis.
Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.
No more than 14 days lapse in gefitinib treatment between the patient completing the preceding gefitinib clinical study and beginning of this study except when agreed by the AstraZeneca physician.
Withdrawal, at any time, from the preceding gefitinib study.
Adults or skeletally mature adolescents (ie, radiographic evidence of at least 1 mature long bone [eg, humerus with closed growth epiphyseal plate]) equal or greater than 12 years of age
Known or suspected current diagnosis of non GCTB giant cell-rich tumors
Planned invasive dental procedure for the course of the study
Has completed study 3200K1-4000-WW, including 2 weeks of therapy and completion of all post baseline efficacy, safety, and health outcomes assessments.
Is receiving opioids on a regular schedule, not just as needed to control pain.
Currently using an opioid antagonist or partial antagonist.
Patients with familial adenomatous polyposis (FAP) and duodenal adenomatous polyposis without current lower tract adenomatous polyposis i.e. status/post (s/p) ileostomy
Blood urea nitrogen (BUN) > 25mg%
Patients with symptoms of active gastroesophageal reflux disease (GERD) (symptomatic despite medication or current erosive esophagitis on endoscopy)
Patients must have a normal echocardiogram (EF > 50% normal) without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. The Sponsor must be provided with copies of these tests BEFORE Sponsor will approve enrollment. In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.
Failure to meet any of the criteria set forth in Section 3.1.
Atrial fibrillation,
Thromboembolic events,
The PI and the Clinical Coordinator will be asked to verify that their referred patients do not have these exclusionary histories listed in 3.2 and a copy of this verification must be sent to the Sponsor before the Sponsor will approve of enrollment. Referring physicians will not need to sign. (Template for verification letter Appendix C).
Must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received AdV-tk + prodrug on this study may receive an additional AdV-tk + prodrug course at recurrence if eligibility criteria are still met.
Other patient eligibility requirements\r\n * Human immunodeficiency virus (HIV) 1 and HIV 2 negative\r\n * Not pregnant or at risk for pregnancy and willing to use acceptable birth control methods\r\n * No uncontrolled drug of alcohol abuse; patients will be screened for drug and alcohol abuse by a pediatric psychologist who is a member of the HSCT team; this information will not be recorded in the patients’ hospital chart\r\n * Signed informed consent by patient or legal guardian in accordance with research ethics board guidelines or institutional review board (IRB)\r\n * Lansky or Karnofsky performance score of 0, 1 or 2\r\n * Suitable haploidentical donor available\r\n * Cryopreserved autologous stem cells (minimum 1 x 10^6 cluster of differentiation [CD]34+ cells/kg) available for infusion for patient with solid tumors; subjects with solid tumors who have not had stem cells collected for clinical purposes prior to enrolling in the study will undergo autologous stem cell harvest following standard clinical procedures before beginning the study conditioning regimen
Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
Immunocompromised participants with primary or secondary immunodeficiency
Symptoms suggestive of influenza-like illness
Adults ? 18 years old
Primary refractory MM
Serum bilirubin greater than 1.25 times the upper limit of reference range (ULRR).
Keratoconjunctivitis sicca or incompletely treated eye infection.
Have at least one of the following symptoms affecting sleep: a) not feeling refreshed on awakening b) difficulty falling asleep c) waking up during the night d) have difficulty falling back asleep at night after awakening e) waking up too early in the morning f) excessive sleepiness during the day
Have a known major sleep disorder documented by prior diagnosis, such as: a) sleep disordered breathing b) narcolepsy c) periodic limb movement disorder d) parasomnias
Have any other functional tumors if they have familial Multiple Endocrine Neoplasia Syndrome 1 or 2 (MEN 1 or MEN 2).
Participated or completed a GSK sponsored pazopanib study and remains eligible for continued treatment with pazopanib and lapatinib (if on combination therapy).
Your doctor does not think you would be a good candidate for the study
Diagnosis of other \congenital\ aplastic anemias such as: Diamond-Blackfan; Shwachman-Diamond; congenital amegakaryocytosis
Randomization within 112 days of completion of surgical \r\n* The primary region must be included on cross-sectional imaging (e.g. sinus/neck if arising from sinonasal primary; pelvis if genitourinary); radiographic changes considered nonspecific or possibly due to surgery or radiation are not considered evidence of disease
Subjects must be discontinued from ipilimumab or nivolumab as monotherapy or with the combination regimen
Subjects treated with systemic Corticosteroid (CST) within 1 week before randomization and subjects treated with infliximab within 7 weeks before randomization
Subjects allergic to infliximab, inactive components of infliximab, murine proteins and methylprednisolone
MELD Score < 15
History of orthotopic liver transplantation, clinical symptoms of portal hypertension, Whipple's procedure, hepatic artery anatomy incompatible with perfusion or known unresolved venous shunting
Brain lesions with a propensity to bleed
Known esophageal varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer
Neutrophils < 1,500/µL
Any subjects with muscle-invasive TCC (stages T2 - T4) OR any known TCC of the ureter or renal pelvis are not allowed
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
At least two bi-dimensionally measurable nodal lesions ? 1.5 centimeters (cm) in its longest diameter by imaging
The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed Exclusion Criteria Specific to Obinutuzumab-Containing Cohorts: Hypersensitivity to obinutuzumab
Carcinomatous meningitis.
Skin biopsy specimen of representative lesion obtained at screening of study and deemed diagnostic of mycosis fungoides by principal investigator
Exclusion of people that do not understand the risks, such as decisionally-impaired individuals, prisoners, and vulnerable populations
Subjects deemed unsuitable candidates and not medically optimized for RARC
Subjects with tumors lying < 1 cm from sensitive structures such as the ureter, prostate or adjacent bowel
Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
Absolute contraindications: venous injury at the level of the femoral veins or proximally; known or suspected thrombosis of the femoral or iliac veins on the proposed side of venous cannulation, ambulatory patient
Relative contraindications: presence of bleeding disorders; distortion of anatomy due to local injury or deformity; previous long-term venous catheterization; history of vasculitis; previous injection of sclerosis agents; previous radiation therapy
Known carcinomatous meningitis
Histological diagnosis of AL amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens; the type must have been confirmed unequivocally
Ability to complete questionnaire(s) by themselves or with assistance
NT-ProBNP > 8,500 pg/mL
Intrahepatic cholangiocarcinoma; a histological diagnosis is mandated; a diagnosis of adenocarcinoma with staining pattern consistent with cholangiocarcinoma and with a clinical presentation consistent with cholangiocarcinoma will be acceptable for enrollment as this is a typical intrahepatic cholangiocarcinoma presentation
History of biliary stent, internal biliary drain, or prior procedure compromising the ampulla of Vater (diagnostic endoscopic retrograde cholangiopancreatography [ERCP] is permissible)
Known dihydropyrimidine dehydrogenase deficiency
Subject must be participating in an Astellas-sponsored ASP8273 study which has completed, at a minimum, the primary analysis or have completed the individual study evaluation period requirements. Subject must not have met any discontinuation criteria in the parent study.
Subject should be deriving clinical benefit without any persistent intolerable toxicity from continued treatment of ASP8273.
Permeability-glycoprotein (P-gp) substrates with a narrow therapeutic index
Currently enrolled in another interventional study
Patients must have no signs of significant rhabdomyolysis determined by creatine phosphokinase (CPK) levels with a creatine kinase (CK) < 5 times the upper limit of normal
Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, human immunodeficiency virus (HIV) protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem, and amlodipine
Microsatellite instability as determined by MSI-plus assay
Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician and the study principal investigator (PI)
Previous enrollment in the present study
Ability to take pills by mouth
Be eligible and reasonably fit to undergo potentially curative resection
Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula
Inoperable on the basis of co-existent medical problems
Neutrophils < 1.5 x 10^9/L
Legal incapacity
Histological or cytologic confirmation of unresectable or metastatic cholangiocarcinoma (intrahepatic, hilar, extrahepatic bile duct)
Ability to complete a patient medication diary by themselves or with assistance
For patients enrolled on celecoxib cohort: history of ulcer disease or gastrointestinal bleeding, hypersensitivity or asthma to celecoxib, sulfa drugs, aspirin or other nonsteroidal anti-inflammatory drug (NSAID)
Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
Lack of availability of a patient for immunological and clinical follow-up assessment
Granulocytes > 1,500/ml
Patients should have a FLT3 mutation, either internal tandem duplication (ITD) or kinase domain mutation or activation loop mutation
Glycosylated hemoglobin (HbA1c) < 7.0%
Prior administration of an aurora A kinase-targeted agent, including alisertib
Requirement for constant administration of H2 antagonist
Relapsed patients:\r\n* Second or greater relapse OR\r\n* AML in first relapse AND has received >= 450 mg/m^2 daunorubicin equivalents \r\n* NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:\r\n** Doxorubicin: 1\r\n** Mitoxantrone: 3\r\n** Idarubicin: 3\r\n** Epirubicin: 0.5
Any form of active primary or secondary immunodeficiency
Serum sodium level is ? 130 mmol/L
Female subject must either be:
Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
Inability to obtain Foundation One testing on archival tissue, or, lack of previous Next Generation Sequencing incorporating testing for NOTCH -1, -2, -3, and -4
Have a willingness to comply with follow-up HRQOL (health related quality of life) surveys and PSA assessments
Planned elective radical prostatectomy with bilateral nerve sparing technique that can include high or low fascia
Is allergic to aminoglycoside antibiotics (such as gentamicin and/or streptomycin)
Serum FLC ? 100 mg/L, provided that the serum FLC ratio is abnormal.
Smoldering MM.
Documented active systemic amyloid light chain amyloidosis.
There is no line limit for the dose escalation cohort and the dose expansion cohort
Have undergone clearance after baseline ophthalmologic exam (at least fundoscopic exam, visual acuity, intraocular pressure, assessment of visual fields and measurement of color vision)
Inorganic phosphorus =< ULN
Ionized calcium =< ULN
Homozygous UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 (i.e. 7 TA repeats) gene alleles; the UGT1A1 test should be conducted per local institutional practice
Current evidence of corneal or retinal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination
Unresolved diarrhea and bowel obstruction
Renal failure requiring hemodialysis or peritoneal dialysis
Patients with Gilbert’s syndrome unless homozygosity for the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 mutation has been excluded
Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation, plus one other lesion that can be measured
Willing to sign a durable power of attorney
Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis
Active infection with Epstein-Barr virus (EBV) as defined as EBV viral load >= 10,000 copies per mL of whole blood; EBV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active EBV infection
Active infection with cytomegalovirus (CMV) as defined as CMV viral load >= 10,000 copies per mL of whole blood; CMV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active CMV infection
Significant (presumed) risk factors for toxicity due to IASA therapy including, but not limited to: major uncorrectable coagulopathy, bowel perforation, ongoing bacteremia, mesenteric insufficiency, are exclusionary; in these or any questionable cases, discussion with the PI is required
Willing to sign a durable power of attorney
Smoldering MM.
Presence of an enhancing solid renal mass =< 3.0 cm on radiological examination
< 90% solid component on screening cross-sectional imaging
Subjects deemed unsuitable candidates and not medically optimized for partial nephrectomy
Tumors greater than 3.0 cm at their widest point
Subjects with tumors lying < 1 cm from sensitive structures such as the ureter, renal vessels or adjacent bowel
Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
TSER genotype *2/*2
Histologically or cytologically confirmed adenocarcinoma of the rectum that was clinically staged T3, T4 or node-positive (defined as >= N1 per American Joint Committee on Cancer [AJCC] 7th edition) that was treated with the following treatment with curative intent:\r\n* Curative surgical resection\r\n* Pre- or post-operative chemoradiation; and at least 3 months of combined adjuvant OR neoadjuvant systemic chemotherapy (equivalent to 6 cycles of leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX] or infusional fluorouracil [5FU])
Ability to complete medication diary by themselves or with assistance
Use of the following strong inhibitors are prohibited =< 7 days prior to registration\r\n* Boceprevir (Victrelis™)\r\n* Clarithromycin (Biaxin®, Biaxin XL®)\r\n* Conivaptan (Vaprisol®)\r\n* Grapefruit juice\r\n* Indinavir (Crixivan®)\r\n* Itraconazole (Sporanox®)\r\n* Ketoconazole (Nizoral®)\r\n* Lopinavir/ritonavir (Kaletra®)\r\n* Mibefradil\r\n* Nefazodone (Serzone®)\r\n* Nelfinavir (Viracept®)\r\n* Posaconazole (Noxafil®)\r\n* Ritonavir (Norvir®)\r\n* Saquinavir (Invirase®)\r\n* Telaprevir (Incivek®)\r\n* Telithromycin (Ketek®)
Receiving erythroid stimulating agents (erythropoietin [EPO]: Procrit, Aranesp)
Histologically confirmed diagnosis of metastatic melanoma with the presence of the B-Raf proto-oncogene, serine/threonine kinase (BRAFV600) mutation
Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
Tumor located peripherally within the lung (peripheral defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions) and not touching the mediastinal pleura
Only one subject per household may participate
Refusal to participate in the long-term follow-up protocol (2006-0676)
Judged by the study doctor to be a suitable candidate for a radical prostatectomy
Favorable operative risk defined as American Society of Anesthesiology Score (ASA score) =< 3
Newly developed inoperable brain metastases (first occurrence) without associated hemorrhage or midline shift
Lactate dehydrogenase (LDH): there is no restriction
Basic metabolic and hepatic function panels
Temperature =< 38 Celsius (C) (=< 100.4 Fahrenheit [F])
Hematocrit (HCT) >= 30%
Research blood including 40 mL of blood in a heparinized tube for peripheral blood mononuclear cell (PBMC) collection and 10 mL of blood for serum collection (generally in a red top tube) within 30 days of leukapheresis collection
NY-ESO-1 positive by IHC (for this study, even a small level of positivity is acceptable); for patients with < 5% NY-ESO-1 by IHC positivity, the level of staining should be discussed with the patient and they should be informed that this will likely effect the efficacy of the therapy; this conversation must be documented in the patient's medical chart
Patients must have NY-ESO-1 specific cells already produced or in production; these cells may be either in the process of their final expansion (for fresh infusion) or expanded and frozen at the time of enrollment
Ages 50-70 years,
Has a single lesion with a maximum size of ? 12 mm with ? 10 mm of capsular contact as confirmed by MR imaging,
Has ? 33% positive biopsy cores
Are interested in future fertility,
Have had prior transurethral prostatectomy (TURP), or urethral stent,
Patient has a score >= 12 on the Patient Health Questionnaire (PHQ)-9 questionnaire
Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
Patient has a General Anxiety Disorder (GAD)-7 mood scale score >= 15
Blood urea nitrogen (BUN) =< 30 mg/dl
Prior resection of cerebral metastases
Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 19-day period for this trial is not clinically acceptable
Must have HERV-K(HML2) viral load of >= 1 x 10^4 using a gag primer reverse transcriptase (RT)-polymerase chain reaction (PCR) assay
Patients on drugs that interfere with renal function or drugs that compete with tenofovir for active binding sites (i.e. intravenous cidofovir, acyclovir, ganciclovir, and valganciclovir)
Patient using herbal and dietary supplements that may interact with CYP3A4
Heart rate <50 beats per minute;
Complete left bundle branch block;
Atrial fibrillation; and
Abnormal baseline Troponin-I.
Patients must have worst pain rated as no worse than 3 out of 10 on the following question (i.e., a pain score of 0, 1, 2, or 3): “In the past week, how much pain have you had on a scale of 0 to 10, where 0 equals no pain and 10 means the worst pain you can imagine; \ NOTE: this question regarding patient’s pain should be completed within one week prior to registration; this question may be asked orally prior to consent up to 7 days prior to registration; the response will be recorded on the registration checklist
No active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
Negative inked histologic margins from mastectomy pathology (no invasive cells at margin)
No significant post mastectomy complications requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation, nodal completion and routine reconstruction is acceptable
Radiation oncologist intends to treat all target volumes and respect all normal tissues in accordance with the dosimetric constraints described (simulation before registration recommended)
Radiation oncologist is NOT planning to utilize a chest wall/scar boost
Patient must have undergone immediate reconstruction at the time of mastectomy or be planning to undergo reconstruction within 8 months after radiation
No acute gastrointestinal conditions, such as: obstruction, fecal impaction, obstipation, acute surgical abdomen, ongoing need for manual maneuvers to induce bowel movements (such as digital evacuation)
Post-menopausal as defined by at least ONE of the following:\r\n* 12 months (365 days) without a period;\r\n* Bilateral oophorectomy;\r\n* Chemically induced menopause as long as there are no plans to stop during the study;\r\n* For women 57 and under, if at least one ovary and woman has had hysterectomy, must have follicle stimulating hormone (FSH) (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (< 10 for ultra sensitive assay: < 25-30 otherwise); (Note: women 58 and older do not have to have hormonal tests)\r\n* At least one ovary intact, with a uterus, and 180 days without a period with FSH (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (generally that is < 10 for ultra sensitive assay: < 25-30 otherwise) (Note: women 58 and older do not have to have hormonal tests)
Antidepressants for mood and hot flashes, including selective serotonin reuptake inhibitors (SSRI’s) will be allowed if patients have been on a stable dose for the last 60 days and the dose is not expected to change during the course of the study; only subthreshold or low dose antidepressants will be allowed, not antidepressants that have been titrated up to the highest doses for depression management (i.e. Effexor 37.5 -75 mg or Lexapro 5-10 mg or Celexa 10 – 20 mg)
Proficient in English (due to number of questionnaires not validated in other languages)
Diagnosis of depression, major depressive disorder (MDD), suicidal ideations or anxiety disorders in the past 5 years per the medical chart based on Diagnostic and Statistical Manual (DSM) IV diagnoses
Be scheduled to receive an antiemetic regimen that does not contain Akynzeo; in addition, the antiemetic regimen must conform with American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines at cycle 1
CYCLE II PORTION ONLY: Only participants with a nausea score >= 3 at least once on the diary assessment from cycle 1 can be randomized for cycle 2
Have clinical evidence of current or impending bowel obstruction
Have dementia
Be taking benzodiazepines
Be taking amifostine (Ethiofos)
>= 6 score on the worst fatigue question of the BFI (Brief Fatigue Inventory, question 3); it is not required for the patient to complete the entire BFI to meet this criterion
Ability to complete questionnaire(s) by themselves or with assistance
History of or currently taking medications for attention deficit hyperactivity disorder, severe anxiety disorder, schizophrenia, or substance abuse by patient record and/or self-report
Currently using any other pharmacologic agents or nonpharmacologic interventions to specifically treat fatigue, including psychostimulants, antidepressants, acupuncture, etc. will be excluded; Note: antidepressants used to treat items other than fatigue (such as hot flashes or depression) are allowed if the patient has been on a stable dose for >= 30 days prior to registration and plans to continue for the duration of the trial; erythropoietin agents to treat anemia are allowed; exercise is allowed
Motivated to stop smoking, as indicated by a score of 6 or above on the Contemplation Ladder
No allergies to and not currently using varenicline
No suicidal thoughts as indicated by a positive (1+) response to question 9 on the PHQ9
No other household member or relative participating in the study
A diagnosis of radionecrosis will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation
Symptomatic brain radionecrosis to at least one lesion following radiosurgery treatment for brain metastases where symptomatic is defined as:\r\n* New or increasing headache associated with mass effect, sensory or motor abnormality, cognitive changes, speech difficulty, balance or coordination difficulty, cranial nerve deficits\r\n* Symptoms are persistent or worsening despite administration of at least dexamethasone 4 mg daily for 1 week
Clinical eligibility supported by central imaging real-time review\r\n* The presence of at least the following conventional magnetic resonance (MR) image characteristic:\r\n** Conventional MR\r\n*** Lesion quotient of < 0.3, where lesion quotient is defined as the proportional value of the maximum axial cross-sectional area of the transverse relaxation time (T2)-weighted defined lesion over the maximum axial cross-sectional area of the contrast-enhancing lesion on the longitudinal relaxation time (T1)-weighted post-gadolinium sequence on a comparable axial slice
If the conventional MR findings are not seen, the following dynamic susceptibility-contrast (DSC) MR characteristics may be used to meet eligibility for this study:\r\n* DSC MR\r\n** The cut-offs below will be based on gradient echo type echo planar imaging (GRE- EPI) DSC perfusion images, acquired without using a gadolinium pre-load:\r\n*** Relative cerebral blood volume (rCBV) < 1.5 in the enhancing-lesion relative to normal-appearing white matter (NAWM)\r\n*** Percentage of signal recovery (PSR) >= 76%, where PSR is determined by comparing the lower signal intensity during passage of the contrast bolus with the post-contrast signal intensity on the signal intensity-time curve
Blood urea nitrogen measurement (BUN) < 30 mg/dL
Self-reported cognitive problem plus a measured memory deficit (score =< 7 on single trial of eligibility pre-screen Hopkins Verbal Learning Test-Revised [HVLT-R] form C)
Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-V criteria for insomnia and score >= 10 on the Insomnia Severity Index
Have contraindications to functional testing or yoga participation according to the treating physician or the physician's designee
Patient must be premenopausal at breast cancer diagnosis, as determined locally and documented in patient record; (Note: it is understood that patients’ menopausal status may be unclear at the time of study enrollment)
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines
Patient must be accessible for follow-up
Score >= 10 on the Generalized Anxiety Disorder-7 Questionnaire (GAD-7) and/or a score >= 8 on the Patient Health Questionnaire-9 Item (PHQ-9), indicating clinically significant anxiety or depressive symptoms, respectively
Residency in a rural zip code defined as below by the Rural-Urban Commuting Areas (RUCA) version 3.1; residential zip codes are assigned a RUCA code based on size of its largest population center and commuting patterns; a spreadsheet with eligibility by zip code will be provided to all participating sites\r\n* Rural: 4.0, 4.2, 5.0, 5.2, 6.0, 6.1, 7.0, 7.2, 7.3, 7.4, 8.0, 8.2, 8.3, 8.4, 9.0, 9.1, 9.2, 10.0, 10.2, 10.3, 10.4, 10.5, and 10.6
Residency in one of the following states: Georgia, Illinois, Minnesota, Missouri, New Mexico, North Carolina, North Dakota, South Carolina, Virginia, and Wisconsin
Current psychotherapy (regular appointment[s] with a psychologist, counselor, or therapist within the last 30 days)
Global cognitive impairment based on education-adjusted scores (details below) on the Telephone Interview for Cognitive Status-modified
Active suicidal ideation with plan and intent
Failure/inability/unwillingness to provide names and contact information for two family members or friends to serve as emergency contacts during the course of the study
Diagnosis of ALL, in first remission; enrollment on a Children Oncology Group (COG) therapeutic study for ALL is not required
Receiving continuous oral 6MP during the maintenance phase of therapy for ALL (held only for toxicity or illness), and will be returning to the clinic every 4 weeks for scheduled appointments while enrolled on COG ACCL1033 (between days 1 and 141)
Has a designated parent or caregiver who is willing to enter into a mutual agreement with the patient to participate in a daily supervised medication administration routine
All patients must have undergone a cone biopsy or loop electrosurgical excision procedure (LEEP); depth of invasion must be =< 10 mm
Patient must have Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Oncology physicians must work at a National Cancer Institute (NCI) Community Oncology Research Program (NCORP) practice site with no plans to leave that NCORP practice site or retire at the time of enrollment into the study
Have at least one geriatric assessment domain meet the cut-off score for impairment other than polypharmacy
Able to provide informed consent, or if the oncology physician determines the patient to not have decision-making capacity, a patient-designated health care proxy (or authorized representative per institutional policies) must sign consent by the baseline visit; if the participant is found to be impaired on the Blessed-Orientation Memory Concentration Test (BOMC) during screening; they must have a health care proxy or authorized representative to be eligible to enroll
Patients must have LVEF >= 50% by 2-dimensional (D) echocardiogram within 28 days prior to registration; the echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab; ECHO should not be submitted for central read until patient has been otherwise deemed eligible
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
The presence of a physical or cognitive impairment that would prevent a person from engaging in survey research (such as blindness, deafness, or dementia)
KEY INFORMANT: Member of the lung cancer screening team who is (or would be) responsible for implementation and/or supporting smoking cessation support for patients receiving lung cancer screening; this will include the program champion (intervention clinic only) and is likely to include: imaging facility program directors, health care providers (e.g., physicians, radiological technicians), and other staff (e.g., receptionist); coordinators of centralized services for tobacco cessation at the component/subcomponent would also be eligible
KEY INFORMANT: Agrees to participate in a confidential 1-on-1 semi-structured interview with the research team
KEY INFORMANT: Agrees to have the interview taped, transcribed and qualitatively analyzed
KEY INFORMANT: Unwilling to participate
PATIENT: Lives in a state where their institutions’ PC clinicians are licensed to practice
PATIENT: They are already receiving PC or hospice services
PATIENT: They have cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation
CAREGIVER: They have cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation
Caregivers that are illiterate will be excluded from this study
CD4 lymphocyte count is highly encouraged
Blood urea nitrogen (BUN) < 30mg/dl
The following baseline neurocognitive assessments must be completed and uploaded prior to step 2 registration: HVLT-R (recall, delayed recall, and recognition), TMT parts A and B, and COWA; the neurocognitive assessment will be uploaded into a folder in the NRG Medidiata RAVE System for evaluation by Dr. Wefel; once the upload and scoring of the tools are complete, a notification will be sent within 3 business days to the research associate (RA) to proceed to step 2; in order for the patient to be eligible, at least 5 of the 6 neurocognitive assessments must be able to be scored (i.e. free of any errors)
Completion of all items on the following baseline quality of life forms: MDASI-BT, LASA QOL, WPAI-GH and Employment Questionnaire; these quality of life forms will be required and data entered at step 2 registration
Have chronic nausea that has been present for at least one week (worst daily score > 3, 0-10 visual analogue scale) or vomiting at least five times over past one week
Women who are morbidly obese (BMI >= 40) undergoing laparotomy for any indication
Women with laparotomy incisions left open due to case classification as \contaminated\ or \dirty\
Women with laparotomy incisions unable to be closed primarily due to tissue or fascial damage
Women undergoing panniculectomy at the time of laparotomy
Women with sensitivity to silver
Self-reported current smoker
Has a working telephone number
Has a valid home address
Another household member enrolled in the study
Patient and partner are married or cohabitating and relationship duration >= 1 year
Patient has an Impact of Events Scale (IES) score >= 16 and/or partner has an IES score of >= 17 at the time of initial screening for eligibility
Neither has a significant hearing impairment precluding intervention session participation
Live within one hour commuting distance to the center where they were recruited
Patient has a doctor diagnosis of COPD
Primary closure of wound
Flap coverage or skin graft
Repeat surgeries for oncologic reasons (positive margins)
Known inherited predisposition to thrombosis
Has been treated with mastectomy
After completion of all three screening questionnaires, participant must score accordingly on at least one questionnaire to be eligible:\r\n* Score >= 8 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS)-Anxiety/Depression Scale OR\r\n* Score >= 4 on the Distress Thermometer OR\r\n* Score > 5 on the Modified Cancer Acceptance Scale
Willing/able to attend brief introductory session and use assigned device for the assigned period of time (15 minutes once or twice per day), at least 5 days per week for 12 weeks
Must have telephone
Hearing loss that would preclude participating in interventions; adequate hearing to participate will be determined via: (1) response of “no” to the question [“Do you have a hearing problem now?”]; participants with hearing aids will be allowed to enroll as long as their hearing is adequate to hear the sounds on the study devices; if necessary, potential study participants will receive a brief test trial with the RESPeRATE device; if they indicate inability to hear the guiding tones, they will not be enrolled in the study
CORTISOL EXCLUSION: Participants with endocrine disorders (e.g., diabetes and thyroid disorders) or on steroid-based medications are excluded from the cortisol portion of the study (with the exception of topical hydrocortisone that is permitted)
Paid employment (full time or part time) at time of consent
Has a smartphone (iPhone or Android)
Has low confidence in requesting workplace accommodations (based on a brief screening survey). Low confidence is defined by having a score of 7 or lower on any of the five measures
Requirement of assistive devices (e.g., cane) for ambulation
Plans for moving to a new home or workplace during, pre-, or post-intervention period
Having musculoskeletal pain, defined as regional (joints, extremities, back, neck) or more generalized (fibromyalgia or chronic widespread pain)
Having a pain rating of 4 or greater in worst pain on a 0-10 numerical rating scale in the preceding week (patients with a neuropathic component to their pain that involves the extremities or back will be eligible)
Have non-musculoskeletal pain syndromes (headache, facial pain, chest pain, visceral abdominal pain) if these are the sole source of pain, but can be present as co-morbid conditions as long as a patient has a primary musculoskeletal pain condition defined as above
Phantom limb pain
Have a pending pain-related Veterans Administration (VA) or social security or worker's compensation (comp) disability claim by self-report
Have an implanted electronically charged medical device
Have their own e-mail address, or be willing to sign up for a new one
Currently already enrolled on the TrueNTH website
Have had at least one prior episode of fever and neutropenia (ANC < 500/mm^3 or expected to fall below < 500/mm^3) during doxorubicin and cyclophosphamide (AC)
Pathologically confirmed NHL
Previously enrollment in this study
Patients scoring >= 11 on the Blessed Orientation-Memory-Concentration Test (BOMC) (implying cognitive impairment) will be excluded since their ability to reliably complete the questionnaire will be in doubt
Salvage RC
Must be able to perform basic activities of daily living (as determined by referring study recruiter at intake)
Must be cognitively intact and free of serious psychiatric illness (as determined by study recruiter at intake)
Patient is currently receiving or planned to receive concurrent total parenteral nutrition and/or metoclopramide
Patient has constipation that was not primarily caused by opioids, as determined by the investigator
Patient has a history of irritable bowel syndrome, signs of active gastrointestinal (GI) bleeding, acute surgical abdomen, bowel stents, indwelling peritoneal catheter, mechanical GI obstruction, fecal impaction, or fecal ostomy
Patient has motility/neurologic disorders including autonomic failure (spinal cord lesions, tumor invasion of nerves) and/or poorly controlled endocrine/metabolic disorders (hypercalcemia, hypokalemia, diabetes, hypothyroidism), as determined by the investigator
A text messaging plan that includes a minimum of 150 text messages a month at no additional cost
Hematocrit > 50%
Severe untreated sleep apnea (treatment is defined as therapy with continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], adaptive servo ventilation [ASV], or other positive air pressure device)
Major psychiatric disorder, such as schizophrenia, bipolar disorder, or untreated depression (treatment for depression is defined as current therapy with antidepressant medication or cognitive behavioral therapy [CBT])
Use of the following treatments for erectile dysfunction (ED): penile implants, vacuum pump devices, intra-cavernosal injections
Overt cognitive difficulty demonstrated by not being clearly oriented to person or place or time
Zubrod performance status > 2, or self-reports either not being up and about more than 50% of waking hours or unable to provide self-care
History of current oropharyngeal dysphagia unrelated to cancer diagnosis (e.g. dysphagia due to underlying neurogenic disorder)
Orthopedic, neurologic, or musculoskeletal disability that would interfere with the functional task of standing on a weight scale
Consented to enroll in a trial with a toxicity endpoint
Designated by the patient as a person closely involved in their care
TEMPLATE MODIFICATION:
ANTIBODY PROPHYLAXIS:
PORT SITE CLOSURE TECHNIQUE:
Normal sinus rhythm with resting heart rate >= 80 bpm on screening electrocardiogram (EKG)
Patients with other established indications for ivabradine: stable, symptomatic chronic heart failure (HF) with a left ventricular ejection fraction ? 35% and in sinus rhythm with a resting heart rate (HR) ? 70 bpm, who are taking maximally tolerated doses of beta-blockers or have contraindications to beta-blocker use
Significant cognitive impairment or documented psychologic impairment
American Society of Anesthesiologists (ASA) status > 3
Diagnosed with DCIS, LCIS, ADH, or ALH (the most recent, highest risk lesion is the “index lesion”) between January 1, 2012 and September 30, 2016
Treated and followed at one of the study sites (including affiliated network sites) and for whom treatment and surveillance data are available, for at least 1 year of follow up after date of diagnosis
Participants with bilateral synchronous or metachronous disease (DCIS, LCIS, ADH, ALH) are eligible
A caregiver of a participating lung cancer survivor\r\n*An enrolled survivor may designate one primary caregiver to participate in the study; (a caregiver cannot participate without an enrolled survivor)
Individuals with significant psychiatric disturbance that require a higher level of care; this determination will be at the discretion of the healthcare provider, site principal investigator (PI); as appropriate and determined by the site PI, the study PI may be consulted to discuss determination of participant eligibility
Individuals with substance abuse/dependence problems that require a higher level of care; this determination will be at the discretion of the healthcare provider or site PI; as appropriate and determined by the site PI, the study PI may be consulted to discuss determination of participant eligibility
Incarcerated individuals or individuals detained within the legal system
Beginning a new course of chemotherapy and/or immunotherapy (with a side effect profile that includes the symptoms monitored by SCH) that is planned for a minimum of three cycles
Cognitively capable to use the phone unassisted as verified by research staff
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
Score in the range of 'very low' or 'low' food security status on the United States Department of Agriculture (USDA) Household Food Security Module (score of 3 or higher)
Living independently (no patient in an assisted living facility) in New York City (NYC)
CLINICIAN: Has a Doctor of Medicine (MD) or Doctor of Osteopathic Medicine (DO) degree
CLINICIAN: Is the treating physician providing care to a patient enrolled to the study
Presence of cognitive impairment disorder (i.e. delirium or dementia) sufficient to preclude meaningful informed consent and/or data collection, as detected during the ICCAN intake process
Patient's household is currently receiving or applying for Supplemental Nutrition Assistance Program (SNAP) benefits (formerly known as food stamps)
FOCUS GROUPS:\r\n* Has a household member who has already participated (or agreed to participate)
Commit to the STOP Program by completing the online course and sharing lessons learned with other CCPs at the monthly virtual meetings that will take place during the 6 months following course completion
RANDOMIZED INTERVENTION: Current ICs to a patient with GBM
RANDOMIZED INTERVENTION: Score of > 4 on the Distress Thermometer (DT) and indication that this distress is related in some way to the caregiving role per self-report
In the judgment of the consenting professional, clinician or principal investigator (PI) and/or as per medical record, severe psychopathology or cognitive impairment likely to interfere with the participation or completion of the protocol or ability to provide meaningful information.
Documentation of a low-risk PCa diagnosis as evidenced by clinical features of the\r\nfollowing criteria:\r\n* PSA test at diagnosis =< 15 ng/ml\r\n* Localized PCa (cT1/T2,N0,M0)\r\n* Biopsy Gleason grade 2-6 OR (or 3+4 AND <=33% cores are positive for adenocarcinoma)\r\n** A minimum of 10 diagnostic cores taken by a systematic directed approach. Sampling may be obtained by target transrectal ultrasound (TRUS) or magnetic resonance imaging (MRI) imaging.\r\n* No treatment yet\r\n** No previous radiation or simultaneous use of androgen deprivation\r\n** Prior use of 5-alpha reductase inhibitor is allowed if they have been stopped for 6 or more months and biopsy performed when patient was not\r\ntaking the drug\r\n* English language proficient and ability to provide informed consent form (ICF)\r\n* Managing urologist considers them a candidate for active surveillance
If their managing urologist does NOT deem them as a candidate for active surveillance.
Visual or hearing impairment that would prevent ability to engage in the telephone session or study materials
Women who receive Oncotype Dx testing
PARENT/CAREGIVER: One or both parents self-identify as Hispanic/Latino and the primary participating parent/caregiver is monolingual or bilingual Spanish speaking
CHILD: Children treated for ALL or AML or LL aged 5-12 years and their parents/caregivers
CHILD: Child understands English and is enrolled in school (but can be bilingual)
Recent or current participation in educational/behavioral intervention study with similar focus
Self-reported shortness of breath (a score of 2 or greater on the Modified Medical Research Council Dyspnea Scale)
Cognitive or psychiatric conditions prohibiting study consent or participation
A treating clinician that feels the patient is inappropriate for the study
Able/willing to have an online interaction with a Reimagine Pillar Guide
Patient participants will have an appointment in the Thoracic Oncology Program at the Brigham and Women’s Hospital
AIM 2: Must have an active telephone number
CLINICAL STAFF: Primary care physicians, radiation oncologist, medical oncologist and other providers (i.e. nurse practitioners, navigator, social worker etc.) who refer patients to thoracic clinic will also be recruited for interviews about delivery of tobacco treatment services
AIM 2: Patients needing immediate medical intervention, for example, conditions such as; hypercalcemia causing lethargy and confusion, acute respiratory distress, dehydration, and/or hypotension
Patient has a spouse/partner other or close family member who he/she defines as the primary caregiver
Individuals with diminished mental capacity
Prisoners
Children
Patient is currently enrolled in hospice
Patient lives with a partner (spouse/significant other – includes homo- and heterosexual couples)
Individuals with diminished mental capacity
Prisoners
Pain at baseline as measured by a BPI worst pain score average of >= 3; the BPI worst pain score average will be based on the worst pain scores completed by the patient in the 7 consecutive pretreatment days; a minimum of 4 days of pain scores must be completed by the patient in the 7 day window in order to calculate the average worst pain score; the investigator will optimize the subject’s pain regimen prior to study entry
Prior exposure to radium-223
Received systemic therapy with radionuclides (e.g. strontium-89, samarium-153, rhenium-186 or rhenium-188) for the treatment of bone metastases
Patient with NRS (0-10 scale) pain score ? 4 irrespective of medication
Targeted bone/tumor interface are ExAblate device accessible and are located in ribs, extremities (excluding joints), pelvis, shoulders and in the posterior aspects of the following spinal vertebra: Lumbar vertebra (L3 - L5), Sacral vertebra (S1 - S5)
Able to communicate sensations during the ExAblate treatment
Worst pain NRS still ? 4 And
Patients with persistent distinguishable pain associated with 1 site to be treated (if patient has pain from additional sites, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the NRS compared to the site to be treated).
Need surgical stabilization of the affected bony structure (>7 fracture risk score, see Section 7.4) OR
Unstable angina pectoris on medication
Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (approximately 2 hrs.)
Patient whose bone-lesion interface is < 10-mm from the skin
Significant food allergies which would make the subject unable to consume the food provided (soy or nut allergy)
Reside in a non-metro county of the United States according to the United States Department of Agriculture (USDA) Rural-Urban Continuum Codes (6 -9) (RUCC) or at a rural zip-code by the USDA Rural Urban Commuting Area (RUCA) codes (10.X)
Have an email address at which to receive CaringGuidance prompts
Those mentally or physically unable to read the consent form or other study materials and/or participate in the consent and engagement with the CaringGuidance program; women who have been hospitalized for mental health issues or substance abuse in the past year are ineligible
Dyspnea with an average intensity >= 4 on the dyspnea NRS (range 0-10) over the past week.
Seen at an outpatient clinic at MD Anderson Cancer Center or The Harris Health System (LBJ) Hospital General Oncology Clinic.
Delirium (i.e., score >13 on the Memorial Delirium Assessment Scale; range 1-30).
Postsurgical open wound that has not healed at the time of enrollment.
Heart failure exacerbation at the time of study enrollment.
Expected to undergo therapeutic thoracentesis in the next 2 weeks.
High anxiety score (>=15/21) on the Hospital Anxiety and Depression Scale (HADS).
101 Subject was previously enrolled in Study 20062004.
BC patients scheduled to undergo chemo regimen other than the 12-week, 16-week, 18-week, 20-week, or 24-week regimen
Currently employed in night shift work
Confounding underlying medical illnesses which may cause fatigue (e.g., severe anemia not controlled by medication, per self-report corroborated by medical chart review (e.g., hemoglobin [Hb] < 10gm/dl))
Eye diseases which limit the ability of light to be processed (e.g., untreated cataracts, severe glaucoma, macular degeneration, blindness, pupil dilation problems or retina damage)
Lives outside of the United States throughout duration of study
Moderate to severe CIPN, defined by symptoms such as numbness, tingling, or pain ratings of 4 or greater on a 0-10 numeric rating scale (NRS)
Men that utilize English or Spanish as their primary spoken or written language and identify with a Latino ethnicity and/or culture
Individuals that are unwilling or unable to attend study visits or are planning to move out of a study site coverage area during the subject’s anticipated participation in the study
Treated with intent to cure
Had their cancer care primarily managed by either Johns Hopkins Medical Institution (JHMI) or Peninsula Regional Medical Center (PRMC), with JHMI or PRMC primarily responsible for the patients’ survivorship care
Has private insurance, or covered by Medicare or Medicaid
Not treated with intent to cure
Did not have cancer care primarily managed within one of the 4 participating clinics, or JHMI or PRMC is not primarily responsible for the patients’ survivorship care
Does not have health insurance at screening
Have evidence of at least mild clinical depression on a standardized screening questionnaire
Unable to commit to intervention schedule (6 weekly group meetings)
Actively practicing mindfulness meditation
Be a resident of the United States of America
Subject has a hematologic malignancy with hypoproliferative thrombocytopenia and is expected to have PLT count(s) ? 10,000/µL requiring ? 2 PLT transfusions
Fibrinogen ? 100 mg/dL
IC from the subject or assent from the subject and consent from a parent or guardian, if the subject is < 18 years of age
Planned administration of bedside LR PLT transfusion(s)
Subject is anticipated to need washed or volume reduced PLT during the course of this study
Presently with or a history of acute promyelocytic leukemia (APML), idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or hemolytic uremic syndrome (HUS)
Splenomegaly (presence of a palpable spleen whose border could be felt more than 4 cm below the costal margin)
Currently taking, or participating in a clinical study involving PLT substitutes, PLT growth factors, or pharmacologic agents intended to enhance (ie, antifibrinolytic agents) or decrease PLT hemostatic function
Currently receiving palliative or hospice care
Being able and willing to attend study appointments
Have an active serious mental illness (e.g., schizophrenia, bipolar disorder) as indicated by medical records
If visual, hearing, or cognitive impairment will interfere with intervention
This study was designed to include women and minorities, but was not designed to measure differences between them; males and females will be recruited with no preference to gender; minorities will actively be recruited to participate; no exclusion to this study will be based on race
Race: African-Americans and non-Hispanic whites
Able to perform basic activities of daily living (ADLs)
Able to hear normal conversation
Reporting a severity of 3 or higher on fatigue using a 0-10 standardized scale at intake.
Residing in a nursing home
Bedridden
Currently receiving reflexology or meditative practices
Suspected or diagnosed deep vein thrombosis or painful foot neuropathy.
PHASE II: Current physical activity level exceeding Centers for Disease Control and Prevention (CDC) guidelines for activity (60 min of moderate-vigorous exercise/day for 5+ days/week (wk) including 3+ days of vigorous intensity activities and muscle-strengthening exercises on 3+ days/wk and bone strengthening exercises on 3+ days/wk for children < 18 and 150 min of moderate vigorous exercise or 75 min of vigorous exercise/wk and 2+ days of muscle strengthening activities for adults >= 18); the CDC guidelines are used to determine exercise prescription in our intervention; individuals already exceeding the guidelines would be unlikely to benefit from participating
Are ambulatory
Able to give assent according to institutional guidelines
Have parental consent to participate
Valid email address
Self-reported sleep duration of 6 hours per night or less
Endorses fatigue as determined by eligibility screening and a score of < 43 on Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F)
Being evaluated or likely to be evaluated for a medical cause of fatigue (e.g., anemia, hypothyroidism) during the study; (per provider report)
Have diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated (as assessed by screening questions)
For aim 3: Receiving CTX for a cancer diagnosis on a 7, 14, or 21 day schedule with the CTX dose given on day 1
Has subjective sleep disturbance (i.e., a self-rated score of fairly bad or very bad on question 13 of the Pittsburgh Sleep Quality Index [during the past month, how would you rate your sleep quality overall? 0=very good; 1=fairly good; 2=fairly bad; 3=very bad])
Have a diagnosed sleep disorder (i.e., obstructive sleep apnea or narcolepsy)
Women with non-palpable malignant lesions, requiring image guided localization.
Undergoing lumpectomy (partial mastectomy) procedure
Families of all children < 17 years of age admitted to the hospital during the study period who screen positive for secondhand smoke exposure
Families of all children who have at least one custodial parent smoker
Families of all children who are in the hospital for >= 24 hours
Children in foster care or with unclear custody (i.e. children admitted with non-accidental trauma)
Previous androgen blockade (e.g. antiandrogens) given for greater than 2 weeks in the last 3 months; anti-androgens used during the initiation of ADT to avoid a flare phenomenon are acceptable for up to 4 weeks
Serum vitamin D 25, hydroxy (OH) < 12 ng/mL
Previous exposure to enzalutamide
Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline, defined as at least one of the following:\r\n* Achieving a plateau in oxygen consumption concurrent with an increase in power output\r\n* Respiratory exchange ratio >= 1.1 (RER)\r\n* Volitional exhaustion with a rating of perceived exertion >= 17 (RPE)
Must be able to complete an acceptable muscular strength test (assessed using calculated one-repetition maximum [1-RM]) at baseline in the opinion of the fitness specialist, exercise physiologist, or trained designee administering the test
Subjects who have had treatments with GnRH agonists/antagonists and/or anti-androgens within 1 year of randomization
Meet standard criteria as defined by the institution for a myeloablative allogeneic stem cell transplantation, with myeloablative defined as using conditioning regimens containing:\r\n* Total-body irradiation (TBI) >= 1200 cGy, or \r\n* Busulfan >= 12.8 mg/kg
Concurrent enrollment on other clinical research studies that contain an interventional therapy is not permitted while subjects are receiving pasireotide or within 5 half lives of finishing pasireotide; however, subjects may concurrently enroll in non-interventional studies (e.g. biobanking, mobile health tracking)
Known gallbladder or bile duct disease, symptomatic cholelithiasis, acute or chronic pancreatitis
Patients must have confirmed and measurable sickle cell disease, defined by sickle cell anemia (SS) or sickle beta (SB) thalassemia confirmed by hemoglobin fractionation
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
Patients with type I hypersensitivity reactions to chemotherapy agents including, but not exclusive to, platins, taxanes, or monoclonal agents as evidenced by typical immunoglobulin (Ig)E-mediated symptoms (ie. flushing, hives, dyspnea, wheezing, nausea, itchy eyes, nasal congestion, hypotension, angioedema) or tryptase level elevated above baseline during an infusion reaction\r\n* For various reasons, some, but not all, patients enrolled in the desensitization program may not have positive skin test data to confirm an IgE-mediated reaction; these reasons include 1) cutaneous toxicity of the drug precluding testing, 2) limited sensitivity of skin testing for the drug being tested, 3) lack of adequate testing reagent and controls
Patients with breakthrough reactions requiring multiple desensitization interventions including failed 16-step protocols or intervention with additional antihistamine (requiring > 50 mg of short-acting 1st-generation antihistamine – i.e. diphenhydramine or hydroxyzine -or > 10 mg of long-acting 2nd generation antihistamine – i.e. cetirizine or loratadine)
Medically unable to undergo desensitization
Known sensitivity to omalizumab
CAREGIVERS: Primary caregiver for study eligible patient
Myeloablative preparative regimen (for SAA any conditioning therapy allowed)
Clinically significant fractures as defined by International Society for Clinical Densitometry (ISCD) (a long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities) indicated by a cast or a spine x-ray within the last 2 weeks
Impending invasive dental procedure that would be expected to occur during study participation (through day 360)
Subjects receiving procoagulant agent including desmopressin acetate (DDAVP), recombinant human antihemophilic factor (FVII) or prothrombin complex concentrate within 24 hours of enrollment
Disseminated intravascular coagulation
Fibrinogen level < 150 mg/dl
Patient requiring platelet transfusion threshold of > 20 x 10^9/L
Non-ambulatory
Concurrent diagnosis of organic brain syndrome, dementia, mental retardation, or significant sensory deficit
Major mental illness (e.g., schizophrenia, psychotic disorder)
Absolute neutrophil count (ANC) persistently >= 1500/mm^3 (as measured by 3 complete blood counts [CBCs] done over 6 weeks or 2 successive monthly CBCs) despite 6?MP >= 150% of Children’s Oncology Group (COG) dosing
Subject must currently be participating in an ibrutinib clinical trial, deriving clinical benefit from treatment with ibrutinib in the opinion of the treating physician and do not have access to commercial ibrutinib within their region.
Must abstain from grapefruit juice
Concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (i.e. quality of life) are allowed
completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening
BRAF V600E mutation
Women aged 18 and above;
Have high grade squamous intraepithelial lesion (HSIL) of the vulva (VIN2 or VIN3) caused by infection with HPV types 16 and/or 18 confirmed at screening visit;
Biopsy-proven differentiated VIN;
Allergy to imiquimod 5% cream or to an inactive ingredient in imiquimod 5% cream;
Active B symptoms
LVEF of at least 50%
Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin or ?675 mg/m2 of EPI.
Inclusion Criteria:\n\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\n        visit www.BMSStudyConnect.com\n\n          -  Kidney tumor has been completely resected 4 to 12 weeks prior to randomization\n\n          -  Pathologic TNM staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G\n             any, N0 M0; pT3, G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0\n\n          -  Post-nephrectomy tumor shows RCC with a predominantly clear cell histology, including\n             participants with sarcomatoid features\n\n        Exclusion Criteria:\n\n          -  Participants with an active known or suspected autoimmune disease\n\n          -  Known history of positive test for human immunodeficiency virus (HIV) or known\n             acquired immunodeficiency syndrome (AIDS)\n\n          -  Any severe or serious, acute or chronic medical or psychiatric condition, or\n             laboratory abnormality that may increase the risk associated with study participation\n\n          -  Participants with a condition requiring systemic treatment with corticosteroids\n\n        Other protocol defined inclusion/exclusion criteria could apply
Others:
Glycosylated hemoglobin is <=6.5% hyperglycemic participants permitted if glucose is well controlled by hypoglycemic medication).
At least one \target lesion\ to be used to assess response, as defined by RECIST 1.1 criteria. Tumors within a previously irradiated field will be designated as \non-target\ lesions unless previous progression is documented;
GOG performance status 0-2 (refer to Appendix A);
Subjects with nodular lymphocyte-predominant HL
Concurrent ocular or intraocular condition that requires medical or surgical intervention to prevent or treat vision loss
Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study
DCIS presentation as a palpable mass
Skin lesions on the breast that disrupt the stratum corneum (e.g. eczema, ulceration)
Current smokers
Men are excluded from this study
Subject has agreed to abide by all protocol required procedures including study related assessments, and management by the treating institution for the duration of the study and long term follow-up.
Subject has a diagnosis of high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11) or t(12; 22) (q13;q12)
Subject has advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma. Inoperable refers to a tumor lesion in which clear margins cannot be obtained without leading to significant functional compromise
Any previous gene therapy using an integrating vector.
Radiotherapy to the target lesions within 3 months prior lymphodepleting chemotherapy. A lesion with unequivocal progression may be considered a target lesion. There is no washout period for palliative radiation to non-target lesions.
Positive serology for HTLV 1 or 2.
Subjects who have relapsed or refractory MDS.
Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
Patients must not have active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) which requires intermittent or chronic treatment with an anti-herpetic drug other than intermittent topical use
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
TanyN+M0 or T3-4N any M0 tumors
Disease must be clinically limited to the esophagus or GEJ; GEJ tumors must be Siewert type I-III
Tumors with significant involvement of the proximal stomach which, in the opinion of the treating thoracic surgeon, would require an esophagogastrectomy
Subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which subject is enrolling from.
Subject is currently participating in an investigator-initiated interventional trial and receiving enzalutamide.
Others:
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, or
Both men and women in the lenalidomide combination arm (Cohort D) must adhere to the guidelines of the RevAssist program (United States participants) or, if not using commercial supplies, must adhere to the Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual.
Permanently discontinued from any Medivation sponsored study with talazoparib alone or in combination with another agent.
Known intolerance to lenvatinib, everolimus (or other rapamycin derivatives), or any of the excipients
Participants must be classified into one of two cohorts of recurrent or persistent endometrial cancer of any histology:\r\n* The first cohort (MSI/POLE cohort) includes endometrial cancers that are: MSI-H as determined by immunohistochemical complete loss of expression (absence of nuclear immunoreactivity) of at least one of the mismatch repair genes MSH2, MSH6, MLH1 and PMS2; this test is now done routinely for every newly diagnosed endometrial cancer patient in most centers in the United States (US); and/OR: POLE-mutated, i.e. endometrial cancers known to harbor mutations in the exonuclease domain (amino acid residues 268–471) of polymerase e (POLE) as determined by targeted sequencing or other next generation sequencing assay; any Clinical Laboratory Improvement Amendments (CLIA)-approved genomic test documenting mutations in the exonuclease domain of POLE gene (amino acid residues 268–471) in the tumor will be accepted as proof of presence of POLE mutations and will lead to classification into this patient cohort\r\n* The second cohort (MSS cohort) includes: endometrial cancers that are MSS as determined by normal immunohistochemical nuclear expression of all the mismatch repair genes MSH2, MSH6, MLH1 and PMS2; tumors which have not been sequenced for POLE mutations (i.e. their POLE mutations status is unknown) but are MSS, will be included in this cohort
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
Breastfeeding mothers are not eligible
Participants must be candidates for RP and considered surgically resectable by urologic evaluation
Serum potassium >= 3.5 mmol/L
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and or at least one hour after the dose abiraterone acetate is taken
Matched (8/8) or mismatched (7/8) related, unrelated HCT
Preparative regimen: both reduced intensity and ablative regimens are permitted; each center will pre-specify the regimen they intend to use during the conduct of the study
Prior to Administration of Ibrutinib (Day 60 to Day 90 post HCT)
PRE-SCT
T deplete HCT
Umbilical cord HCT
PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT)
Patients must have histologically confirmed head and neck cancer (squamous cell histology), and may be poorly differentiated, stages IVA, IVB, and select cases of stage III or any stage that meets criterion\r\n* Human papilloma virus (HPV) status is required prior to randomization for oropharyngeal primary tumors, other anatomic sites will be classified as HPV- unless requested per the treating physician\r\n* Epstein Barr virus (EBV) status is required prior to randomization for nasopharyngeal primary tumors, other anatomic sites will be classified as HPV- unless requested per the treating physician
The patient must have failed no more than one regimen of bevacizumab.
7 days from administration of non-cytotoxic agents [e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)]
Skull defects such as missing bone flap, a shunt, or bullet fragments.
Known sensitivity to conductive hydrogels.
Concomitant malignancies
Prior adverse reaction to tetanus toxoid-containing vaccines
Have previously completed or withdrawn from this study or any other study investigating prexasertib or a checkpoint kinase I (CHK1) inhibitor or have shown hypersensitivity to any of the components of the prexasertib formulation
Clinical signs or symptoms of active GI obstruction or requirement of routine parenteral nutrition or tube feedings
A candidate for:
Subject agrees to return device to Mentor if device is explanted
Physician determines implant volume appropriate for the patient taking into account the subject's BMI and chest width
Confirmed or suspected diagnosis of the following rheumatological autoimmune diseases or immune compromised status: SLE, Sjogren's syndrome, scleroderma, polymyositis, or any connective tissue disorder, rheumatoid arthritis, crystalline arthritis, infectious arthritis, spondyloarthropathies, any other inflammatory arthritis, fibromyalgia, or chronic fatigue syndrome
Currently has a condition that could compromise or complicate wound healing. Note, obesity alone is not an exclusion. All surgical risk factors (obesity, diabetes, smoking history, and prior radiation) should be considered in totality for proper subject selection
Anatomic or physiologic abnormality that could lead to significant postoperative adverse events
Anticipated need for use of ADM/mesh at the time of implant or implant exchange
Works for Mentor or the study doctor or is directly related to anyone who works for Mentor or the study doctor
Documented MSI-H or dMMR-positive tumor as determined by local laboratory for Part 1B and Part 2B pembrolizumab combination MSI-H/dMMR expansion cohorts only.
Vulnerable populations (adults unable to consent, individuals who are not yet adults, wards of the state, prisoners)
Vulnerable population: adults unable to consent, individuals who are not yet adults (infants, children, teenagers), pregnant women, and prisoners
They are already receiving PC or hospice services
They have cognitive or psychiatric conditions as determined by the treating oncologist to prohibit study consent or participation
Patients who are incompetent for interview (documented diagnosis of active psychosis or dementia) or unable to provide informed consent as assessed by the interviewer; or too sick to participate, as judged by a member of the research team or the exercise physiologist, or have been treated for another cancer
Self-reported ability to walk 400-meters (approximately one city block) without sitting, leaning, or the help of another person or walker
Written physician approval
Prior chemotherapies are permitted, except with prior treatments with taxanes, vinca alcaloids, gemcitabine, eribulin, ixabepilone, platinum drugs
Adult caregivers of patients undergoing autologous or allogeneic HCT at Massachusetts General Hospital (MGH), and they must attend the HCT consent visit with the patient
A relative or a friend who either lives with the patient or has in-person contact with him or her at least twice per week and is identified as the primary caregiver for transplant
Previous cancer genetic testing or counseling, or prior germline multigene panel testing
Demonstrated attention difficulties (T-score of at least 65 on attention questionnaire or 1 or more standard deviations below mean on direct attention measures)
Computer capability at home or provided a departmental iPad Mini to borrow for study purposes
Pain in the abdomen with an average daily pain rating of >= 4 out of 10, using the following question from the Brief Pain Inventory (BPI): “Please rate your pain by circling the one number that best describes your (abdominal) pain/discomfort on average over the past week (Scale 0-10; 0= No pain, 10= Pain as bad as you can imagine)”
Scheduled to receive RT with curative intent with the expectation that some portion of the mucosa of the upper aerodigestive tract will receive a dose of at least 50 gray.
Under formal pain management contract with a pain management specialist.
Radiosensitive histology with planned RT dose less than 50 gray.
A relative or a friend upon whom the patient relies for help and who likely to be present during hospitalizations or clinic appointments, or willing to participate by phone
Experience ? 2 concurrent symptoms (fatigue, sleep disruption, depressive symptoms, and/or cognitive dysfunction as measured by 4 screening instruments)
Be either phase advanced or delayed (morning or evening types by the Horne-Ostberg Morningness-Eveningness Questionnaire [MEQ] ? 59 or ? 41)
Sighted
Mentally competent to consent
Are engaged in shift work or travel across more than three time zones within 2 weeks prior to study
Have a current diagnosis of seasonal affective disorder or substance abuse
Have a current diagnosis of major Axis I psychiatric disorders (e.g. depressive disorders), neurological impairments, or muscular dystrophies
Take prescribed sedative hypnotics or steroids; individuals who have eye conditions (glaucoma or retinal disease), problems triggered by bright light (e.g., migraine), or take photosensitizing medications (e.g., some porphyrin drugs, antipsychotics, antiarrhythmic agents) will be excluded for safety of using bright light
Are of limited decision making capacity, including those who score 16 or less on the Montreal Cognitive Assessment (MoCA) assessment
Participants who are deemed qualified for yoga movements according to the Yoga Qualifying Movements Screening Checklist (a checklist developed by researchers at the University of California, Los Angeles to promote yoga safety through assessing the eligibility of each patient)
Subjects currently receiving hemodialysis
Subjects currently admitted to an inpatient unit at Michigan Medicine
Has a minimum appointment time of 60 minutes
Individuals with visual impairment or blindness will be excluded
Current smokers who would like help quitting (? 5 cigarettes per day and/or have a breath carbon monoxide [CO] reading of ? 8 parts per million [ppm)]
Able to engage using at least one of the intervention formats
Enrollment in another cessation program
Have contraindications for NRT
Do not have contact information (e.g., address, telephone number)
(Patient participation) First outpatient consultation visit with a palliative care specialist
(Patient participation) Normal cognitive status, defined as a normal state of arousal and an absence of obvious clinical findings of confusion, memory deficits or concentration deficits, as determined by the patient's physician
(Caregiver participation) accompanied the patient to the clinic visit
(Caregiver participation) is identified by the patient as someone who is actively involved in their overall care
(Caregiver participation) is willing to participate in the study and able to complete the questionnaires
(Physician participation) a palliative medicine specialist
(Physician participation) seeing the patient in consultation on the day of the study
(Physician participation) willing to participate in the study
Refusal to participate in the study
Have undergone a lumpectomy or mastectomy
Currently participate in less than 60 minutes of structured exercise/week
Willing to travel to the exercise facility at University of Southern California (USC)
Men must be obese (BMI > 25) and sedentary (< 60 minutes of structured exercise per week)
Are unable to travel to the exercise facility at USC
Significant insomnia as evidenced by an Insomnia Severity Index score >= 12
Motivated and able to follow the demands of the SHUTi program, to keep sleep records, complete self-report symptom reports and make changes in their sleep schedule, including restricting their sleep
Prior attempt(s) to treat insomnia using cognitive-behavioral treatment for insomnia
Diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated, or other sleep disorder
Employment that involves irregular sleep patterns, such as shift-work or frequent long-distance travel that involves adjusting to different time zones, or employment in a position that could impact public safety (such as operating heavy machinery)
Refusal to modify or reduce excessive alcohol use that is likely to interfere with an individual’s sleep
Able to participate safely in all program sessions
Cognitively able to consent to participate
CAREGIVER: >= 21 years
Members of all races and ethnic groups will be included
Patients must be indicated for major head and neck surgery, defined as surgeries with an anticipated post-surgical hospital stay of 4 or more days; examples of major surgeries include, but are not limited to, total laryngectomy, large oral cavity, oropharyngeal, salivary gland, or soft tissue resections requiring free flap or major regional flap (e.g. pectoralis major flap), and large skull base procedures requiring extensive skull base reconstruction
Patients currently taking IMPACT or other immunonutrition products (arginine-containing supplements) will be excluded; other forms of nutritional supplementation, such as caloric supplementation, tube feeding, or other dietary supplements are allowed on study
Patient has not completed a Physician Orders for Scope of Treatment (POST) form
Patient scores >= 7 on the Mini-Mental Adjustment to Cancer cognitive avoidance subscale
Patient is willing and able to consent and travel to the class location for 6 weekly 2-hour sessions
Patient has a family member or close friend eligible and interested in participating in the study
FCG is willing and able to consent and travel to the class location for 6 weekly 2-hour sessions
FCG has adequate English fluency for completion of data collection
Patient reports a score of > 2 on the Activities and Function item from the Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative Oncology Group score)
Patient makes 3 or more errors on a validated 6-item cognitive screener or exhibits significant psychiatric or cognitive impairment (e.g., dementia/delirium, retardation, active psychosis) that in the judgment of the investigators would preclude providing informed consent and study participation
FCG exhibits significant psychiatric or cognitive impairment (e.g., dementia/delirium, retardation, active psychosis) that in the judgment of the investigators would preclude providing informed consent and study participation
Scheduled for oxaliplatin treatment in modified leucovorin calcium, fluorouracil and oxaliplatin regimen (mFOLFOX)6-based chemotherapy regimen
Currently treated with any of the following contraindicated medications:\r\n* Saquinavir, Lopinavir, Amprenavir, Atazanavir, Delavirdine \r\n* Mexiletine (and other types of sodium-channel blocker antiarrhythmics)\r\n* Phenytoin, Carbamazepine, Oxcarbazepine, Lamotrigine\r\n* Amiodarone \r\n* Dronedarone \r\n* Dihydroergotamine \r\n* Cimetidine
Willingness and ability to participate in study assessments and the eight-week intervention
Self-reported completion of at least an eighth-grade education
Post lumpectomy or mastectomy
Self-report of moderate to high levels of stress using the Perceived Stress Scale
Current diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar disorder)
Report of at least 90 minutes of mindfulness activity (e.g., meditation, yoga) per week
Claustrophobia
Unable to lie on the back for an hour
Have arm lymphedema on one side only
Have confirmed LE based on bioimpedance measurements with an LDex score of > 7.1 (which corresponds to a bioimpedance resistance ratio of 2 standard deviations [SD] above normative values)
Have stable arm LE; LE will be considered “stable” if during the 3 months prior to study enrollment there was no arm infection requiring antibiotics, no change in ability to perform activities of daily living related to LE, and no subjective report of significant persistent changes in limb volume
Be mentally and physically able to participate in the study
Be able to attend the sessions at the University of California, San Francisco (UCSF) Parnassus campus
Bilateral upper extremity LE
Current infection or lymphangitis involving the affected arm
Pre-existing LE prior to their BC diagnosis
Have a condition that precludes measurement of LE using bioelectrical impedance spectroscopy (BIS), including pregnancy
Current venous thrombosis in either upper extremity or be on current anticoagulant therapy
Extremity edema due to heart failure
Meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-V) criteria for current major psychiatric illness, such as bipolar disorder, major depression, active suicidal intent, or psychosis that could be exacerbated by the administration of cannabis
Meet criteria for major neurological disorder, such as mild cognitive impairment or neurodegenerative disorders (such as movement disorders, dementia), that could be exacerbated by the administration of cannabis
Compromised immunity
PATIENT ONLY: Having a spouse/romantic partner (including same-sex) and who is willing to participate
PATIENT ONLY: Regularly (self-defined) participation in psychotherapy or a formal cancer support group
PATIENT ONLY: Cognitive deficits that would impede the completion of self-report instruments as deemed by the clinical team
Subject is able to tolerate endoscopy
Subjects with an esophageal stent in situ at the time of study enrollment
Present for CNB
Who underwent or who will undergo lung resection at Brigham and Women’s Hospital (BWH)
Patients with baseline immobility (i.e. wheelchair-bound, use of any walking assistance device, or gait alterations)
Anaphylaxis to local anesthetics or narcotics
Technical contraindications to epidural placement: previous thoracic spinal surgery or local skin or soft tissue infection at proposed site for epidural insertion
Psychiatric (untreated or poorly controlled schizophrenia, major depression, or bipolar disorder), or communication (language) barrier that would preclude accurate assessment of postoperative pain and/or ability to answer questionnaires (need to be able to read, comprehend, and answer questions)
Patient refusal to participate in randomization
Patients with previous ventral hernia repair, cosmetic abdominoplasty or anterior abdominal wall reconstruction
Undergoing bilateral mastectomy reconstruction with tissue expanders (ipsilateral therapeutic/contralateral prophylactic) planned to be exchanged for breast implants
Is medically, psychiatrically, or otherwise unable to participate (as determined by a physician or study principal investigator [PI])
Unwilling or unable to participate in group 3RP sessions delivered via the Partners Telehealth videoconferencing software
At least moderate pain (pain score >= 4) at recruitment
Palliative Performance Scale (PPS) of 60 or higher at recruitment
Serious mental illness (e.g., schizophrenia), which may interfere with engagement in the intervention
All races and ethnicities will be included.
Subjects will be excluded if they do not attend pre-operative clinic dedicated to RC subjects.
Subjects with allergies to any supplements.
Subjects with galactosemia will be excluded.
Previous HSCT procedure (autologous or allogeneic) pregnancy
Eye Diseases which limit the ability of light to be processed (e.g., untreated cataracts, severe glaucoma, macular degeneration, blindness, pupil dilation problems or retina damage)
Focus groups consisting of men who live, work, or worship in the 4 predetermined neighborhoods
Adequate vision and hearing for valid completion of study measures
Psychiatric condition that would preclude or take precedence over study participation (e.g., active psychosis, suicidal ideation)
Intelligence quotient (IQ) below 70 based on baseline/screening assessment
Treatment with psychotropic medication (psychostimulant, antidepressant, anxiolytic, antipsychotic) within the past two weeks, unless being prescribed specifically as an anti-emetic
Parent/legal guardian/caregiver that speaks English available to assist in participant’s training
Significant cognitive impairment as determined by either an intelligence quotient (IQ) of =< 70 or by clinician judgment
Major sensory or motor impairment that would preclude valid cognitive testing
Major psychological condition that would preclude completion of the intervention
Anticipated to undergo pancreatectomy in >= 6 weeks from enrollment
Able to understand the description of the study and willing to participate
Able to understand the exercise program
Able to maintain daily exercise logs
Meet all screening requirements
Unable to complete the baseline assessment questionnaires or functional assessments
Recent fracture or acute musculoskeletal injury that precludes the ability to weight bear fully on all 4 limbs in order to participate in an exercise intervention
Numeric pain rating scale of >= 7 out of 10
Brief Fatigue Inventory (BFI) score > 25
Satisfactory results of screening safety labs, serum testosterone test and drug test
Inability to lay supine for one hour at a time, given the nature of the massage intervention
Subjects who are actively suicidal or homicidal
Subjects who have used massage as a therapeutic modality (medical or psychological) at any point in their lives for the treatment of medical conditions
Subjects who have massages on a regular basis; regular massage usage will be operationally defined as receiving 4 or more massages/year for the last 5 years
Subjects currently employing any other complementary and alternative medicine (CAM) manual therapy and/or holistic therapies to treat a perceived health problem; however, since past experience with CAM therapies should not confound any of the analyses of the experiments proposed in this study, we will not exclude individuals who have engaged in a CAM manual therapy in the past, nor will we exclude individuals who practice yoga or meditation for well-being, take vitamins or use nicotine
CAREGIVER: Unpaid individuals involved in assisting the cancer patient with activities of daily living and/or medical tasks
PATIENT AND CAREGIVER: Oriented to place, person, and time
PATIENT AND CAREGIVER: Have an active telephone service, either cellular or landline
Are able to tolerate surgery (i.e., segmentectomy, lobectomy or bilobectomy) as indicated by standard clinical pre-op evaluation, including pulmonary function tests and cardiac evaluation (if indicated)
Exhibit American College of Sports Medicine contraindications to exercise which include a resting heart rate of > 120 beats per minute (bpm), blood pressure > 180/100 mmHg or unstable angina
Are unable to walk or to complete the 6-minute walk test\r\n* According to our current standard of care, those participants will be referred to physical therapy for evaluation and treatment and will be excluded from the study as unsupervised exercise would not be safe
A healthcare professional, a patient or caregiver in the Radiation Oncology Department at the University of Pennsylvania
Any healthcare professional or patient/caregiver not working in or being seen at Radiation Oncology Department at the University of Pennsylvania
Subjects must have intact preoperative erectile function, sufficient for penetrative intercourse without medication nor assistive device, as defined by a Sexual Health Inventory for Men/International Index of Erectile Function (SHIM/IIEF)-2 score 22 or higher, which is collected as part of routine care.
Lack of successful intraoperative nerve sparing.
Patient on stable analgesic regimen for > 7 days without escalation during study period with rescue or immediate release medication every 3 hours or longer
Transportation issues interfering with return study visits
Presence of conditions where significant elevations in blood pressure would be a serious hazard
Baseline tachycardia, heart rate (HR) > 100
History of seizures, elevated intracranial pressure (ICP) or cerebrospinal fluid (CSF) obstructive states (e.g. severe head injury, central congenital or mass lesions)
Conditions that may increase intraocular pressure (e.g. glaucoma, acute globe injury)
Porphyria (possibility of triggering a porphyric reaction)
Intractable vomiting
Any histologic subtype
First or recurrent presentations
No vascular invasion or resection/repair/reconstruction that results in decreased perfusion of the extremity
Vascular invasion or resection/repair/reconstruction that results in decreased perfusion of the extremity
Able and willing to complete study tasks as evidenced by at least the following: fluent English speaker; hearing and language comprehension; and, sufficient literacy to complete study forms and questionnaires
Depression or anxiety as defined either by ongoing pharmacological treatment for depression or anxiety or a Hospital Anxiety and Depression Scale (HADS) score >= 11 on initial screening; those individuals taking psychoactive medications for treatment of hot flashes are eligible if they have been on a stable dose for at least three months
Dementia as assessed by a mini-mental status exam (MMSE) score < 24 on initial screening
Self-reported consumption of > 14 alcoholic drinks per week or positive screening on the CAGE questionnaire in relation to the past year; NOTE: A single, standard alcoholic drink is defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor
Skin conditions involving open sores on the scalp that would prevent proper application of the electrodes
Hairstyles that obstruct placement of the electrodes including cornrows, dreadlocks, braids or other hair accessories that cannot be removed
Is scheduled to undergo cystoscopy with bladder resection procedure under general anesthesia requiring neuromuscular relaxation using rocuronium bromide to secure airway and requiring neuromuscular reversal at The University of Texas Monroe Dunaway (MD) Anderson Cancer Center - Mays Clinic (ambulatory care building [ACB]-outpatient)
Classified by the American Society of Anesthesiologists (ASA) as class I - IV
Is known or suspected to have neuromuscular disorders (ex: myasthenia gravis)
Survival 2-5 years after last HCT when first approached for enrollment
In remission at time of study entry, may be receiving chemoprevention
Medical or other issue prohibiting computer use, reading or ability to comply with all study procedures or unable to communicate via phone (e.g., significant vision, hearing or cognitive impairment, major illness, hospitalization)
Residing in an institution or other living situation where health care decisions are not made by the participant (e.g., hospitalized, prisoners, living in a rehabilitation facility)
Does not complete baseline patient-reported outcome (PRO) assessment items required to determine stratification or whether the survivor meets inclusion and exclusion criteria
Concurrent liposomal doxorubicin or any other liposomal agent
No significant hearing impairment that would prevent participation in sessions
Live within a 1 hour commuting distance from Rutgers Cancer Institute of New Jersey
Subjects with a diagnosis of differentiated thyroid cancer who have undergone total or near-total thyroidectomy and are candidates for iodine I-131 (I-131) treatment at Thomas Jefferson University Hospital (TJUH) are eligible to participate
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men. A standard drink contains .6 ounces of pure alcohol. Generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey). While on study, patients should limit their alcohol consumption to no more than 8 drinks
No documented bacteremia at time of initial screening
Patients who are incompetent for interview (documented diagnosis of active psychosis or dementia) or unable to provide informed consent as assessed by the interviewer; or too sick to participate, as judged by a member of the research team
Subjects who have been drinking > 5 alcoholic drinks daily for the last year
Subjects on strong CYP 3A4 inducers or inhibitors who are unable to have those agents replaced with clinical alternatives prior to beginning the study; length of washout period will be 7 days; notably, in the case of allogeneic transplant recipients requiring cyclosporine or tacrolimus, no empiric dose adjustments will be required due to close level monitoring and adjustments, which are standard in Oregon Health & Science University (OHSU) protocols
Subjects unable to discontinue benzodiazepines will not be allowed as hypnotics; additional antiemetics will be allowed for rescue but not for prophylaxis
Be first-generation immigrants
Speak Chinese (Mandarin and/or Cantonese)
Have not had recurrence
Have hypothyroidism and anemia
Who are using acupuncture
The child has a significant cognitive impairment that might hinder participation (determination made in consultation with attending physician, oncologist, and parents)
Enrollment in the SATISFY-SOS study (WUSTL IRB# 201203088, NCT02032030)
Known contraindications to peripheral nerve block placement
Skull or bony defect in the area contacting the immobilization straps
RT delivered by clinical setup only (no CT simulation)
Required laboratory parameters: Patients able to adequately perform pulmonary function testing per American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines, as determined by the enrolling investigator and trained respiratory therapists
Clinical asthma (variable and recurrent symptoms of airflow obstruction and airway hyper-responsiveness)
Inability to perform pulmonary function testing (PFT), as determined by the enrolling investigator or PFT lab
Patient is planned to receive hypofractionated palliative radiation =< 10 fractions
All races and ethnic groups are eligible for this trial
Patient has uncontrolled or rapidly escalating background pain
Patient has bradyarrhythmia
Patient is considered medically unstable
Patient is thought to be at risk for misuse, abuse, addiction or overdose for schedule II controlled substance, as evidenced by the following:\r\n* An Opioid Risk Tool (ORT) score of greater/less than or equal to 8.2 \r\n* A review of the California Prescription Control Monitoring Program (PDMP) Controlled Substance Utilization Review and Evaluation System (CURES) report demonstrates multiple prescribing providers and/or multiple pharmacies in the last 30 days; the CURES report will also be used to verify opioid use, opioid dose, and current prescribing providers
Has a primary care provider at Columbia University Medical Center (CUMC)/New York Presbyterian (NYP)
Willingness and ability to complete the entire workshop, including the interviews and questionnaires (there is no predetermined qualification with regard to the ability to hold an artist tool; accommodations and creative solutions will be made to facilitate participation)
Ages 25-65 years
Parent must live at least 50% of the time in the home and have a child 5-17 years old living at home who has been told their parent’s cancer diagnosis
CO-PARENTS
If a biological parent lives in the home, and is physically well themselves, this person must be the co-parent
If a biological parent does not live in the home (or has died), the co-parent does not have to be a biological parent; therefore, co-parents may be step-parents, lesbian, gay, bi-sexual or transgender (LGBT) partners, grandparents, aunts, uncles, etc if they otherwise meet eligibility criteria
CHILDREN
The patient and co-parent must agree to focus on the same child throughout the study and consent to have the child participate before the child's assent will be sought
Children aged 5-13 years of age will participate with a waiver of assent
Children aged 14-17 will assent to participate in the research study by signing a separate assent form
ALL PARTICIPANTS
Participants must live within 35 miles of the University of Washington, Seattle, WA to receive the in-person version of the intervention
Parents and co-parents selecting the telephone version of the intervention may live any distance from the University of Washington
The triad will be ineligible if any member lives in the home less than 50% of the time
If any member of the triad retracts consent or assent prior to completion of the post-intervention surveys, then all members will be excluded from the study thereafter
The child will be excluded if he or she has learning challenges as assessed by the patient or co-parent; patients and co-parents will be instructed to consider any formal diagnoses of a learning disability of the presence of an Individual Education Plan (IEP) when making this assessment
Is not a candidate for immediate hysterectomy, following evaluation by a physician, due to desire to preserve fertility, due to degree of obesity, due to comorbidities, or due to patient refusal of hysterectomy
Must agree to take progestin agents (i.e., oral agents or MIRENA intrauterine device [IUD] which are accepted treatments for low grade uterine malignancies to control their disease while the intervention is ongoing)\r\n* Note: potential participants WILL NOT be asked to delay surgery to participate in this pilot study
In judgement of a physician, is not a candidate for progestin agents
Average nausea numeric rating scale >= 4/10 over past 24 hours at screening
Able to complete study assessments, including keeping a daily diary
Delirium (i.e. Memorial Delirium Rating Scale > 13)
Clinical evidence of bowel obstruction at the time of study enrollment
On scheduled CYP3A4 substrates with narrow safety range at the time of study enrollment (alfentanil, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus)
On scheduled strong or moderate CYP3A4 inhibitors (boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole; amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil) within one week of study enrollment
Existing CVD
Contraindications to exercise
Travel distance greater than 50 miles
Presence of fatigue on FACIT-F subscale of =< 34 on a 0 to 52 scale (in which 52 = no fatigue and 0 = worst possible fatigue)
CRP must be >= 3 mg/l in the absence of any other more likely cause of increased CRP like an infection or an autoimmune disorder
Patient must be willing to engage in telephone follow up with research staff
Regularly engaged in moderate or vigorous-intensity exercise for at least 5 times a week
Phase II: Not adherent to sun protection recommendations (i.e., mean score < 4 [which corresponds to “often”] on a 5-point scale [from 1 = “never” to 5 = “always”] that assesses the frequency of engaging in four sun protection behaviors)
Women who will be treated at the Johns Hopkins Hospital, Sibley Memorial Hospital or who will be treated by oncologists in the community as long as we will have access to treatment records
Women must be willing to receive follow up care either at Hopkins or with their local oncologist for at least 1 year
Women who have a smart phone
Poor image quality on baseline echocardiogram or anatomic limitations that preclude the acquisition of good quality images such as recent mastectomy or surgery
Previous anthracycline exposure
Rhythms other than sinus rhythm
Own a smart-phone (Android or i-Phone operating system [iOS])
Capable of downloading and running the study application (app)
PATIENTS: On scheduled haloperidol for delirium (=< 8 mg in the past 24 h)or rescue haloperidol of >= 4 mg for restlessness/agitation in the past 24 h
FAMILY CAREGIVERS: Patient’s spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
Significant pain during core biopsy as reported by the patient
Preoperative parathyroid hormone (PTH) elevated beyond normal range or inappropriately high for associated calcium level
Patient has recurrent hyperparathyroidism
Does not plan to undergo ovarian stimulation and oocyte retrieval prior to diagnosis
Currently owns a cell phone, uses text messaging services and is willing to accept text messages for this study
Part-time driver (fewer than 5 shifts/week, totaling less than 35 hours per week)
Must have refractory CINV defined as nausea and/or vomiting that occurs after the first cycle of cancer targeted therapy despite guideline-based prophylaxis and after first-line rescue medication with either a dopamine receptor antagonist, steroid, and/or benzodiazepine
INCLUSION CRITERIA FOR PARENTS: Parents of children who are scheduled to receive cancer-directed therapy at Seattle Children's Hospital
INCLUSION CRITERIA FOR PARENTS: Parents of children who has provided written informed consent (child aged 18 years and older), written assent (child aged 13-17 years), verbal assent (child aged 7-12 years)
INCLUSION CRITERIA FOR PATIENTS: Child has provided written informed consent (child aged 18 years and older), written assent (child aged 13-17 years), verbal assent (child aged 7-12 years)
EXCLUSION CRITERIA FOR PARENTS: Parent is cognitively or physically unable to participate in interactive interview
CAREGIVERS: Family member or friend of an eligible patient.
CLINICIANS: Oncology nurses and oncologists practicing at participating clinics.
CAREGIVERS: Unable to complete the baseline interview.
Able to exercise safely on a treadmill\r\n* Eligibility to exercise safely on a treadmill will be determined by physical examination during visit 1; if during visit 2 the subject is unable to complete or exercise safely on a treadmill, then the subject will be considered as withdrawn from the study
Have reliable transportation to the testing facilities
Subjects must have a personal mobile device compatible for the activity monitor
Patients must have documented opportunistic CMV infection, or reactivation; the criteria include (both of the following criteria must be met)\r\n* Patients may have asymptomatic viremia (> 1000 copies/ml) OR presence of symptoms secondary to CMV infection, AND\r\n* Patients must have ONE OF THE NEXT FOUR CRITERIA:\r\n** Absence of an improvement of viral load after >= 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold) or \r\n** New, persistent and/or worsening CMV-related symptoms, signs and/or markers of end organ compromise while on antiviral therapy with ganciclovir, valganciclovir or foscarnet, or\r\n** Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir or foscarnet\r\n** Second recurrence of CMV viremia, CMV-related symptoms, signs and/or markers of end organ compromise
Treatment with antithymocyte globulin within 28 days of planned infusion of virus – specific, antigen selected T cells
Must have evidence of a serologic response (i.e. be seropositive) against CMV
Must be capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood
All subjects who receive a radial forearm free flaps in the included time period, including subjects with head and neck cancer, traumatic defects, chronic wounds, or any other problems that require a radical forearm free flap for reconstruction
Have had a distal, anterograde fasciocutaneous flap
All smokers and tobacco users will be included in this study
Subjects who have had an osteocutaneous or musculocutaneous flap
Subjects who have a radial forearm flap with a proximal skin flap or subjects that receive a “reverse” radial forearm flap
Physician verification of ability to participate in the intervention
Cognitive or hearing impairment
Unable to provide meaningful consent (i.e., impairment such that descriptions of the research are not clearly understood)
Presence of a health problem that precludes safe participation in the intervention
Re-initiating ADT after being on holiday for longer than their ADT dosage (e.g. If the man’s dosage is every six months and he has been off ADT for more than six he is eligible)
Reachable consistently by telephone; and
Able to travel to University of Kansas Medical Center (KUMC) for data collection
Not reachable consistently by telephone; and
Not able to travel to KUMC for data collection
Esophageal carcinoma, undergoing minimally invasive esophagectomy with intrathoracic anastomosis
Individuals who are already meeting four or more of the six target dietary behaviors: >= 5 servings/day of vegetables, >= 3 servings/day of whole grains, >= 2 servings/week of dark meat fish, no processed meat, no sweetened beverages, and =< 1 alcoholic drink/day (d) for women and =< 2 alcoholic drinks/d for men
A first-, second-, or third-degree relative (e.g., son, brother, nephew, or cousin) of an individual with a documented BRCA1 or BRCA2 pathogenic variant
Family history suggestive of a hereditary cancer syndrome not attributable to the BRCA1 or BRCA2 mutation in their family, based on pedigree review by the study team
An uncertain risk of carrying the familial BRCA1 or BRCA2 mutation (e.g., because it is not clear on what side of the family the mutation is segregating), based on pedigree review by the study team
Have one or more children who are BRCA1 or BRCA2 positive
Any anemia treatment within 4 weeks before inclusion (oral iron, IV iron, or erythropoiesis-stimulating agents), or transfusion of packed red blood cells (PRBCs) in 2 weeks
Hemochromatosis or other iron storage disorders
Documented consent to participation to include the following study specific procedures:\r\n* Be able to provide up to six serial stool collections at home and deliver to FedEx location that day as per standard operating procedure\r\n* Have three 10-ml blood samples taken during a routine clinic visit\r\n* To not take probiotic supplements except as oriented\r\n* If randomized to the probiotic-supplemented group (the yogurt-based supplement Activia), be willing to comply with daily intake and record this intake as a component of a dietary log; the patient will be asked not to take any yogurt or yogurt-containing foods beyond this\r\n* If randomized to the probiotic-restricted group, agree not to consume yogurt or yogurt-containing foods\r\n* Maintain a dietary log and stool frequency log
PATIENT: No evidence of thought disorder, delusions, or active suicidal ideation is observed or reported
PATIENT: Evidence of thought disorder, delusions, hallucinations, or suicidal ideation
CAREGIVER: Evidence of thought disorder, delusions, hallucinations, or suicidal ideation
No plan to initiate a new program that could affect well-being during the study period (e.g., psychotherapy, new exercise regimen, meditation classes)
Other factors that at the discretion of the investigators would adversely affect study participation
Dyspnea numeric rating scale at rest >= 3 of 10 (average over last 24 hour)
Memorial Delirium Rating Scale > 13
Hemodynamic instability
Respiratory failure requiring mechanical ventilation or non-invasive ventilation
Frequent use of rescue opioids > 8 x/day or rescue bronchodilators > 8 x/day over last 24 hours
Currently requiring high flow oxygen for oxygenation
Admission to the MSKCC Adult BMT service for an outpatient HSCT for a hematologic malignancy
Physically and cognitively able to participate in the study as determined by the investigators
HSCT CGs: Physically and cognitively able to participate in the study as determined by the investigators
HSCT DYADS: In addition to meeting the inclusion criteria for HSCT patients and HSCT CGs, both parties must provide mutual agreement to participate as a dyad
HSCT CLINICIANS: Member of MSKCC BMT patient care team for at least one year
Physically and cognitively unable to participate in the study as determined by the investigators
HSCT CGs: Inability to complete role responsibilities 24 hours per day for at least 50% of time (>= 50 days)
HSCT CGs: Physically and cognitively unable to participate in the study as determined by the investigators
HSCT DYADS: Participants must not meet the exclusion criteria for HSCT patients and HSCT CGs
Must either be getting her first mammogram or based on prior experience be expecting level 3, 4 or 5 pain
Must have two breasts
May not have taken ibuprofen or other pain medication within the last 12 hours (aspirin [ASA] 81 mg dose is allowed)
Must not have broken or irritated skin (as determined by the study nurses or delegated research staff)
Lymphedema Group: Lymphedema, symptomatic of stage II or III based upon screening responses; or lymphedema index (L-Dex) reading of >= 7 at initial visit
Lymphedema Group: Has compression sleeve
Lymphedema Group: Willing to do guided and home yoga practice
Lymphedema Group: Willing and able to provide informed consent as demonstrated by passing screening tool questions that includes the Short Portable Mental Status Questionnaire
Lymphedema Group: Medical clearance
Lymphedema Group: Reliable transportation to the study site
Medical conditions that would prohibit the safe implementation of a yoga practice (e.g., vertigo, compromised mental status)
No Lymphedema Group: No known lymphedema or intermittent swelling, not symptomatic of stage II or III lymphedema (L-Dex >= 7)
No Lymphedema Group: Willing to do guided and home yoga practice
No Lymphedema Group: Willing and able to provide informed consent as demonstrated by passing screening tool questions that includes the Short Portable Mental Status Questionnaire
No Lymphedema Group: Medical clearance
No Lymphedema Group: Reliable transportation to the study site
Smoke >= 5 cigarettes (cig)/day during the last week
Be open to biomarker feedback
Not actively trying to quit
During the first in-person session (phase 1), a smoker must have elevated carbon monoxide (CO) to confirm final eligibility (CO >= 10 ppm)
Approved to be contacted by the treating oncologist/nurse practitioner
Have impaired quality of life (report a score of 5 or less on question 30 of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30] “How would you rate your overall quality of life during the past week?” [Answers range from 1 – very poor to 7 – excellent]).
Patients must be able to understand and operate the mobile device independently; therefore we will exclude those the provider team considers unable to do so
Patients who have a cognitive disorder which impacts the ability to follow directions or adhere to safety rules; this will be determined by the physical therapist by assessing whether a neurological disorder or musculoskeletal disorder would prevent the patient from safely exercising
Patients who have a neurological or structural disorder which would impact use of exercise equipment; this will be determined by the physical therapist by assessing whether a neurological disorder or musculoskeletal disorder would prevent the patient from safely exercising
Any patient who, in the opinion of the investigators, will be unable to comply with a supervised exercise regimen based on their developmental stage
All ethnicities eligible
Currently receiving home delivered meals from other sources
Requirement for enteral or parenteral nutrition at time of diagnosis
Incarcerated individuals
Planning to receive first-line chemotherapy at Massachusetts General Hospital (MGH)
Significant psychiatric, cognitive or other comorbid disease which the treating clinician believes prohibits informed consent or participation in the study
Oncology Clinician: Current Massachusetts General Hospital (MGH) Cancer Center oncology clinician (board-certified physicians or mid-level practitioners)
Geriatrics Clinician: Current MGH Geriatric Medicine clinician (board-certified physicians or mid-level practitioners)
Palliative Care Clinician: Current MGH palliative care clinician (board-certified physicians or mid-level practitioners)
Planning to receive care at MGH
Significant psychiatric, cognitive or other comorbid disease which the treating clinician believes prohibits informed consent or participation in the study
No medical problems for geriatric clinician to address (e.g. comorbidities, polypharmacy, etc.)
Able and willing to attend in-person PCO workshop at a location convenient to them
Patients who report that they are unable to complete basic functional (e.g., driving, walking) and self-care (e.g., bathing, dressing) activities because of their likely inability to attend the required in-person intervention session
Anesthetic plan must include arterial line (femoral, radial, brachial, dorsalis pedis) either prior to induction of anesthesia or immediately after induction of anesthesia
All patients must also have 3 pre-op blood pressures (BP) to average for determining individual perioperative BP goal; it is preferred to utilize office visit BP's to reduce \whitecoat\ effect seen the morning of surgery
All patients must have a thoracic epidural placed pre-operatively for perioperative analgesia; epidural will be loaded with 2 mg of duramorph after induction of anesthesia and will be started at a rate of 6 ml/hr upon the conclusion of the surgery; a solution of 0.1 % bupivacaine with 2 mcg/ml epinephrine will be used for analgesia; epidural rate will be adjusted for optimal coverage and stable hemodynamics
Patients with sustained preoperative dysrhythmias, based on literature regarding accuracy of FloTrac (i.e., atrial flutter, atrial fibrillation)
Women diagnosed with breast cancer stages I-III initiating first line adjuvant aromatase inhibitor (AI) therapy with any of the Food and Drug Administration (FDA)-approved AIs (anastrozole, exemestane, letrozole)
Significant uncontrolled psychiatric disorder (e.g. psychotic disorder, bipolar disorder, major depression) or other co-morbid disease (e.g. dementia, cognitive impairment) which the treating clinician believes prohibits informed consent or participation in the study
Subjects must have a Single Item Screening Scale for Fatigue score of >= 4 (out of 10 points, 0 being no fatigue and 10 being severe, incapacitating fatigue) to be eligible for the trial
Subjects who exhibit signs of an infection at screening will be rescheduled when symptoms have resolved
Subjects who exhibit signs of infection or a significant change from baseline test measurements via safety labs will be informed
Postmenopausal women, defined by lack of a menstrual period for an entire year
Completed a minimum of 8 years of education
Eating disorders
Prisoners
Having a pain intensity rating of >= 5; a pain score of 5 is considered to be moderate pain
Patient at University of Michigan Gynecologic Oncology Clinic
Positive depression screen (PHQ-9 score >= 8) or current antidepressant treatment
Participants must self-identify as Hispanic/Latina
Participants must be willing and able to receive email newsletters via computer or smartphone for 12 months’ AND/OR willing and able to receive texts via cellphone for 12 months\r\n* Participants must have a personal email address to receive newsletters\r\n** If a participant does not have an email address but has access to a smartphone or a computer, at the baseline data collection visit Columbia University Medical Center (CUMC) study staff will create a free personal Google Gmail email account.
Participants must be willing and able to attend four 4-hour in-person sessions
Participants must not be active smokers within the past 30 days; active smoking is defined as any smoking, even a puff; if identified as a smoker, the individual will be referred the New York (NY) State Smoking Cessation Quit line (nysmokefree.com) which is available in English and Spanish
EXCLUSION - STUDY 1: Lower extremity major amputation
EXCLUSION - STUDY 1: Have other medical conditions that may affect their balance and gait, or are unable to ambulate without assistance
EXCLUSION - STUDY 1: Under the circumstance that a subject develops CIPN during study 1, the subject will be withdrawn from the study but may be asked to participate in study 2
Ability to provide informed consent
Ability to provide a written physician's clearance
Patients must be new to the Survivorship Clinic (within 12 months of first visit).
Dysphagia or requirement for artificial feeding
NIH lung score 3
The subject has a surgical indication for pancreatectomy (pancreaticoduodenectomy, distal pancreatectomy, total pancreatectomy)
The subject is willing to consent to randomization of lavage vs. standard lavage
The subject is not willing to consent to EIPL-S lavage vs. EIPL-D lavage vs. standard
Known benign or indolent disease, including benign pancreatic cystic tumors or pancreatic endocrine tumors
Significant insomnia as evidenced by an Insomnia Severity Index score >= 12
Motivated and able to follow the demands of the CBTI-CS program, to keep sleep records, complete self-report symptom reports and make changes in their sleep schedule, including restricting their sleep
Have diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated or other sleep disorder
Employment that involves irregular sleep patterns, such as shift-work or frequent long-distance travel that involves adjusting to different time zones, or employment in a position that could impact public safety (such as operating heavy machinery)
Refusal to modify or reduce excessive alcohol use that is likely to interfere with an individual’s sleep
Have pain severity (arithmetic mean of four pain severity items) >= 2 on Brief Pain Inventory (BPI)
Have worst pain >= to 4 (0-10 numeric rating scale [NRS]) in the preceding week
Currently receiving acupuncture for any condition or if they have ever used acupuncture before
Reports a fall within the past 1 year OR self-reports that they are concerned about falling
The patient for whom they are a caregiver does not consent to participate
Patient has ongoing vomiting, retching, dry heaves, or clinically significant nausea caused by any etiology, or has had such symptoms within 24 hours prior to the start of day 1 of the study intervention, or has a history of anticipatory nausea and vomiting
Phase II: Patients will be excluded from participating in this research study if they:\r\n* Are already receiving palliative care in the outpatient setting\r\n* Need immediate palliative care and/or hospice care (as determined by their oncology team)\r\n* Have active, untreated, unstable, serious mental illness (e.g., active, untreated psychotic, bipolar, or substance-dependence disorder) interfering with ability to participate\r\n* Have a cognitive impairment (e.g., delirium, dementia) interfering with ability to participate
Self-reported new onset since initiation of treatment cognitive dysfunction as determined by telephone screen using the brief (3 questions) assessment established by Ercoli et al. (endorsement on all three questions):\r\n* Do you think or feel that your memory or mental ability has gotten worse since you completed your breast cancer treatment? \r\n* Do you think that your mind isn't as sharp now as it was before your breast cancer treatments?\r\n* Do you feel like these problems have made it harder to function on your job or take care of things around the home?
As per self-report participants with pacemakers, intracranial electrodes, implanted defibrillators or any other prosthesis
Mallampati I-III
Able to bite upper lip via Upper Lip Bite Test (ULBT)
Inter-incisor distance > 2.5 cm
Thyromental distance > 6 cm
ASA IV-V
Liquid only diet < 2 hrs and/or solids < 8 hrs
Exhibits signs of respiratory tract pathology (including a sore throat preoperatively)
Unable to bite upper lip via Upper Lip Bite Test (ULBT)
Inter-incisor distance < 2.5 cm
Thyromental distance < 6 cm
Airway pathology/facial abnormality
Presence of hepatopetal flow
Choledochoenteric anastomosis; transpapillary biliary stent, or sphincterotomy of duodenal papilla
Contraindications to hepatic artery embolization:\r\n* High risk of hepatic failure, indicated by the constellation of greater than 50% liver replacement by tumor, lactate dehydrogenase (LDH) > 425 mU/ml, serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase [AST]) > 100mU/ml; and bilirubin > 2 mg/dl\r\n* Portal vein occlusion without hepatopetal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow\r\n* Hepatic encephalopathy
Participated in a previous elotuzumab protocol (including, but not limited to HuLuc63-1703, CA204007, CA204009, or CA204011) and is deemed by the investigator to be deriving benefit from elotuzumab and/or other study drugs as defined by the previous protocol
All subjects previously discontinued from an elotuzumab study for any reason
Have been scheduled for an intramedullary nailing (IM) surgery with the department of Orthopaedic Oncology at University of Texas (UT) MD Anderson Cancer Center
The oncologist \would not be surprised if the patient died in the next year\
Planning to receive ongoing care from a participating oncologist and willing to be seen at least monthly
Clinician inclusion criteria:\r\n* Oncology staff nurses who undergo training to deploy CONNECT, oncologists, and practice managers at participating sites will be eligible to participate
Unable to complete the baseline interview
ECOG PS of 3 (capable of limited self-care; confined to a bed or chair > 50 % of waking hours) or 4 (cannot carry on any self-care; totally confined to bed or chair)
As per medical record, moderate erectile functioning pre-surgery (i.e., 15 or greater on the International Index of Erectile Function [IIEF] Erectile Function Domain [EFD] score, or graded their erections as a 1 or 2 on the standard 5 point Urology Erectile Function scale, or have a score of 6 or greater on the 1-10 pre-surgery erectile function scale on the SMRP assessment or have a total score of 15 or greater on items 2-7 on the Prostate Quality of Life Survey: Sexual Domain)
As per self report or as per medical record starting penile injections as part of the erectile rehabilitation program at MSKCC
Both cavernous nerves fully resected as per surgery report (nerve sparing score of 8 in MSKCC surgeon note), or documented in the progress note that the nerves were fully resected
As per self report, specific injection phobia
As per self report or as documented in the medical record, current untreated (e.g. no medication, no therapy) major psychiatric disorder (schizophrenia, major depression); patients diagnosed with a major psychiatric disorder will be reviewed by the study principal investigator (PI) to determine eligibility prior to consent
Have reported pain as a concern as well as psychological distress on a National Comprehensive Cancer Network (NCCN) screener
Ambulatory or able to engage in walking for at least 45 minutes per intervention visit
Sedentary lifestyle, as engaging in less than 100 minutes structured aerobic walking, cycling or swimming per week
Non-ambulatory
Concurrent diagnosis of organic brain syndrome, dementia, mental retardation, or significant sensory deficit
Major mental illness (e.g., schizophrenia, major depressive disorder)
PHASE 2: PEER MENTOR ELIGIBILITY: Self-reported primary responsibility for care and “complete readiness” using the Readiness for Transition Questionnaire
PHASE 2: PATIENT ELIGIBILITY: Currently does not independently self-manage follow-up care according to self-report (i.e., reports low readiness to assume total responsibility for care [score of 1 or 2 out of 4 on overall readiness item OR scores < 3 on any of the 10-item responsibility scale) using the Readiness for Transition Questionnaire)
PHASE 3B: PEER MENTOR ELIGIBILITY: Self-reported primary responsibility for care and “complete readiness” using the Readiness for Transition Questionnaire
PHASE 3B: PATIENT ELIGIBILITY: Currently does not independently self-manage follow-up care according to self- report (i.e., reports low readiness to assume total responsibility for care [score of 1 or 2 out of 4 on overall readiness item OR scores < 3 on any of the 10-item responsibility scale) using the Readiness for Transition Questionnaire)
PHASE 1: PATIENT EXCLUSION CRITERIA: Physician- or self-reported cognitive delay or impairment that would prevent self-management of healthcare
PHASE 1: PARENT EXCLUSION CRITERIA: Patient has physician- or caregiver-reported cognitive delay or impairment that would prevent self-management of healthcare
PHASE 2: PATIENT EXCLUSION CRITERIA: Physician- or self-reported cognitive delay or impairment that would prevent self-management of healthcare
PHASE 3A/3B: PATIENT EXCLUSION CRITERIA: Physician- or self-reported cognitive delay or impairment that would prevent self-management of healthcare
Patient is self-identified as African-American
Patient has serious psychiatric condition (e.g., bipolar disorder, schizophrenia or other psychosis, bulimia or anorexia nervosa, suicide attempt within 6 months or current active suicidal ideation) that would compromise the patient’s ability to complete the study, at the discretion of the investigator
Eligible treatment sites are:\r\n*Weight bearing sites\r\n** Pelvis (excluding pubis) \r\n** Femur\r\n** Sacrum and/or sacroiliac joints\r\n** Tibia\r\n** Up to 5 consecutive cervical, thoracic or lumbar vertebral bodies\r\n** Lumbosacral spine\r\n*Non-weight bearing sites\r\n** Up to 3 consecutive ribs\r\n** Humerus\r\n** Fibula\r\n** Radius +/- ulna\r\n** Clavicle\r\n** Sternum\r\n** Scapula\r\n** Pubis\r\nIf multiple sites are treated, the treatment site is included as weight-bearing if any of the sites include the pelvis, sacrum, femur or tibia
Painful metastases to the skull, hands, feet are not eligible treatment sites, but can be treated off study with conventional fractionation at the discretion of the treating physician
A score of >= 4 on the Distress Thermometer (DT) and indication that this distress is related in some way to the caregiving role; potential participants will be asked whether or not their distress is in any way related to their caregiving experience; individuals who answer \no\ will be asked whether or not their distress started or has gotten worse since the patient began treatment or was diagnosed
As per self-report, is a heavy drinker (regularly having more than 14 alcoholic beverages per week for men, 7 for women)
As per self-report, engaging in night shift work
As per self-report, currently engaged in ongoing psychotherapy
AYA Inclusion Criteria:\n\n          -  Ever diagnosed with cancer;\n\n          -  Knows his or her cancer status;\n\n          -  Ages of 14 up to 20 years;\n\n          -  Ability to speak English;\n\n          -  Consent from the legal guardian for adolescents aged 14-17;\n\n          -  Consent from a surrogate for adolescents aged 18-20;\n\n          -  Assent from adolescent aged 14-17;\n\n          -  Consent from adolescent aged 18-20;\n\n        Inclusion Criteria for Legal Guardians of Adolescents Age 14-17:\n\n          -  Legal guardian of assenting adolescent participant;\n\n          -  Knows cancer status of adolescent;\n\n          -  Adolescent willingness to discuss problems related to cancer with them;\n\n          -  Age 18 or older;\n\n          -  Ability to speak English;\n\n          -  Consent to participate; Consent for his/her adolescent to participate;\n\n        Inclusion Criteria for Surrogates of AYAs Age 18-20:\n\n          -  Selected by adolescent aged 18 to 20;\n\n          -  Knows cancer status of adolescent;\n\n          -  Age 18 or older;\n\n          -  Ability to speak English;\n\n          -  Willingness to discuss problems related to cancer and EOL;\n\n          -  Consent to participate;\n\n        Exclusion Criteria - for AYA or surrogate decision-maker:\n\n        Developmental delay; foster care; active homicidality or suicidality, depression in the\n        severe range
One or more significant medical conditions or other issues that in the physician’s judgment preclude participation in the walking intervention
Undergoing pancreatic resection
Indication for operative intervention being chronic pancreatitis
Non-smokers
Diet restrictions including vegetarianism, veganism, soy-free diet
CRITERIA FOR SURVIVORS:
Have a co-survivor (friend or family member) willing to participate in this research study
Willing and able to attend study visits at the University of Wisconsin (UW) – Madison
Any individual considered to be that of a “vulnerable group”, including pregnant women and prisoners
Diagnosis of plasma cell dyscrasia
Appropriate homebound setting as defined by one of the following:\r\n* Lodging at Memorial Sloan-Kettering (MSK) residence\r\n* Staying at home or a \home equivalent\ in any one of the zip codes; home equivalent is defined as a residence which may or may not be the primary residence of the patient\r\n* \Home equivalent\ must pass the \Home Environment Screening Tool\ for homebound stem cell transplantation (not required for MSK recognized lodging facility)
Adequate caregiver support as defined by:\r\n* Single or multiple informal caregivers willing and able to provide 24 hour a day, seven day a week supervision of the transplant recipient in their home or \home-like\ environment\r\n* Caregiver willing and able to fulfill the basic stem cell transplant caregiver education requirements as determined by caregiver and healthcare team, including social worker
Have Wi-Fi connection
Sorror co-morbidity index > 4
Inadequate housing arrangements
Inadequate caregiver arrangements
YBCS: Able to consent to the study
HCP: HCP of breast cancer patients/HCP designated by a YBCS study participant: oncologists and their advanced nurse practitioners; and primary care providers in family medicine, internal medicine and gynecology
HCP: Able to consent to the study
To be randomized, participants must have the presence of at least 1 reproductive health issue (e.g., birth control practices, fertility concerns, hot flashes, or sexual dysfunction/vaginal discomfort) and 70% adherence on reporting daily hot flashes through text messages during the 1-week run in period
Identifies a DCG involved in his/her care, support, or care planning
DCG: Identifies himself/herself as a DCG for the patient
DCG: Lives > 1 hour travel time away from the patient
DCG: Cognitive impairment
Referred to Section of Speech Pathology and Audiology for swallowing evaluation
Scheduled for abdominal-based autologous breast reconstruction (deep inferior epigastric perforator [DIEP], muscle-sparing [MS]-transverse rectus abdominis [TRAM], or TRAM)
Cognitive impairment
Significant preoperative chronic pain (requiring daily narcotics) or neuropathic pain (requiring daily use of pregabalin or gabapentin) within the previous 3 months
Taking a third-generation AI (e.g., anastrozole [Arimidex], letrozole [Femara], or exemestane [Aromasin]) for at least 3 months with sufficient time left in their AI prescription to complete all study assessments (e.g., at least one year left on AIs)
Experiencing ongoing pain and/or stiffness in one or more joints, which started or worsened after initiation of AI therapy
Having a baseline worst pain score over the past week on the Brief Pain Inventory–Short Form (BPI-SF) of >= 3 on a 0 to 10 scale
Be willing to be randomized to experimental conditions
Inflammatory, metabolic or neuropathic arthropathies at the time of recruitment; this includes international classification of diseases (ICD) 10 codes M05-M14
Fibromyalgia (ICD 10 code M79.7)
Consistent with previous chemoprevention adherence research, patients will be excluded due to the presence of the following psychiatric conditions:\r\n* A lifetime history of dementia (ICD 10 codes F01-, F02-, F03-, F04-);\r\n* A lifetime history of a psychotic disorder (ICD 10 codes: F20-F-29);\r\n* A current diagnosis of a manic episode (ICD 10 codes F30-);\r\n* Current uncontrolled major depressive disorder (ICD 10 codes F33-);\r\n* A current diagnosis of any mental and behavioral disorders due to psychoactive substance use (excluding nicotine-related diagnoses) (ICD 10 codes: F10- F19-, except for nicotine-related diagnoses); and,\r\n* Current intoxication
And/or in the rare instance of the presence of a comorbidity that does not fall into any of the above mentioned exclusion criteria, but that is clinically determined to significantly interfere with the patient’s ability to participate in the study (e.g., cognitive impairment)
The child does not have learning challenges
Parents will be excluded if they are enrolled in hospice at time of enrollment; (however, they will be allowed to continue in the study if they enroll in hospice after beginning the study)
Parents will be ineligible if their child lives in the home less than 50% of the time
Planned chemotherapeutic regimen for subject must meet all of the following criteria:\r\n* A known myelosuppressive regimen which includes a combination of at least two of the following agents: actinomycin, carboplatin, cisplatin, cyclophosphamide, daunorubicin, doxorubicin, etoposide, ifosfamide, topotecan\r\n* At least 4 consecutive cycles\r\n* Cycle length is either 14 or 21 days\r\n* Regimen must either alternate chemotherapeutic agents in an X-Y-X-Y format, such that the same chemotherapy is given every other cycle (e.g. vincristine/doxorubicin/cyclophosphamide | ifosfamide/etoposide), or repeat the same chemotherapeutic agents each cycle in an X-X-X-X format (e.g. repeated cycles of cisplatin/etoposide/bleomycin); questions regarding whether or not a patient’s chemotherapy plan meets inclusion criteria will be decided by the study chair
Pre-existing neutropenia or neutrophil qualitative or quantitative disorder
Enrolled on a therapeutic or supportive care clinical trial
Incarceration
Is scheduled to undergo radical prostatectomy (i.e. robot-assisted or open-approach)
Currently not practicing yoga as a form of exercise and/or meditation
Does not have neurological or musculoskeletal co-morbidity inhibiting exercise
Has never been diagnosed by health care professionals to have absolute contraindications to exercise testing
Willing to participate in yoga therapy for twelve weeks if randomized to intervention group
Willing to undergo phlebotomy
Is NOT scheduled to undergo radical prostatectomy (i.e. robot-assisted or open-approach)
Currently practicing yoga as a form of exercise and/or meditation
Has neurological or musculoskeletal co-morbidity inhibiting exercise
Has been diagnosed by health care professionals to have absolute contraindications to exercise testing
Unwilling to participate in yoga therapy for twelve weeks if randomized to intervention group
Unwilling to undergo phlebotomy
Scheduled for major pancreatectomy (i.e., pancreaticoduodenectomy, total pancreatectomy, or a distal pancreatectomy)
Be able to complete a steep ramp test
Physician consent to participate in vigorous aerobic or resistance exercise training
Experiences shortness of breath, chest discomfort, or palpitations when performing activities of daily living
Has been told by a doctor to have a heart condition and recommended only medically supervised activity
Men participating in vigorous exercise for 75 minutes or more per week, and/or structured resistance exercise on three or more days per week are not eligible
Men who do not complete the baseline lifestyle and quality-of-life questionnaires and food frequency questionnaire (FFQ) will not be eligible
Ureteral stent in place at study registration
Patient reports pain, spasms, or urgency symptoms after stent placement, which are thought to be unrelated to other causes as per the patient or healthcare provider or both (documentation in the medical record is unnecessary)
Active cholecystitis
Current daily smoker
At least moderately interested in quitting and willing to choose a quit smoking date within the next 12 weeks
Participating in a current smoking cessation treatment (counseling or using nicotine replacement therapy [NRT], bupropion, or varenicline)
No phone
Note: additional contraindications for individual nicotine replacement therapies and drugs (bupropion, or varenicline) are embedded within each study component to further screen participants when smoking cessation options are being considered
Obese breast cancer survivors and their overweight or obese partners
Individuals with the following characteristics will be excluded: male breast cancer survivors, non-ambulatory, unable to provide informed consent; have a major mental illness (i.e., schizophrenia); have a mental illness that is not being treated/controlled (i.e., bipolar disorder); and reside > 100 miles from the research site
Pain score >= 4 on a 0-10 numeric pain scale and/or grade 3 neuropathic symptoms according to the National Cancer Institute’s 4 point grading scale
No plans to change pain medication regimen during the course of the study
Willing to come to MD Anderson (MDA) for the therapy sessions; or willing to participate in the therapy sessions at their homes and live within a 45 minute drive of MDA main campus; or can participate in the therapy sessions from one of MDA’s Regional Care Centers
T?cell prolymphocytic leukemia (PLL) in partial remission (PR) or better prior to transplantation; must also have =< 20% of bone marrow cellularity involved by PLL (to lower risk of graft rejection)
No previous allogeneic HSCT
Pregnancy as assessed on baseline blood hCG level
Patients with pain at rest or with movement measured by numeric rating scale (NRS) > 2
Contraindication to epidural catheter placement including bleeding diathesis (essential thrombocythemia, idiopathic thrombocytopenic purpura, von Willebrand disease, and hemophilia A or B), neurological dysfunction (multiple sclerosis, subacute myelo-opticoneuropathy or preexisting lower limb neurological deficit), prior extensive spinal surgery or major spinal deformity, pre-operative use of anti-coagulant with planned use of therapeutic dose of anti-coagulant in post-operatively, documented pre-operative coagulopathy (international normalized ratio [INR] greater than 1.3 not on Coumadin or partial thromboplastin time [PTT] greater than 42), platelets less than 100,000/uL, or evidence of infection at potential epidural site
Subjects must have a phone
Practicing mindfulness meditation for an average of more than 1 hour/week or have taken mindfulness training in the past
Prisoner or incarcerated
Enrollment on the St. Jude Lifetime Cohort (SJLIFE) protocol
Lives within a 45 minute drive of greater Memphis area ATC Fitness Center
Contra-indications to resistance training or protein supplementation (e.g. renal) (physicians will verify if they can participate)
Normal cognition
No evidence of significant anxiety or depression as determined by a total HADS scores of < 21
Has a self-reported history of diagnosed sleep disorders (e.g., obstructive sleep apnea, insomnia), comorbidities associated with poor sleep or fatigue (e.g., chronic fatigue syndrome), or a job with night shifts
Currently on gabapentin
Prior non-tolerance of gabapentin
Upper extremity deformity contralateral to the site of disease that could interfere with accurate point location or alter the energy pathway as defined by traditional acupuncture theory
Pre-existing nausea and vomiting, defined as nausea or vomiting requiring pharmacological treatment greater than 3 times in the week preceding screening
Diagnosis of NF1 through germline mutation OR clinical diagnosis; for the clinical diagnosis of NF1 all study subjects must have two or more diagnostic criteria for NF1 listed below (National Institutes of Health [NIH] Consensus Conference):\r\n* Six or more cafe-au-lait spots (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in postpubertal subjects)\r\n* >= 2 neurofibromas or 1 plexiform neurofibroma\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Participants must have documentation of a plexiform neurofibroma (PN), based on either clinical exam or imaging
Patient must self-report having chronic pain for at least the past 3 months that has interfered with their daily functioning, as assessed by the Pain Interference Index (must get a mean score of 2.0 or higher, or score a 3 on three or more individual items)
No anticipated major changes in their pain treatment regimen (i.e., new class of pain medication starting or change in the class of pain medication) or enrollment on a new treatment study presumed to impact pain in the near future
Subjects who are participating in any other treatment studies, either medical or behavioral, specifically for pain management
Current pain level >= 3 and at least one prior score >= 3 on a 0-10 scale as reported in inquiries of electronic health records (EPIC)
Actively receiving care at the Duke Cancer Center, Durham Regional Hospital, or Duke Raleigh Hospital
Able/willing to have an online interaction with a Pillars4Life group weekly for nine weeks
Ambulatory or able to engage in walking for at least 15 minutes
Sedentary lifestyle, as engaging in less than 100 minutes structured aerobic walking, cycling or swimming per week
Non-ambulatory
Concurrent diagnosis of organic brain syndrome, dementia, mental retardation, or significant sensory deficit
Major mental illness (e.g., schizophrenia, major depressive disorder)
Presence of do not resuscitate (DNR)/do not intubate (DNI) orders at study entry
Clinical evidence of left heart failure as the main etiology for respiratory compromise
Evidence of active intrathoracic malignancy (primary or metastatic) in the lungs or pleural space that is a significant cause of respiratory insufficiency
Shock (need for vasopressor therapy or mean arterial pressure [MAP] < 60 despite fluid administration)
Oliguric acute renal failure (urine output < 500 ml/day) unless already on hemodialysis
Patient already on NIPPV at the time of screening
pH < 7.30 or partial pressure of carbon dioxide (pCO2) > 50 (if available)
Fixed upper airway obstruction
Glasgow Coma Scale (GCS) < 8 or inadequate airway protective reflexes
Undrained pneumothorax/pneumomediastinum
Copious secretions (> 20 cc/hr sputum production or > 100 cc's hemoptysis/24 hrs)
Risk for gastric aspiration (ie; ileus, esophageal or bowel obstruction, active vomiting)
Refusal to receive NIPPV
Respiratory arrest
Patient must be able to ambulate and complete the 6 minute walk test without use of a walker, cane, or any assist devices
Any patient who is unable to comprehend and operate the activity tracker at the discretion of the enrolling provider
Physician (oncologist) clearance to participate in exercise at moderate to high intensity
Normal body temperature (=< 100 degrees F)
Orthopedic or other restrictions or contraindications to high-intensity (cycling) exercise
Presence of fever (>= 100 degrees F)
Primary treatment is active surveillance (AS) with planned annual surveillance biopsies
Physically able to undertake a diet and exercise program
Doctor of medicine (MD) confirmed cognitive impairment
Cognitive impairment documented in the medical record
Undergoing or initiating active surveillance
Low to moderate fitness level at baseline (to be assessed via interview with the exercise staff and through the CPET)
Medical clearance based on medical chart review and normal electrocardiogram (ECG) (administered by a trained health professional) to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention
Able to achieve and complete an acceptable cardiopulmonary exercise test defined as follows: achieving peak or plateau in oxygen consumption concurrent with increased power output; a respiratory exchange ratio >= 1.1 or volitional exhaustion-rating of perceived exertion > 19
NON-RANDOMIZED OBSERVATIONAL COMPONENT ELIGIBILITY:\r\nMedical clearance based on medical chart review and normal electrocardiogram (ECG) (administered by a trained health professional) to undergo a symptom-limited cardiopulmonary exercise test and aerobic training intervention
Significant physiological or psychological impairment that interferes with participation (e.g., migraines, bipolar disorder, psychosis, seasonal affective disorder)
Patient is a prisoner or incarcerated
Anemia (defined as having a hemoglobin level less than 11.7 g/dL for white women, following the Ohio State University (OSU) hospital’s criteria, and 11.5 for African American women, based on data from Beutler and Waalen)
Smoking
Individuals who routinely take fish oil, krill oil, or flaxseed (oil, pills, or powder) or consume more than two portions of oily fish per week
Women with blood pressures above 180/100 or below 80/50
Participants will be recruited by BMT registered nurse (RN) coordinators and physicians prior to patient admission to the Pediatric BMT Unit; caregiver (age 18 years or older) of any patient eligible to undergo autologous or allogeneic BMT and any patient (age 10 years or older) eligible to undergo autologous or allogeneic BMT will be recruited during the “Pre-Transplant Work-up” stage in the outpatient setting
CAREGIVER PARTICIPANTS:
Caregiver (age 18 years or older) of a patient who will be hospitalized to undergo first-time autologous (self) or allogeneic (alternative donor) BMT in the University of Michigan Mott Children’s Hospital Pediatric BMT Unit
PATIENT PARTICIPANTS:
Patient who will be hospitalized to undergo first-time autologous or allogeneic BMT will be given the opportunity to assent/consent and participate in the study; with his/her permission, the patient will also be provided with their own iPad® BMT Roadmap information system to use
The patient will also be provided with their own Philips Equivital® non-invasive, wearable activity monitoring device that will track activity and rest levels
Distal symmetric pain distribution (both feet, with or without pain in hands)
Score of 4 or more on Douleur Neuropathique 4 (DN4) neuropathic pain questionnaire
Patient report of average daily pain intensity > 3 on 0-10 Numerical Rating Scale (NRS) in the past week
All patients must have no more than 3 contiguous vertebral body levels treated at a single site, and no more than 3 discontiguous vertebral body levels treated
All patients must be deemed at \high risk\ of developing vertebral body fracture by having at least one of the following characteristics: \r\n* Spine Instability Neoplastic Score classification of \Indeterminate\ deemed as a score from 7 to 12\r\n* Pre-existing vertebral body fracture\r\n* Planned radiation dose of 24 Gy
Patients must be diagnosed with a primary glioma and have refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period) on non-enzyme inducing anti-epileptic regimen that can include, but not limited to the following: levetiracetam (Keppra) or Keppra XR, lamotrigine (Lamictal) or Lamictal XR, gabapentin (Neurontin), tiagabine (Gabitril), topiramate (Topamax), valproic acid (Depakene)/valproate (Depacon), zonisamide (Zonegran), lacosamide (Vimpat), and clonazepam (Klonopin)
Hematocrit >= 29%
Inability to complete or perform measures of patient-reported outcomes or neurocognitive testing on the computer
Previous history of suicidal ideation, homicidal ideation, depression leading to hospitalization or mood disturbance leading to hospitalization
Insurance information will be reviewed to ensure geriatric referral is covered for all potential participants
Seen at Supportive Care, cardiopulmonary center, thoracic radiation oncology or thoracic medical oncology
Resting dyspnea modified Borg Scale > 7 of 10 at enrollment
Delirium (i.e., Memorial Delirium Rating Scale > 13)
Thrombosis of lower extremities in the last week
Acute myocarditis, pericarditis, or endocarditis in the last week
Symptomatic aortic stenosis or syncope in the last week
Suspected dissecting aneurysm
Airway obstruction requiring stenting within 1 week of study enrollment or scheduled during the study period
Pneumonia requiring antibiotics at the time of study enrollment
Able to walk without an assistive device
Able to complete a minimum of 4 days of in-home activity monitoring before operation
Open, hybrid, robotic, laparoscopic, or laparoscopic-assisted procedure exceeding 2 hours
Currently residing in nursing or assisted living facility
Neurologic disorder that impairs ambulation (e.g. Parkinson’s)
Receiving a G-CSF after the institution practice change
Taking daily antihistamines for allergies, asthma, or other indications, not including bone pain
There will be no discrimination based on gender, race, creed, or ethnic background; Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance scale (KPS) will not be employed
Hematologic malignancies including acute and chronic leukemias, myelodysplastic syndromes, and myeloma
Hepatic dysfunction (elevated transaminases or bilirubin > 3 times normal), drawn within 28 days of consent
Treatment entails significant risk for symptomatic mucositis likely to require opioid analgesia, as per the discretion of treating physician/nurse practitioner (NP)
There are no exceptions to exclusion; the Data and Safety Monitoring Committee (DSMC) will not approve exceptions
Presence of a proportion of ductal carcinoma in situ (DCIS) in the core biopsy specimen which is compatible with extensive intraductal component (EIC)
Cognitive impairment as indicated by a baseline Folstein Mini-Mental Status Examination of < 25
Requires voriconazole to prevent or treat invasive fungal infection (IFI) post HSCT
Receiving one of the following drugs and cannot be discontinued at least 24 hours before starting therapy, including: pimozide, quinidine, astemizole, ergot alkaloids
Receiving or anticipated need for methadone as co-administration with voriconazole potentially increases methadone exposure
Self-identify as Latina
Can identify at least one primary, adult caregiver
Inability to provide informed consent in English or Spanish as determined by trained mental health professional study personnel
Must be willing to come to MD Anderson Main Campus (Texas Medical Center) for intervention
Patient self-report neuropathy score greater than or equal to 3 on a 0 to 10 numeric scale and/or grade 2 or 3 neuropathy (according to the National Cancer Institute Common Toxicity Criteria 4 point grading scale)
PATIENT:
A home that is deemed, upon inspection, in suitable condition to serve as a medical home, within a 90-minute driving distance of Duke
Lack of a caregiver
CAREGIVER:
Identified by patient as their primary caregiver
Elective craniotomy for supratentorial brain tumors
First craniotomy
American Society of Anesthesiologists (ASA) I-III
Traumatic lesions/hematomas
Emergency case
Necessity of awake procedure requiring intraoperative participation of patient due to the presence of the lesion in eloquent brain areas
Prisoners
Report sleep disturbance of 8 or greater on the Insomnia Severity Index (ISI), and report insomnia that began or got worse with diagnosis of cancer or treatment with chemotherapy
Able to fast for 12 hours for blood work and basal metabolic rate (BMR) measurement
SUBJECT: Have parent-reported or documented difficulties in attention, processing speed, memory, or learning as assessed by the screening questions (a score of at least 3 on any one of the 4 questions or the participant having >= 1/2 standard deviation [SD] decline in test scores, scores < 85, or special education services or accommodations).
SUBJECT: Must have a parent or legal guardian willing to complete the parent proxy behavioral questionnaires and help their child participate in the study procedures at home.
PARENT OR GUARDIAN: Parent or Guardian of participating subject.
SUBJECT: Significant medical problems, such as severe uncontrolled illnesses, or physical impairments that prohibit the child from exercising at moderate to vigorous levels based on the clinical judgment of the examining physician or nurse practitioner.
SUBJECT: Significant cognitive, behavioral, or emotional impairments as judged by an investigator that would prevent the child from understanding or completing the intervention or assessment measures.
SUBJECT: Unable to travel to National Institute of Health (NIH) for the evaluations.
PARENT OR GUARDIAN: Parent or guardian of an ineligible subject.
Loss of a child 39 years old or younger as reported in the child's medical record or by parent report
Biological or adoptive parent or stepparent as reported in the child's medical record or by parent report
Score of 34 or greater (>= 34) on the Prolonged Grief (PG)-13 at screening
Residing in New York, New Jersey, Connecticut, or Pennsylvania for part 1 step 1 (P1S1); residing in New York for P1S2; and residing in New York or New Jersey or ability to complete sessions in New York or New Jersey for part 2, as reported in the child's medical record or by parent report
SUPPORT PROVIDER: Must reside in New York or New Jersey or ability to complete sessions in New York or New Jersey
Significant psychiatric disturbance sufficient, in the investigator's judgment, to preclude completion of the assessment measures, interview or informed consent
Another parent or primary caregiver of the child has been enrolled in the study
SUPPORT PROVIDER: Significant psychiatric disturbance sufficient, in the investigator's judgment, to preclude completion of the assessment measures, interview or informed consent
Moderate to severe pain, as specified by a baseline pain rating score of 5 or above on a scale from 0 (no pain) to 10 (worst pain imaginable) despite current opioid therapy
Pain management plan (as developed by Interventional Pain Service, patient and primary service) that includes placement of an intrathecal drug delivery system for pain management
Patients who are not a candidate for intrathecal drug therapy due to coagulopathy, concurrent necessary use of blood thinners, presence of systemic infection, drug allergy to analgesic agent, evidence of cerebrospinal fluid (CSF) obstruction or other technical factor
Scheduled for partial nephrectomy of renal mass
Solitary kidney
Currently practicing nurse
Involved in direct patient care
Self-identify in one of the following primary practice roles--case managers, clinical nurse specialists, nurse practitioners, managers/coordinators, nurse navigators, patient educators, and staff nurses
Available email address
Research nurses, nurses without direct patient care, and nurse managers/directors (i.e. not involved in direct patient care)
Lack of email address
Ambulatory
Receiving erythropoietin stimulating agents prior to admission
Chronic renal failure in renal replacement therapy
Documented wish against transfusion for personal or religious beliefs
Patient cannot previously have been on the trial for another induction, salvage, or consolidation attempt
Participants must be oriented to person, place, and time
Participants must also meet at least two of the following criteria related to lifestyle: 1) consume less than 3 servings of fruit and vegetable/day; 2) engage in less than 75 minutes moderate/vigorous activity per week, defined as anything that causes small increases in breathing or heart rate for a sustained amount of time (e.g., brisk walking, bicycling); and 3) engage in a mind-body practice less than 4 times a month
Prior history of treatment with recombinant thrombopoietin (TPO) or TPO-receptor (R) agonists
Concomitant participation in any other investigational treatment study; simultaneous participation in non-therapeutic or observational studies will not be an exclusion criterion
No appropriate caregivers identified
Preceding allogeneic HSCT
Any patient who has undergone a single or double umbilical cord blood transplant (UCBT) except those with primary myelofibrosis
Must have achieved neutrophil engraftment (defined as an absolute neutrophil count [ANC] > 500 for three consecutive days) and be off daily filgrastim (G-CSF) prior to starting romiplostim; intermittent G-CSF is allowed
Between day +28 and day +42 status post myeloablative or nonmyeloablative UCBT (single or double cord blood transplant)
No prior HSCT
Report a clinical pain score of >= 3/10
PHASE II: Patient is within the recruitment window of discharge home to 6 weeks post-discharge home date
Known or judged to be cognitively impaired (e.g., dementia, retardation, psychosis)
Have vaginal dryness, dyspareunia, or >= 3 urinary tract infections per year since starting AI therapy
Patient undergoing any resection requiring an anastomosis to the esophagus for curative intent; including but not limited to esophagectomy or total gastrectomy
Performing less than 150 minutes of structured moderate-intensity or strenuous intensity exercise per week
Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria:\r\n* Achieving a plateau in oxygen consumption, concurrent with an increase in power output\r\n* A respiratory exchange ratio >= 1.10\r\n* Attainment of maximal predicted heart rate (HR max) (i.e., within 10 beats per minute [bpm] of age-predicted HR max [HR max = 220-Age[years])\r\n* Volitional exhaustion, as measured by a rating of perceived exertion (RPE) >= 18 on the BORG scale
Willingness to be randomized to one of the study arms
Permission from treating/study physician to participate in RT
Milk protein intolerance/allergies (lactose intolerance is acceptable)
Subjects currently using N-acetylcysteine, alpha-lipoic acid supplements, or dry whey protein supplements
Stroke within the past 2 years
Subjects currently participating in a RT program
Dietary eligibility requirements from a 7-day food record fruit and vegetable (FV) intake less than < 5.5 servings/day, not including potatoes and iceberg lettuce
Be chronically fatigued as defined by having a >= 4 on the Brief Fatigue Inventory
Cannot supplement with fish oil and other omega-3-fatty acids
Have a diagnosis of untreated hypo- or hyper- thyroidism
Reasonably good health
Subject must be capable and reliable to participate in all study related procedures
Subjects taking Digitalis are ineligible
Subjects with any pathology associated with altered serum calcium levels
Hearing level threshold =< 25 dB at all frequencies in both ears to be evaluable for evaluation of pantoprazole's effect on cisplatin ototoxicity; patients with hearing loss can be enrolled but will not be evaluable for ototoxicity objective
Hepatic: < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
A home that is deemed, upon inspection, in suitable condition to serve as a medical home, within a 90-minute driving distance of Duke Adult Bone Marrow Transplant (ABMT) clinic
Lack of a caregiver
Experiencing disability as indicated by a score of >= 3 on the Vulnerable Elder survey
Moderate or worse cognitive impairment as indicated by a score of 3 or less on the Callahan six-item cognitive screening tool
Has a Diagnostic and Statistical Manual (DSM) IV diagnosis of Major Depressive Disorder
Has a Hamilton Rating Scale for Depression (HAM-D) 24-item score of more than 20
Failed to receive satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current depressive episode
Has unstable suicidal ideation as determined by the patient's treating psychiatrist
Recurring seizures resulting from the head injury
Clear cognitive sequelae from the head injury and cognitive rehabilitation following the injury
Subjects with mucositis pain refractory to topical management, defined as any self-reported pain score of >= 2 in the 24 hours prior to enrollment despite use of topical agents as prescribed
Each patient must satisfy at least one of the following criteria:\r\n* The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or\r\n* The patient must have microbiological evidence of CMV viremia or tissue invasion as attested by viral culture, or detection of levels of CMV DNA in the blood or body fluids consistent with CMV infection
Patient must also satisfy at least one of the following criteria:\r\n* The patient's CMV infection is clinically progressing or CMV viremia is persistent or increasing (as evidenced by quantitation of CMV DNA in the blood) despite two weeks induction therapy with antiviral drugs; or\r\n* The patient has developed CMV viremia as attested by viral culture, or detection of levels of CMV DNA in blood or body fluids while receiving prophylactic doses of antiviral drugs to prevent CMV infection post-transplant; or\r\n* The patient is unable to sustain treatment with antiviral drugs due to drug associated toxicities (e.g. myelosuppression [absolute neutrophil count (ANC) < 1000 ul/ml without filgrastim (GCSF) support] or nephrotoxicity [corrected creatinine clearance =< 60 ml/min/1.73 m^2 or serum creatinine > 2 mg/dl])
Dysfunctions of lungs, liver, gastrointestinal tract, hematopoietic and central nervous systems will not affect eligibility for this protocol
Patients must meet the following clinical criteria to receive CMVpp65-CTL infusions\r\n* Stable blood pressure and circulation, not requiring pressor support\r\n* Evidence of adequate cardiac function as demonstrated by electrocardiogram (EKG) and/or echocardiography\r\n* A life expectancy of at least 3 weeks, even if requiring artificial ventilation\r\n* There are no age restrictions
DONORS IN GROUP 1 (HISTORICAL DONORS): Donors in Group 1 would have already been determined to be eligible and will have donated blood or leukocytes to establish CMV-specific T-cells under Institutional Review Board (IRB) # 05-065, 07-055, 95-024, or 11-130; there are no additional eligibility requirements for these donors
DONORS IN GROUP 2 & 3 (PROSPECTIVE AND VOLUNTEER DONORS): Transplant donors and healthy human leukocyte antigen (HLA) typed volunteers who agree to provide T-cells for third-party donation (groups 2 and 3) will need to meet the following eligibility requirements prior to donation:\r\n* Donors must satisfy the criteria specified in Food and Drug Administration (FDA) 21 Code of Federal Regulations (CFR) 1271\r\n* Donors must be typed for HLA-A, B, C and DR\r\n* Donors must have a hemoglobin value > 10 g/dl\r\n* Donors must be capable of undergoing, at least, a single standard 2 blood volume leukapheresis or a donation of one unit of whole blood
=< 2 prior chemotherapeutic regimens
Study participation will occur during the first cycle of 5 day temozolomide course
Hematocrit > 29%
Approved rescue medication for the treatment of nausea and vomiting is permitted at the discretion of the investigator; the rescue antiemetics allowed will include: ondansetron, granisetron and lorazepam
No prior nitrosourea (e.g. lomustine, carmustine)
Received any drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent: 5-hydroxytryptamine type 3 (HT3) receptor or substance P/neurokinin 1(NK1) receptor antagonists; dopamine receptor antagonists (metoclopramide); phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide; haloperidol, droperidol, tetrahydrocannabinol, or nabilone
Ongoing vomiting from any organic etiology
Will receive radiotherapy of cranium within one week prior to or during the study
Participants have to relate that tingling or pain was at least a four out of ten problem during the prior week, on a 0-10 scale where zero was no problem and ten was the worst possible problem and expected to have tingling or pain of at least 4/10 at the time of the first treatment
Ability to complete questionnaire(s) by themselves or with assistance
Case review by the study chair, or designate, as a case where treatment should be tried
Skin conditions such as open sores that would prevent proper application of the electrodes
Post-menopausal, defined as:\r\n* Age >= 45 with no menses for at least 2 years\r\n* Chemically induced menopause through ovarian suppression, as determined by the primary oncologist
Performing less than 150 minutes of structured moderate-intensity or strenuous intensity exercise per week
Exercise intolerance, defined by a VO2peak below that predicted for active age- and sex-matched individuals
Willing to be randomized to one of the study arms
Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria:\r\n* Achieving a plateau in oxygen consumption, concurrent with an increase in power output;\r\n* A respiratory exchange ratio >= 1.10;\r\n* Attainment of maximal predicted heart rate (HRmax) (i.e., within 10 beats per minute [bpm] of age-predicted HRmax);\r\n* Volitional exhaustion, as measured by a rating of perceived exertion (RPE) >= 18 on the BORG scale
Have a Distress Thermometer score of 4 or greater or a score of >= 6 on the Depression or Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS)
In the investigator's judgment, participants must have satisfactory cognitive function to provide valid informed consent and participate in Geriatric Specific Psychoeducational Intervention; the Blessed Orientation-Memory-Concentration test (BOMC) will be used as a cognitive screening tool; patients must have a BOMC score less than or equal to 11
Significant psychiatric disturbance sufficient, in the investigator's judgment, to preclude participation in the intervention (e.g., acute psychiatric symptoms which requires individual treatment)
As per self-report or review of the patient’s medical record, if the patient is taking anti-depressant medication, fewer than three months on the same dose of anti-depressant medication
Actively participating in protocol 07-094 or 11-021
Patients MUST also be ready to receive a cycle of chemotherapy that predictably renders neutropenia at least 70% of the time OR has a risk of febrile neutropenia of at least 20%; this can be any cycle number; it does NOT need to be the FIRST cycle of chemotherapy they are to receive; it is also OK if the patient will be getting granulocyte stimulation factor support; however, if the patient meets above criteria and the chemotherapy he/she will receive causes neutropenia 70% of the time or confers a risk of febrile neutropenia of at least 20%, but is not listed, please contact study Karen Moody, MD, overall study principal investigator, for clarification of eligibility
Asplenia
Patients must have a smart phone, be able to have their oral oncolytic filled at the University of Michigan Comprehensive Cancer Center pharmacy and be newly prescribed capecitabine (Xeloda)
Patients who do not have a smart phone, have a serious mental illness or cognitive impairment, e.g., psychosis or dementia, do not speak English or cannot fill their oral oncolytic prescription at the\r\nUniversity of Michigan Comprehensive Cancer Center pharmacy will be unable to participate in this study
Able and willing to follow prescribed diet intervention
Intestinal obstruction
Able and willing to document symptoms and treatment details as often as needed, not to exceed daily notes
Able and willing to have photographs of the affected area taken regularly
Smoker
Current smoker of >= 10 cigarettes per day, on average
Any Food and Drug Administration (FDA) contraindication for NRT use, including: allergy to nicotine patches and/or nicotine lozenges; severe kidney or liver disease; unstable angina or serious arrhythmia; epilepsy or seizure disorder; myocardial infarction in the past 3 months
Cognitive or psychiatric disorder that would interfere with ability to provide informed consent or answer survey questions reliably\r\n* Any of these Diagnostic and Statistical Manual-5 (DSM-5) cognitive and psychiatric disorders would make someone ineligible: bipolar; delusional; dissociative; intellectual developmental; neurocognitive; psychotic; schizophreniform, schizophrenia, and schizoaffective
Subjects are status post (s/p) breast surgical intervention, to include mastectomy, partial mastectomy, lumpectomy, or reconstruction
Subjects report persistent pain in the distribution of the intercostobrachial nerve (ICBN): The residual breast, surgical bed, ipsilateral medial arm, and/or axilla following tissue healing (> 3 months post-procedure)
Positive response to local anesthetic peripheral nerve block performed under imaging guidance, defined as a >= 50% change in Visual Analog Scale (VAS) pain intensity
Underlying cervical segmentation or other cervical spinal anomaly that results in differential nerve root pressures
Location of pain is outside the distribution of the ICBN, can be directly attributable to trauma to a nerve other than the ICBN, or is consistent with trauma during breast surgery to a nerve other than the ICNB (e.g. medial and lateral pectoral nerve; long thoracic nerve; thoracodorsal nerve; other intercostal nerves)
Immunosuppression
Diagnosis of NSCLC
Any prisoner and.or other vulnerable person
Patients who underwent a linear closure on the face at University Hospitals (UH) Mohs clinic
Breakthrough dyspnea, defined as dyspnea with an average intensity level over the past 7 days of at least 3/10 on a numeric rating scale upon significant exertion or continuous dyspnea =< 7/10 with worsening upon significant exertion
Ambulatory and able to walk with or without walking aid
Able to complete study assessments
Dyspnea at rest >= 7/10 at the time of enrollment
Delirium (i.e. memorial delirium rating scale > 13)
Resting heart rate > 120 at the time of study enrollment
Patients seen in the outpatient palliative care clinic or inpatients seen by the palliative care consult team or the fatigue clinic
Presence of fatigue on a numerical scale during the last 24 hours of more or equal to 4 on a 0 to 10 scale on which 0 equals no fatigue and 10 worst possible fatigue
Presence of relatively intact cognition defined by normal Mini Mental State Questionnaire according to age and education level; a score of 24 or above is usually considered normal
Patient willing to keep a daily fatigue diary, engage in daily telephone follow up with a nurse and after 7 days of treatment either return for a follow up visit or this can be done over the telephone
Currently on methylphenidate or has been on methylphenidate within the last 10 days
CAGE questionnaire score is 2 or above on a 0 to 4 scale
Does not meet recommended guidelines for PA (< 100 min of moderate activity and < 75 min of vigorous activity per week)
Have a smart phone (or can borrow a study-provided iPod Touch) and willing to use it for the mobile app and Facebook group
Agree to install and share data from the FitBit Flex smart phone app with the investigators
Young adults (YA) survivors who are currently meeting PA guidelines, or individuals who are determined by the investigators to not be physically able to participate in an independent exercise intervention such as hospitalized, wheel chair bound, unable to ambulate independently, on oxygen
Disorders of hemostasis including von Willebrand disease, hemophilia, platelet function disorders
History of alloimmunization (defined as platelet refractoriness with panel reactive antibody [PRA] > 25%) at the time of or prior to enrollment
Willingness to be followed for the planned duration of the trial (2 years)
Patients must be receiving a fractionated total body radiation (FTBI) based- myeloablative conditioning regimen; (acceptable conditioning regimens include total body irradiation [TBI] + cyclophosphamide or TBI + etoposide)
Cognitively able to complete interviews as judged by the study team
Declined participation in the study
Subjects are currently receiving ADT for prostate cancer and will continue on ADT for at least 13 weeks after enrollment. Patient may have been started on ADT at any past time point because patients experience hot flashes throughout ADT treatment.
Subjects are experiencing bothersome hot flashes per the study questionnaires.
Able to obtain and take an acceptable form of vitamin B6.
Subjects are currently taking vitamin supplementation which includes vitamin B6 at doses > 10 mg.
Diagnosis of cancer related pain currently treated with first line strong oral opioid analgesics such as morphine, oxycodone, oxymorphone, hydromorphone or hydrocodone
Able to complete study assessments
Cognitive impairment with a Memorial Delirium Assessment Scale (MDAS) score of 7 or higher or diagnosed with neurocognitive impairment by the treating SCC physician
Renal insufficiency defined as estimated glomerular filtration rate of < 60 or hepatic insufficiency defined as transaminitis or hyperbilirubinemia of > 1.5 times the highest normal value
Non-malignant pain
Patients receiving methadone or transdermal fentanyl due to reasons such as long and variable half-life and transdermal rather than oral route for delivery of opioids
Meet the screening criteria for psychological distress (National Comprehensive Cancer Network (NCCN) distress > 2).
Have a 5-year survival rate of 50% or greater as deemed by their oncologist, surgeon, or other relevant attending physician (suggesting a reasonable rate of cure or prolonged medical survival with state-of-the-art medical care).
Diagnosis of mental retardation.
Acute suicidal behavior.
At least 1 year after HCT
Major psychiatric diagnosis that impairs cognitive functioning or is not controlled at the time of the approach.
Admitted to the hospital
Able to follow instructions
Patients with disposition to be transitioned to inpatient hospice or inpatient palliative care unit
CMV seropositive (recipient)
Planned HCT with minimal to no-T cell depletion of graft
Medically indicated subunit (Engerix-B for HBV, Gardasil for HPV) or killed vaccine (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
Alemtuzumab or any equivalent in vivo T-cell depleting agent (or CD34+ selection)
Antiviral medications with known therapeutic effects on CMV such as ganciclovir/valganciclovir (GCV/VAL), foscarnet (FOS), Cidofovir, CMX-001, maribavir; acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
Neuropathic pain score >= 4 on a 0-10 numeric pain scale (numeric rating scale [NRS]) and/or grade 3 or higher neuropathic symptoms according to the National Cancer Institute’s 4 point grading scale.
No plans to change pain medication regimen during the course of the study.
Willing to come to MD Anderson for the intake and follow up data acquisition and to receive their equipment.
Willing to allow research staff to come to their homes or to return the equipment to MD Anderson (MDA) in the case of equipment malfunction.
Live within a 50 mile radius of MD Anderson’s main campus.
Men or women with a history of CRF as defined by a score >= 4 on the numeric analogue scale (0 – 10) (Eligibility Question Fatigue Scale)
Cognitively able to complete assessments as judged by the study team
Have schizophrenia or any other psychotic disorder
Have a diagnosed sleep disorder including untreated obstructive sleep apnea, periodic limb movement disorder, or restless leg syndrome
Has gastrointestinal symptoms with severity score of =< 60 out of 100 visual analog scale for irritable bowel syndrome (VAS-IBS) in at least 2 out of 7 items measured
Able to eat by mouth
Has intestinal obstruction
Patient is currently on antibiotics
Undergoing elective craniotomy for supratentorial tumors
Emergency craniotomies
Infratentorial tumors
Previous neurosurgery on the brain
Radiographic evidence of a biliary hilar stricture OR intrahepatic but no extrahepatic biliary ductal dilation.
Known radiographic evidence of a Bismuth-Corlette type 1 biliary stricture.
Known diagnosis of primary sclerosing cholangitis without suspicion of dominant hilar stricture.
Known IgG4-mediated cholangiopathy.
Significant peri-hepatic ascites interfering with safe/effective PTBD.
Known upper gastrointestinal (UGI) tract obstruction precluding ERC.
Known regional malignant-appearing adenopathy or extra-biliary mass, indicating the need for concurrent endoscopic ultrasound with fine needle aspiration (EUS-FNA).
Prior endoscopic retrograde cholangiopancreatography (ERCP) or PTBD for hilar obstruction.
Surgically altered luminal anatomy other than prior Billroth reconstruction.
Standard general contraindications to ERCP or PTBD (e.g. hemodynamic instability, uncorrected coagulopathy).
All gynecologic laparoscopic/robotic surgeries EXCEPT diagnostic laparoscopies
If patient agrees to participate in the optional patient reported outcomes portion of the study, patient must be English speaking and willing to complete the MD Anderson Symptom Inventory (MDASI) questionnaires
FCGs: Willingness to participate in study activities including data collection
FCGs: Find conversations around religion or spirituality emotionally upsetting
No race-ethnic restriction
CAREGIVERS
Planning to live with the patient for the duration of RT
CARE-RECIPIENTS
Able to complete the onsite training and home self-care activities for LEF management
Willing to come to MD Anderson Main Campus (Texas Medical Center) for enrollment
Patient self-reported ESAS psychological scale score (sum of anxiety and depression scores) between 4 and 11 (and/or) individual anxiety or depression score between 4 and 7 on a 0 to 10 numeric scale, where 10 is the worst possible
Diagnosis of a formal thought disorder (e.g., schizophrenia)
A principal diagnosis of major depressive disorder (MDD)
Subnormal intellectual potential (intelligence quotient [IQ] below 80)
A Mini-Mental State Exam Score (MMSE) of at least 26
Bladder cancer, undergoing radical cystectomy and ileal conduit diversion
Follow-up either here at University of Southern California (USC) or centers that are available to transfer the requested clinical and radiological data
Previous scar or mesh at the level of ileal conduit
Undergoing elective open radical cystectomy
Allergy or adverse reaction to ropivacaine (ropivacaine hydrochloride) or any amide type of local anesthesia
Thrombocytopenia
Positive screen for sexual dysfunction that is causing distress based on the National Comprehensive Cancer Network (NCCN) survivorship guidelines
Admitted to Lunder at Massachusetts General Hospital
Admitted electively
Participated during a previous admission
Known or suspected gynecologic or other abdominal malignancy (such as colorectal, liver, pancreatic, kidney and stomach) for which laparotomy is planned
Sensitivity to silver
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking or strength training intervention
Be receiving hospital-based treatment so that acupressure treatments and parents can be trained and monitored
Availability and willingness of a parent or caregiver to deliver acupressure for ages 5-17; for young adults ages 18-21 participation of a parent, close friend or family member/caregiver is preferred but not required
Study materials will be available in English or Spanish; if families would like to be part of the trial, but do not speak either of these two languages, arrangements can be made to include them using University of California at San Francisco (UCSF)'s translation services
Receiving treatment at UCSF Benioff Children’s Hospital San Francisco or Oakland
Willingness to be randomized
Self-reported inability to walk 2 blocks (at any pace)
Previously on ADT
Ability to tolerate thin liquids by mouth at the time of admission
Participants with evidence of diarrhea as defined by three or more loose or liquid stools per day or loose watery stool (greater volume of stool), that occurs more frequently than usual and lasting for more than three days prior to admission, history of inflammatory bowel disease, irritable bowel syndrome, colectomy or bariatric surgery, celiac disease
CMV seropositive (recipient)
Planned HCT with no ex-vivo T cell depletion of graft; conditioning and immunosuppressive regimens according to institutional guidelines are permitted
Approved to be contacted by the treating urologist
Patients who are pregnant or nursing; to date, no fetal studies in animals or humans have been performed; the possibility of harm to a fetus is likely
Reside in Southern California
BCS treated at Kaiser, an health maintenance organization (HMO) provider, will be excluded since their SCP implementation project is underway
Eligible metastatic lesions: 1) a solitary spine metastasis; 2) two contiguous spine levels involved; or 3) a maximum of 3 separate sites; each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies; epidural compression (arrow) is eligible when there is a >= 3 mm gap between the spinal cord and the edge of the epidural lesion; a paraspinal mass =< 5 cm is allowed
There can be multiple small metastatic lesions shown in other vertebral bodies; the metastatic lesion of each spine should be less than 20% of the vertebral body as opposed to the diffuse vertebral involvement; these small lesions are often seen in the MRI even when bone scan or PET was negative; most of these lesions are not clinically required to be treated and are therefore not included in the target volume of this protocol; only the painful spine (pain score >= 5) is to be treated
Numerical Rating Pain Scale within 1 week prior to registration; the patient must have a score on the scale of >= 5 for at least one of the planned sites for spine radiosurgery; documentation of the patient's initial pain score is required; patients taking medication for pain at the time of registration are eligible
Neurological examination within 1 week prior to registration to rule out rapid neurologic decline; patients with mild to moderate neurological signs are eligible; these neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 (lower extremity for ambulation or upper extremity for raising arms and/or arm function)
Spine instability due to a compression fracture
Bony retropulsion causing neurologic abnormality
Patients allergic to contrast dye used in MRIs or CT scans or who cannot be premedicated for the use of contrast dye
Patient with Rheumatoid Arthritis and other inflammatory diseases that would impact the correlative studies
Illiterate participants
Deaf participants
Fluent in reading, comprehension and communication in the English language; (persons who are unable to meet this requirement are excluded from the current proposal)
No evidence of dementia (Mini Mental State Examination [MMSE] >= 23) but some evidence of cognitive impairment (each subject will be required to answer in the affirmative: ‘do you have problems with memory and attention since having chemotherapy, and do you believe chemotherapy contributed to the problems?’)
Acceptable hemoglobin and hematocrit level based on complete blood count (CBC)
All subjects must be willing to be monitored for adequacy of nutritional intake during the intervention, as is the current standard of clinical practice
Subjects with metabolic abnormalities (e.g. thyroid disorders, insulin dependent diabetes, rheumatologic disease etc.); subjects with metabolic disorders (a) who are otherwise eligible, (b) treated for hypothyroidism by their primary MD with Synthroid (levothyroxine) and (c) with the approval of the Moffitt treating oncologist will not be excluded from the study
Gastrointestinal obstruction or an active peptic ulcer
Participants will be recruited by BMT register nurse (RN) coordinators and physicians prior to patient admission to the BMT Unit; caregiver of any patient eligible to undergo autologous or allogeneic BMT and any patient eligible to undergo autologous or allogeneic BMT will be recruited during the “Pre-Transplant Work-up” stage in the outpatient setting
CAREGIVER PARTICIPANTS:
Caregiver of a patient who will be hospitalized to undergo first-time autologous (self) or allogeneic (alternative donor) BMT in the University of Michigan Mott Children’s Hospital BMT Unit
PATIENT PARTICIPANTS:
Have a permanent ostomy or anastomosis
At least a fifth grade education
Known major psychiatric or neurological diagnosis
Any significant comorbid conditions that would interfere with or preclude participation in an exercise intervention, including orthopedic conditions such as advanced osteoarthritis, mobility-limiting amputations or chronic injuries, or mobility-limiting acute orthopedic injuries
Widespread chronic pain conditions such as fibromyalgia
Parents or adult primary caregiver (e.g., grandmother) of children ages 5 to 17 in treatment remission and has completed intensive therapy for ALL or AML
Parents of childhood cancer survivors who are now 18 years or older and who were previously treated for ALL or AML (do not need to live with the child)
One or both of the parents will self-identify as Hispanic/Latino, the primary participating parent will be either Spanish speaking, bilingual, or is bilingual but identifies their primary language as English and will live with the child
Parent/Caregiver: parents or adult primary caregiver (e.g., grandmother) of children treated for ALL or AML
Parent/Caregiver: one or both of the parents will self-identify as Hispanic/Latino, the primary participating parent will be either Spanish speaking, bilingual, or is bilingual but identifies their primary language as English and will live with the child
Child: existing history of severe cognitive impairment (intelligence quotient [IQ] =< 70) as reported by the parents or the child's City of Hope medical records, or by the child's performance score on the Wechsler Intelligence Scale for Children (WISC) Working Memory and Processing Speed index measures administered in this study
Report sitting for >= 8 accumulated waking hours on a typical day
Are willing and able to attend 3 study visits at the University of Wisconsin (UW)
Are willing to attempt reduction of sitting time
Are able to move from sitting to standing without difficulty and to walk 1 block
CMV seropositive (recipient)
Planned HCT with minimal to no-T cell depletion of graft
Medically indicated subunit (Engerix-B for HBV; Gardasil for human papillomavirus [HPV]) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
Alemtuzumab or any equivalent in vivo T-cell depleting agent
Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), foscarnet (FOS), Cidofovir, CMX-001, maribavir; acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
Minorities will be recruited; no exclusion to this study will be based on race
Patients must not have history of or presence of Mobitz type II 2nd degree or 3rd degree atrioventricular block or sick sinus syndrome, unless patient has a pacemaker
Substantial dementia (based on Folstein Mini Mental State Examination < 24 out of 30)
Acute medical conditions, such as acute flare-up of joint condition or infection
Participants must not be actively receiving physical therapy in a relevant area (e.g. leg strengthening, balance and gait training), at time of enrollment, or participating in intensive (30 min per day) aerobic program three times per week
Alcohol intake > 3 oz/day
Hemiplegia or lower limb amputation
Unable to maintain safe stance and walk, either with or without an assistive device
Have no documented or observable psychiatric or neurological disorders that would interfere with study participation (e.g., dementia, psychosis)
Have not attended or scheduled an upcoming appointment for GC at the time of recruitment
Received a referral letter for GC from their MCC physician
Of Ashkenazi Jewish descent
Have a mailing address and working telephone number
Sleep apnea
Planned less than two week hospitalization
Has an outpatient appointment within University of North Carolina (UNC) Chapel Hill Lineberger Comprehensive Cancer Center
Willing to complete the UNC GA
Has at least one functional deficit as defined by GA screen
Willing to be randomized into either study arm
Ability to safely participate in outpatient rehabilitation program
Unable to safely participate in outpatient rehabilitation
Currently receiving rehabilitation
This study will be conducted in people scheduled to undergo baseline LDCT as part of the City of Hope (COH) LCS program
Ideally, patients' refractory cGvHD should be controlled to a degree that would potentially permit no additional requirement for systemic IST before and following TLI =< d -15 and >= d +45, respectively (NOTE: Relatively minor dose modifications of ongoing medications and topical therapies will be exempt)
The ability to administer protocol doses of TLI (i.e., 100, 150, 200, 250 or 300 cGy) without exceeding cumulative doses of radiation must be established; for patients with prior radiotherapy exposure, this determination will be made by Dr. Greven (or her designee) using published guidelines for excessive organ exposure; (in rare cases, this may apply to retreatment; if so, all of eligibility requirements must be met again)
NOTE: If such hematologic abnormalities are present and deemed due to the process of cGvHD, these requirements may be waived with the approval of the principal investigator (PI)
Able to verbally report pain
Able to indicate pain on a VAS
Able to perform motor/sensory tests
Able to undergo a 4-hour (h) intrathecal catheter placement
Other therapeutic and palliative options have been exhausted
Inability to receive lumbar intrathecal injection because of other factors
Diagnosis of meningitis or encephalitis
Have fatigue and/or two other target symptoms
Have been using a Wii Fit
Subjects with cold agglutinin disease or cold urticaria
Subjects receiving chemotherapy with concurrent anthracycline and taxane (AT or Taxotere-Adriamycin-Cytoxan [TAC])
Subjects with anemia (defined as a hemoglobin < 12) who have a ferritin < 40 ng/mL and iron percentage of saturation (% sat) < 20%
Subjects who have lichen planus or lupus
Lives within a two-hour commuting distance from the recruitment site
No hearing impairment
Arthralgia is moderate to severe joint symptoms-pain, stiffness or achiness-defined as a score of >= 3 on the Patient Reported Outcomes Measurement Information System (PROMIS) Pain Intensity scale (inquiring about pain, stiffness or achiness); the “at its worst” score will be used to determine study eligibility
Patient-assessed ability to walk unassisted
Currently walking =< 30 minutes/day for < 5 days a week (via self-report)
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
Less than moderate to severe joint symptoms-pain, stiffness or achiness-defined as a score of =< 3 on the PROMIS Pain Intensity Short Form (SF) 3a (inquiring pain, stiffness or achiness); the “at its worst” score will be used to determine study ineligibility
Currently walking, on average, more than 150 minutes per week
Living within a 50 mile radius of the City of Hope
Patients undergoing allogeneic transplant must have, or be scheduled to have, an external tunneled central venous catheter (CVC) (Broviacs, Hickmans, tunneled percutaneously inserted central catheter [PICCs], etc.) and/or non-tunneled percutaneously inserted central catheter (PICC) that is expected to remain in place for an additional >= 3 months
Patients using prophylactic antimicrobial locks in the CVC at the time of enrollment and those who are scheduled to receive antimicrobial locks in the CVC as part of a treatment plan are ineligible
Neurological function class of 0-2
Neuropsychological tests will be performed by a trained examiner
Long-term follow up must be possible
Completed in person pre–test counseling
Communication difficulties to include\r\n* Uncorrected or uncompensated hearing and/or vision impairment\r\n* Uncorrected or uncompensated speech defects
Incarceration/ward of the state status
Inability to increase food intake (e.g., esophageal obstruction, intractable nausea and vomiting)
Self-identify as Hispanic or Latina
Be capable of speaking and reading Spanish
Have no documented or observable visual, auditory, psychiatric, or neurological disorders that would interfere with participation (e.g., blindness, deafness, psychosis, or dementia)
Lactating females are not eligible unless they have agreed not to breastfeed their infants
TRIAL SUBJECTS:
PEER NAVIGATORS:
At least 25 years of age who self-identifies as African-American
Previously participated in any type of research study
Has at least high school education
Has a valid driver’s license
Owns an operational vehicle
Previously identified cognitive impairment, which in the judgment of the principal or associate investigators would compromise the donor’s ability to understand the educational materials or the board game rules and procedures, and is likely to interfere with the study procedures or results
Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations
Signed Health Insurance Portability and Accountability Act (HIPAA) compliant research authorization
Inability to perform the testing procedure (for example, because of aphasia, motor deficits affecting the dominant hand, or intelligence quotient [IQ] < 70)
Treatment with other stimulant medications within 14 days of registration; however, a diagnosis of attention-deficit hyperactivity disorder (ADHD) does NOT exclude a child from participation
Patients being treated with antibacterial agents, other than any of the following:\r\n* Cotrimoxazole or other agents including dapsone, atovaquone, and pentamidine administered for Pneumocystitis jiroveci (PCP) prophylaxis\r\n* Topical antibiotics\r\n* Central venous catheter antibiotic lock therapy\r\n* Note: prophylactic antifungal therapy is NOT an exclusion criterion
Girth >= 2 cm circumferential difference and/or volume >= 200 mL compared to the uninvolved upper extremity at any 4 cm segment
Able to commit to a long term follow-up schedule
Presence of other extremity lymphedema (primary or secondary)
Artificial joints in the upper quadrants
Renal failure
Arterial insufficiency
Medication(s) known to affect body fluid balance
Lifetime cumulative anthracycline dose: >= 300 mg/m^2 without the protection of dexrazoxane (Zinecard) therapy
Bradycardia: heart rate < 50 beats per minute (BPM)
Anemia (hematocrit < 28%)
Unwillingness or inability to cooperate, or, for the parents or guardians of minors, to give consent, or for the child to give assent, or any condition of sufficient severity to impair cooperation with the study
Women who report themselves to be of Latino or Hispanic ethnic background (defined as Spanish, Mexican, Central or South American, Cuban, Puerto Rican, Dominican, or other Hispanic origin)
Women who are under- or uninsured and come from low-income communities
Previous participation in GCRA
Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry
GENERAL MEDICAL EXCLUSIONS
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Inadequately controlled hypertension (defined as the normal published range for age and height)
American Society of Anesthesiologists Status > III, assigned at time of pre operative visit
Have at least one geriatric assessment domain meet the cut-off score for impairment other than polypharmacy
Subject has adequate understanding of the English language because not all GA measures have been validated in other languages
Have already made a decision to not undergo any cancer treatment (e.g., being followed in best supportive care or hospice)
ENTRY CRITERIA FOR CAREGIVERS: a caregiver can be anyone age 21 or over who is able to understand spoken English and understand the study process and provide informed consent; one caregiver for each patient will be eligible and must be chosen by the patient; for the purposes of this study, a caregiver is defined as a valued and trusted person in a patient’s life who is supportive in health care matters by providing valuable social support and/or direct assistive care; the caregiver accompanies the patient to medical appointments, is able to listen and give thoughtful advice and may be a family member, partner, friend, or professional caregiver
INCLUSION CRITERIA FOR CAREGIVERS: selected by the patient when asked if there is a “family member, partner, friend or caregiver (age 21 or older) with whom you discuss or who can be helpful in health-related matters”; patients who cannot identify such a person (“caregiver”) can be eligible for the study; a caregiver need not be someone who lives with the patient or provides direct hands-on care; a caregiver can be any person who provides support (in any way) to the patient
INCLUSION CRITERIA FOR CAREGIVERS: if a health care proxy signs consent for or with a patient, and wants to participate in the caregiver portion of the study, this same person will always be the caregiver selected; if a health care proxy does not want to enroll as a caregiver in the study or, if enrolled, chooses to stop their own participation in the caregiver portion of the study, but is able to assist the patient in completing the study, the patient can still participate; in other words, the health care proxy can choose NOT to participate in the caregiver portion of the study; this does not preclude the patient from participating in the patient portion of the study with the health care proxy’s assistance
EXCLUSION CRITERIA FOR CAREGIVERS: caregivers unable to understand the consent form due to cognitive, health, or sensory impairment will be excluded
Must have a willing unrelated adult donor (bone marrow or peripheral blood); donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity; the use of mismatched donors in which disparity is only in the host versus graft direction (because of recipient homozygosity) is discouraged because of the potentially heightened risk for graft rejection; centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1
The patient is enrolled on a COG trial that utilizes unrelated donor HSCT and requires that patients be transplanted using an approach specified by the protocol that is in conflict with the approach specified in this protocol
Having 1 clinical pain rating of >= 3 gathered as part of routine clinic visits or reports pain of > 3 at least three days in the last two week upon accrual
Cognitive impairment (part II only)
Undergoing an exploratory laparotomy for suspected gynecologic cancer, which includes metastatic disease from neoplasia originating in other organs
Planned participation in the Gynecologic Enhanced Recovery Pathway
Consents to being part of a randomized, single-blinded study
Sensitivity to amide-type local anesthetics
Ability to complete questionnaire(s) by themselves or with assistance
Treatment plan to receive standard cisplatin monotherapy administered either every three weeks (80-100 mg/m2 for 3 doses) or weekly (30-40 mg/m2 for 6-7 doses). The decision on which chemotherapy regimen to use in combination with IMRT and GC4419 will be at the discretion of the investigator.
Prior radiotherapy to the region of the study cancer or adjacent anatomical sites or more than 25% of total body marrow-bearing area (potentially interfering with chemotolerance)
Requirement for significantly modified diet (liquids and/or solids) due to compromised oral/pharyngeal function at baseline
Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure
Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal (ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted)
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
Prior allergic reaction to memantine (memantine hydrochloride)
Patients must have aromatase inhibitor (AI)-associated musculoskeletal symptoms that began or increased after starting AI therapy; new musculoskeletal pain must not be due specifically to fracture or traumatic injury
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Allowable planned chemotherapy regimens (with or without ovarian suppression) are:\r\n* 6 cycles of a taxane (T) anthracycline (A) and cyclophosphamide (C)\r\n* 4 cycles of an anthracycline and cyclophosphamide plus 4 cycles of a taxane\r\n* 6 cycles of a taxane plus a platinum analogue with or without one or more human epidermal growth factor receptor 2 (HeR-2) targeted therapies such as trastuzumab +/- pertuzumab\r\n* 6 cycles of an anthracycline plus a taxane\r\n* 6 cycles of cyclophosphamide, an anthracycline and fluorouracil
Able and willing to go at least 24-36 hours without narcotic pain medicine, muscle relaxants, sedatives, sleeping pills and alcohol prior to their cognitive testing; they should not have required chronic sedatives, sleeping aids, or narcotic pain medications on a daily basis prior to their diagnosis
Women who are currently on omega-3 fatty acid supplements with > 500 mg of eicosapentaenoic acid (EPA) + DHA daily or 250 mg of DHA alone and or who have chronically been on more than 1 fish oil capsule per day; there is no exclusion based on fish intake
Individuals who are not willing to stop fish or krill oil supplements during the study; (note that there is no limit to fish intake or omega-3 fatty acid [FA] in food)
Individuals who are not likely to be able to go for 24 yours without sleeping pills, sedatives, narcotic pain medications, or chlorpromazine (ativan)
Individuals who do not have a high school education or are not fluent in English
Functionally appropriate to participate in the intervention, as assessed by 3 functional assessment items from the European Quality of Life-5 dimension (EQ-5D)
Endorsement of at least one sexual symptom
CARE RECIPIENT:
CAREGIVER:
Primary nonprofessional, non-paid caregiver, as identified by the care recipient
Obtains a score of > 6 on the shortened Center for Epidemiologic Studies - Depression (CES-D)
Currently considers self to be a primary caregiver for anyone else other than children
Currently receiving any type of formal counseling for depressive symptoms (allowing caregivers who receive outside counseling for depressive symptoms could contaminate treatment groups)
Patients who are not current with CRC screening, defined as not having completed a home fecal occult blood test (FOBT) within the past year; a flexible sigmoidoscopy within the past 5 years; or a colonoscopy within the past 10 years
Co-morbidity that is estimated to limit life-expectancy to less than 5 years as estimated by the treating nurse or provider
Women of reproductive capability will be enrolled; contraception is not necessary
Cognitive impairment as assessed by the 6-item Mini-Mental Status Exam
Too sick to participate, as determined by the treating oncologist
Current engagement in yoga practice >= 1 day per week
Have completed their course of CTX
Have an average pain intensity score in their feet and/or hands of >= 3 on a 0 to 10 numeric rating scale (NRS) and/or a rating of >= 3 on a 0 to 10 NRSs on any one of the following sensations from the Pain Qualities Assessment Scale (i.e., numb, tender, shooting, sensitive, electrical, tingling radiating, throbbing, unpleasant)
Does NOT have changes in sensation and/or pain in their hands or feet
Patients report a history of peripheral vascular disease, diabetes, vitamin B12 deficiency, thyroid dysfunction, human immunodeficiency virus (HIV) neuropathy, cervical or lumbar pain with radiculopathy, or another painful condition that is difficult for them to distinguish from their CIN
Coming with the patient at the Seidman Comprehensive Cancer Center at University Hospitals Case Medical Center (UHCMC)
Currently practicing mindfulness-based interventions (yoga, meditation, deep breathing)
Claustrophobia requiring anxiolytics or sedation; or
Wake Forest University student
Have volunteered as a student strategist at Comprehensive Cancer Center of Wake Forest University (CCCWFU); all strategists are required to have gone through Take the Fight (TTF) training prior to their volunteer work
Patients have to relate that tingling or pain was at least a four out of ten problem =< 7 days prior to registration, on a 0-10 scale where zero was no problem and ten was the worst possible problem\r\n* Note: the patient is expected to have tingling or pain of at least 4/10 at the time of the first treatment
Ability to complete questionnaire(s) by themselves or with assistance
Case review by the study chair, or designate, as a case where treatment should be tried
Existing operational implantable drug delivery systems, e.g. Medtronic Synchromed
Skin conditions such as open sores that would prevent proper application of the electrodes
Referral to pulmonary or interventional radiology services for large-volume thoracentesis
Study subject has any disease or condition that interferes with safe completion of the study including:\r\n* Coagulopathy, with criteria left at the discretion of the operator\r\n* Hemodynamic instability with systolic blood pressure < 90 mmHg or heart rate > 120 beats/min, unless deemed to be stable with these values by the attending physicians
Referral is for diagnostic thoracentesis only
Inability to assume or maintain a seated position for the procedure
Presence of multiple loculations on bedside pre-procedure ultrasound
Cognitive impairment or mental illness that would impair ability to provide consent or participate in the program
Major psychiatric disorder (e.g., psychosis, personality disorder)
Past participation in an MBCT group
Elective minimally invasive operation
No planned ostomy creation at time of enrollment
Tracheo-esophageal fistula
Absence of dysphagia
Participants will self-identify racial/ethnic status as African American (black or of African descent), Hispanic (Latino), or Caucasian (white)
Participants may be on anti-depressants and/or anxiolytics as long as the dosing has remained stable over the preceding 4 weeks
Assessed as competent based on responses to mental status screener
Concurrent participation in Lineberger Comprehensive Cancer Center (LCCC)1311 or LCCC1234
Willing to wear the FitBit throughout the study period
Co-morbid illness that would contraindicate maximal effort exercise testing or participation in regular exercise programming as determined by the treating physician or exercise physiologist
Pancreaticoduodenectomy
Firm gland texture
PREOPERATIVE FACTORS:
Poor preoperative performance status as defined by: timed get up and go (< 15 seconds)
INTRAOPERATIVE FACTORS:
Failure to extubate at the conclusion of the case
Operative time > 8 hours
Ambulatory without assistive devices
No active lymphedema
No active kidney stones
No active gout
No active diverticulitis
No pituitary diseases or growth
Able to commit to LOFT training 2 times/week for 4 weeks
individuals who are non-ambulatory
FACT-Cog score less than 59 on the Perceived Cognitive Impairment subscale
Subjective complaint of cognitive concerns at time of enrollment
Agree to complete study surveys
Patients who have significant personality disorders or unstable psychiatric disorders (including active major depression, substance abuse, psychosis or bipolar disorder) as assessed by the interviewing clinician
Scheduled to undergo an elective open or laparoscopic Whipple procedure
Surgeon’s opinion at the time of dissection that the subject’s well-being (e.g. bleeding or other independent acute health problems) would be compromised
Hearing level and cognitive ability to follow test directions
T1N0M0 and T2N0M0 glottic lesions
Subjects have to be willing to attend weekly voice therapy sessions
Neurological or cognitive impairment
Vocal fold paralysis
Subjects with an invasive malignancy over the previous 2 years except treated basal or squamous carcinomas of the skin completely resected intraepithelial carcinoma of the cervix and completely resected papillary thyroid and follicular thyroid cancers; other completely resected cancers greater than 2 years may be considered after review by the principal investigator (PI)
Subjects who are unable to complete the symptom diary
CIPN neuropathy: received neurotoxic chemotherapy in any setting as cancer treatment; including taxanes-such as paclitaxel or docetaxel; platinum-based compounds such as carboplatin or cis-platinum or oxaliplatin; or, vinca alkaloids such as vincristine, vinblastine, or vinorelbine, or proteasome inhibitors such as bortezomib\r\n* NOTE: patients should no longer be receiving the therapy that caused the CIPN, or have recently started a new treatment that may worsen CIPN; patients on a treatment that may cause CIPN for a period of time where CIPN does not appear to be worsening may be allowed at discretion at the principal investigator
An average daily pain rating of >= 4 out of 10
Other identified causes of painful paresthesias existing prior to chemotherapy (e.g., radiation or malignant plexopathy, lumbar or cervical radiculopathy, pre-existing peripheral neuropathy of another etiology: e.g., carpal tunnel syndrome, B12 deficiency, acquired immune deficiency syndrome [AIDS], monoclonal gammopathy, diabetes, heavy metal poisoning amyloidosis, syphilis, hyperthyroidism or hypothyroidism, inherited neuropathy, etc.) that might be responsible for the patient’s current neuropathic symptoms
Skin conditions such as open sores that would prevent proper application of the electrodes
1st episode of CDI
Diarrhea associated with C. difficile positive stool assay
Admitted in the hospital at the time of enrollment
Hypotension or shock
Acute abdomen
Admission to intensive care unit on enrollment
Currently receiving other alternative treatment for CDI (e.g. antibiotics other than metronidazole or vancomycin; probiotics; immunoglobulin therapy; fecal transplant)
Unavailable for follow-up visits
Treating physician approval to participate in study
Women who are already participating in a formal or medically prescribed weight management program
Persistent genitourinary symptoms causing discomfort for more than 2 weeks prior to the visit with the physician
Chronic GVHD manifestations that can be followed on physical or laboratory exam; these include but are not necessarily limited to:\r\n* Skin changes \r\n* Oral mucosa changes\r\n* Bronchiolitis obliterans\r\n* Ocular changes
Transfusion independent
Ability to complete questionnaire(s) alone or with assistance
Previous bowel resection which, in the opinion of the investigator, would decrease the benefit of the probiotic; patients who have undergone recent bowel surgeries which would not decrease the benefit of the probiotic are eligible provided they are more than 30 days from surgery with no serious complications
Current heterosexual or lesbian sexual partner
Non-ambulatory
Concurrent diagnosis of organic brain syndrome, dementia, mental retardation, or significant sensory deficit
Major mental illness (e.g, schizophrenia, major depressive disorder)
Residence > 70 miles from research site
Completion of successful fMRI safety screening
Able to undergo informed consent procedures and 3 hours of testing, plus 8 1-hour cognitive rehabilitation sessions with breaks
History of brain injury that significantly impacted cognition; as indicated responses on the Ohio State University Traumatic Brain Injury Identification Method (OSU TBI-ID) greater or equal to any of the following: 30 minutes or more of loss of consciousness (LOC), two or more mild cases within two weeks of each other, or any injury with loss of consciousness before the age of 15
A score of 25 or more on the Patient Health Questionnaire (PHQ-9) on the first visit
A score of 26 or below on the Mini Mental Status Exam (MMSE) triggers a review by an investigational team before enrolling
A score above 45 on the Wender Utah Rating Scale for attention deficit disorder (ADD) (WURS)
Patients who have practiced yoga or taken yoga classes in the year prior to study enrollment or who are currently engaged in a regular mind-body practice
Are deaf or hearing-disabled.
Profess extreme dislike of music.
Wait time is longer than 240 min.
Underlying structural brain abnormality or neurologic comorbidity.
At risk for mucositis OR with stage I mucositis or esophagitis (i.e. radiotherapy to the head, neck, esophagus or lung OR treatment with fluorouracil (5-FU) or other chemotherapeutic agents that are known to cause mucositis or esophagitis) or at risk for xerostomia
They are already receiving PC or hospice services
They have cognitive or psychiatric conditions as determined by the treating oncologist that prohibits study consent or participation
Prospective study: completed primary treatment for breast malignancies; receive survivorship care at Thomas Jefferson University (TJU) or Reading Health System (RHS)
Prospective study: Physically capable of using a tablet computer (no severe visual, hearing, or hand motor deficits)
Vulnerable populations: cognitively impaired; prisoners; terminally ill; elderly and infirm; drug addicts
Have daily use of an iPhone or iPad that meets the following technical specifications: at least iOS 8; for iPhones, must be iPhone 5 or above
Patients with a current history (in the past 30 days) of heaving drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men; patients who feel they cannot comply with this recommendation are not eligible
Patients admitted to the acute inpatient rehabilitation unit and those seen in the Physical Medicine and Rehabilitation outpatient clinic
A relative or a friend who either lives with the patient or has in-person contact with him or her at least twice per week and is identified as the primary caregiver for transplant
Significant uncontrolled psychiatric disorder (psychotic disorder, bipolar disorder, major depression) or other co-morbid disease (dementia, cognitive impairment), which the treating clinician believes prohibits the ability to participate in study procedures
Normal cognitive status as determined by the interviewer based on the ability to understand the nature of the study and consent process.
Co-morbid delirium, dementia, mental illness, or neurocognitive deficit prohibiting informed consent and/or ability to complete study procedures
Bothersome hot flashes (defined by their occurrence of >= 28 times per week and of sufficient severity to prompt the patient to seek therapeutic intervention)
Ability to complete questionnaire(s) by themselves or with assistance
C-reactive protein (CRP) must be >= 10 mg/l in the absence of any other more likely cause of increased CRP like an infection or an autoimmune disorder
Patient willing to keep a daily diary, engage in telephone follow up with a nurse
Currently on fish oil or has been on fish oil within the last 10 days
Renal failure requiring hemo-or peritoneal dialysis
Chronic daily opioid requirement
Followed in the Adult Long Term Follow Up Program
Approval of Oncology provider for participation in this study
Participation in more than 240 minutes of moderate-intensity exercise per week (as determined by Leisure Score Index of Godin-Leisure-Time Exercise Questionnaire [LSI] questionnaire)
Patient expresses inability or unfamiliarity with using SMS/MMS messaging on their phone and is unwilling to be trained in the use of this technology
Unmanaged lymphedema
Medical contraindications to home-based exercise or low-fat, high fruit and vegetable diet
Functional limitations requiring a walker/scooter/wheelchair for daily activities
Vigorous exercise > or = 60 min/week or moderate exercise > or = 150 min/week; if a combination of moderate and vigorous exercise are preformed, the minutes of moderate exercise/week plus 2 x minutes of vigorous exercise/week > or = 150 min/week
Resistance training on > or = 2 days/week accounting for more than 30 minutes of strength training per week
Known chronic aspiration
Participants with acute, active gastrointestinal infection (e.g., typhlitis, diverticulitis, appendicitis)
Dementia (i.e., 290.XX or 331.XX)
Has a partner or spouse who is >= 21
Score of >= 3 on Patient Care Monitor Sexual Concerns screening item
No hearing impairment in patient or partner
Overt cognitive dysfunction or psychiatric disturbance such as suicidal ideation or severe mental illness, as observed or judged by the researcher, referring source, or other qualified observer
Autologous transplant recipients with multiple myeloma or lymphoma (both Hodgkin’s and Non-Hodgkin’s types) receiving the most common autologous regimens, melphalan and cyclophosphamide, carmustine, and etoposide (CBV)/carmustine, etoposide, cytarabine, and melphalan (BEAM)
Allogeneic transplant recipients undergoing fully ablative transplants
Those receiving reduced intensity regimens (a small proportion of allogeneic transplant recipients at UWCCC)
Past participation in ACT or formal mindfulness training, and
Be under the care of a MCC physician
New onset or worsening of fatigue since starting TKI
Confirmed acute lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis
Ability to complete questionnaire(s) by themselves or with assistance
Thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) that will be continued on study
Mechanical heart valve
Documented hemorrhagic tendencies
Bacterial endocarditis
Recent injury which may result in impaired mobility
Family member or friend of an adult patient with a new diagnosis of stage II-IV cancers of the tongue, gum, oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, or parotid who is receiving radiation therapy for curative intent
Identified by the patient as his/her primary caregiver who is providing daily assistance and/or emotional support
Cognitively intact, as evidenced by orientation to person, place, and time
Caregivers do not need to reside with the patient
Medically capable of performing moderate intensity exercise
African-Americans and non-Hispanic Whites
Any caregiver is considered eligible for this study; the caregiver is the person identified by the patient as the one who provides the most regular physical and/or emotional support
Caregivers must be willing to complete surveys at baseline and on monthly basis
Women who report a change in their body/self-image since diagnosis and wish to improve it; specifically, two screening questions will be used: has your body image or self-image changed in an unwanted way since your cancer diagnosis? (answer must be yes) would you like to be able to do something to improve your body image or self-image? (answer must be yes) answers to both questions must be yes for a woman to be eligible
Diagnosis of a major depressive episode, an acute anxiety disorder, psychosis, post-traumatic stress disorder (PTSD), or schizophrenia as listed in the patient’s medical history per Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria in the chart and/or by self-report; assessing the concomitant medications will provide some insight into whether this needs further evaluation
Latino
Spanish-speaking
There will be no restrictions on time since diagnosis for participants
Individuals who lack the capacity to consent will be excluded from this study
Opioid tolerant, taking daily doses of strong opioid pain medication in the past 1 week
Inpatient at MD Anderson seen by palliative care team
Memorial Delirium Assessment Scale > 13/30
Cut-annoyed-guilty-eye (CAGE) positivity (>= 2/4)
Be able to walk unassisted
Be willing and able to travel to UCSF for pre- and post-study blood collection
Not able to travel to UCSF for the pre- and post-study blood collection
Patients may or may not report any of symptoms related to lymphedema (i.e. swelling, heaviness, tightness, firmness, numbness, tingling, stiffness, limb fatigue, limb weakness, and impaired limb mobility of shoulder, arm, elbow, wrist, and fingers)
Ability to give informed consent before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject)
Ability and willingness to communicate the intensity of pain using NRS at the frequency dictated by the protocol
Patients with sinusitis, obstruction of nasal passages, nasopharyngeal cancer, paranasal sinus malignancies, or any conditions in the nasopharyngeal anatomical area that may affect the absorption of fentanyl nasal spray
Previous participation in randomization in this trial
Blindness or severity of visual impairment that precludes one’s ability to view images/text
Patient with known tracheobronchial anatomical anomalies
Patient requiring emergency operations
Patient requiring sizes not available in DLT or VDLT
Own a smartphone (in order to receive text messages and utilize the phone app)
Provide consent and permission to review their medical records
Prior lumpectomy
Deemed appropriate for treatment in the prone position by the treating physician
Able to tolerate prone position and breath hold during CT simulation
The patient has a cell phone capable of receiving text messages
The patient cannot receive text messages
ONCOLOGIST: Be a physician specializing in medical oncology
ONCOLOGIST: Care for oncology patients at the Indiana University (IU) Simon Cancer Center or an affiliated clinic (e.g., Spring Mill Clinic, Eskenazi Health, IU Health North, IU Health West)
ONCOLOGIST: Be willing to attend the 5-session MODEL Care program for providers at the specified location, date, and time
ONCOLOGY NURSE: Be a registered nurse or advanced practice nurse who provides care to patients seen by an enrolled oncologist
ONCOLOGY NURSE: Be willing to attend the 5-session MODEL Care intervention for providers at the specified location, date, and time
PATIENT: Be receiving care from a medical oncologist enrolled in the study
PATIENT: Be willing and able to travel to the class location for 6 weekly 2-hour sessions
PATIENT: Have a family member or friend eligible and interested in participating in the MODEL Care study
PATIENT: Not have completed a Physician Orders for Scope of Treatment (POST) form
PATIENT: Eastern Cooperative Oncology Group (ECOG) performance status of > 2 or Karnofsky performance status < 60 (suggesting patient is capable of only limited self-care, confined to bed or chair more than 50% of waking hours, or requires considerable assistance and frequent medical care) as rated by the attending oncologist
PATIENT: Currently receiving hospice care
FAMILY CAREGIVER: Chosen by a family member or friend with cancer to join them in participating in the MODEL Care study
FAMILY CAREGIVER: Willing and able to travel to the class location for 6 weekly 2-hour sessions
SCREENING PHASE: Currently taking anti-neuropathy medication such as gabapentin, pregabalin, duloxetine, or glutamine
INTERVENTION PHASE: Currently taking anti-neuropathy medication such as gabapentin, pregabalin, duloxetine, or glutamine
Anticipated radical cystectomy with ileal conduit or orthotopic neobladder
Active alcohol dependence, defined as 2 or more positive questions on the CAGE alcoholism questionnaire
Resident of Oahu, Hawaii (HI)
Approval for participation in the trial by attending physician
PATIENT: Participants must be under the care of an oncologist (who does not practice as a palliative care physician for that patient), but their current plan may or may not include chemotherapy or other forms of tumor-directed therapies
CAREGIVER: Family caregiver must live with the patient or have in-person contact with him or her at least twice per week
All couples co-habiting for at least 3 years with current partner who is willing to participate in study
Consume excessive amounts of alcohol (> 30 drinks/week)
Being active (self-reported >= 150 min/week [wk] moderate – strenuous-intensity exercise)
No evidence of recurrence
Being inactive (self-reported =< 150 min/wk moderate – strenuous-intensity exercise)
Possession of smartphone to have a Fitbit synced to
Cognitively able to participate in interactive interviews
Cognitively or physically unable to participate in interactive interview
Long term survivor of ALL
History of executive dysfunction, documented by SJLIFE neurocognitive testing, and defined as having an age-adjusted standard score < 20th percentile on Trail Making Test Part B, Verbal Fluency, or Digit Span Backward
History of self-reported executive dysfunction in daily life, defined as having a standardized score < 20th percentile on Behavior Rating Inventory of Executive Function (BRIEF) Initiate, Shift, or Working Memory domains OR having scored < 20th percentile on the Childhood Cancer Survivor Study Neurocognitive Questionnaire Task Efficiency or Memory domains
Any survivor with full scale intelligence quotient (IQ) < 80
Currently has breast implant (which limits the performance of many yoga poses)
Unlikely to be compliant with the study intervention
Ability to complete questionnaires by themselves or with assistance
Diagnosis of fibromyalgia
Pancreatic adenocarcinoma, biopsy-proven or suspected
Scheduled for intended pancreatectomy, > 4 weeks until planned resection
Able to understand the description of the study and willing to participate
Able to understand the exercise intervention and able to maintain a daily exercise log
Unable to complete the baseline assessment questionnaires or functional assessments
Recent fracture or acute musculoskeletal injury that precludes the ability to weight bear fully on all 4 limbs in order to participate in an exercise intervention
Numeric pain rating scale of >= 7 out of 10
Treatment plan that includes external beam radiation at a mean dose of at least 24 Gy or more to one of the parotid glands (the other gland can receive less than 24 Gy)
Anatomically intact parotid and submandibular glands
Must be right-handed
Upper or lower extremity deformities (ie, missing limbs or scars that prevent needle insertion at the acupuncture points) that could interfere with accurate acupoint location or alter the energy pathway as defined by traditional acupuncture theory
Documented history of mental incapacitation or significant emotional or psychiatric disorder (i.e. bipolar, schizophrenia) that, in the opinion of the investigator, precludes study entry as these patients may not be able to cooperate with this slightly invasive procedure or with the data collection process
Current smoker or quit smoking within the past 15 years
Report clinically significant anxiety symptoms (i.e., Hospital Anxiety and Depression Scale Questionnaire [HADS]-anxiety subscale >= 8)
Anxiety is principal psychiatric problem
Co-morbid delirium, dementia, or active and untreated psychotic, bipolar or substance-dependence disorder interfering with consent
Plasma iPTH ?70 pg/mL if taking <1200 IU vitamin D
RCT: Participants will come from urban and rural regions of the country
CANCER PATIENT GROUP: Caucasian or African-American/Black
NON-CANCER PATIENT GROUP: Sedentary defined as < 60 minutes of recreation or work requiring modest PA/week
Not willing or able to follow procedures specified by the study and/or instructions of the researcher; prior to randomization, participants must provide a signed authorization and medical clearance from their personal physician or our nurse practitioner
Histologic documentation of malignancy currently undergoing a course of RT (with or without chemotherapy) including the oral cavity and/or oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e., stereotactic body radiation therapy [SBRT] is not allowed)
Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0 using the Acute Radiation Morbidity Scoring Criteria
Ability to complete questionnaire(s) by themselves or with assistance
No cryotherapy for prophylactic mucosal protection within 6 weeks prior to registration
Target lesion of any size
Target lesion located 1.5 cm or more away from visceral pleura based on the needle path
Skin thickness =< 7 cm (from skin to pleura)
Needle path without transgression of pleural fissure, bleb, or bulla is possible
Coaxial biopsy technique using Angiotech 19-gauge introducer needle
Needle length =< 15 cm
INDIVIDUAL INTERVIEWS:
Are within traveling distance to Fox Chase Cancer Center (FCCC) and Mount Sinai Medical Center (MSMC)
Are within traveling distance to FCCC, MSMC, Rutgers Cancer Institute of New Jersey, or Temple University Hospital (TUH)
Significant uncontrolled psychiatric disorder (psychotic disorder, bipolar disorder, major depression) or other co-morbid disease (dementia, cognitive impairment), which the treating clinician believes prohibits informed consent or participation in the study
A relative or a friend, identified by the patient who either lives with the patient or has in-person contact with him or her at least twice per week
Patient and caregiver must be willing to be videotaped
Treated at one of the Survivorship Centers of Excellence or their community affiliates
One or more significant medical conditions that in the treatment team’s judgment preclude participation in the walking intervention
Have BFI =< 3
Currently on hospice care
Open pancreatoduodenectomy for any diagnosis
Prisoners
Heart rate >= 50 beats per minute
Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or atrioventricular (AV) block
Enrollment in a therapeutic intervention trial in the breast medicine service
Willing to attend monthly clinic visits at University of California, San Francisco (UCSF)
Physically unable or unwilling to participate in recommended exercise programs or travel to UCSF on a monthly basis
Planned fractionated external beam radiotherapy to be delivered by opposing, tangential beams to 50.4 Gy in 28 fractions with a planned photon or electron boost of 10 Gy in 5 fractions (for a total of 33 fractions)
Any infection or unhealed wound of the radiotherapy portal areas, or generalized dermatitis
Planned relocation which would make follow-up visits impossible during the course of the study
Resectable pancreatic ductal adenocarcinoma (R-PDAC): no evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery; there must be a clearly defined fat plane between SMA and celiac axis; patent superior mesenteric vein (SMV/portal vein [PV]) with no distortion of venous architecture
Patient unable or not willing to perform all study related biopsies and blood draws for exploratory endpoints will not be enrolled on study as all study related procedures are mandatory
Subjects must be willing to undergo a cystoscopy on study for investigational product removal.
Eligible for and willing to undergo RC per the attending urologist.
Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so.
Previous exposure to gemcitabine instillations.
Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200.
Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening.
Bladder Post-Void Residual Volume (PVR) of > 250-mL.
Difficulty providing blood samples.
All patients who do not have a documented NF1 mutation must meet the clinical diagnosis of NF1 using the National Institutes of Health (NIH) Consensus Conference criteria; in addition to tibial pseudarthrosis, one or more of the following diagnostic criteria for NF1 must be present:\r\n* Six or more cafe-au-lait spots (>= 0.5cm prepubertal; >= 1.5cm postpubertal)\r\n* Freckling in the axilla or groin\r\n* Optic pathway glioma\r\n* Two or more iris Lisch nodules\r\n* Two or more neurofibromas or one plexiform neurofibroma\r\n* A first-degree relative with NF1
Patients must have tibial pseudarthrosis that has the potential to cause significant morbidity; radiographic findings (anterior-posterior [AP] & lateral leg radiographs) must support the diagnosis of tibial pseudarthrosis with chronic non-union
Lack of documentation for a diagnosis of NF1
Tibial fracture without evidence of pseudarthrosis or tibial dysplasia
Tibial dysplasia/bowing without fracture or pseudarthrosis
Plexiform neurofibroma of any size, or nodular neurofibroma of > 3 cm diameter involving the ipsilateral leg, including the hip\r\n* If presence of plexiform is suspected but not certain on physical exam, MRI of the leg may be indicated to rule this out
Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree
Visual impairment from any cause
Precocious puberty from any cause
Inadequate neurovascular status in the involved limb that may jeopardize healing
Other injury or condition that prevents ambulation or completion of study assessments
Two or more prior surgeries for tibial pseudarthrosis
Bilateral tibial dysplasia
Severe vitamin D deficiency with serum 25-OH vitamin D < 10 ng/ml (25 nmol/l) \r\n* Patients with vitamin D levels < 10 ng/ml may be treated with vitamin D and reconsidered for enrollment when levels are sufficient
Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU, nab-paclitaxel (or other taxanes) or gemcitabine Exclusion Criteria Specific to Bevacizumab-Containign Arms (Arms A, B, and F) (Patients who meet any of the following criteria will be excluded from enrollment into bevacizumab-containing Arms A, B, and F:)
Clinical signs or symptoms of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses of large volume. HCC participants (Arm A and F) with vascular invasion of the portal or hepatic veins may be enrolled
HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry
Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone.
Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia
Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required
Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed
Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ?3% FLT3-ITD/total FLT3);
Leukapheresis;
Growth factor/cytokine support;
Complete left bundle branch block;
The effusion is an exudate (per Light's criteria) in the context of histocytologically proven malignancy elsewhere, with no other clear cause for fluid identified.
Subject has sufficient pleural fluid to allow safe insertion of an IPC. 7. Subject has negative pregnancy test if appropriate. 8. Subject or caregiver is able to perform home drainage of the pleural effusion (a caregiver can be a friend, family member or paid healthcare professional and applies to US sites only; UK subjects will have drainage managed by home-care nurses).
Subject has significant trapped lung, or a proximal bronchial obstruction which is likely to lead to trapped lung. For a subject to be eligible for this study, 2 separate study center clinicians must agree that there is no significant trapped lung on the same CXR using visual estimation (reference guide). The CXR used to make this decision must have been performed ?30 days preceding the consent form being signed, and must have been performed preferably on the same day, but no more than 7 calendar days after a pleural drainage. Significant trapped lung is deemed present if any 1 of the following criteria is met:
A CXR shows hydropneumothorax.
A CXR shows ?20% of the affected hemithorax to be free of the expected lung parenchymal markings and there is no suggestion of pleural fluid.
A CXR shows ?20% of the affected hemithorax to be occupied with pleural fluid AFTER a pleural aspiration which resulted in symptoms suggestive of trapped lung (e.g., chest pain or cough).
Subject has had a lobectomy or pneumonectomy on the side of the effusion. 10. Subject has undergone a previous attempt at ipsilateral pleurodesis which has failed.
Subject has bilateral pleural effusions, with both being at least moderate in size (greater than one-third of the hemithorax on CXR).
Subject has evidence of fluid loculation such that attempts at pleurodesis are likely to be futile.
Subject has a mediastinal shift of ?2 cm toward the side of the effusion. 15. Subject is receiving concurrent intrapleural chemotherapy or radiation therapy to the ipsilateral chest.
Subject has no access to a telephone. 18. Subject has no documented blood values (complete blood count [CBC], coagulation tests, urea and electrolytes, and liver function tests [LFTs]) within the last 10 days.
Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of 1 or more lesions that measure at least 2.0 cm in the longest dimension (as assessed radiographically)
History of listeriosis or vaccination with a listeria-based vaccine or prophylactic vaccine (eg, influenza, pneumococcal, diphtheria, tetanus, and pertussis [dTP/dTAP]) within 28 days of study treatment
Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or XRT, abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with FLT3-ITD, or presenting WBC>100K, or
Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g. anthracycline and infusional cytarabine given as 7+3), or;
Blast count ?20%
Congestive heart failure or documented cardiomyopathy with an EF ?50%, provided that EF ?35% or,
Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g., anthracycline and infusional cytarabine given as 7+3); or
Blast count ? 20% (WHO criteria)
Have a circulating blast count of less than 200/mm3 (control with hydroxyurea or similar agent is allowed);
Psychiatric disorder that would preclude study participation
ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening
Patient has a Karnofsky performance status (KPS) ? 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)
Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin
Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening
Planned dose-dense chemotherapy with combination carboplatin and paclitaxel given intravenously
The subject requires concomitant treatment with the following inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4):\r\n* Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin\r\n* Antifungals: itraconzaole, ketoconazole, voriconazole, fluconazole, posaconazole\r\n* Antidepressants: nefazodone\r\n* Antidiuretic: conivaptan\r\n* Anti-retrovirals: delaviridine or protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir, nelfinavir) or cobicistat-boosted antiretrovirals\r\n* Gastrointestinal (GI): cimetidine, aprepitant\r\n* Hepatitis C: boceprevir, telaprevir\r\n* Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids
Has glucose-6-phosphate dehydrogenase (G6PD) deficiency
The volume of the tumor bed (TB) clinical target volume (CTV) is less than 25% of the whole breast planning target volume (PTV) which is a criteria used for partial breast alone trials
Multifocal disease is allowed if it was removed by a single lumpectomy resection and the patient remained a candidate for breast conservation
The patient must be less than 6’ 6” in height
The patient must feel comfortable in the prone position
Unable to fit into the immobilization breast cup with an adequate seal
Male gender
Glycosylated hemoglobin (Hb A1c) =< 7%
Evidence of low-volume peritoneal disease defined by a peritoneal carcinomatosis index (PCI) =< 10 based on cross-sectional imaging and/or diagnostic laparoscopy findings
No parenchymal hepatic metastases
No cross sectional imaging findings indicative of multi-segmental (> 1 site) small bowel obstruction, or small bowel loops matted together, or gross disease of the small bowel mesentery characterized by distortion, thickening or loss of mesenteric vascular clarity
No clinical or radiological evidence of hematogenous or distant nodal (retroperitoneal, pelvic, mediastinal, peri-portal or peri-aortic) metastasis
Serum renal functional parameters, blood urea nitrogen (BUN) and creatinine within normal limits
No psychiatric or addictive disorders or other conditions that would preclude the patient from meeting the study requirements
Peritoneal carcinomatosis index (PCI) >= 10
A single, biopsy-proven SISCCA as defined by the LAST criteria (=< 3 mm depth of invasion, horizontal spread of =< 7 mm, and completely excised with at least 1 mm margin clear of cancer irrespective of the amount of HSIL) documented per investigator assessment in combination with the pathology report within 16 weeks before Segment B enrollment
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
Prior to Segment B enrollment, participants on combination anti-retroviral therapy (cART) will be required to have a minimum CD4 count of >= 200 and participants not on cART will be required to have a minimum CD4 count of >= 350 to be eligible for the study; participants not currently on cART who have a CD4 count >= 200 and who agree to start cART immediately will be eligible for participation; laboratory data should be obtained within 16 weeks prior to Segment B enrollment
Anal cancer that cannot be completely excised with a >= 1 mm clear margin from surrounding tissue or where excision to obtain a clear margin would compromise sphincter function or anal canal diameter
The participant’s SISCCA must not have been ablated
Concurrent anal canal or perianal HSIL or condyloma that in the judgment of the clinician cannot be cleared or can only be cleared with undue morbidity to the participant
Baseline AFP ?400 nanograms/milliliter.
Creatinine clearance ?60 milliliters/minute.
Absolute neutrophil count ?1.0 × 10^9/Liter, hemoglobin ?9 grams/deciliter, and platelets ?75 × 10^9/Liter.
Natural menopause with last menses >1 year ago
NSCLC with evidence of a centrally cavitating lesion
Evidence of complete or partial bowel obstruction
Need of total parenteral nutrition
Significantly diseased (as determined by the principal investigator [PI] or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
Subjects must be already enrolled in P.R.O.G.E.C.T observational registry (HSC #12614)
Symptoms of gross hematuria or gross hemoptysis.
Report cognitive impairment since starting chemotherapy as assessed by four questions from the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog)
Willing to come to MD Anderson Cancer Center (MDACC) or Hospital Israelita Albert Einstein (HIAE) for the meditation sessions and assessment sessions
Right handed (quantitative EEG [qEEG] database comparison is specific to handedness; by requiring all participants be right handed, we will be consistent across EEG analysis)
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Willing to come to MDACC and HIAE for the assessment session
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Right handed
Diagnosis of a formal thought disorder (e.g., schizophrenia)
Mini-Mental State Examination score of 23 or below
Factors contraindicated to fMRI
Any extreme mobility issues (e.g. unable to get in or out of a chair unassisted, extremity issues such as neuropathy that limits physical manipulation of objects
Regularly practiced meditation (greater than once per week) in the year prior to study enrollment
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Diagnosis of a formal thought disorder (e.g. schizophrenia)
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Mini-Mental State Examination score of 23 or below
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Undergoing chemotherapy
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Any extreme mobility issues (e.g. unable to get in or out of a chair unassisted, extremity issues such as neuropathy that limits physical manipulation of objects)
PILOT PARTICIPANTS AND HEALTHY CONTROLS ONLY: Patients who have regularly practiced meditation (greater than once per week) in the year prior to study enrollment
Eastern Cooperative Oncology Group (ECOG) ranging from 0 (asymptomatic) to 2 (symptomatic and in bed > 50% of the day)
Uses smart mobile phone (either iOS [iPhone] or Android device)
Individuals with co-morbid acute or untreated psychiatric symptoms (e.g., psychosis) or neurologic dysfunction will be excluded
Phase 1: Clinician participants must be oncology clinicians (i.e. physicians and nurse practitioners) who maintain at least 25% clinical practice at the MGH Cancer Center or one of its community affiliates at the North Shore, Emerson Hospital and MGH West
Phase 1: For this proposed study, four groups of stakeholders will provide ongoing feedback about the study design, methods, and results; to be eligible as a stakeholder, the participant must be able to represent the interests and perspective of at least one of the following stakeholder groups: 1) oncology patient or family member; 2) oncology physician; 3) cancer practice setting administrator; and 4) health system, community, and society
Active Clostridium difficile infection or on prophylactic or tapering antibiotics for Clostridium difficile infection
Suicidal ideation, as determined via Patient Health Questionnaire (PHQ)-9
Receiving radiation therapy of any type at Dana-Farber Cancer Institute (DFCI), Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), or affiliated network sites (including but not limited to partial breast irradiation, two-field, three-field, and four-field plans)
Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) subscale score >= 10 pre-radiation therapy and decrease in FACIT-F of 10 points or more as compared to prior FACIT
Participants with major depressive disorder and/or suicidal ideation as determined by PHQ-9
Participants who are receiving any other investigational agents that might interact with study medication or influence the measurement of study outcomes
COHORT A:
COHORT B:
Cohorts A & B:
Ability to complete questionnaire(s) by themselves or with assistance
Utilization of amifostine during radiotherapy
Referred to MSK’s Tobacco Cessation Program
Have sufficient sensory acuity (i.e., auditory, visual) and manual dexterity to use a computer game as per judgment of clinician or consenting professional
Can be reached by telephone
Immediate reconstruction with tissue expander (Group 2) or permanent implant (Group 1) prior to radiation therapy (RT) performed at MSKCC
If PMRT is recommended, the treatment fields will include the axillary, supraclavicular, and internal mammary nodes
Absence of a breast reconstruction prior to RT (placement of tissue expander is sufficient for group 2)
Able to complete an acceptable baseline CPET, as determined by the absence of remarkable electrocardiogram (ECG) findings or other inappropriate response to exercise
Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria:\r\n* Achieving a plateau in oxygen consumption, concurrent with an increase in power output\r\n* A respiratory exchange ratio >= 1.10\r\n* Attainment of maximal predicted heart rate (maximum heart rate [HRmax])\r\n* Volitional exhaustion, as measured by a rating of perceived exertion (RPE) >= 18 on the BORG scale
Medical clearance from attending oncologist or attending radiation oncologist to undergo a symptom-limited cardiopulmonary exercise test
Previously experienced paclitaxel induced pain during a current or past paclitaxel treatment that the treating healthcare provider thinks is consistent with the paclitaxel-induced acute pain syndrome; note: formal documentation of prior pain is not required
Ability to complete the questionnaires or to do so with assistance
Currently receiving Dilantin (phenytoin) or auranofin or another gold-containing compound
Anemia (hemoglobin [Hgb] < 8.0 gm/dl) or leukopenia (absolute neutrophil count [ANC] < 1,000/mcL); use of red cell transfusions, erythropoietin, or filgrastim (G-CSF), as ordered by the managing oncology service, is acceptable and does not preclude participation
Scheduled for elective radical cystectomy and urinary diversion for bladder cancer
Caregivers: Absence of a serious medical condition likely to influence cortisol assessment in their hair
Caregivers: Alcohol consumption less than 2 drinks/day
Patient and caregiver: Children under the age of 18 do not receive HSCTs in either program
Histological or cytological confirmed ER and/or PR positivity
Previous, preoperative celiac nerve block
Presumed ampullary or duodenal cancer based on preoperative work-up or intraoperative findings
Benign tumors, neuroendocrine tumors, soft tissue tumors based on preoperative work-up or intraoperative findings
Patient reports moderate to severe bother for at least one symptom, defined by a Rotterdam Symptom item score >= 2 on a 1-4 scale, for depressive symptoms, anxiety, pain, fatigue, sleep problems, or breathlessness
Patient is willing to participate in this study
Caregiver has a T score >= 55 (at least one half standard deviation above the population mean) on either the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety or Depression measure or a Distress Thermometer score of 3 or higher
Caregiver is willing to participate in this study
Patient makes 3 or more errors on a validated 6-item cognitive screener or exhibits significant psychiatric or cognitive impairment (dementia/delirium, retardation, active psychosis) that in the judgment of the investigators would preclude providing informed consent and study participation
Patient is receiving hospice care
Patient has a Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative Oncology Group score) > 2
Patient does not have working phone service
Caregiver exhibits significant psychiatric or cognitive impairment (dementia/delirium, retardation, active psychosis) that in the judgment of the investigators would preclude providing informed consent and study participation
Caregiver does not have working phone service
Pfannenstiel or transverse abdominal incision
Prisoner
Mental incapacity
Prior history of hernia repair with mesh, or multiple (> 1) prior hernia repairs, or plan to use mesh for hernia closure in current surgical procedure
Second (2nd) or third (3rd) degree heart block as assessed by preoperative electrocardiogram (EKG)
Current or past diagnosis of a major psychiatric disorder precluding adequate outcome responses such as schizophrenia, dementia, delirium etc. as recorded in the pre-operative record
Documentation of congestive heart failure and ejection fraction < 30% if recorded in the pre-operative record
Participants with serious or unstable illness, as determined by study physicians and clinicians, may be deemed unfit to participate
Participants who have recently started or changed doses of psychoactive medication which might affect psychological outcome measures in the judgment of the study PI; allowable time frames are medication-specific and will be determined by the study PI
Report all three symptoms as present in the past week with worst severity rating >= 3 (0-10 scale) for at least two of the three symptoms
Pain that is post-operative (< 3 months since surgery) or neuropathic pain; (Note: grade 1 chemotherapy-induced peripheral neuropathy [CIPN] is not anticipated to meet threshold criteria on the Neuropathic Pain Screening questionnaire); patients with more than one type of pain who are able to isolate and identify a non-neuropathic pain experience (e.g., persons with diabetic neuropathic foot pain as well as nociceptive cancer-related abdominal pain) may be included with the principal investigator (PI)’s approval
Willing to participate in the guided and home yoga practice
Willing to drive to the study site
Medical clearance by Dr. Murphy
Admitted to Acute Palliative Care Unit (APCU)
Delirium as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria
Hyperactive/mixed delirium with RASS >= 2 in the last 24 hours
On scheduled haloperidol of =< 8 mg in the last 24 hours
FAMILY CAREGIVERS:
On regular doses of benzodiazepine or chlorpromazine within the past 48 hours
Heart failure exacerbation at the time of enrollment
Patients with a subjective history of an extreme dry mouth syndrome that prevents them from producing adequate amounts of saliva (approximately 2 mL in 15-20 min)
Total bilirubin < 2.0 mg/dl; unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal liver function tests (LFTs) as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation
Aspartate aminotransferase (AST) < 5 x upper limit of normal (ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal LFTs as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation
History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
Post-transplant exposure to T-cell or IL-2 targeted medication (e.g. anti-thymocyte globulin [ATG], alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior
Active malignant relapse
Ability to complete questionnaire(s) by themselves or with assistance
Current enrollment in any other trial that entails the concurrent administration of any other agent designed to enhance postoperative recovery
Breakthrough dyspnea, defined in this study as dyspnea on exertion with an average intensity level >= 3/10 on the numeric rating scale
Ambulatory and able to walk with or without walking aid
Able to complete study assessments
Dyspnea at rest >= 7/10 at the time of enrollment
Delirium (i.e. memorial delirium rating scale > 13)
Resting heart rate > 120 at the time of study enrollment
Vulnerable populations: there is no inclusion of fetuses, neonates, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations, except that it is possible that a subject might be pregnant
Breakthrough dyspnea, defined in this study as dyspnea on exertion with an average intensity level >= 3/10 on the numeric rating scale
Ambulatory and able to walk with or without walking aid
Able to complete study assessments
Dyspnea at rest >= 7/10 at the time of enrollment
Delirium (i.e. Memorial delirium rating scale > 13)
Resting heart rate > 120 at the time of study enrollment
Patients who are not able to use telephone-based interactive voice response software due to physical limitations (e.g., impaired hearing)
Prior allogeneic SCT
Previous diagnosis of lymphedema
Stage II lymphedema based upon International Society of Lymphedema (the limb is firm in places, elevation does not reduce swelling, it may or may not pit with pressure, and skin changes may be noted)
Receiving hospice care
Post-completion of treatment (may be on hormone therapy, such as tamoxifen, or monoclonal antibody, such as Herceptin or pertuzumab) for any type of cancer as confirmed by the medical record at MSKCC, by self-report, or by outside correspondence, including a study checklist signed by a physician for patients outside of MSKCC
PHASE II: A score of >= 4 on the Distress Thermometer (DT) and indication that this distress is related in some way to the patient's breast cancer or survivorship
Significant psychiatric or cognitive disturbance sufficient, in the investigator's judgment, to preclude providing informed consent or participating in the groups (i.e., acute psychiatric symptoms which require individual treatment)
Clear indication for anticoagulation (e.g., atrial fibrillation) anticipated during the study period
Clear indication for antiplatelet agents (e.g., cardiac stents); a patient receiving aspirin for primary prevention prior to index stroke may be enrolled as long as study investigators believe it would be safe for the patient to stop aspirin if the patient was randomized to the enoxaparin arm
Symptomatic carotid stenosis
Unavailability for follow-up
Planning on remaining in the area for at least 1 year
CLINICIAN: Has an doctor of medicine (MD) or doctor of osteopathic medicine (DO) degree
CLINICIAN: Is the treating physician providing care to a patient enrolled to the study
Presence of untreated psychiatric disturbance (i.e. acute psychiatric symptoms which require individual treatment) and/or cognitive impairment disorder (e.g., delirium or dementia) verified by medical record sufficient to preclude completion of the assessment measures, interview or informed consent
Has another family member already enrolled in ICCAN (as determined by patient report)
Sedentary, as per the leisure score index (LSI) of the Godin leisure-time exercise questionnaire (GLTEQ); participants who perform regular moderate or vigorous intensity exercise at least 5 days/week, for at least 30 minutes/session, are not eligible
Able to complete an acceptable baseline cardiopulmonary exercise testing (CPET), as determined by the absence of remarkable electrocardiography (ECG) findings or other inappropriate response to exercise
Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria:\r\n* Achieving a plateau in oxygen consumption, concurrent with an increase in power output;\r\n* A respiratory exchange ratio >= 1.10;\r\n* Attainment of maximal predicted heart rate (HRmax) (i.e., within 10 beats per minute (bpm) of age-predicted HRmax;\r\n* Volitional exhaustion, as measured by a rating of perceived exertion (RPE) >= 18 on the Borg scale
Medical clearance from primary attending oncologist to undergo a symptom-limited CPET and aerobic training intervention
Willing to be randomized to one of the study arms
Cohort 1 participant: \r\n* Has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/or executive functioning =< 10th percentile\r\n* Is absent of delayed sleep onset latency defined as an inability to fall asleep within 30 minutes < once a week during the past month
Cohort 2 participant:\r\n* Has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/ or executive functioning =< 10th percentile\r\n* Has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes >= once a week during the past month
Cohort 3 participant:\r\n* Is absent of neurocognitive impairment defined as performance > 10th percentile on all six measures of attention, memory, and executive functioning\r\n* Has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes >= once a week during the past month
Patient must receive any one of the following conditioning regimens: total body radiation (single or fractionated dose)/cyclophosphamide, busulfan/cyclophosphamide, or fludarabine/busulfan/lymphocyte immune globulin (ATGAM/thymoglobulin [thymo])
Patient must not have had prior exposure to brentuximab vedotin
Self-identify as Latino
Not incarcerated
Diagnosis of any stage of multiple myeloma based on standard criteria as follows:\r\n* Major criteria\r\n1. Plasmacytomas on tissue biopsy\r\n2. Bone marrow plasmacytosis (> 30% plasma cells)\r\n3. Monoclonal immunoglobulin spike on serum electrophoresis (immunoglobulin G [IgG] > 3.5 G/dL or immunoglobulin A [IgA] > 2.0 G/dL) or kappa or lambda light chain excretion > 1 G/day on 24 hour urine protein electrophoresis\r\n* Minor criteria\r\na. Bone marrow plasmacytosis (10 to 30% plasma cells)\r\nb. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria\r\nc. Lytic bone lesions\r\nd. Normal immunoglobulin M (IgM) < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL\r\n* Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:\r\n** Any two of the major criteria\r\n** Major criterion 1 plus minor criterion b, c, or d\r\n** Major criterion 3 plus minor criterion a or c\r\n** Minor criteria a, b and c or a, b and d
Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis
Dyspnea with an average intensity level > 3/10 on the numeric rating scale over the past week
Outpatients at Monroe Dunaway (MD) Anderson Cancer Center seen by the Supportive Care, Rehabilitation Service, Thoracic Oncology or Pulmonary Medicine
Permission from the attending medical oncologist if the patient is currently on an interventional cancer therapy trial
Delirium (i.e. memorial delirium rating scale > 13)
Heart failure exacerbation at the time of study enrollment
The scheduled procedure will be performed via midline laparotomy
The planned procedure is a clean-contaminated (class II) case (includes gastric, small bowel, and colorectal resections, as well as bile or pancreatic duct transections)
Emergent cases will not be included in the study
Clean (class I), contaminated (class III) and dirty (class IV) procedures will likewise be excluded, as well as ones performed completely laparoscopically
The planned procedure involves foreign material (such as mesh or subcutaneous drains) being left in the subcutaneous space at the time of surgery (for example, a ventral hernia repair); surgical drains that are placed to drain an intraabdominal space and exit the abdominal wall remote from the incision are allowed in the study
Memorial delirium assessment scale =< 13
Controlled pain and depression symptoms, if present (defined as no change in the morphine equivalent dose of 30% or change in the dose of antidepressant medication in the past 2 weeks)
Have a major contraindication to methylphenidate (MP) (e.g., allergy/hypersensitivity to study medications or their constituents), light therapy (e.g., currently receiving ultraviolet A [UVA]/ultraviolet B [UVB] therapy), cognitive behavioral therapy (e.g., schizophrenia), or conditions making adherence difficult as determined by the attending physician
Regularly used cognitive behavioral therapy in the last 6 weeks for sleep disturbance
Unable to complete the baseline assessment forms or to understand the recommendations for participation in the study
Currently with a diagnosis of major depression, manic depressive disorder, obsessive-compulsive disorder, or schizophrenia)
Have glaucoma
Currently receiving anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, clonidine, and/or tricyclic drugs (imipramine, clomipramine, or desipramine)
Persons with congenital blindness and self-reported acquired blindness (independent of the cause) with no light perception
Patients with a subjective history of an extreme dry mouth syndrome that prevents them from producing adequate amounts of saliva (approximately 2 mL in 15-20 min)
Requiring mechanical ventilation
Vasopressor requirement
Known cirrhosis
One consistent parent is willing and available to participate in all parent and evaluation sessions
AYA is not married and has no children
Cognitive impairments that would make it difficult for AYA/parents to participate in the intervention or complete questionnaires (determination in consultation with attending physician, oncologist, and, for adolescents below age 18, the parents)
Patients must be willing to submit blood and urine samples for serum hormones (estradiol, FSH, LH), inflammatory biomarkers (serum TNFalpha, IL-6, IL-12, CRP and urine CTX-II),urine AI metabolites, and deoxyribonucleic acid (DNA) analysis (CYP19A1), and must be given the option to consent to use of remaining specimens for future translational medicine studies; baseline samples must be obtained prior to beginning intervention
At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the database
Patients with positive RSV by rapid antigen testing and/or culture in bronchoalveolar lavage regardless of the chest radiographic findings
Patients with known risk factors for thromboembolism (e.g. Factor V Leiden mutation, antithrombin III (ATIII) deficiency, Protein C and S deficiency, antiphospholipid syndrome, portal hypertension, etc.)
Subjects must agree to not use any over-the-counter or prescription vaginal preparations (lubricants, creams, gels, ointments, solutions) during the four weeks of treatment with topical fluocinonide cream
Subjects must have ability to read, comprehend, and complete patient questionnaires independently or with assistance
Subject reported symptoms of vaginal infection with significant vaginal discharge or odor
Known vaginal pathology other than vaginal atrophy that could explain vaginal symptoms
Known intolerance of topical steroid preparations
Patients must not have any of the following serious concomitant skin disorders that, in the investigator’s opinion, could interfere with assessment of EGFRI induced skin toxicity: atopic dermatitis (eczema), contact dermatitis, psoriasis, rosacea, severe photosensitivity, scleroderma, steroid-induced acne, xerosis
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Rate fatigue at least 1 or higher on a scale of 0-10
Have no clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale (MDAS) score of =< 13 at baseline
Be willing to engage in follow-up telephone calls with a research nurse/coordinator
Be willing to participate in the exercise and in cognitive behavioral therapy (CBT)
Have a major contraindication to methylphenidate hydrochloride (MP) (e.g., allergy/hypersensitivity to study medications or their constituents), exercise (e.g., cardiac disease), cognitive behavioral therapy (e.g., schizophrenia), or conditions making adherence difficult as determined by the attending physician
Are regularly engaged in moderate- or vigorous-intensity exercise for at least 150 minutes per week
Regularly used cognitive behavioral therapy in the last 6 weeks
Be unable to complete the baseline assessment forms or to understand the recommendations for participation in the study
Have glaucoma
Be currently receiving anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and/or tricyclic drugs (imipramine, clomipramine, or desipramine)
Planning to receive care at the participating institution
Significant psychiatric or other co-morbid disease, which the treating clinician believes prohibits informed consent or participation in the study
Rate fatigue on a numerical scale during the previous 24 hours as >= 4 on a 0 to 10 scale (0 = no fatigue and 10 = worst possible fatigue)
Memorial delirium assessment scale =< 13
Controlled pain and depression symptoms, if present (defined as no change in the morphine equivalent dose of 30% or change in the dose of antidepressant medication in the past 2 weeks)
Currently taking ginseng, methylphenidate or modafinil or have taken it within the previous 10 days
Currently with a diagnosis of major depression, manic depressive disorder, obsessive-compulsive disorder, or schizophrenia
No concurrent full dose anticoagulant therapy; =< 1 mg/day of Coumadin for preventing catheter clots allowed
Patients needing anti-emetic treatment for breakthrough nausea/vomiting may also receive anti-emetic agents on an as needed (PRN) basis
Signed HIPAA compliant research authorization (or equivalent for international sites) to release Personal Health Information to the SunCoast CCOP Research Base must be obtained prior to registration
Scheduled use of antiemetic agents other than ondansetron, granisetron, dexamethasone or aprepitant; patients may receive other antiemetic agents PRN for breakthrough nausea / vomiting but not on a scheduled basis
Prior administration of denosumab
More than 1 previous dose of IV bisphosphonate administration
Planned invasive dental procedures
Subject will not be available for follow-up assessment
Less than 120 minutes of exercise per week (as determined by Leisure Score Index of Godin Leisure-Time Exercise Questionnaire [LSI])
Approval by oncologist or surgeon
Willingness to be randomized
Absolute contraindications to maximal exercise testing as recommended by the American Thoracic Society and exercise testing guidelines for cancer patients
Participating in another clinical study with competing study outcomes
Any condition associated with increased risk of metformin-associated lactic acidosis (prior renal failure or liver failure, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)
Treatment plan that includes external beam radiation at a mean dose of at least 24 Gy or more to one of the parotid glands (the other gland can receive less than 24 Gy)
Anatomically intact parotid and submandibular glands
Upper or lower extremity deformities that could interfere with accurate acupoint location or alter the energy pathway as defined by traditional acupuncture theory
Subjects must have HL, NHL, or MM requiring PBSCT
Subjects must have a psychological and emotional state that, in the view of the investigators, allows adherence to the protocol
Female subjects capable of reproduction, and male subjects who have partners capable of reproduction, must agree to the following:
Female subjects who are surgically sterilized or who have not experienced menses for at least two years are not required to have a pregnancy test
Menopausal status not specified
Pulse ? 60 beats/minute
No hereditary or idiopathic angioedema
Karnofsky performance status >= 70 (Radiation Therapy Oncology Group [RTOG] recursive partitioning analysis [RPA] class I & II)
Undergoing an autologous or reduced intensity conditioning (RIC) allogeneic HSCT
Medical or psychiatric conditions (beyond ovarian cancer, its treatment, and its symptoms) that would impair our ability to test study hypotheses (e.g. cardiac, pulmonary, or orthopedic history that would prohibit a program of walking for exercise; psychotic disorders, dementia, inability to give informed consent)
Be planning to receive a conditioning regimen for stem cell transplant (SCT) consisting of cyclophosphamide and total body irradiation and must meet inclusion criteria for SCT which include:
PATIENT PARTICIPANTS
PEER MENTORS
PEER MENTORS:
Serum potassium >= 3.8 mmol/L
Known sensitivity to lenalidomide or other thalidomide derivatives
Known primary benign or malignant hematologic disorder which can cause anemia.
Transferrin saturation < 20% and ferritin < 50 ng/mL as assessed by the central laboratory during screening. Subjects must have both to be excluded (supplementation and retest acceptable).
Plan to receive any RBC transfusion between randomization and study day 1.
Previously randomized to this study.
Prisoner or patient in custody
Patient on psychiatric hold
Physically unable to participate in the study
Chronic transfusion-dependent anemia with exposure to at least 5 RBCT
Interested in reducing transfusion exposure
Receiving erythropoietin stimulating agent
Hemolytic anemia
Coagulopathies including disseminated intravascular coagulation (DIC), receiving anticoagulant or antiplatelet agents
Participation in a therapeutic clinical trial
Clinical diagnosis of insomnia as identified through the screening Insomnia Severity Index score > 14
Ability to operate the accelerometer (Actiwatch Spectrum Pro)
Second or third shift workers or others with non-traditional sleep schedules
Outpatients with MPE undergoing IPC placement
Sufficient mental capacity to answer SF-6D and Borg score questions
Chronic insomnia has been defined in previous research:as the presence of (1) three or more episodes of insomnia (i.e., ? 30minuteSOL, ? 60minute wake after sleep onset (WASO), or ? 6.5 hour total sleep time (TST) per night) of per week and (2) daytime effects of insomnia, such as irritability, difficulty concentrating, or fatigue for at least one month.
have the permission of their oncologists to participate.
untreated sleep disorders such as sleep apnea
Normal cognition and willingness to complete fatigue and quality of life forms at each designated time point along with a patient observation form and pill diary
Active psychosis
Acute febrile illness
An expected hospital stay of 3-4 weeks or longer
Radiologic evidence of at least 1 measurable lytic lesion in the arm, pelvis or leg
Completion of two years monthly zoledronic acid therapy
Prior exposure to sotatercept
Patient who have reported fatigue moderate or higher fatigue (based on the 0-10 Fatigue scale, a fatigue score of 5 or higher) while on radiation treatment
Patient who have reported less than moderate fatigue (based on the 0-10 Fatigue scale, a fatigue score less than 5)
BFI score must meet at least one of the below criteria:\r\n* Total BFI < 50\r\n* Dietary subscale < 11\r\n* Frequency subscale < 19\r\n* Urgency subscale < 12
Immune suppressive medication
Congenital spinal defect/paraplegia
Rectal prolapse
Active anal/rectal abscess
Pediatric patients with ALL diagnosis, treated at the University of Minnesota Amplatz\n             Children's Hospital or Children's Hospitals and Clinics of Minnesota
Not smoking
Currently not involved in a regular (3 times per week) exercise program
Individuals with previous radiation treatments to the breast or axilla areas
Prior diagnosis of lymphedema
Inmates
Presence of erectile dysfunction symptoms
Cognitive impairment (>= 5 on the Short Portable Mental Status Questionnaire [SPMSQ])
Taking nitrates of any kind
Having untreated clinical depression and other psychotic mental disorders (e.g., bipolar, schizophrenia) (>= 27 on the Center for Epidemiological Studies Depression Scale [CES-D])
Patients with a history of left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis)
Patient must have a solitary, polar, clinical T1 renal mass
Patient has a single functioning kidney
Unilateral upper limb secondary lymphedema
Patient or legal representative must agree to blood serum assessment including, complete blood count (CBC) with differential, comprehensive metabolic panel and serum osmolality at every sanctioned evaluation; additionally physician may require cardiac evaluation with echocardiogram, electrocardiogram, brain naturetic peptide or urinalysis if deemed appropriate
Patient or legal representative must consent to multi-bio-frequency impedance analysis (MFBIA); the details are to be covered in consent
Patient or legal guardian willing to sign consent for skin biopsies and phlebotomy
Patient or family is unable or unwilling to self/home administer subcutaneous experimental drug; study nurse or physician will train individuals on proper administration techniques
Patient or caregivers who are unwilling or incapable of maintaining a detailed log of number of injections, the date, time and site of administration
Patient with primary lymphedema; if edema can be explained by systemic or congenital illnesses, that patient will not be eligible for this study
Neutrophils less than 1.5 x 10^9/L
Serum bilirubin > 1.5 x the upper limit of reference range (ULRR)
Alkaline phosphatase (ALP) > 2 x ULRR, or > 4 x ULRR if judged by the investigator to be related to liver metastases
Known hypersensitivity to VPA, valproate sodium, disodium valproate, or any ingredient in the respective formulation
Clinical evidence of skin infection at the potential site of IPC placement
The following drugs will not be administered concurrently with VPA: carbapenem antibiotics; clonazepam; topiramate; felbamate; lorazepam; barbiturates; carbamazepine; chlorpromazine; ethosuximide; guanfacine; lamotrigine; methylfolate oxcarbazepine; paliperidone; phenytoin; primidone; protease inhibitors; rifampin; risperidone; rufinamide; salicylates; temozolomide; tricyclic antidepressants; vorinostat; zidovudine
Ability to complete the 4 or 6 weeks of acupuncture and follow-up assessments
Mental incapacitation or significant emotional or psychological disorder that, in the opinion of the investigators, precludes study entry
Women using systemic or vaginal estrogen, testosterone, or dehydroepiandrosterone (DHEA) during the Randomized Trial study will be excluded
< 19 years old
undergoing a procedure other than laparotomy
chronic narcotic pain medication users
Granulocytes >= 2,000/ml
Report sleep disturbance of 8 (sum total of all 7 items) or greater on the Insomnia Severity Index\r\n* (Note: this measure will be repeated again at baseline assessment)
Be able and willing to wear an Actiwatch for the entire 24 hours of each day they are scheduled to wear it
Have sleep problems that began before diagnosis and have not changed since diagnosis
Take medication for sleep (e.g., hypnotics and sedatives) every night; melatonin is permitted
Patients who are shift workers are excluded; shift worker is defined as someone who has irregular work and sleep hours (such as working a non-traditional schedule: e.g., 4pm-midnight or 10pm-6am; a rotating schedule e.g., alternating between day and night shifts, or starting work between 4am and 7am)
7+3: Standard-dose cytarabine 100-200 mg per meter squared continuous infusion for 7 days with idarubicin 12 mg per meter squared or daunarubicin 45-90 mg per meter squared for 3 days
High-dose cytarabine-based (HIDAC) chemotherapy administering a total cytarabine dose of ? 4 g per meter squared alone or in combination with other anti-leukemic agents (for example, anthracyclines, purine nucleoside inhibitors, etoposide, etc.)
Undergoing active treatment or in remission and undergoing active surveillance
Those with concurrent diagnosis of organic brain syndrome, dementia, mental retardation, non-English speaking, or significant sensory deficit
Major mental illness (e.g., schizophrenia, psychotic disorder)
Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. However, potential subjects with an ECOG of 3 may be enrolled provided their condition does not preclude performing the actions required by study participation (e.g., opening medication bottles, swishing the oral rinse and spitting out, completing or participating in completion of daily diaries and FACT-H&N forms).
Plan to be treated with cetuximab (Erbitux®)
Has incompletely healed sites of dental extractions
Has known allergies or intolerance to brilacidin, cisplatin or carboplatin
Patients included in the study will have a hematologic malignancy (any stage or grade) for which they are undergoing preparation for allogeneic HSCT; participants in the study will be restricted to those undergoing HSCT under reduced-intensity protocols 9924 and 9907
No restrictions or requirements will be placed on race
INCLUSION CRITERIA FOR PATIENTS: Agrees to family member (family member; significant other; friend) participation in study and to selecting the individual who could participate
Self-report of moderate or higher pain on average during the last week (> 3 on a 0-10 pain intensity numeric scale)
Mentally and physically able to participate and complete surveys over the phone
Both heterosexual and same sex couples will be eligible
Spouses/partners could not participate if the patient refused participation
Presence of a sun tan in the area
Fitzpatrick skin types V, VI
Ambulatory Post Acute Care (APC) score between 53 and 66
Ability to complete questionnaire(s) by themselves or with assistance
Have working phone to communicate with study team
Sufficient auditory acuity
Intact cognitive status
Patient being treated at St. Jude Children's Research Hospital
Pre-morbid condition that prevents patient from ambulating
Intra-operative injuries (for example: rectal injury)
Inadequate hemostasis
Any prisoner and/or other vulnerable persons as defined by NIH (45 CFR 46, Subpart B, C, and D)
Of any ethnicity
Caregivers will be eligible for enrollment if they identify as the person who provides instrumental care such as transportation for a patient who is receiving HSCT
Do not have cognitive or psychiatric conditions prohibiting participation
Endorse a moderate level of anxiety (e.g., greater than or equal to 8 on the Hospital Anxiety and Depression Scale [HADS-A])
Have no contra-indication to moderate to vigorous aerobic exercise
For Aim 2 only: individuals who took part in the focus group
At least 1 night of planned inpatient stay
Living in Maryland, Northern Virginia, or the Washington District of Columbia (D.C.) metropolitan area
Those who are unable to understand Korean
Any current axis I diagnosis
Any musculoskeletal problems that would interfere with the NET therapy
Are in the terminal stages of illness
Agree to travel to the Seattle Cancer Care Alliance (SCCA) or University of Washington (UW) School of Nursing for 2-3 in person assessments over the 12-13 weeks of the study
Self-report of learning disabilities
Substance addiction
Diagnosis of psychiatric disorders of psychosis, schizophrenia, or bipolar disorder
Mini mental state exam score less than 19
Previous participation in cognitive training program
Visual impairments such as uncorrected vision or color blindness
Uncorrected hearing impairments
Inability to use a mouse or computer keys to navigate around the computer screen
Experiencing disrupted sleep (determined by Pittsburgh Sleep Quality Index)
Must be either morning or evening types (determined by Horne-Ostberg Morningness-Eveningness Questionnaire [MEQ])
Sighted and mentally competent to consent
Patients who have eye conditions (glaucoma or retinal disease), problems triggered by bright light (e.g. migraine), or take photosensitizing medications (e.g. some porphyrin drugs, antipsychotics, antiarrhythmic agents) will be excluded for safety of using bright light
ADULT PARTICIPANTS:
Patient deprived of freedom, under supervision or guardianship
Patient unable to attend to scheduled medical monitoring due to geographical, social or mental reasons
Immune compromised or other serious medical conditions, other than cancer diagnostic, at enrollment; immune compromised subjects will be defined as having absolute neutrophil count (ANC) less than 1000 as determined by complete blood count testing (CBD) performed weekly as standard of care in individuals receiving chemoradiation
Willing to provide locator information for follow-up contact
Ownership of smartphone with following specifications: wireless capability, running on iPhone operating system (iOS) or Android operating system, current software (4.4 Android; 8.0 iOS or later), and, adequate memory to run the AMT program (43 megabyte[M] Android; 30.2M iOS)
Unfamiliar with mobile phones/tablets, including ability to download and register the Headspace app
Become unable to participate in a fully app and web-based intervention trial
Unwilling to complete online questionnaires
Planned total laryngectomy at Barnes Jewish Hospital (BJH)
Subjects receiving the short-course fractionation radiation therapy (i.e., 16 sessions or 20 sessions at 2.4 to 2.6 Gy fractions per session, with or without boost)
Previous diagnosis of radiosensitivity disorder (i.e., ataxia telangiectasia)
Current daily application of a prescribed topical product to the skin within the RT area for an unrelated skin condition that cannot be discontinued during the participation in this clinical trial
Presence of any active dermatological issues in radiation treatment area (i.e., fungal skin infection, dermatitis, psoriasis plaques, etc)
Must report at least one of the following: a. “How tired did you feel in the past week?” at least 4 on a 10 point scale (with 0 = not tired at all and 10 = extremely tired) b. “Did you have trouble sleeping in the past week?” with the answer “yes” c. “What was your average pain in the past week?” at least 4 on a 10 point scale (with 0 = no pain and 10 = extremely severe pain)
No diagnosis of sleep apnea or restless leg syndrome that is currently interfering with sleep
Enrollment on the SJLIFE protocol
Arm circumference between 22-47 cm
Patient being treated at St. Jude Children’s Research Hospital
Physician approval to participate in intervention
Ability to come to standing from seated position without assistance
Adolescent gives assent
Carry a diagnosis of metastatic colon, rectum, or small bowel adenocarcinoma
Have a distress level of >= 3 on the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT); this is required for intervention group participants only to be able to show improvement in mood/quality of life (QOL)
Deafness, current meditation practice (> 2 episodes or > 1 hour total, weekly), and current enrollment in a stress reduction program
Are to undergo laparotomy
Immobility as defined by inability to ambulate unassisted
Patient currently residing in a skilled nursing facility
Planned greater than one night admission to the intensive care unit (ICU)
Must have cancer-related fatigue, as indicated by a response of 4 or greater when asked to rate their level of fatigue at its worst in the past week on an 11-point scale anchored by “0” = no fatigue and “10” = as bad as you can imagine
Have used marine omega-3 supplements at any time within previous 3 months (this includes prescription omega-3 drugs such as Lovaza®)
INFORMAL CAREGIVERS: The primary informal caregiver as identified by patients participating in the study; this refers to either a family member or friend who will be providing the majority of care following surgery
Participants must have been in their spousal relationship for at least the past 1 year
At least one pulmonary metastasis ? 3.0 cm in maximum diameter resulting from distant primary cancers or at least one recurrence of primary lung cancer ? 3.0 cm in maximum diameter.
Tumor abutting main stem bronchus, main pulmonary artery branches, esophagus and/or trachea.
Tumors located < 3 cm of staple lines or other metal objects.
The subject is undergoing one of the following reconstructive procedures that requires latissimus dorsi muscle harvest: a. post-mastectomy breast reconstruction procedure (either nipple or skin sparing) in which a female subject needs additional muscle coverage over an implant, but does not need additional skin (i.e., patient is a candidate for a pedicled latissimus dorsi muscle flap procedure); b. scalp reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; c. upper extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; or, d. lower extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage
The subject is diabetic
The subject has had prior back or axillary surgeries which could compromise the blood supply of the flap
Women who self-identify as Black;
No active suicidality;
No substance dependence within the past year;
Available for follow-up over the course of the study;
Endorse moderate stress or distress as measured by a score of 4 or above on the a distress thermometer and an adapted thermometer of stress;
Women who do not self-identify as Black;
Active suicidality;
Substance dependence within the past year;
Not available for follow-up over the course of the study;
Score below 4 on a distress thermometer and an adapted thermometer of stress;
Women with scleroderma or discoid lupus
Adult (? 18 years at time of allogeneic HCT recipient at participating transplant centers)
All diagnoses will be eligible
All conditioning regimens will be eligible (in case of allogeneic HCT, patient could have received myeloablative or non-myeloablative/reduced-intensity conditioning)
Patient must have a valid mailing address within the United States to receive study materials
EXPERT PANEL:
A convenience sample of 10-15 experts (at least three lymphedema therapists and a varying number of HNC medical, radiation, and surgical oncologists, HNC nurse practitioners, speech and language pathologists, and nursing and informatics scientists) will be recruited to inform development of videos, protocol, and educational manual
Knowledgeable in either HNC or lymphedema management or informatics
LYMPHEDEMA THERAPISTS:
Subsequent to the development of the materials, five additional therapists will be recruited to conduct an unbiased test of the therapists’ training video and protocol
Certified lymphedema therapists
PATIENT PARTICIPANTS:
A convenience sample of 10-15 HNC survivors (based on data saturation) will be recruited and interviewed about their status/needs for conducting lymphedema self-care; then, an additional 10 HNC survivors will be recruited to undergo a training session with the study therapist and test the patient video and educational manual
Able to complete the onsite training and home self-care activities for lymphedema management
Patients with medical conditions (e.g., acute infection, congestive heart failure, renal failure, cardiac or pulmonary edema, sensitive carotid sinus, severe carotid blockage, and uncontrolled hypertension) that would prohibit the safe implementation of home-based self-care of lymphedema will be excluded
Current participation in an intervention targeting diet or exercise
Inoperable malignant neoplasm causing biliary obstruction or stricture that requires a fully covered metal stent
Undergone or is planning to undergo brachytherapy with transpapillary or percutaneous implantation of intracavitary radiation sources
Endoscopic procedures are contraindicated
Current anatomy upstream of intended stent placement compromising the flow of bile from the liver such that stent placement may not alleviate the biliary obstruction symptoms
Presence of an esophageal or duodenal stent
Jaundice secondary to a cause other than biliary duct obstruction
Additional endoscopic restrictions as specified in the Clinical Investigation Plan
Patients plan to have primary surgery at either the University of Chicago Hospital or the University of Wisconsin Hospital
Plasma creatine phosphokinase (CK) < 1.5 x ULN
Inadequately controlled pain even with the use of morphine (visual analog scale [VAS] score > 5)
Patient with aplastic anemia will be excluded
Patient with rapidly escalating pain that require hospitalization or an intravenous opioid therapy
Opiate-induced uncontrolled constipation or bowel obstruction
Investigator is able to insert and deploy the Blowfish Catheter into the airway after recanalization
acute kidney injury
Individuals with neurological, mental or psychiatric disorders
Use of pulmonary airway stents and/or ongoing or initiation of local external beam or brachytherapy radiation
Participants must not have documented or observable visual, auditory, psychiatric, or neurological disorders that would interfere with study participation (e.g., blindness, deafness, psychosis, or dementia)
Able and willing to receive phone calls
Difficulty hearing on the telephone
Cognitive deficits
Hospice care at enrollment
Patients will be free of signs and symptoms of infection at the time of entering the study and, most importantly, will be encouraged to have sufficient donors to administer prophylactic white cell transfusion twice a week for six weeks in order to assess their effectiveness
Able to self-administer topical interventions or provide for another person to apply the topical interventions
Patients with pre-existing dermatologic condition affecting the face and chest that would impair assessment of papulopustular rash, including dense and/or long facial hair (per investigator discretion)
Receiving radiotherapy or chemoradiation
Ages 18-65 (women above the age of 65 may be included at principal investigator [PI] discretion)
Patients will be between 6 months and 4-years post radiation treatment; ongoing chemoprevention therapy is permissible; based on International Classification of Diseases (ICD)-10 proposed criteria, a diagnosis of CRF will require evidence from the history, physical exam, and laboratory findings that the fatigue is a consequence of cancer or cancer therapy and not primarily a consequence of comorbid psychiatric disorders (schizophrenia, depression, generalized anxiety disorder, bipolar disorder, dementia, delirium or obsessive–compulsive disorder [OCD])
Brief Fatigue Inventory (BFI) score of > 25
Inability to lay supine for one hour at a time, given the nature of the massage intervention
Subjects who are actively suicidal or homicidal
Subjects who have used massage as a therapeutic modality (medical or psychological) at any point in their lives for the treatment of medical conditions
Subjects who have massages on a regular basis; regular massage usage will be operationally defined as receiving 4 or more massages/year for the last 5 years
Subjects currently employing any other complementary and alternative medicine (CAM) manual therapy and/or holistic therapies to treat a perceived health problem; however, since past experience with CAM therapies should not confound any of the analyses of the experiments proposed in this study, we will not exclude individuals who have engaged in a CAM manual therapy in the past, nor will we exclude individuals who practice yoga or meditation for well-being, take vitamins or use nicotine
Adults over the age of 65 will generally be excluded from the study; older subjects could be included at the discretion of the PI
Women who become pregnant while enrolled will be discontinued from the study and will be instructed to exercise, which is the standard recommendation for cancer-related fatigue
Receiving any agent classified as an antioxidant
Chronic immunosuppression
Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure
Subjects with pathologically-proven gynecologic malignancies
Taking vismodegib daily at time of enrollment
At least one muscle spasm per day at time of screening
Muscle spasms onset after starting vismodegib
Known deficiency in carnitine (genetic, etc.)
Residual grade > 1 skin toxicity, cellulitis, or incompletely healed wound(s) at intended site of study drug application at the time of the start of radiation therapy (RT)
Any topical treatment for neuropathy or other serious skin condition on the hands or feet
Patients who have any confounding medical or neurological conditions that have the potential to affect cognition, speech or swallowing function; i.e. stroke, neurodegenerative disease, neuromuscular movement disorders, head injury, etcetera
The affected arm must be > 2 cm larger than the unaffected arm; differences of 2 cm or more between the affected and unaffected arm are considered by experts to be clinically significant; each affected arm will be measured in two areas: upper arm and forearm; the larger of the two measures -upper arm or forearm- will be used for analysis
Bilateral lymphedema
Has an implanted electronically charged medical device
Women who are being seen at the Women's Health Center by the Gynecologic Oncology group at the University of Minnesota if planned surgery includes an exploratory laparotomy
< 19 years old
Undergoing a procedure other than laparotomy
Chronic narcotic pain medication user
American Society of Anesthesiologists (ASA) score of > or = 3
Any condition that would exclude women from undergoing regional anesthesia
Chemotherapy regimen: Doxorubicin/cyclophosphamide. Antiemetic regimen: Aprepitant + palonosetron + dexamethasone on Day 1 and aprepitant + dexamethasone on Days 2 & 3.
Chemotherapy regimen: Doxorubicin/cyclophosphamide/docetaxel. Antiemetic regimen: Aprepitant + palonosetron + dexamethasone on Day 1 and aprepitant + dexamethasone on Days 2 & 3.
Chemotherapy regimen: Docetaxel/cyclophosphamide. Antiemetic regimen: Palonosetron on Day 1 + dexamethasone on Days 1, 2, & 3. Note: Fosaprepitant will be allowed in place of aprepitant, and either granisetron or ondansetron, on one or more days, will be allowed in place of palonosetron.
Have a response of > 3 or greater on a question assessing expected nausea as assessed on a 5-point Likert-scale anchored at one end by 1 = \I am certain I WILL NOT have this,\ and at the other end by 5 = \I am certain I WILL have this.\
Postmenopausal (confirmed by self-report on the Health History Questionnaire; menopausal status could also be confirmed by a recent [< 6 months from enrollment] laboratory report documenting serum follicle-stimulating hormone [FSH] > 30 mIU/ml and/or serum estradiol < 30 pg/ml)
Cognitive difficulties that preclude answering the survey questions, participating in the exercise classes or performance tests, or providing informed consent (confirmed by the professional opinion of the Principal Investigator, Dr. Kerri Winters-Stone)
Currently 2-10 years after first HCT
Does not have internet and email access; note that survivors otherwise eligible, but excluded from full study participation because of this exclusion, will be asked to fill out a mailed copy of the baseline assessment for use in secondary aims analyses; they will be sent an information form and a copy of the tailored ‘My Health Action Plan’ health care guideline for transplant survivors also provided to randomized participants
English insufficient to complete baseline patient-reported outcomes (PRO) assessments
Has received treatment for a recurrent or 2nd cancer that required > surgical excision in the past 2 years or did not have a hematologic malignancy or myelodysplasia diagnosis or did not receive a first transplant between 2-10 years before approach for the study; (these participants will be ineligible for randomization, but will have intervention site access if they complete baseline PRO assessment)
Scores 20 or above on the patient health questionnaire (PHQ)-8 depression measure (indicating severe depression); these participants will be contacted by a study psychologist to evaluate and provide resources to address their needs (2% of enrollees in our previous study); they will be ineligible for randomization, but will have intervention site access if they complete baseline PRO assessment
Residing in an institution or other living situation where health care decisions are not made by the participant (e.g., hospitalized, prisoners, living in a rehabilitation facility)
Does not complete baseline PRO assessment items required to determine stratification or whether the survivor meets inclusion and exclusion criteria
Has medical or health issues prohibiting computer use (e.g., vision-impaired, cognitively impaired, illness or accident impairing computer function)
Available multivirus-specific CTLs
Myeloablative preparative regimen (i.e., >= TBI 12.0 Gy, >= busulfan (BU) 8.0 mg/kg PO, >= BU 6.4 mg/kg intravenously (IV), >= treosulfan 42 g/m^2 IV) according to investigational study or standard treatment plan; other \myeloablative\ preparative regimens are acceptable as long as they are approved by the principal investigator or designee
Cyclosporine (CSP)-based postgrafting immunosuppression
Nonmyeloablative preparative regimen
Participant has symptoms of NP/PN with onset within 7 days after one of the following vincristine doses +/- 3 days: protocol week 1 or week 2 (induction), week 7 (reinduction I), or week 17 (reinduction II)
Patient is expected to receive 2 weekly doses of vincristine as outlined by the Total XVI or “as per TOTXVI” protocol while on study drug (i.e. no known dosage reductions or planned missed doses)
Previous participation in this study
Unremitting pain that resulted in a return visit to the oncologist. The 'worst pain' in the last 24 hours must be reported to be 4 or above on a scale of 0 (no pain) to 10 (pain as bad as subject can imagine) despite pharmaceutical pain management
Tumors must be suitable for cryoablation
The subject is willing to consent to randomization to the intraperitoneal drain vs. no drain group
The subject is not willing to consent to randomization to the intraperitoneal drain vs. no drain group
Anaphylaxis to local anesthetics or narcotics
Technical contraindications to epidural placement: previous thoracic spinal surgery or local skin or soft tissue infection at proposed site for epidural insertion
Educational, psychiatric (untreated or poorly controlled schizophrenia, major depression, or bipolar disorder), or communication (language) barrier that would preclude accurate assessment of postoperative pain and/or ability to answer questionnaires (need to be able to read, comprehend, and answer questions)
Patient refusal to participate in randomization
Patients requiring additional intra-operative skin resections of greater than 1 cm beyond the skin edge as a result of mastectomy flap devascularization
Subjects who are taking drugs known to interact with posaconazole and that may lead to life-threatening side effects (terfenadine, cisapride, and ebastine at entry or within 24 hours before entry, or astemizole at entry or within 10 days before entry)
Subjects who are planned to receive > 2 mg flat dose of vinca alkaloids
Subjects with renal insufficiency (estimated creatinine clearance less than 20 mL/minute at baseline or likely to require dialysis during the study)
Subjects who will be receiving dasatinib
Tolerate sitting in a rocking or nonrocking chair
Able to ambulate
Scheduled to receive epidural or intravenous patient controlled analgesia
Cognitively intact
All others will be excluded
Adequate visual accuracy allowing eye testing
Diagnosis of osteoporosis
Must be in general good health
Fitzpatrick skin type I-VI
Currently taking ketoconazole, colestipol, cholestyramine, phenobarbitol, phenytoin, or mineral oil
Currently consuming 800 IU or more of vitamin D a day
Will be treated according to the Armstrong method
Patients undergoing minimally invasive radical-prostatectomy (including robotic and laparoscopic) at Washington University in Saint Louis (WUSTL)/Siteman Cancer Center (SCC)
Have a known urethral stricture, colostomy, or inability to urinate requiring chronic urinary catheter; only men who are cleared by their physician to safely participate in a physical exercise program (including walking and lifting weights) will be eligible for this study
All ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
Able to be accompanied by their spouse or significant other partner/friend (spouse, significant other, partner, or friend)
Able to travel to the retreat site
Must be right handed
CAREGIVERS ONLY: Must be primary caregiver of the patient
CAREGIVERS ONLY: Must be an adult (>=18 years old)
Previous or existing pathology of the external or middle ear which would preclude auditory testing and/or intratympanic dexamethasone delivery
Previous or existing pathology of the central nervous system with potential to impact auditory pathways (i.e. major head trauma, meningitis, encephalitis, brain metastasis, vestibular schwannoma)
Patient unsuitable for or refusing radical cystectomy
N0
M0
American Society of Anesthesiologists (ASA) < 4
Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
Known uncontrolled cytomegalovirus (CMV) polymerase chain reaction (PCR) reactivation per institutional standards; once CMV has been treated and stable per institutional standards, patient may be enrolled; CMV PCR will be tested within two weeks prior to starting study drug
Mental incapacitation or significant emotional or psychological disorder that, in the opinion of the investigators, precludes study entry (these patients may not be able to cooperate with this slightly invasive procedure or with the data collection process)
Currently pregnant (certain acupuncture applications have been reported to stimulate uterine contractions)
Ability to engage safely in moderate exercise as determined by their treating physician
Acute or chronic bone/joint/muscular abnormalities compromising their ability to exercise
Neurological conditions that affect balance and, or muscle strength
Three umbilical cord blood (UCB) units composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm
Natural Killer Cell Malignancies
Willingness to have photographs taken to document lesions
Consent for sample collection for urine, hematology, histopathology and microbial profiling
No signs or symptoms of BRONJ
Willingness to provide consent for sample collection for blood, urine and saliva
Salivary gland hypofunction regardless of underlying pathology
Cognitive, language or hearing problems
Participation in another research project that might interfere with completion of this study
Planned course of definitive or post-operative radiotherapy (RT) to a total dose of ? 60 Gy using 1.8 to 2.0 Gy per fraction
Ability to complete questionnaire(s) by themselves or with assistance
Patient has not yet started current course of RT
Split-course RT is planned
Phase 2 only: be currently sedentary (i.e., engage in < or = 60 minutes of purposeful moderate-intensity PA/week)
Watch less than 3 hours of television per day
Be currently enrolled in another intervention study or recently completed a study promoting healthy lifestyle behaviors (diet and/or exercise)
Ability to complete questionnaire(s) by themselves or with assistance
Current diagnosis of cancer that supports the use of continuous definitive or adjuvant external-beam RT to the pelvis to a minimum dose of 4500 cGy with the following parameters:\r\n* The pelvis must be encompassed by the planned RT fields; the superior border may not lie inferior to the most inferior aspect of the sacroiliac joints; portions of the rectum may have special blocking, depending upon disease site\r\n* The total prescription dose must lie between 4500-5350 cGy (inclusive); a boost to primary tumor or tumor bed may be planned\r\n* Planned treatment is to be given 4-5 times per week on a one–treatment-per-day basis; the daily prescribed dose must lie between 170-210 cGy (inclusive) per day
Will receive concurrent administration of chemotherapy (fluorouracil [5-FU], capecitabine, cisplatin, oxaliplatin, carboplatin, and/or mitomycin C) during pelvic RT
Split-course RT is planned
Proton RT
Women over the age of 18 who are postmenopausal and wish to avoid hormonal therapy to treat menopausal symptoms
If women have had a hysterectomy and still have their ovaries, they must meet the FSH criteria described above
Possession of a CD/DVD player or ability to play a CD
Diagnosis of major depressive episode, acute anxiety disorder, liver or kidney dysfunction (defined by SGOT and creatinine levels 1.5 x upper limit of normal) as listed in the patient’s medical history in the chart within the past year and by self report
Bothersome hot flashes (defined by their occurrence >= 28 times per week [about 4 per day]) and of sufficient severity to make the patient desire therapeutic intervention
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:\r\n* Patients are pre-menopausal; OR\r\n* Post-menopausal aged 45-69 with any of the following three risks factors:\r\n** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or\r\n** Family history of breast cancer (first degree relative with breast cancer), or, participant positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or\r\n** Currently on hormone therapy; OR\r\n* Post-menopausal ages 70-74 with either of the following two risk factors:\r\n** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or\r\n** Currently on hormone therapy
For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND for whom a prior mammogram interpretation is not available, breast density will be determined by the radiologist’s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic 2D portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
Breast density will be determined by prior mammography reports, when available, or by radiologist review of prior imaging; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report
First-degree relatives (parents, siblings and adult children >= 25 years of age) of the CRC participants who do not have LS
Individuals who are cognitively impaired are eligible for the study and consent for participation must be given by a legal authorized representative or parent; pregnant women are eligible for the study
All consecutive subjects undergoing routine (standard of care) Lugol’s chromoendoscopic evaluation for suspected or known squamous cell neoplasia will be enrolled as well as any outgoing subjects referred to the clinic with any prior history of squamous cell dysplasia and/or neoplasia will also be considered eligible as they will serve as study population for the surveillance group
Have an interval from their chest RT to the time of enrollment of at least 8 years
Have a smartphone
Willing to have about 40 mL of blood (approximately 3 tablespoons) drawn
Receives screening breast MRIs at an outside facility other than the consenting institution
Have a valid United States mailing address for receipt of saliva kit
Have one blood relative with a mutation in BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, or PMS2
Unwilling to complete baseline and follow-up questionnaires
Reside in California or receive care at a Sanford Health site
Patient with poor bowel preparation
All consecutive outpatients with > 1 cm biopsy-proven Barrett’s esophagus who are undergoing standard of care endoscopic surveillance for metaplasia, dysplasia, or neoplasia
Known advanced adenocarcinoma of the distal esophagus, or dysplastic/suspected malignant esophageal lesion greater than 2 cm in size not amenable to EMR
Inability to tolerate sedated upper endoscopy due to cardiopulmonary instability or other
Patients with known, untreated esophageal strictures, prior partial esophageal resection, or altered anatomy preventing passage of the endomicroscope
CESM is an imaging exam that uses radiation and is not typically employed in women younger than age 30 due to potentially negative biologic effects on glandular breast tissue.
Participants who had a percutaneous breast biopsy (to include stereotactic, tomosynthesis, or ultrasound guided) that revealed ADH.
CLINICAL PROCOTOL USED AS REFERENCE FOR THIS STUDY:
Participants with a core biopsy diagnosis of atypia with associated malignancy (in the same quadrant) will be excluded.
Participants with persistent asthma as defined by the National Heart, Lung, and Blood Institute.
Participants who are breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to contrast administration in the mother.
Pregnant women are excluded from this study because CESM uses radiation with the potential for teratogenic or abortifacient effects. This will be defined by a urine pregnancy test prior to the CESM study.
INCLUSION - PATIENT: Group 2 will consist of women who presented for a screening mammogram (2D or 3D tomosynthesis) AND who have had a biopsy recommended after diagnostic workup:\r\n* Initial presentation for routine breast cancer screening with mammogram (2D or 3D tomosynthesis) and/or ultrasound and\r\n* Biopsy recommended after subsequent diagnostic workup (breast imaging reporting and data system [BI-RADS] 4 or 5)
EXCLUSION - PATIENT: Unable to tolerate exam (i.e., secondary to untreatable claustrophobia, positioning constraints/unable to lie prone)
EXCLUSION - PATIENT: Breast implants (silicone or saline)
Participants with persistent asthma as defined by the National Heart, Lung, and Blood Institute
CESM studies will include at least four low energy and four recombined images (left craniocaudal [LCC], left mediolateral oblique view [LMLO], right craniocaudal [RCC], right mediolateral oblique [RMLO])
Imaging sets with implants
Imaging sets in which a biopsy was recommended, but biopsy was not performed and 2-year imaging follow-up is not available
Rural Appalachian resident
No cognitive impairment
Has not had one of the following CRC tests:\r\n* Fecal occult blood test within the past year\r\n* Flexible sigmoidoscopy within the past five years or\r\n* Colonoscopy within the past ten years
Participants from Franklin County or from Appalachia Ohio (depending on program location)
One or more SYHC visits in the last year
Not up­-to-­date with screening (up to date with screening will be defined by Healthcare Effectiveness Data and Information Set [HEDIS] and Uniform Data System [UDS] criteria, which require presence of guaiac fecal occult blood test [gFOBT]/fecal occult blood test [FIT] in the last year, sigmoidoscopy in the last 5 years, or colonoscopy in the last 10 years)
Insured by MediCal, Medicare, or private health insurance
Uninsured
HIV positive individuals seeking dental care at Bering Omega/Houston Area Community Services
Patient's current participation in a tobacco cessation program
Be non-adherent to one or more recommended screenings for BC, CC, or CRC by Medical Record Review (MRR)
Reside in one of 32 rural counties in Indiana (IN) or Ohio (OH)
Plan to move outside of the country within the next year
Reside in a nursing home or other institution
Subjects are scheduled for colposcopy clinic based on screening with abnormal pap smear or have repeat colposcopy indicated for specific clinical indications, based off of the most recent American Society of Colposcopy and Cytology guidelines
Uninsured or on public Medicaid insurance
With income at or below 250% of the poverty line
Women with heterogeneously dense or extremely dense parenchyma by prior digital mammography report (i.e., \dense breasts\), presenting for routine annual mammography with digital breast tomosynthesis
For women who have not had any prior mammography (i.e. this is their first, baseline, mammogram), the breast tissue must be dense (heterogeneously dense or extremely dense) on the current mammogram
Prior mammogram (if any) more than 3 years ago
Signs or symptoms of breast disease including lump, bloody or spontaneous clear nipple discharge, eczema of the nipple
Current routine mammogram has been/will be performed more than 8 weeks prior to scheduled screening ultrasound
Previous diagnosis of Barrett’s esophagus, confirmed by pathology
Esophageal ulcerations
Esophageal candida
Esophageal varices
Asymptomatic women presenting to the imaging center for a screening mammogram
No requirement for sedation
BRCA 1 or 2 mutation
Women scheduled for screening CEDM alone
Prisoners are excluded
Patients must also have a treatment plan that includes liver function assessment with indocyanine green (IC-GREEN)
Non-pregnant female volunteer
INHALATION: Patient has known respiration problems (i.e., emphysema)
INHALATION: Are a smoker
Should generally be between the ages of 30 and 55; can be older or younger than this range depending on family history, genetic mutation status, or other factors; or as specified by separate protocols for approved intervention trials
Have a known high penetrance mutation associated with hereditary breast or ovarian cancer (including BRCA1, BRCA2, p53, PTRN, ATM, PALB2, mutations associated with the Lynch Syndrome, etc.)
If undergoing regular screening, subject must have a mammogram performed at the University of Kansas Medical Center or other accredited facility within 1 year prior to their RPFNA procedure; mammograms must be read as not suspicious for breast cancer (American College of Radiology [ACR] class I-III) unless issue resolved with other procedures
Must be willing to discontinue aspirin, nonsteroidal antiinflammatory drugs (NSAIDS), or supplements such as fish oil 3 weeks prior to the procedure (to decrease soft tissue bleeding)
Must be willing to have about 40 cc of blood (approximately 8 tablespoons) drawn at each aspiration visit
Must be willing to keep the clinic informed of their breast health status for 10 years when requested
If currently menstruating, must know the date of the first day of their latest menstrual cycle
If applicable, must be willing to collect a urine specimen and bring to the clinic; depending on specific planned uses, this may be a 24-hour collection, a 12-hour fasting collection, or a first morning collection
If applicable, must be willing to collect a stool specimen and bring to the clinic; special collection kits will be provided
Metastatic malignancy to other organs, excluding Hodgkin’s or non-Hodgkins lymphoma
Women on Coumadin, Xarelto, or other anticoagulants
Men over the age of 18 will be asked to participate in the educational component of the program; men over the age of 40 will be offered the screening component after the educational portion of the event; participants over age of 40 will have the opportunity to make an informed decision in regards to prostate cancer screening based on this information and the educational material; American Cancer Society (ACS) guidelines recommend having a discussion about screening in men who have a expected mortality of greater than 10 years; data on comorbidities and 10-year mortalities will be collected on every participant using the University of California at San Francisco (UCSF) mortality index
Educational component: men over the age of 18
Screening component: men over age 40
Atrial fibrillation
Previous reactions to iodinated contrast media
Willingness to undergo EUS with possible fine needle aspiration (FNA)
Willingness to undergo radiographic evaluation if screening findings are abnormal
Previous partial or complete resection of the pancreas for adenocarcinoma
Prior partial or total gastrectomy with Billroth II or Roux-en-Y anastomosis
Patents must be scheduled for routine screening DBT
Patient must agree to not undergo screening ultrasound (of breast) for the duration of the 1 year study period
Pre-existing neuropathy, neuropathic pain, or nerve injury;
Pain or significant arthritis in the toes of either foot;
Significant damage or deformity to the feet that would alter blood flow or make it impossible to measure/interpret findings;
Diagnosis of restless leg syndrome or other movement disorders that would prevent accurate data from being able to be collected.
PRE-TEST: Adults who can meet with Research Staff at Washington University in St. Louis in-person to complete study requirements
Adherent to CRCS guidelines defined as a home-based fecal occult blood test (FOBT) in the past year, a sigmoidoscopy (SIG) in the past 5 years, or a colonoscopy (COL) in the past 10 years
PRELIMINARY TEST: Ages 18-65
RANDOMIZED CONTROL TRIAL:
No Pap test in the last 3 years
Resident of an Ohio Appalachia county
No history of hysterectomy; women will not be eligible for the pilot randomized controlled trial (RCT) if they participated in the focus groups that helped develop this study (focus groups were institutional review board [IRB] approved as Protocol 2014C0086) or the preliminary device test; we will also require women to read and understand English and have the ability to provide informed consent, which will be inferred upon completion and return of the study eligibility, consent, and Health Insurance Portability and Accountability Act (HIPAA) forms
Individuals that fall within the age range for CRC screening surveillance from AHP
Are eligible for CRC screening surveillance from AHP
Was seen in the last 18 months a provider at one of the primary medical care clinics from the University of: General Internal Medicine (Lowry, Anschutz), Family Medicine (Westminster, Stapleton, Park Meadows, Boulder), or the Women's Integrated Services in Health (WISH) Clinic, and the individual’s primary medical care provider has provided approval for AHP CRC outreach to an AHP staff person, and have no record of a colonoscopy within the last 10 years, flexible sigmoidoscopy or double-contrast barium enema within the past 5 years, or fecal occult blood test (FOBT) within the past year
Individuals that have limited cognitive function/developmental disabilities
Are not eligible for CRC screening surveillance from AHP
Have a terminal medical illness that would otherwise categorize them as inappropriate candidates for CRC screening; these are: the individual must have any of the following noted in their EPIC electronic medical records (EMR): personal history of CRC, colectomy, colostomy, or ileostomy
Currently prescribed plavix (clopidogrel)
Have arrhythmia/atrial fibrillation
Have cardiomyopathy
Currently weighs > 350 pounds
Have cystic fibrosis
Are insured by the Colorado indigent care program (CICP) or Medicaid-Old age pension, American Association of Retired Persons (AARP) Medicare/Secure Horizons (except private fee-for-service [PFFS]), Denver Health Managed Medicaid, Evercare; Kaiser (not the prescriber of origin), Medicare Complete, New Medicaid, New CICP
Haitian, Hispanic, or African American
Report not having had a pap smear in the last three years
Live in the cities of Miami/Little Haiti, Hialeah or unincorporated southern Miami-Dade
Report having had a hysterectomy
Individuals who are not yet adults (infants, children, teenagers)
Prisoners
Health care centers
Community physicians, colorectal cancer survivors, family advocates, researchers, and representatives of community-based organizations
Subjects that are unable to swallow a tablet/pill for any reason
Subjects with a previous esophagectomy
Subjects with esophageal varices
Able to comprehend the full nature and purpose of the study, including possible risks and side effects.
Providers at selected primary care practices in the Cleveland Clinic Health System
Patients who are scheduled for a routine appointment with participating providers, who would utilize a guide to aid in decision making for prostate cancer screening, specifically men ages 40-69
Acknowledge sex with men in lifetime
Reside in Harris County, Texas
Have no current doctor's diagnosis of anal condyloma, hemorrhoids, fissures, or anal cancer
Men with current anal disease diagnosed by a doctor (e.g., condyloma, hemorrhoids, fissures or malignant tumors) will be excluded
Be self-identified as Latino/Hispanic
Referral from a primary care physician for colonoscopy (either diagnostic or screening)
Have telephone service
Hospice/Nursing Home
Women with pacemakers
Received treatment of cervical dysplasia with LEEP, cone biopsy, laser procedure or cryotherapy within THREE years
Decisionally impaired adults requiring a legally authorized representative
Patients with history of segmental resections are eligible (i.e. right colectomy, extended right colectomy, transverse colectomy, left colectomy, extended left colectomy, sigmoid colectomy, low anterior resection, abdominoperineal resection); the definition of resection does not include endomucosal resection (EMR); patients that have received total proctocolectomy are ineligible\r\n* In addition to segmental resections, the following types of procedures are allowed: polypectomy: for Tis (stage 0) or pT1 patients only, resection may consist entirely of polypectomy (without completion of partial colectomy) if ALL of the following criteria are met:\r\n** Single specimen, completely removed\r\n** Clear margins\r\n** None of the following must be present:\r\n*** Moderate or poor differentiation\r\n*** Lymphovascular invasion\r\n*** Perineural invasion\r\n* Transanal excision is allowed for pT1 rectal cancer patients with well or moderately differentiated tumors if National Comprehensive Cancer Network (NCCN) criteria for transanal excision are met, as stipulated here:\r\n** < 30% circumference of bowel\r\n** < 3 cm in size\r\n** Margin clear (> 3 mm)\r\n** Mobile, nonfixed\r\n** Within 8cm of anal verge\r\n** T1 only\r\n** Endoscopically removed polyp with cancer\r\n** No lymphovascular invasion or perineural invasion\r\n** Well to moderately differentiated\r\n** No evidence of lymphadenopathy on pretreatment imaging\r\n***When the lesion can be adequately identified in the rectum, transanal endoscopic microsurgery (TEM) may be used; TEM for more proximal lesions may be technically feasible
A total WBC >= 3.1 x 10^3/mcL is allowed for non-Hispanic black males (NHBM) and total WBC >= 3.4 x 10^3/mcL for non-Hispanic black females (NHBF) \r\n* Exception: If the WBC is lower than the above levels, the patient may be enrolled IF the absolute neutrophil count (ANC) is >= 1.3 for NHBM, >= 1.4 for NHBF, or >= 1.5 for all.
SPECIMEN SUBMISSION AND SUBSTUDY CRITERIA
As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patients must not have a serious psychiatric illness (e.g. lifetime bipolar disorder, schizophrenia or other psychosis, serious personality disorder, severe major depressive disorder or recent suicide or psychiatric hospitalization) (previous 12 months), or a history of an eating disorder (anorexia nervosa or bulimia nervosa)
Patients must be willing to provide name and appropriate telephone contact information and be willing to be contacted periodically via telephone by The University of Arizona Cancer Center (AZCC) staff for completion of individualized lifestyle intervention coaching, completion of the Pittsburgh Sleep Quality Index, and for clarification of patient-completed responses if necessary; patient must be willing to have Arizona Food Frequency Questionnaire (AFFQ), Arizona Physical Activity Questionnaire (APAQ), baseline questionnaire, and personal contact information sent to AZCC
Vegan vegetarians
Patient must have a lifetime cumulative anthracycline dose of >= 250 mg/m^2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the anthracycline dose threshold must be met as part of the treatment of a cancer that was diagnosed at < 22 years of age\r\n* Note: Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used to document lifetime receipt of anthracycline dose
Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device
Bradycardia: heart rate < 50 beats per minute (BPM)
Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or hypothyroidism) not controlled with medication
Anemia (hematocrit < 28%)
Lactating females are not eligible unless they have agreed to not breastfeed their infants
Patient must have completed curative chemotherapy within past 90 days at a Childrens Oncology Group (COG) institution
Able to hold breath for 10 seconds
Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
Able to exercise on a treadmill or stationary cycle
Participants in other ongoing clinical trials are eligible for this study
CONTROL (HEALTHY) GROUP: Able to hold breath for 10 seconds
CONTROL (HEALTHY) GROUP: Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
CONTROL (HEALTHY) GROUP: Able to exercise on a treadmill or stationary cycle
If previously measured, known LVEF < 50%
Symptomatic claustrophobia
CONTROL (HEALTHY) GROUP: If previously measured, known LVEF < 50%
CONTROL (HEALTHY) GROUP: Symptomatic claustrophobia
Biopsy-proven anal HSIL at baseline (anal intraepithelial neoplasia [AIN]2 with a positive cyclin-dependent kinase inhibitor 2A [p16] stain, AIN2-3, or AIN3)
At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
Active diagnosis of alcoholism
Currently receiving tamoxifen or raloxifene
Receiving pyrimethamine, cimetidine, rifampin or cephalexin
Qualifying cytological atypia in RPFNA, Masood score of 14-17; the qualifying RPFNA (of one or both breasts) must be send to Dr. Seewaldt's laboratory for cytological scoring and proteomic analysis; score results must be received from Dr. Seewaldt’s lab prior to patient registration/randomization; test must be done =< 90 days prior to registration/randomization\r\n* Note: Only the contralateral breast can be aspirated in women with DCIS and those undergoing surgery for an atypical lesion; the decision to aspirate the contralateral breast is at the discretion of the woman’s surgeon
Women eligible to take tamoxifen must be offered tamoxifen prevention as part of their clinical care and have refused tamoxifen treatment
Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin
Renal function < 30% of normal for age and size as determined by the Schwartz formula
Planned myeloablative conditioning regimen
Confirmed acute index (original venous thrombotic) event: lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis for which the patient has received >= 180 days (but =< 365 days) of anticoagulant therapy prior to registration; the date, imaging modality, and location of index event will be required; the date of initiation and specific type of anticoagulants used will also be required
Mechanical heart valve
Documented hemorrhagic tendencies (e.g., hemophilia)
Bacterial endocarditis
Known diagnosis of disseminated intravascular coagulation (DIC)
Known intolerance of niacin or ascorbic acid (including known glucose-6-phosphate dehydrogenase [G6PD] deficiency)
primary bone malignancies or aggressive benign bone tumors of the femur or tibia, soft-tissue sarcomas which have invaded the femur or tibia, or oligometastatic bone disease of the femur or tibia in a patient expected to live at least one year post-operatively; and
current known Methicillin-resistant Staphylococcus Aureus (MRSA) colonization;
current known Vancomycin Resistant Enterococcus (VRE) colonization;
documented anaphylaxis or angioedema to penicillin or cefazolin (Ancef);
reconstruction to include structural allograft;
enrolled in a competing study; and
Available for duration of study
Parent/legal guardian expected to be available for entire study
Parent/legal guardian can be reached by telephone or email
Recipients of CD34 selected grafts or other manipulated grafts (with any form of ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count > 100; (please note: post-transplant Cytoxan for haploidentical transplants is allowable)
FOR THE 31 SUBJECTS ENROLLED IN YEAR 1: Recipients of CD34 selected grafts or other manipulated grafts (with any form of ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count > 100; (please note: post-transplant cytoxan for haploidentical transplants is allowable)
Presence of an external central line
Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:\r\n* Genetic diagnosis with confirmed APC mutation (Clinical Laboratory Improvement Act [CLIA] certified lab or research testing)\r\n* Obligate carrier\r\n* Clinical diagnosis of classic FAP with >= 100 colorectal adenomas status post colectomy and a family history of FAP\r\n* Clinical diagnosis of FAP, based on personal and family history; Note: This criterion requires documented review and agreement from either the study chair or the Cancer Prevention Network (CPN) lead investigator
Willing to discontinue smoking for the duration of study intervention
Willing to provide mandatory biospecimens as specified in the protocol
Use of potent CYP3A4 inhibitors, including but not limited to ketoconazole, atazanavir, clarithromycin, indinavir,\r\nitraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
History of any upper gastrointestinal (GI) surgery that does not permit access to or evaluation of a 10 cm segment of the duodenum that includes the duodenal bulb, i.e. whipple procedure or similar
Spigelman 2?3
Unexplained persistent elevation of transaminases (> 3 times upper limits of normal)
Presence of at least 1 fallopian tube and 1 ovary; (please note: prior unilateral salpingectomy is allowed; prior bilateral salpingectomy is not allowed)
Women with elevated levels of CA125 (> 50) or transvaginal ultrasound suggesting cancer, unless findings are consistent with endometriosis; CA125 and transvaginal ultrasounds must be the most recent, but no older than 1 year from the date of enrollment
Previous prophylactic HPV vaccination
Anticipated desensitization treatment; this decision to exclude will be based on the site clinician’s judgement; desensitization procedures vary somewhat among the five participating transplant centers, which does not permit proposing uniform criteria across all study sites for determining exclusion due to desensitization; in general, women who have received a prior transplant, have unsuitable scores on Calculated Panel Reactive Antibody (PRA) percentage (institution-specific thresholds), or an ABO incompatible donor are likely to undergo desensitization at one or more of the study centers; these factors, among others, will be used by the study clinician to determine exclusion due to anticipated desensitization in the study
Pre-intervention biopsy sample collected
Use of potent CYP3A4 inhibitors, such as ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
Participants who cannot have their warfarin, Lovenox, Plavix, or other comparable medications held for percutaneous or transjugular liver biopsy and surgery if so indicated
AIM 1 (SURVEY)
Scheduled for a return clinic visit at one of the participating institutions
AIM 2 (VACCINE EVALUATION)
Medical clearance from treating clinician for study participation
AIM 2 (VACCINE EVALUATION)
Thrombocytopenia (platelet count < 50 K) or coagulation disorder that would contraindicate intramuscular injection
Female, and a) currently pregnant or lactating, or b) of childbearing potential and unwilling to avoid pregnancy during the vaccine phase of study (beginning at day 1 and continuing until at least 4 weeks after all 3 vaccine doses have been administered)
Available for duration of study
Can be reached by telephone or email
CD34 selection or total cell depletion outside haploidentical transplants
Mammographically dense breast (heterogeneously dense [C] or extremely dense [D], based on American College of Radiology [ACR] BIRADS fifth edition classification or heterogeneously dense [3] or extremely dense [4], based on ACR BIRADS fourth edition classification) in either breast
Women who are using postmenopausal hormones, and are planning to continue the same regimen through the study intervention are eligible to participate
Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study
Women with “mosaic mammographic screening views”, i.e., whose larger breast size precludes being imaged within a single mammographic screening view
Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration)
Serum or plasma HCV RNA level >= 10,000 IU/mL
Screening HCV genotype, demonstrating genotype 1
12-lead electrocardiogram (ECG) showing normal heart rhythm; note: if there are abnormalities, then the abnormalities must be deemed of no clinical significance
Tattoos, scars, active lesions, or rashes =< 2 cm of the intended site of study treatment
Willingness to avoid alternative/additional vitamin D3 supplementation for the duration of the trial
Self-reported consumption of more than 4 alcoholic drinks per day
LVEF >50%, or an LVEF within the normal limits of the institution's specific testing (MUGA or ECHO)
ANC ? 1,000/?L
ALT and AST ? 1.5 ULN of institution's range
Involved in other experimental protocols except with permission of other PI
Must be designated as an American College of Radiology (ACR) designated lung cancer screening site
Must be reachable by telephone
PATIENT (AS PER SELF-REPORT)
NRT is medically contraindicated (e.g., recent heart attack within the last 2 weeks or, unstable/worsening angina)
Subjects deemed potentially eligible by their treating physicians will be screened for enrollment after d+60 from transplantation
Recurrent pancreatitis episode is iatrogenic (endoscopic retrograde cholangiopancreatography [ERCP] induced)
Participants must be pre- or post-menopausal
Participants must have a diagnosis of DCIS made by core needle biopsy
Lactate dehydrogenase < 2 x ULN
Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive therapy that might interfere with appropriate immune response
No recent or planned immunotherapy
Symptomatic claustrophobia
Hematocrit >= the lower institutional limit
Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
Gastric intolerance attributable to ASA or NSAIDs
Adult asthma
Are taking drugs known to interact with zileuton, including theophylline, warfarin, and propranolol
Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
Urine cotinine level, if collected at screening, does not confirm active smoking status
Bradycardia defined as HR. < 50 bpm
Right bundle branch block + left anterior hemiblock (bifascicular block)
Positive FOBT during the study period
No medical contra-indication for colonoscopy
Women must indicate that they are still considering future pregnancy and childbearing
Women must be willing to take supplemental omega-3 fatty acids provided by the study
Women actively undergoing in-vitro fertilization or fertility treatments are excluded
Must be candidates for reduced-intensity conditioning regimens.
Be willing to avoid pregnancy or fathering children.
Prior malignancies.
Smoking history of >= 30 pack?years AND either current smoker (still smoking or quit < 1 year prior to pre?registration) OR former smoker (quit 1?15 years prior to pre?registration); Note: Pack years is determined by multiplying the number of packs smoked per day by the number of years smoked
Known non?alcoholic steatohepatitis (NASH) or non?alcoholic fatty liver disease (NAFLD)
Positive antinuclear antibody (ANA) result
FOCUS GROUP: Who are enrolled at Group Health at least one year prior to mammogram, receive care in the greater Seattle area and have had a negative mammogram (breast imaging-reporting and data system [BIRADS] 1 or 2 assessment) as part of their routine care within the past 6 months
BETA/USABILITY TESTING: Who are enrolled at Group Health, receive care in the greater Seattle area and have had a negative mammogram (BIRADS assessment of 1 or 2) as part of their routine care
BETA/USABILITY TESTING: Will have been enrolled for year prior to the mammogram at Group Health
RANDOMIZED CONTROLLED TRIAL: Who are enrolled at Group Health, and have had a negative mammogram as part of their routine care
RANDOMIZED CONTROLLED TRIAL: Must also have a valid email address
FOCUS GROUP: Not able to speak and read English; not able to physically attend the focus group location and time, women who do not wish to be contacted or involved in research, women who have died between mammogram and recruitment data pull date, and women who have disenrolled from Group Health between mammogram and pull date
BETA/USABILITY TESTING AND THE TRIAL: who have disenrolled from Group Health between her mammogram and the record pull date, who have died, and those who have indicated that they do not want to be contacted for research, if they participated in our previous intervention development activities, or if they died or disenrolled from health plan between mammogram and start of recruitment
Prior cholangiocarcinoma
Medical contraindications to blood draw (e.g., hemophilia)
Self-described betel nut chewer (chewed betel nut for at least 3 years, and at a rate of at least 3 days per week); must be class 2 betel nut chewers: that is, must chew a quid consisting of areca nut, slaked lime, betel leaf, tobacco, and other optional ingredients, and not swallow the quid
Chews betel nut alone (i.e., without quid)
One or more Padua-based risk factor:\r\n* History of previous venous thromboembolic event (excluding superficial vein thrombosis)\r\n* Reduced mobility (Eastern Cooperative Oncology Group [ECOG] performance status 3 or 4)\r\n* Established hereditary thrombophilia (e.g. Factor V Leiden, G20210 prothrombin mutation, protein C or S deficiency, antithrombin deficiency)\r\n* Recent surgery within the last 30 days\r\n* Age >= 70 years\r\n* Congestive heart failure (New York Heart Association [NYHA] class III or IV)\r\n* Complicated respiratory insufficiency (defined as an increased requirement for supplementary oxygen of at least 2L)\r\n* Acute myocardial infarction or ischemic stroke\r\n* Obesity (body mass index [BMI] >= 30)\r\n* Receiving hormonal agents (e.g. tamoxifen, estrogen, testosterone)\r\n* Acute infection (i.e. requiring antimicrobial therapy)
Known diagnosis of disseminated intravascular coagulation
Bacterial endocarditis
RECIPIENT: CMV seropositive
RECIPIENT: Medically indicated subunit (Engerix?B for HBV; Gardasil for human papillomavirus [HPV]) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
RECIPIENT: Alemtuzumab or any equivalent in vivo T?cell depleting agent
RECIPIENT: Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valganciclovir (VAL), FOS, Cidofovir, CMX?001, maribavir. Acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent Herpes simplex virus (HSV)
RECIPIENT: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment (Letermovir is permitted)
Ability to take digital time stamped photos.
Previous participation in this trial. Participation is defined as screening. Re-screening is not allowed.
Subjects considered by the investigator as unsuitable for the study for reasons not otherwise stated.
MD Anderson patient
Current smoker (i.e., at least 10 cigarettes/day)
Smoking for at least one year
Carbon monoxide (CO) level of 5 ppm or greater, confirming smoking status
Currently elevated depressive symptoms; (Patient Health Questionnaire [PHQ] 2 > 2)
Currently own an iOS mobile phone (iPhone) using iOS 9.0 or later and reports regular use (at least weekly) of at least 1 iOS app
Endorsing current suicidal ideation or intent
Meeting criteria for a current major depressive episode measured by the PHQ-9
Subject considered by the investigator an unsuitable candidate for receipt of a smoking cessation treatment or unstable to be followed up throughout the entire duration of the study
WHITE, NON-HISPANIC: Study participants will not have had a skin examination within the last year and will be of European ancestry. The study sample will be limited to non-Hispanic whites because i) skin type is the overwhelming risk factor for cutaneous melanoma resulting in very low incidence of this disease among persons who are black, Asian, Native American or Pacific Islander, and ii) the prior genetic investigation upon which this application is based was undertaken in a non-Hispanic white population. Thus at this time, inference of genetic risk attributable to MC1R variants is unknown for individuals not identifying as non-Hispanic white eliminating any direct inference of the proposed intervention to a non-Hispanic white population.
HISPANIC/LATINOS (H/L): Self-report Hispanic ethnicity (there will be no exclusions based on reported race).
WHITE, NON-HISPANIC: Participant whose medical records or self-report indicate any race or ethnicity identification aside from white, non-Hispanic.
WHITE, NON-HISPANIC: Participants reporting sun-sensitive phenotypes.
WHITE, NON-HISPANIC: Participants having had a skin examination within the past year.
H/L: Participants having had a skin examination within the past year.
Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season
Subjects who had or are suspected to have had an influenza infection in the current influenza season
Subjects who have already received the seasonal influenza vaccine in the current influenza vaccination season
Participants must have Lynch syndrome defined as meeting any of the following: (1) Mutation-positive Lynch syndrome: carriers or obligate carriers (by pedigree) of a pathogenic mutation in one of the deoxyribonucleic acid (DNA) mismatch repair (MMR) genes (i.e. MLH1, MSH2/EPCAM, MSH6, or PMS2) or (2) Mutation-negative Lynch syndrome: patients with a personal history of a non-sporadic MMR deficient premalignant lesion (i.e. polyp) or a non sporadic MMR deficient malignant tumor (where non-sporadic MMR deficient is defined by: microsatellite instability high by either immunohistochemistry or microsatellite instability (MSI) testing or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, and/or no evidence of BRAF mutation in cases with loss of both MLH1 and PMS2) but germline MMR genetic testing showed either a variant of unknown significance or mutation negative result or had declined germline MMR genetic testing.
Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e. participants must have at least part of the descending/sigmoid colon and/or rectum intact).
Participants must consent to two standard of care lower gastro-intestinal GI endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies that will be 12 months (+/-21 days) apart.
Must have normal cardiopulmonary exercise test prior to exercise participation.
Individuals who are status post total proctocolectomy (i.e. removal of all colon and rectum).
Individuals who are unable to participate in cycling due to musculoskeletal limitations.
Individuals who are unable to identify cycling classes in their community for exercise.
Smokes a minimum of 3 cigarettes per day over the past year.
Expired carbon monoxide reading >= 6.
Valid home address.
Functioning telephone number.
At least marginal health literacy.
Endorse current psychosis.
Physically unable to wear equipment and provide a good reading of physiological measures.
Involvement in a smoking program or currently trying to quit.
Another household member being enrolled in the study.
No prior experience with a smart phone.
If the study staff or principal investigator (PI) have serious concerns about the participant’s ability to engage in and/or complete the study protocol.
Inclusion Criteria:\n\n        Cycle 1:\n\n        The following inclusion criteria must be checked prior to inclusion at Cycle 1:\n\n          1. Patient read, understood and signed the written informed consent before any study\n             related activity, agreeing to participate in the study and to comply with study\n             requirements.\n\n          2. Female patient of at least 8 years of age.\n\n          3. Histologically or cytologically confirmed breast cancer, including recurrent or\n             metastatic.\n\n          4. Naïve to moderately or highly emetogenic antineoplastic agents.\n\n          5. Scheduled to receive at least 4 consecutive cycles of an AC combination regimen.\n\n             Notes:\n\n               1. additional not emetogenic, minimally or low emetogenic antineoplastic agents are\n                  permitted at any time after start of AC combination on Day 1.\n\n               2. additional highly or moderately emetogenic antineoplastic agents are only allowed\n                  on Day 1 after the start of AC combination, provided their administration is\n                  completed within 6 hours from the start of the AC combination administration.\n\n          6. ECOG Performance Status of 0 or 1.\n\n          7. Patient shall be: a) of non-childbearing potential or b) of childbearing potential\n             using reliable contraceptive measures and having a negative urine pregnancy test\n             within 24 hours prior to dose of investigational product.\n\n             Notes:\n\n               1. Female patients of non-childberaring potential are defined as being in\n                  post-menopausal state since at least 1 year; or having documented surgical\n                  sterilization or hysterectomy at least 3 months before study participation.\n\n               2. Reliable contraceptive measures include implants, injectables, combined oral\n                  contraceptives, intrauterine devices, vasectomized partner or complete (long\n                  term) sexual abstinence;\n\n          8. Hematologic and metabolic status adequate for receiving a cycle of AC chemotherapy\n             based on investigator's assessment.\n\n          9. If the patient has a known hepatic or renal impairment, she may be enrolled in the\n             study at the discretion of the Investigator.\n\n         10. Able to read, understand, follow the study procedure and complete the patient diary.\n\n        All inclusion criteria will be checked at screening visit (Visit 1 of Cycle 1); inclusion\n        criteria 7 will be re-checked at Day 1 (Visit 2).\n\n        Cycles 2 to 4:\n\n        The following inclusion criteria must be checked prior to inclusion at each repeated cycle:\n\n          1. Participation in the study during the next cycle of chemotherapy is considered\n             appropriate by the Investigator and does not pose unwarranted risk to the patient.\n\n          2. Scheduled to receive an AC chemotherapy regimen or AC chemotherapy together with other\n             chemotherapies as defined in Inclusion criterion #5 for Cycle 1.\n\n          3. Patient shall be: a) of non-childbearing potential or b) of childbearing potential\n             using reliable contraceptive measures and having a negative urine pregnancy test\n             within 24 hours prior to dosing of investigational product.\n\n          4. Adequate hematologic and metabolic status for receiving a cycle of AC chemotherapy\n             according to the Investigator's opinion.\n\n        All inclusion criteria will be checked at screening visit (Visit 1); inclusion criterion #3\n        will be re-checked at Day 1 (Visit 2).\n\n        Exclusion Criteria:\n\n        Cycle 1:\n\n        The following exclusion criteria must be checked prior to inclusion at Cycle 1:\n\n          1. Lactating patient.\n\n          2. Current use of illicit drugs or current evidence of alcohol abuse.\n\n          3. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition\n             to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 and up\n             to Day 1 of Cycle 2.\n\n          4. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis\n             within 1 week prior to the start of AC chemotherapy administration on Day 1 or between\n             Days 1 to 5, inclusive.\n\n          5. Any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute)\n             within 24 hours prior to the start of AC chemotherapy administration on Day 1.\n\n          6. Symptomatic primary or metastatic central nervous system (CNS) malignancy.\n\n          7. Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial\n             pressure, hypercalcemia, an active infection or any illness or medical conditions\n             (other than malignancy) that, in the opinion of the Investigator, may confound the\n             results of the study, represent another potential etiology for emesis and nausea\n             (other than chemotherapy-induced nausea and vomiting [CINV]) or pose unwarranted risks\n             in administering the study drugs to the patient.\n\n          8. Known hypersensitivity or contraindication to 5 hydroxytryptamine type 3 (5-HT3)\n             receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron,\n             tropisetron, ramosetron), to dexamethasone, or to neurokinin-1 (NK1) receptor\n             antagonists (e.g., aprepitant, rolapitant).\n\n          9. Known contraindication to the IV administration of 50 mL 5% glucose solution.\n\n         10. Participation in a previous clinical trial involving IV fosnetupitant or oral\n             netupitant administered alone or in combination with palonosetron.\n\n         11. Any investigational drugs taken within 4 weeks prior to Day 1, and/or is scheduled to\n             receive any investigational drug (other than those planned by the study protocol)\n             during the present study.\n\n         12. Systemic corticosteroid therapy within 72 hours prior to the start of AC chemotherapy\n             administration on Day 1, except the dexamethasone provided as additional study drug.\n             However, topical and inhaled corticosteroids are permitted.\n\n         13. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy\n             during the study participation.\n\n         14. Other than as administered as part of the study protocol, any medication with known or\n             potential antiemetic activity within 24 hours prior to the start of AC chemotherapy\n             administration on Day 1, including:\n\n               -  5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron,\n                  tropisetron, ramosetron, palonosetron)\n\n               -  NK1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant or any\n                  other new drug of this class)\n\n               -  benzamides (e.g., metoclopramide, alizapride)\n\n               -  phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine,\n                  thiethylperazine, chlorpromazine)\n\n               -  benzodiazepines (except if the subject is receiving such medication for sleep or\n                  anxiety and has been on a stable dose for at least seven days prior to Day 1).\n\n               -  butyrophenones (e.g., haloperidol, droperidol)\n\n               -  anticholinergics (e.g., scopolamine, with the exception of inhaled\n                  anticholinergics for respiratory disorders, e.g., ipratropium bromide)\n\n               -  antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine, chlorpheniramine)\n\n               -  domperidone\n\n               -  mirtazapine\n\n               -  olanzapine\n\n               -  prescribed cannabinoids (e.g., tetrahydrocannabinol or nabilone)\n\n               -  Over The Counter (OTC) antiemetics, OTC cold or OTC allergy medications.\n\n         15. Scheduled to receive any strong or moderate inhibitor of CYP3A4 during the efficacy\n             assessment period (Day 1 to Day 5, inclusive) or its intake within 1 week prior to Day\n             1.\n\n         16. Scheduled to receive any CYP3A4 inducer during the efficacy assessment period (Day 1\n             to Day 5, inclusive) or its intake within 4 weeks prior to Day 1, with the exception\n             of corticosteroids (for which exclusion criterion #12 applies).\n\n         17. History or predisposition to cardiac conduction abnormalities, except for incomplete\n             right bundle branch block.\n\n         18. History of risk factors for Torsades de Pointes (heart failure, hypokalemia, family\n             history of Long QT Syndrome).\n\n         19. Severe or uncontrolled cardiovascular diseases, including myocardial infarction within\n             3 months prior to Day 1, unstable angina pectoris, significant valvular or pericardial\n             disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure\n             (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial\n             hypertension.\n\n        All exclusion criteria with the exception of criteria #5, #12, and #14 will be checked at\n        screening visit (Visit 1). Exclusion criteria #5, #12, and #14 will be checked at Day 1\n        (Visit 2) only.\n\n        Exclusion criteria #3, #4, #7, #11, #13, #15, and #16 need to be re-checked at Day 1 (Visit\n        2).\n\n        Cycles 2 to 4:\n\n        The following exclusion criteria must be checked prior to inclusion at each repeated cycle:\n\n          1. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition\n             to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 of\n             current cycle and up to Day 1 of the next cycle.\n\n          2. Active infection or uncontrolled disease that may pose unwarranted risks in\n             administering the study drugs to the patient.\n\n          3. Started any of the prohibited medications.\n\n          4. Any vomiting, retching, or nausea (grade ? 1 as defined by National Cancer Institute)\n             within 24 hours prior to the start of AC chemotherapy administration on Day 1.\n\n          5. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis\n             within 1 week prior to the start of AC chemotherapy administration on Day 1 or between\n             Days 1 to 5.\n\n          6. Symptomatic primary or metastatic CNS malignancy.\n\n          7. Any illness or medical condition that, in the opinion of the investigator, may\n             confound the results of the study or pose unwarranted risks in administering the\n             investigational product or dexamethasone to the patient.\n\n        All exclusion criteria, with exception of criterion #4, will be checked at screening visit\n        (Visit 1). Exclusion criterion #4 will be checked at Day 1 (Visit 2) only. Exclusion\n        criteria #2, #3 and #5 need to be re-checked at Day 1 (Visit 2).
Under active surveillance
Angina
Uncontrolled sinus tachycardia (> 120 beats per minute)
Not compliant with recommended sun protection, as determined by at least one of the following criteria:\r\n* Any intentional sunbathing, artificial tanning or a sunburn in the past 5 years\r\n* Having a moderate to light complexion (Fitzpatrick skin types I-IV) and not using sunscreen >= 90% of the time during incidental sun exposure
Enrolled on Dana-Farber Cancer Institute (DFCI) protocol 17-385 or any other sun protection intervention in the past 5 years
Any impairment (e.g., hearing, visual, cognitive) that interferes with the ability to complete all measures independently
Considered eligible for Ohio Expanded Food and Nutrition Education Program (EFNEP) income guidelines
Located in the greater Cleveland metropolitan area
Answers ‘no’ to all questions on the PA Readiness Questionnaire (PAR-Q) or is cleared in writing by a physician
Does not have schizophrenia
Participants need to have had a mammogram within 180 days of day 0 (normal/benign bi-rads 1 or 2) with no suspicion of a mass and no further routine breast imaging planned during the course of the study (4 weeks)
Ability to avoid exposure of the treated breast area to sunlight and artificial ultraviolet light during the use of bexarotene gel
Skin lesions that disrupt the stratum corneum (eg., eczema, ulceration) or any breakdown of the skin
Dietary vitamin A intake >= 5,000 IU/day (as determined by dietary supplementation)
PHASE I: MedStar Georgetown University Hospital (MGUH) pediatric primary care providers (pPCP) providers
All newly referred patients to colposcopy clinic at Siteman Cancer Center at Washington University (SIUM) and Washington University School of Medicine (WUSM)
Diagnosis of an abnormal Pap will be confirmed by pathology report
Members of all races and ethnic groups are eligible for this trial
HPV positive by the GeneXpert hrHPV assay with HPV16, HPV 18/45, or HPV31/33/35/52/58 detected; Note: participants who are hrHPV positive with only HPV51/59 or HPV 39/68/56/66 detected are not eligible
Prior hysterectomy with removal of the cervix
Prior HPV vaccination
CD4 count < 200 cells/mm^3 within 6 months of entry\r\n* Note: This refers to any CD4 obtained for routine care; documentation of CD4 is not required prior to entry
By self-assessment, currently performing 60 minutes or less of purposeful exercise per week but able to walk at least 30 minutes on a level surface
Live in the greater Kansas City metropolitan area
Willing to participate in a controlled dietary intervention with portion controlled meals and partial meal replacements plus 35 servings of fruits and vegetables/week for 6 months and track food intake and exercise
Planned allogeneic HCT using fludarabine phosphate (FLU)/melphalan hydrochloride (MEL) or FLU/busulfan (BU) conditioning
Subjects will be eligible if their planned conditioning regimen for allogeneic HCT consists of one of the two following standard reduced intensity conditioning regimens:\r\n* FLU/MEL: fludarabine phosphate (fludarabine) 120 to 180 mg/m^2; melphalan hydrochloride (melphalan) =< 150 mg/m^2\r\n* FLU/BU: fludarabine 120 to 180 mg/m^2; busulfan =< 8 mg/kg orally or =< 6.4 mg/kg intravenously
Between day +60 and day +90 after allogeneic HCT
Interest and willingness to commit to the 8 week Getting Ahead training program that will occur over 16 sessions occurring twice a week
Willingness to commit to follow-up with his/her primary care provider after completion of the Getting Ahead training program
Scheduled and eligible to receive at least one moderately or highly emetogenic chemotherapeutic agent on Day 1 only or for multiple days.
If the patient is female, she shall: a) not have attained menarche yet or b) have attained menarche and have a negative pregnancy test at the screening visit and at Day
The patient and/or parents/caregivers are expected by the Investigator to be non-compliant with the study procedures.
Patient has received or is scheduled to receive total body irradiation, total nodal irradiation, upper abdomen radiotherapy, half or upper body irradiation, radiotherapy of the cranium, craniospinal regions, head and neck, lower thorax region or the pelvis within 1 week prior to study entry (Day 1) or within 120 h after start of chemotherapy administration on Day 1.
Patient who received any drug with potential anti-emetic effect within 24 h prior to the start of reference chemotherapy, including but not limited to: NK1- receptor antagonists (e.g., aprepitant or any other new drug of this class); 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron); Benzamides (e.g., metoclopramide, alizapride); Phenothiazines (e.g., prochlorperazine, promethazine, perphenazine, fluphenazine, chlorpromazine, thiethylperazine); Benzodiazepines initiated 48 h prior to study drug administration or expected to be received within 120 h following initiation of chemotherapy, except for single doses of midazolam, temazepam or triazolam; Butyrophenones (e.g., droperidol, haloperidol); Anticholinergics (e.g., scopolamine, with the exception of inhaled anticholinergics for respiratory disorders e.g., ipratropium bromide); Antihistamines (e.g., diphenhydramine, cyclizine, hydroxyzine, chlorpheniramine, dimenhydrinate, meclizine); Domperidone; Mirtazapine; Olanzapine; Prescribed cannabinoids (e.g., tetrahydrocannabinol, nabilone); Over the Counter (OTC) antiemetics, OTC cold or OTC allergy medications; Herbal preparations containing ephedra or ginger.
Intake of alcohol, food or beverages (e.g., grapefruit, cranberry, pomegranate and aloe vera juices, German chamomile) known to interfere with either CYP3A4 or CYP2D6 metabolic enzymes within 1 week prior to Day 1 and during the overall study period.
Enrolment in a previous study with netupitant (either alone or in combination with palonosetron).
Patient must be cleared pre-transplant by Radiation Oncology to be able to receive 400 cGy
Primary site may include oral cavity, pharynx, or larynx; oropharynx primaries must be human papilloma virus (HPV) (-) as defined by routine p16 immunohistochemistry (IHC) at the local site
Current and former tobacco users are eligible; the tobacco use assessment form must be completed following consent, to assure eligibility; patients must have >= 10 pack-year cumulative tobacco exposure or its equivalent to be eligible; this is defined as follows:\r\n* Cigarette exposure: >= 10 pack-years OR\r\n* Cigar exposure: >= 10 cigar-years, where 1 cigar year is defined as having smoked on average >= 1 cigar/day for a year OR\r\n* Chewing tobacco: >= 10 snuff-years, where 1 snuff year is defined as using on average >= 1 pinch (dip) of chewing tobacco/day for a year
Primary oropharyngeal HNSCC which is HPV (+) as defined by p16 IHC
Individuals with normal skin and Fitzpatrick skin type II, III or IV (21 Code of Federal Regulations [CFR] 352.72)
Individuals who are willing to limit sun exposure to the body during the study period, and who agree to wear protective clothing and sun protection factor (SPF) 50 broad spectrum sunscreen or sunblock on exposed skin when they are outdoors
A subgroup of Individuals with 4 benign melanocytic nevi (BN) measuring at least 6 mm in diameter and with evidence of benign features by epiluminescence microscopy (ELM) will be included in the study; these criteria will be considered optional and applicable when the 4 BN are present in surgically accessible areas
Individuals with any inflammation or irritation of the skin at the test area (buttocks), or any skin conditions felt by the study physician to contraindicate enrollment; this includes, but is not limited to, psoriasis or atopic dermatitis within the test area
Individuals who are immunosuppressed by virtue of medication or disease, as determined by the examining study physician; this includes acquired immune deficiency syndrome (AIDS) patients and subjects taking oral steroids
Individuals must not take mega-doses of vitamins; mega-doses are defined as more than 5 capsules of standard multivitamins daily or more than the Tolerable Upper Intake Levels of Vitamins, as defined by the Institute of Medicine, National Academy of Sciences; such vitamin therapy must be discontinued at least 30 days prior to study entry
Individuals with Fitzpatrick skin type I are ineligible
Individuals with Fitzpatrick skin type V or VI are ineligible
Proven or probable aspergillosis or other mold infection or deep mycoses including hepatosplenic candidiasis less than 60 days from first dose of isavuconazole (ISA)
Time interval of at least 6 days duration where complications such as rejection episodes, viral infections, surgical interventions and therapies with mono or polyclonal antibodies are ruled out by the transplant team
Be willing to forego other interventions in the treatment fields than the ones approved by the investigator that would interfere with the protocol or evaluation of the study medication
Cutaneous photosensitivity to wavelengths of 400-450 nm, porphyria or known allergies to porphyrins
Known sensitivity to any of the components of the Levulan Kerastick for topical solution
Patient undergoing an allo-SCT
Male and female and all ethnic groups are eligible
Currently on the wait list for a new garden
Willing to undergo study measurements
Smoke >= 10 cigarettes per day
Their vision should be normal or corrected-to-normal (to ensure that they can accurately see the images on the screen and select the appropriate response)
Serious medical illness unsuitable for the MR scanner based on best clinical judgment
Any neurologic or psychiatric disorder
Smokes first cigarette within 90 minutes after waking
Their vision should be normal or corrected-to-normal (to ensure that they can accurately see the images on the screen and select the appropriate response)
Willing to complete all appointments and change smoking behaviors for 2-weeks
Serious medical illness unsuitable for the magnetic resonance (MR) scanner based on best clinical judgment
Any neurologic or psychiatric disorder except depression, anxiety, or attention-deficit disorder/attention-deficit hyperactivity disorder
Willing to be randomized
Contraindications to NRT
Self-identification as Black/African American
Current smokers (smoked at least 100 lifetime cigarettes and currently smoke on some or every day) who would like help quitting
Eligible for state quitline services
Permanent contact information
Medical contraindications for NRT
Reports being a daily or non-daily smoker (any self-reported smoking in the past 30 days) and is interested in treatment that might change smoking behavior.
Have an address and telephone number where he/she may be reached.
Following good clinical practice guidelines, be medically suitable for one or more pharmacotherapies for smoking cessation including NRT, bupropion or varenicline, at provider discretion.
Unwilling to refrain from other nicotine substitutes (i.e., over-the-counter [OTC] or prescription medication for smoking cessation) or smoking cessation treatments in the next 9 months.
Patient to undergo pancreaticoduodenectomy for pancreatic ductal adenocarcinoma at the Johns Hopkins Hospital
Pancreaticoduodenectomy for an indication that is not pancreatic ductal adenocarcinoma (PDAC)
Laparoscopic or robotic pancreaticoduodenectomy
Patient did not undergo either placement of a preoperative biliary stent/drain or neoadjuvant chemotherapy with or without radiation therapy
Karnofsky performance status: Full intensity conditioning, 80-100%; reduced intensity conditioning, 60-100%
Hematocrit >= 29%
Co-medications that may interact with rolapitant (e.g. metoprolol/beta blocker, codeine, pimozide thioridazine) as reviewed by Duke Preston Robert Tisch Brain Tumor investigator pharmacist
Previous participation in any clinical trial involving rolapitant
Ongoing vomiting from any organic etiology
Patient has ongoing vomiting, retching, dry heaves, or clinically significant nausea caused by any etiology, or has had such symptoms within 24 hours prior to the start of day 1 of the study intervention, or has a history of anticipatory nausea and vomiting
Diagnosis of colorectal adenoma of any grade
Blood urea nitrogen (BUN) =< 40 mg/dL
Negative fecal occult blood test
Women in good general health
By self-assessment, currently performing 60 minutes or less of purposeful exercise per week but able to walk at least 30 minutes on a level surface
Live in the greater Kansas City metropolitan area
Willing to participate in a controlled dietary intervention with portion controlled meals and partial meal replacements plus 35 servings of fruits and vegetables/week for 3 months and track food intake and exercise
Smoking >= 5 tobacco cigarettes/week over the past year
Not currently enrolled in a face-to-face smoking cessation program
Monolingual Spanish-speaking, or bilingual Spanish-English and prefer educational health materials in Spanish
Participants that are unable to provide a mailing address within the mainland United States or Puerto Rico, or are unable to provide a mailing address (i.e., do not have one), will be excluded from participating in the study
Insufficient smoking (< 5 cigs per week) or have recently quit
Currently enrolled in an ‘in-person’ cessation program
Postmenopausal women (defined per provider discretion and notated in the medical record)
Oriented to person, place, and time
Underlying medical problems that contraindicate unsupervised exercise
Uses a walker or wheelchair/scooter
Lives outside the greater Houston area (Harris and contiguous counties)
Is pregnant (self-reported)
Scheduled to receive at least 3 consecutive cycles of THP or TCHP
Able to read, understand, follow the study procedure and complete crofelemer, rescue medication, and bowel movement diaries
Any type of ostomy
Total colectomy
Fecal incontinence
Ongoing radiation induced diarrhea or constipation or planned radiotherapy to the abdomen or pelvis while on study
Anti-thymocyte globulin, alemtuzumab, bortezomib, or post-transplant cyclophosphamide as part of GVHD prophylaxis
Sorror’s co-morbidity factors with total score > 4
Intolerance of warm air stimulus as demonstrated by profound vertigo and nausea
Baseline asymmetric hearing loss (defined by 1) >= 10-dB interaural threshold difference at 3-octave frequencies (250-8,000 Hz), 2) >= 15-dB difference at 2-octave frequencies, and 3) > 15-dB difference at 1-octave frequency)
Active carcinomas or melanomas of the skin of the face, scalp, ear, and neck
Prior melanomas of the skin of the face, scalp, ear, and neck, which are less than 5 years from surgical excision
Moderately sedentary lifestyle (less than 120 minutes/week moderate intensity activity)
PARENTS/PRIMARY CAREGIVERS
Are at least 18 years old
Have at least one child under age 18 who is living in the same household
Are the primary caregiver for the child participating in the study (defined as the individual who is responsible for daily implementation of health-related tasks for the child)
A second parent/caregiver will be eligible to participate in the study if they are at least 18 years old and have at least on child under age 18 who is living in the same household and participating in the study
CHILDREN
Are 8-17 years old
Multiple children from the same family are eligible to participate in the study
Smoke at least 5 cigarettes daily for the past year
Expired-air carbon monoxide (CO) > 8 ppm (if =< 8 ppm, then NicAlert Strip > 2)
Current motivation to quit smoking
Positive urine screen for cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, or phencyclidine (PCP) (NOTES: tetrahydrocannabinol [THC] will be tested but will not be an exclusionary criterion; participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded; participants failing the toxicology screen will be allowed to re-screen once)
Ever used reduced nicotine cigarettes
Smoke ‘roll your own’ cigarettes exclusively
Are currently enrolled in a smoking cessation program
Actively trying to quit
Currently taking the following medications:\r\n* Phenytoin (brand name: Dilantin)\r\n* Carbamazepine (brand name: Tegretol, Carbatrol, Equetro, Epitol)\r\n* Oxcarbazepine (brand name: Trileptal)\r\n* Primidone (brand name: Mysoline)\r\n* Phenobarbital\r\n* Bendamustine (Treanda)\r\n* Clopidogrel (Plavix)\r\n* Clozapine (Clozaril, FazaClo)\r\n* Erlotinib (Tarceva)\r\n* Flecainide (Tambocor)\r\n* Fluvoxamine (Luvox)\r\n* Irinotecan (Camptosar)\r\n* Olanzapine (Zyprexa)\r\n* Ropinirole (Requip)\r\n* Tacrine (Cognex)\r\n* Theophylline (Theo Dur, etc.)
Willingness to undergo screening tests and procedures
Helicobacter pylori negative, defined as negative stool antigen testing and negative histological examination
Patients who are premenopausal defined as an individual with at least six menstrual cycles in the past year\r\n* Women with hysterectomy with intact functioning ovaries who are not having menstrual cycles need to be 45 years of age and under
Completed radical prostatectomy for pathologically-verified adenocarcinoma of the prostate no more than 120 days prior to enrollment; the following procedures are acceptable: radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (with or without robotic assistance; LAPD), radical perineal prostatectomy (RPP)
Serum sodium, potassium, magnesium, phosphate, and calcium > lower limit of normal (LLN)
Radiographically-demonstrable metastases at any time prior to the time of enrollment
Prior history of serious toxicity or a systemic reaction to vaccinia immunization such as myopericarditis progressive vaccinia infection, or eczema vaccinatum
Inflammatory or exfoliative skin diseases such as eczema, psoriasis that disrupt epidermis
Inability to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination or until the vaccination site heals completely: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
Patients with active Clostridium difficile infection at the time of study enrollment; active infection is defined as a stool sample positive for Clostridium difficile toxin via enzyme immunoassay (EIA) and either symptoms (frequent loose stools) OR imaging findings consistent with toxic megacolon
Be interested in quitting smoking
Willing to engage in a 3-day quit attempt as part of study procedures
Breast imaging: class I-III mammogram within 6 months of RPFNA; if class 0 or 4, must be resolved with additional procedures; if breast imaging pre and post study is performed at Kansas University Medical Center (KUMC), then volumetric assessment by Volpara software will be performed
If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones (estring, vagifem, or 0.5 gram or less of conjugated estrogen vaginal cream twice weekly or less often); these vaginal preparations may be continued at the same dose
An RPFNA performed less than six months prior to enrollment on study that exhibits at least 500 cells on the cytology or Ki-67 slide, and a Ki-67 positivity measured on at least 500 cells that is less than 4%
Prior myeloablative allogeneic or autologous HSCT
Women with an abnormal pap test, positive human papillomavirus (HPV) test or any history of cervical dysplasia
Women who have undergone a hysterectomy with removal of the cervix
For patients that present to clinic to have a cervical excisional procedure (LEEP) for an already confirmed diagnosis of high grade cervical dysplasia, HRME imaging study will be performed and cervical biopsies might be taken for research purposes only; any extra biopsies taken will be for research purposes only and our research fund will pay them
Hypertensive-level readings over three weeks, with at least two of three elevated blood pressure (BP) readings (systolic >= 140 and/or diastolic >= 90); OR one hypertensive crisis reading (systolic >= 165 and/or diastolic >= 100) (eligible for the study without having to return for second or third readings) OR have a known diagnosis of hypertension and have elevated values at one reading (eligible for the study without having to return for second or third readings)
Owns a cell phone that can receive text messages and is willing to receive text messages for this study
Part-time driver (drives fewer than 35 hours per week); although it is highly unlikely for NYC taxi drivers to work for multiple garages at study baseline, drivers may switch jobs and/or their garage base affiliation while participating in this study; new jobs and/or garage base affiliations will be tracked during follow-up assessments and noted for potential limitations with study retention and intervention contamination; drivers will be allowed to continue the study even if they are no longer working with the initial garage base
Born in Mexico or born in the United States (U.S.) but self-describes as Mexican-American; Spanish is her/his primary language
Has a minimum of one child between the ages of 9 and 17 who has not received the HPV vaccine and who lives with the parent/guardian as per self-report
Self-identifies as the child's main caregiver
Currently owns a cell phone, uses text messaging services and is willing to accept text messages for this study
Presence of a serious psychiatric or cognitive impairment likely to preclude meaningful informed consent and adherence to the protocol per the consenting professional's judgement
Smoking 5 or more cigarettes, little cigars or cigarillos per day, on average, within the 2 months preceding the screening visit and expired carbon monoxide (CO) greater than or equal to 6 parts per million (ppm); (if < 6, then NicAlert Strip > 2)
Have an address and telephone number where they may be reached
Individuals rated as moderate (9-16) to high (17 or greater) on suicidality as assessed by module B of the MINI
Psychiatric hospitalization within 1 year of screening date
Subject considered by the investigator as unsuitable candidate for receipt of NRT, or unstable to be followed up throughout the entire duration of the study
Unwilling to change hairstyle or remove a wig as necessary for the appointment to accommodate the net that is required to be worn on the scalp during the study procedure
Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, or phencyclidine (PCP)\r\n* Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded\r\n* Participants failing the toxicology screen will be allowed to re-screen once; if they test positive again, they will not be allowed to return for 90 days
Aspartate aminotransferases (AST) =< 3 times ULN
Required prior to infusion of ATLCAR.CD30 cells: AST =< 3 times ULN
Required prior to infusion of ATLCAR.CD30 cells: Serum creatinine =< 1.5 times ULN
Available autologous T cells with >= 15% expression of CD30CAR determined by flow-cytometry required prior to treatment with ATLCAR.CD30 cells
Women scheduled for mastectomy or lumpectomy after DCIS or ADH diagnosis
Direct bili =< 1 x ULN
Women who are taking rapamycin for another diagnosis
Have used smokeless tobacco for the last year, currently (past 30 days) uses smokeless tobacco daily, and chews/dips at least 3 times a day
Have an address in a rural census tract defined by a Rural-Urban Commuting Area (RUCA) code of 4-10 or reside in a county with an Urban Influence Code of 4 or higher or live in a medically underserved area defined as an Index of Medical Underservice (IMU) of 62 or lower
Interested in participating in a cessation program
Currently participating in a smokeless tobacco cessation study
Not currently enrolled in a face-to-face smoking cessation program
Monolingual Spanish-speaking, or bilingual Spanish-English and prefer receiving educational health materials in Spanish
Active hemolytic anemia
Sorror’s co-morbidity factors with total score >= 4\r\n* Important modification to co-morbidity index calculation: DLCO adjusted will not be included in assessment of pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from the trial
Anti-thymocyte globulin as part of the conditioning regimen
Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
Patients with documented contraindications for bupropion (bupropion hydrochloride), including: bulimia nervosa, anorexia nervosa; use of monoamine oxidase inhibitors in the past two weeks; documented seizure disorders or predisposition to seizure (ie stroke, brain metastases); abrupt withdrawal from alcohol, benzodiazepines, or other sedatives; closed-angle glaucoma
Histological or cytological confirmation of NSCLC
Up to three small (? 3 cm each) lung oligometastases will be allowed and/or one oligometastasis at any other site in the body
Poorly controlled intercurrent illnesses
Presence of left bundle branch block (LBBB);
Psychiatric conditions, social situations or substance abuse that precludes the ability of the subject to cooperate with the requirements of the trial and protocol therapy
Parents whose child is a pregnant adolescent
Having impairing hearing or speech
Participants will be excluded from participation in future stages
Performing less than 75 minutes of structured moderate-intensity or strenuous-intensity exercise per week
Able to achieve an acceptable peak baseline CPET, as defined by any of the following criteria:\r\n* Achieving a plateau in oxygen consumption, concurrent with an increase in power output;\r\n* A respiratory exchange ratio of >= 1.10;\r\n* Attainment of maximal predicted heart rate (HRmax) (i.e., within 10 beats per minute [bpm] of age-predicted HRmax);\r\n* Volitional exhaustion, as measured by a rating of perceived exertion (RPE) >= 18 on the BORG scale
Be periodontally healthy; this is defined as all sites with attachment levels =< 2 mm and probing depths =< 3 mm) and caries-free, as evidenced by a DMF (decayed, missing, filled teeth) index of < 5
Be either a current smoker or a never smoker; to define a smoker, we will utilize the Centers for Disease Control definitions; any individual who is currently smoking and has smoked more than 100 cigarettes in their lifetime will be identified as a current smoker; smoking status will be assessed by a questionnaire; smoking status will be conferred using a urine cotinine test at the randomization visit (week-2); the number of cigarettes smoked per day and years of smoking will be used to calculate pack-years, which will be used as a measure of tobacco exposure; a never smoker is defined as a person who has never smoked, or has smoked less than 100 cigarettes in their lifetime, and who has not had a cigarette in over ten years
Agree to follow a berry-free/controlled polyphenol diet and to document consumption of polyphenolic foods each day of the study using a simple daily form
Are alcohol consumers (defined as an average consumption of greater than 1 drink/day over one week [wk] [one drink = 1 oz. liquor, 12 oz. beer])
Willingness to accept randomization to each of the three arms
Ability to send and receive emails
Ability to complete online forms
Self-reported average consumption of > 14 alcoholic drink per week
Plans to relocate from the area within one years
Known diagnosis of familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome)
Any adenoma that was not completely removed during previous colonoscopy
Sexually active women of all ethnicities and races with an intact cervix are eligible for this trial
Normal Pap or Atypical Squamous Cells of Undetermined Significance (ASCUS) Pap test with HPV deoxyribonucleic acid (DNA) negative by reflex testing via Hybrid Capture 2 (Digene Corp., Gaithersburg, MD), a standard clinical assay within clinically acceptable screening guidelines (American Cancer Society [ACS]/American Society for Colposcopy and Cervical Pathology [ASCCP] 2012 Screening Guidelines)
Speaks either English or Spanish, living in or near the Bronx with no plans to move in the next year, able to sign consent and complete questionnaires with aid of trained personnel
Prior use of an HPV vaccine  \r\n* Women in the vaccine-eligible age range cannot have received vaccine prior to enrollment, but will be offered HPV vaccination at the end of the study; in brief, we are interested in the efficacy of intervention in preventing HPV in the absence of HPV vaccination, since most women worldwide who might utilize intervention will not have been vaccinated; this includes United States (US) women in the vaccine “catch-up” 19-26 year old age group (beyond the age groups eligible for Vaccines for Children- funded vaccination) who have so far had very low (< 10%) vaccine uptake; it also includes the entire group of US women > 26 years of age; moreover, it includes women of all ages in developing countries, who most need an HPV prevention strategy, but may never be vaccinated; it should be noted that delaying vaccination in women 19-26 years of age by one year is safe and reasonable, since there is insufficient data to establish a recommendation for or against universal vaccination in this age group as concluded by an American Cancer Society expert panel, which includes the Principal Investigator (PI) of this protocol, Dr. Mark Einstein; it is anticipated that if the intervention gel is efficacious, HPV vaccinated women would need to be studied in a similar future trial with power analysis taking into account vaccine effectiveness as well
Active genital ulcers
Full-time New York City cab drivers
Non-smokers (assessed by modified Behavioral Risk Factor Surveillance System [BRFSS] smoking question within screening tool)
Driver for at least 3 years
Driving schedule does not include overnight shifts, nor does driver have an additional job overnight
Own a smart phone (in order to collect heart rate variability data)
Should self-report \very well\ or \well\ level of English fluency (according to the standard United States [US] census question)
Have working cigarette lighter receptacle/socket inside taxi cab
Resides in a smoking household (where 1 or more household members smoke)
Has a sleep disorder (including insomnia, delayed sleep phase syndrome [DSPS], narcolepsy, night terror, sleep apnea, sleep walking)
Self reports \well\ level of English fluency and indicates a preference for an interpreter
Diagnosis of pelvic malignancy (suspected/confirmed ovarian, endometrial/ uterine, cervical cancers, and vulvar cancers) undergoing surgical debulking
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitor (SNRIs) (common anti-depressant therapies)
With prosthetic heart valves
Known or documented bleeding disorders not limited to: anti-phospholipid syndrome, homozygotes for Factor V Leiden deficiency, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, systemic lupus erythematous, or prothrombin G2020 gene mutation
Protein C deficiency (increased risk of skin necrosis do those on injectable anticoagulation)
Prisoners or individuals who are involuntarily incarcerated
Self-identified African American
Smokes >= 1 cigarettes per day (cpd)
Functioning telephone
Interested in quitting smoking
Medication approval from their own physician
Renal impairment
Another household member enrolled in the study
Active smoking (cigarettes per day [CPD] >= 5) and exhaled carbon monoxide (CO) >= 8 parts per million (ppm)
Subjects on Coumadin or other anticoagulants
Subjects who have had radiation to both breasts or who have undergone bilateral mastectomies
Participants will include current and recently quit former smokers who have at least a 30 pack year smoking history (defined by number of packs smoked per day multiplied by number of years smoked)
Recently quit former smokers will have been quit for a maximum of 1 year
Spanish speakers
Participants must have either sputum cytologic atypia of mild dysplasia or greater or a history of bronchial biopsy with mild or greater dysplasia within the past 12 months
Participants must have the ability to safely undergo bronchoscopy in the judgment of the investigators
Participants must not have used any tobacco product in the past year
Participants must not have been treated with iloprost at any time; Note: participants on the placebo arm of previous iloprost trials are eligible, but participants on the placebo arm of cohort A of this study may not be enrolled in cohort B
PILOTS I, II AND III: Capable of participating in moderate-vigorous unsupervised exercise
PILOTS I, II AND III: Have a cellular telephone and are able and willing to send and receive text messages
PILOT II: BRCA positive OR Lynch syndrome positive individuals
PILOT II (FAMILY MEMBER): Female and male biological and non-biological family members of BRCA-positive individuals OR Lynch syndrome positive individuals
PILOT III: Has experienced fatigue within the past seven days
PILOT III: Less than 150 minutes of exercise per week
PILOT III: Less than 2 days of 15 minutes or more of resistance training per week
PILOTS I, II AND III: Unable to walk without crutches, walker, cane, or other assistive device
PILOTS I, II AND III: Women who are pregnant (by self-report)
Patient elects to undergo active surveillance
Geographically able to have study visits at the University of California, Los Angeles (UCLA) Clinical Research Unit
If subjects are randomized to the control group they agree to not consume fish oil capsules during the 1-year study
Are geographically able to have study visits at UCLA’s Warren Hall or the Clinical Translational Research Center
If continuing in the Control Group portion, agree to not consume fish oil during the duration of the study
Have smoked for at least 3 years;
Smoke at least weekly
Subjects must be willing and able to come to the University of Pittsburgh’s Smoking Research Group lab for 8 visits over a 14- week period, as well as a ninth and final visit 6 months after their quit date, and to monitor behavior via an electronic diary for 8 weeks.
Multiple members of the same household cannot participate.
Additionally, prior to enrollment at first session, reporting smoking 28 or more days of the past 30, or registering a carbon monoxide (CO) reading of 15 or above (as this indicates heavy smoking, and is not consistent with non-daily smoking.)
Smoking 5 or more cigarettes, little cigars or cigarillos per day, on average, within the 2 months preceding the screening visit and expired carbon monoxide (CO) greater than or equal to 6 parts per million (ppm) (if =< 5, then NicAlert strip > 2)
Have an address and telephone number where they may be reached
Individuals rated as moderate (9-16) to high (17 or greater) on suicidality as assessed by module B of the MINI
Psychiatric hospitalization within 1 year of screening date
Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, phencyclidine (PCP), or delta-9-tetrahydrocannabinol (THC); A: participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded; B: participants failing the toxicology screen will be allowed to re-screen once; if they test positive again, they will not be allowed to return
Unwilling to change hairstyle or remove a wig as necessary for the appointment to accommodate the net that is required to be worn on the scalp during the study procedure
ANC ?1000/µL
In addition, they should also have a cell phone with texting capabilities, read and speak English, reside in close proximity to, or can access the Navy Yard stop on the green line, can provide meaningful consent, and medical clearance from a physician or nurse practitioner
Premenopausal
Cannot commit to the intervention schedule
Diagnosis of lobular carcinoma in situ (LCIS), atypical ductal, or lobular hyperplasia.
10% or more probability of BRCA mutation by BRCAPRO or similar model
Baseline mammographic density > 10% based upon the classification system (2 = 11-50%, \scattered fibroglandular densities\; 3 = 51-75%, heterogeneously dense; 4 = >75%, extremely dense). Women with a baseline mammographic density of ? 10% (1 = ?10%, breasts are almost entirely fat) will not be eligible
Mammograms that are reported as suspicious.
Approval for the use of this treatment protocol by the individual institution’s Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U.S. Department of Health and Human Services
Requirement for CD34+ stem cell selection for a second infusion of stem cells following an allogeneic stem cell transplant from a related or unrelated adult donor for the following conditions:\r\n* Primary graft rejection\r\n* Secondary graft rejection\r\n* Poor graft function \r\n* Disease recurrence\r\nNote: pre-infusion conditioning with chemotherapy and/or immunotherapy to be determined by the primary BMT physician and the protocol principal investigator (PI) based on clinical condition of the patient\r\n* Specific Organ System Function Requirements from PBMT 1001\r\n** Myeloablative\r\n*** Cardiac (shortening fraction of > 26% by echo or ejection fraction of > 47%)\r\n*** Renal (creatinine clearance or glomerular filtration rate [GFR] >= 40 ml/min, or > 60 ml/min.1.73 m^2)\r\n*** Pulmonary (DLCO > 50% by pulmonary function test [PFT])\r\n*** Liver (AST/ALT no greater than 3 times the upper limit of normal)\r\n** Reduced Intensity\r\n*** Cardiac (shortening fraction of > 20% by echo or ejection fraction of > 40%)\r\n*** Renal (creatinine clearance or GFR >= 30 ml/min, or > 40 ml/min 1.73 m^2)\r\n*** Pulmonary (DLCO > 40% by PFT)\r\n*** Liver (AST/ALT no greater than 5 times the upper limit of normal)
DONOR: related donors and unrelated adult donors, who are harvested at Columbia University Medical Center (CUMC), will receive filgrastim (G-CSF) 5-10 ug/kg/d subcutaneously x 4 days (or, if unable to tolerate G-CSF, sargramostim [GM-CSF] 250-500 mcg/m^2/day subcutaneously x 4 days) and then undergo leukapheresis; if necessary, plerixafor may be included for mobilization
Currently enrolled at Salish Kootenai College
Have a valid telephone number and email address
Willing to participate in all study components
Self identifies as American Indian or Alaska native
Is a current smoker – self defined
Medically ineligible as a result of screening questions
Infectious disease criteria:\r\n* No active infection; infection controlled with antimicrobial therapy is not excluded\r\n* Human immunodeficiency virus (HIV) negative by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-polymerase chain reaction (RT-PCR) (if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive)\r\n* Hepatitis B and C negative by serology or RT-PCR\r\n* Must complete full screening panel:\r\n** HIV 1, 2 serology and RT-PCR\r\n** Human T-lymphotropic virus (HTLV) 1,2 serology\r\n** Rapid plasma reagin (RPR) serology\r\n** Epstein–Barr virus (EBV) serology\r\n** Cytomegalovirus (CMV) serology\r\n** Herpes simplex virus (HSV) serology\r\n** Varicella zoster virus (VZV) serology
Antithymocyte globulin (ATG) as part of the conditioning regimen
CSP-based postgrafting immunosuppression
Patient is enrolled on an investigational nonmyeloablative HCT protocol or a nonmyeloablative treatment plan with postgrafting CSP that does not use acute GVHD as its primary endpoint (protocol 2546 serves as adjunct protocol); OR
Patients must have a hematologic malignancy treatable by nonmyeloablative HCT; the following diseases will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) and the principal investigator:
Waldenstrom’s macroglobulinemia – must have failed 2 courses of therapy
Patients < 12 years of age must be approved by the principal investigator and by a relevant patient review committee, such as the Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC)
Patients must have either relapsed after previous high-dose chemotherapy and autologous or allogeneic HCT, or else be ineligible for such an approach due to age, failure to mobilize sufficient hematopoietic stem cells, medical comorbidities, or patient refusal
Myeloablative preparative regimen
Patients whose lesions are HPV16+ by polymerase chain reaction (PCR) (treatment groups 1, 2, 3 and 5); group 4 (imiquimod alone: 6 HPV16+ subjects, 12 HPV16- subjects)
Able to complete all mandatory tests
Fair, good or excellent cosmesis, as determined by trained nurse assessment using the Harvard Cosmetic Scale
Active systemic lupus or scleroderma
Indications for comprehensive regional nodal irradiation
HCCs must fall within the Milan/United Network for Organ Sharing (UNOS) T2 criteria (1 lesion 2-5 cm or 3 lesions all =< 3 cm without evidence of vascular invasion/metastasis)
Physiological Model for End-Stage Liver Disease (MELD) >= 30 at screening visit\r\n* If the patient has been dialyzed at least twice within the last 7 days, then the factor used for serum creatinine should be 4.0; any value less than one is given a value of 1 (i.e., if bilirubin is 0.8 a value of 1.0 is used) to prevent the occurrence of scores below 0 (because any positive value below 1 the natural logarithm would yield a negative result); the upper limit of serum creatinine is capped at 4.0; the lower limit of serum sodium (Na) is capped at 125, and the upper limit is capped at 137; after enrollment, if a patient’s MELD increases to 30 or greater, they can still be eligible
Hemophilia
At screening has suspected or confirmed CDI, and is receiving or is planning to receive a 10- to 21-day course of antibacterial drug treatment for CDI
At study infusion has a diagnosis of CDI confirmed by a diagnostic assay which detects the presence of C. difficile toxin in stool, and is still receiving antibacterial drug treatment for CDI.
Patient has diarrhea at the time of enrollment which is Clostridium difficile toxin positive
Patient is allergic to the third or fourth generation celphalosporins, carbapenem, or aminoglycosides which are used to empirically treat LBP bacteremia
ENROLLMENT HAS ENDED
Self-identified foreign born individuals in China, Korea, and Vietnam
Will stay in the targeted area in the next 2 years
Are not aware of HBV infection
Not a resident in the Baltimore Washington Metropolitan area
Known intolerance to NSAIDs
Current smoker
Hair that covers the scalp and is at least 1/4 inch in length
Pre-existing alopecia
scalp metastases or scalp wounds
Subjects must be free of life-threatening illness (e.g., cancer) that would severely limit participation; those with chronic illnesses (e.g., asthma, diabetes) may participate with the permission of their physician
Subjects should have no serious physical activity, diet, or nutrition restrictions that could interfere with changes brought about as a result of the intervention; restrictions that will be screened for are untreated exercise-induced asthma, orthopedic or neurological problems, and medical conditions affecting nutritional status, intestinal absorption, or response to nutritional intervention (e.g. inflammatory bowel disease)
Serious mental illness or developmental disabilities; subjects should be free of serious mental illness or developmental disability that would limit participation, including eating disorders
The study will be nonselect with respect to the racial or ethnic background of the subjects; the racial/ethnic composition of the study sample will be representative of the patient population from which it will be drawn
Have no significant co-morbidity that precludes participation (i.e. acute, life-threatening illness, communication barriers such as a tracheal tube placement, or altered mental status such as dementia)
Be a permanent resident of the state of Kansas or Missouri
Not currently prescribed or taking nicotine replacement therapy or varenicline during this hospitalization
Patient not already seen by UKanQuit staff as part of the hospital based clinical service
Not taking medication to help in quitting smoking prior to admission
Not currently participating in a quit smoking program
Presence of at least 1 CV risk factor:\r\n* Currently on medication for hypertension, or\r\n* Currently on medication for cholesterol or triglyceride, or\r\n* Currently on medication for diabetes, or\r\n* Currently not physically active (self-reported average < 20 minutes/day), or\r\n* Currently smoking.
Pre-existing ischemic heart disease (includes angina if documented in electronic medical record [EMR]) or ongoing cardiomyopathy.
Documented germline pathogenic or likely pathogenic variant in the BRCA1 or BRCA2 genes
Participants must be scheduled for risk-reducing salpingo-oophorectomy with or without hysterectomy – either bilateral or unilateral (if prior unilateral oophorectomy or salpingectomy for benign condition)
Encephalopathy absent
Adult (?18 years)
HSCT recipients who underwent ex vivo T-cell depletion of the graft, or a mismatched, or cord or haplo identical blood transplantation
Premenopausal
Meet all the following criteria related to lifestyle: a) consume less than 3 servings of vegetables (excluding any fried servings) and 1 serving of fruit (not including juice)/day; b) engage in less than 150 minutes moderate/vigorous intensity activity per week, defined as anything that causes small increases in breathing or heart rate for a sustained amount of time (e.g., brisk walking, bicycling); c) engage in a mind-body practice less once per week
Any major thought disorder (e.g., schizophrenia, dementia)
Communication barriers (e.g. hard of hearing)
Extreme orthopedic or mobility issues (e.g., unable to get in and out of a chair unassisted)
Contemplating any new pharmacologic/hormonal or prophylactic surgical intervention within the next year (Note: Individuals taking tamoxifen, Arimidex or other hormonal prevention strategies at time of consent will be eligible)
UCB unit(s) composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm plus an additional cord blood unit to be used as the source to manufacture the Treg product; this UCB unit must be matched at 4-6/6 to the patient, considering HLA-A, B at the antigen level and DRB1 at the allele level
Hyperplastic polyp or/and adenoma cases
Polyps free participants with any of the following high risk of colorectal polyps or cancer: (1) family history of colorectal cancer or polyps; (2) current cigarette smoker; (3) obesity (body mass index [BMI] >= 30 kg/m^2); (4) low intake of fiber (lowest fiber intake quartile: daily intake < 16.6 g); (5) high intake of red meat and well-done or processed meat (mutagenicity index >= 5852)
Consent to be contacted for future studies
Participants with a calcium intake >= 700 mg/day measuring with 24 hour dietary recalls
Participants with a calcium intake < 2000 mg/day measuring with 24 hour dietary recalls
Participants with a calcium/magnesium intake ratio > 2.6
Participants with known genotype for Thr1482Ile polymorphism in TRPM7
Intolerance to magnesium glycinate or microcrystalline cellulose (placebo)
Chronic diarrhea
Pituitary dwarfism
Current use of lithium carbonate therapy (Eskalith, Lithobid, Lithonate, Lithotabs, Apo-Lithium carbonate, Apo-Lithium carbonate SR, Carbolith, Duralith, PMS-Lithium carbonate, PMS-Lithium citrate)
Currently institutionalized
Homeless individuals (address, telephone etc.)
Clinical stage =< T2a by digital rectal exam (DRE)
Biopsies performed at outside institutions should have Gleason score confirmed at the study site by a genitourinary (GU) pathologist to ensure eligibility
Immunodeficiency or splenectomy
Previous adverse reactions to smallpox vaccination
Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination or until the vaccination site heals completely: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, (d) individuals with other acute, chronic, or exfoliative skin condition, or (e) immunocompromised or immunosuppressed persons (by disease or therapy)
Participants who have taken any medicines that are inducers, inhibitors or substrates of select cytochrome (CYP) isozymes within the past 3 months will be excluded; participants who have consumed either grapefruit juice or Seville orange juice in the past 7 days will be excluded
Currently on the wait list for a new garden
Willing to undergo study measurements
Subjects must have an Internet connection and be able and willing to use an applicable device\r\n* If patients do not have an applicable device, they must be willing to borrow an iPad from the study team (to be returned at the conclusion of the study)
Self-identifies as gay or bisexual
Lives in the United States (US)
Glycated hemoglobin (HbA1c) > 8%
Nicotine dependence assessed as > 4 (>= 2 for study 2) with the Fagerstrom Test for Nicotine Dependence
Willingness to abstain from smoking for 8 hours (overnight abstinence) prior to study visits
Mothers/female guardians of elementary aged students
Self identify as Latina
Not a parent of elementary aged student in Duarte Unified School District (DUSD)
Does not self-identify as Latina
Consumes 5+ servings of fruits and vegetables and is active for at least 30 minutes 5+ days per week
Has a condition or psychological difficulties that affects day-to-day activities
Blood urea nitrogen < 2 x ULN
Willing to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of study agent dosing
The presence of gross skin invasion/ulceration by the breast cancer, or inflammatory changes with skin edema AND erythema; Note: Paget's disease is permitted
Women receiving a “nipple delay” procedure prior to mastectomy
Women who were using oral contraceptives or postmenopausal hormones within eight weeks prior to core needle biopsy, and then stopped following core needle biopsy, are not eligible; use of hormone coated IUD like Mirena is allowed
Currently taking spironolactone
Evidence of biochemical recurrence
Smoke at least 10 cigarettes daily for the past year
Expired-air carbon monoxide (CO) > 8 parts per million (ppm)
Medically eligible to receive varenicline
Have renal dysfunction
Have ever used varenicline
The number of participants from the same street address will be limited to 1
Smoke 5 or more cigarettes/day
Willing to take NRT for up to 12 months, and be willing to complete 4 follow-up telephone-based counseling sessions and 3 follow-up visits
Reside in a facility that does not allow smoking (e.g. certain nursing homes)
Subjects demonstrating markedly inappropriate affect or behavior will be excluded from the study
Sodium 135-144 mmol/L (inclusive)
Potassium 3.2-4.8 mmol/L (inclusive)
Participants must be willing to forego foods, beverages and supplements containing pomegranate for the duration of the study
Participants may not be taking carbamazepine (tegretol)
Biopsy-proven Barrett’s esophagus that is non-dysplastic or with low grade dysplasia
Participants must have Lynch syndrome defined as meeting any of the following:\r\n* “Mutation-positive Lynch syndrome”: carriers or obligate carriers (by pedigree) of a pathogenic mutation in one of the DNA mismatch repair (MMR) genes (i.e. mutL homolog 1 [MLH1], mutS homolog 2 [MSH2]/epithelial cell adhesion molecule [EPCAM], mutS homolog 6 [MSH6], or PMS2 postmeiotic segregation increased 2 [S. cerevisiae] [PMS2]) or\r\n* “Mutation-negative Lynch syndrome”: patients with a personal history of a non-sporadic MMR deficient premalignant lesion (i.e. polyp) or a non-sporadic MMR deficient malignant tumor (where “non-sporadic MMR deficient” is defined by: microsatellite-instability high by either immunohistochemistry or microsatellite instability [MSI] testing or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, and/or no evidence of v-raf murine sarcoma viral oncogene homolog B [BRAF] mutation in cases with loss of both MLH1 and PMS2) but germline MMR genetic testing showed either a variant of unknown significance or mutation negative result or had declined germline MMR genetic testing
Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e. participants must have at least part of the descending/sigmoid colon and/or rectum intact)
Participants must consent to one standard of care lower gastrointestinal (GI) endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies and one flexible sigmoidoscopy with biopsies that will be 6 months (+14 days) apart
Leukocyte count >= 3,000/microliter
Individuals who are status post total proctocolectomy (i.e. removal of all colon and rectum)
Gastric paresis
Celiac sprue
Drugs that interfere with mitochondrial function if they are unable to be discontinued 48 hours prior to 13MBT testing will be excluded for this test only but eligible for the rest of the protocol
Chronic alcohol use defined as > 2 standard drinks per day (more than 2 beers, 2 glasses of wine, or 2 shots of liquor per day)
Inability to perform exercise with dominant leg
The subject is scheduled to undergo radical prostatectomy
The subject agrees to stop consuming tea or tea-containing products and quercetin supplements throughout the entire intervention period except for the green tea extract and quercetin provided during study intervention
Prior sensitivity or allergic reaction to tea, tea products or tea and quercetin supplements
Allergies to multiple food items or nutritional supplements
FOCUS GROUPS AND SURVEYS: Healthy volunteers currently living in San Diego, Portland, Albuquerque, Oklahoma, San Francisco/Bay Area, Nashville, Tucson, Los Angeles, New York City, Minneapolis or Duluth, Minnesota (MN) who attend bars or nightclubs; both current (past 30 day) smokers and nonsmokers will be included in the focus groups and surveys
LGBT SUB-STUDY: Participants are healthy volunteers currently living in San Diego Portland, or Albuquerque who attend bars or nightclubs in the LGBT random sample; both current (past 30 day) smokers and nonsmokers will be included in the focus groups and surveys
LGBT SUB-STUDY: Participants who complete the screener, are willing to participate in a longitudinal study for one year, and who self-identify as lesbian, gay, bisexual or transgender will be eligible to participate in the cohort study
QUALITATIVE INTERVIEWS WITH KEY INFORMANTS FROM SOCIAL BRANDING CAMPAIGN: Participants are key informants from the Social Branding bar intervention (i.e. facilitators, brand managers, or cessation counselors) who may be young adults or slightly older
Not living in San Diego, Portland, Albuquerque, Oklahoma, San Francisco/Bay Area, Nashville, Tucson, Los Angeles, New York City, Minneapolis or Duluth MN or currently attending college outside of the target cities
For the LBGT cohort study, subjects will be excluded for unwillingness to provide contact information or if they do not self-identify as LGBT in the screener
For smoking cessation groups, unwillingness to participate or no desire to quit smoking
Known diagnosis of short-segment or long-segment Barrett’s esophagus as previously made by upper endoscopy showing salmon-colored distal esophageal mucosa and biopsies revealing intestinal metaplasia with goblet cells; potential study subjects may be contacted by mailings or phone calls or may be approached in clinic; additionally, potential study subjects may be approached using a web-based recruitment tool; informed consent will be obtained by a research coordinator or study investigator
Willing to donate 90 mL of blood and endoscopic mucosal biopsies for research
At least 2 cm circumferential Barrett’s esophagus segment length (C2M2 by Prague C & M criteria)
Esophageal adenocarcinoma
Known hypercalcemia
Previous ablative therapy for Barrett’s esophagus
Participants planning to undergo elective radiologic studies involving intravascular administration of iodinated contrast materials
50% or higher estimated mammographic density on visual inspection
Prior or current random periareolar fine needle aspiration (RPFNA) evidence of atypia
Known carrier of a BRCA1 or 2 mutation
Have changed type of hormonal contraception during the previous 8 weeks
Considered to be perimenopausal and/or entering the menopause transition
Consumption of systemic antibiotics or commercial supplements containing SDG (e.g. flaxseed or sesame seed supplements) during the 3 weeks prior to baseline RPFNA; consumption of foods containing flaxseed or sesame seed are permitted
Any consumption of prescription anticoagulants, including Coumadin and Lovenox, during the 3 weeks prior to baseline RPFNA
RPFNA specimen exhibits hyperplasia +/- atypia; Masood score of >= 13 with >= 500 cells on the cytology slide
Ki-67 >= 2% positivity (>= 500 cells)
Eligible tumor and premalignant lesion sites include oral cavity (buccal mucosal, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, larynx (glottis, supraglottis, subglottis, epiglottis), hypopharynx paranasal sinus and nasal cavity
Lesion sites include oral cavity (buccal mucosa, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, hypopharynx, larynx (glottis, supraglottis, subglottis, epiglottis), nasopharynx and paranasal sinuses
Participants must have no medical contraindications for flexible laryngoscopy using topical anesthesia, and in the setting of a contraindication to topical anesthesia, general anesthesia may not be used as a substitute
Participants must be willing to abstain from drinking green tea or taking supplements containing green tea or green tea compounds, for the duration of the investigation and for 30 days prior to study entry\r\n* (Please note that patients with a treated T1N0 or T2N0 squamous carcinoma and who do not have a pre-malignant measurable lesion at the time of study entry will not be subjected to a biopsy but will have cytobrush samples taken as specified in the protocol)
Consumption of green tea or supplements containing green tea or tea extract within 30 days prior to enrollment
Current or prior advanced adenomas
Advanced adenomas are defined as subject with polyps >= 1 cm, tubulovillous adenomas (25-75 percent villous features), villous adenomas (> 75 percent villous), or high-grade dysplasia
Serum calcium =< institutional ULN
Total colectomy
Concomitant corticosteroids or anticoagulants needed on a regular or predictable intermittent basis
Scheduled to receive chemotherapy with an anthracycline (doxorubicin [doxorubicin hydrochloride] or epirubicin [epirubicin hydrochloride])
Able to hold breathe for 10 seconds
40 to 75 years of age with diabetes per American College of Cardiology (ACC)/American Heart Association (AHA) ACC/AHA 2013 guidelines
Current use of the following cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4) inhibitors are not allowed: boceprevir, clarithromycin, cyclosporine (oral), darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, gemfibrozil, grapefruit juice > 1 liter per day, itraconazole, lopinavir plus ritonavir, nelfinavir, saquinavir plus ritonavir, telaprevir, tipranavir plus ritonavir
Symptomatic claustrophobia
Women who will be scheduled to undergo an RRSO or RRS
Women who will have at least one fallopian tube removed for risk-reducing reasons (with or without removal of ovar[ries])
Women using non-hormonal forms of contraception\r\n*(Note: If a copper IUD is being used, the IUD must be removed prior to or at time of Mirena insertion)
Any medical contradiction to use of a Mirena IUD, including:\r\n* Pregnancy (a pregnancy test is required prior to study entry)\r\n* Known uterine anomaly that distorts the shape of the uterine cavity \r\n* Acute pelvic inflammatory disease\r\n* Postpartum endometritis or endometrial infection\r\n* Known or suspected uterine or cervical neoplasia\r\n* Known history or suspected breast cancer or other progestin-sensitive cancer\r\n* Uterine bleeding of unknown etiology\r\n* Untreated acute cervicitis, vaginitis, or other lower genital tract infections\r\n* Acute liver disease or liver tumor (benign or malignant)
All participants must be nonsmokers at the time of the study (i.e., have not used any tobacco product); have not smoked an entire cigarette, cigar, or hookah session before
All participants must score 3 out of 5 or above on the place attachment scale (i.e., measuring adolescents’ feeling of attachment to their after-school program)
Histologically confirmed, positive HSIL of CIN2+ or higher (only CIN2+/3 subjects will be selected) cervical biopsy, confirmed by external (independent) pathologist panel within the 12 weeks prior to enrollment. If the standard care biopsy is not available for evaluation by the independent pathologist, a fresh biopsy and endocervical curettage will be required. The extent of colposcopic HSIL disease should not involve more than two quadrants of the cervix. Biopsies should be taken from each affected quadrant
Adequate visualization of entire cervix, cervical lesion(s) and squamous-columnar junction
Agrees to Loop Electrosurgical Excision Procedure (LEEP), Cold Knife Conization (CKC) or Hysterectomy being performed at the end of study according to the standard-of-care
Skin conditions that require consistent use of topical corticosteroids or other local or systemic therapy that may interfere with interpretation or description of skin-related adverse events linked to vaccination
Evidence of hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric, dermatologic, immune disorder, or other disease that may interfere with assessment of safety or efficacy of vaccine activity as indicated in study objectives
Receipt of (e.g. Gardasil® or Cervarix®) HPV preventative vaccines within 8 years of study enrollment
Prior allogeneic HSCT
Eligible for donations of human blood and blood components according to local requirements and regulations
Has a proven or probable invasive fungal infection
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.
Planned to undergo allo-HSCT
The ethnic and racial composition of the subject population will reflect the composition of subjects seeking care at The Ohio State University and James Cancer Hospital and Solove Research Institute; no special groups such as prisoners, children, the mentally disabled, or groups whose ability to give voluntary informed consent may be in question will be used for this study
Must have had a mammogram within the 12 months prior to study enrollment; mammograms must be read as not suspicious for breast cancer (American College of Radiology [ACR] class I-III); subjects with a class IV mammogram may be entered once they have had a negative biopsy
Dietary intake of large amounts of curry, turmeric spices or black pepper on a regular basis
Potential participants must be underactive (defined as participating in moderate or vigorous PA two days per week or less for 30 minutes or less each day)
Planning to move from the area within the next year
Hospitalization due to a psychiatric disorder in the past 3 years
Taking medication that may impair PA tolerance or performance (e.g., beta blockers)
Serum creatinine based on age/gender
BSA (m2) of <0.25
Minimum of 1 cm circumferential Barrett's mucosa on endoscopy or at least 2 cm maximal contiguous extent of Barrett's mucosa
Enrolled in a communication program (university student review)
Self-reported Hispanic/Latino ethnicity
Physically able to engage in low-to-moderate PA
Consumption of fewer than 5 servings of fruits and vegetables per day
Valid home address in the Houston neighborhoods of Gulfton, the East End/Magnolia, or near Northside, or adjacent neighborhoods
Working telephone number
Bilingual Latina
Live in the community
Latina
Reside in the Dan River region of southern Virginia
Hispanic
Current smoker
Interested in making a serious quit attempt in the next 30 days
Non-Hispanic
Non-smoker
Not interested in making a serious quit attempt in the next 30 days
Willing and able to provide stool and blood samples at baseline (week 0), week 4, and week 8
Willing and able to attend a gym 3-5 days a week for 4 weeks between week 5 and week 8
Willing and able to receive weekly phone “check-ins” from a study coordinator
Willing and medically able to exercise safely and independently at a moderate intensity without direct supervision
Willing and able to maintain current dietary behaviors for the duration of the study
Recipients with donor sensitive antibodies (DSA), defined by 2000 or higher median fluorescence intensity (MFI) against one or more class I or II antigens
Biopsy-proven HNC including cancers of the nasopharynx, oropharynx, larynx, hypopharynx, or HNC of unknown primary origin amenable to therapy with radiation and concurrent chemotherapy
Patient planned to receive altered fractionation radiotherapy or multiple fractions per day
Patient is using a pre-existing feeding tube for nutritional support at the time of study entry
Must be underdoing allogeneic or autologous HCT for a malignant or non-malignant disorder
Must have or be scheduled to have a tunneled CVC
Healthy, medically well girls and boys
Previous vaccination against HPV
Known diagnosis of histologically-confirmed BE with or without dysplasia (as defined by the presence of specialized columnar epithelium anywhere in the tubular esophagus with >= 1 cm of circumferential involvement or non-circumferential involvement of specialized columnar epithelium) requiring radiofrequency ablation
Inability to abstain from, NSAID (including aspirin), and selective COX-2 inhibitor therapy at the time of randomization through the completion of the study (the study period is defined as baseline to exit endoscopy at 18 months after randomization which defines the completion of the study); participants may take Tylenol and non-NSAID pain relievers
Surveillance biopsies demonstrating residual BE at qualifying exam
Presence of an esophageal stricture defined as “any recognizable change in esophageal luminal caliber that is accompanied by symptoms of dysphagia, or any asymptomatic narrowing that either will not allow any adult endoscope to pass or allows passage with resistance”
Have smoked 100 cigarettes in their lifetime and currently smoke five or more cigarettes a day on average
Have an address in a rural census tract defined by a Rural-Urban Commuting Areas (RUCA) code of 4-10
Interested in participating in a cessation program
Own a phone that has texting ability and free texting or be willing to receive a phone from study staff
Have general knowledge of text messaging
Are willing to receive and respond to text messages from the study teams, throughout the duration of the study
Already participating in a smoking cessation intervention study
Reside in a rural location as defined by Rural-Urban Commuting Area (RUCA) Codes, Urban Influence Codes, amount of agricultural income, and/or individual commuting patterns
Have clearance from their primary care provider to participate in a diet and exercise weight control intervention
One individual per household will be permitted to enroll in the study
Individuals with end stage renal disease, known glomerular filtration rate (GFR) < 25, current or anticipated dialysis or transplant within the next two years will be excluded; a history of renal transplant is not an exclusion per se if patient does not meet stated renal criteria
Participants who plan to relocate outside of their provider’s service area or who plan to leave their primary care clinic in the next two years will be excluded
Subjects with current or suspected urinary tract or bladder infection(s);
Enrolled in 7th or 8th grade
Willingness to provide contact information including phone number, email address and mailing\r\naddress
STUDY I: Current dual users (of tobacco cigarettes and e-cigarettes) without interest in quitting smoking
STUDY I: Current dual users who have attempted, but not quit smoking
STUDY I: Current e-cigarette users who have successfully quit smoking
STUDY II: Smoking at least one cigarette per week over the past year
STUDY II: Not currently enrolled in a face-to-face smoking cessation program
Serum creatinine based on age/gender
STUDY II: Smoked at least one cigarette over the past week
Clinically evident HSR to oxaliplatin, with symptoms of flushing, urticaria, pruritus, rash, and/or dyspnea without bronchospasm that emerge during or shortly after of oxaliplatin infusion
Responding (complete or partial) or stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria while undergoing treatment with oxaliplatin containing regimen or need to resume an oxaliplatin based regimen in the setting of well-documented recent oxaliplatin hypersensitivity reaction
The study will be conducted in postmenopausal women
Willing and able to travel to the exercise facility
Have undergone a lumpectomy or mastectomy
Asymptomatic current or former smokers (having stopped within the last 20 years)
All current smokers should accept to receive support for smoking cessation
Individual may not be receiving any other investigational agents, antiplatelet agents (e.g. aspirin, clopidogrel [Plavix or others]), anticoagulants (e.g. heparin or heparinoids, Coumadin, or others), methotrexate, lithium
Subjects must have a smart phone (newer generation Android or any iPhone) to be able to track their food intake times
Subjects must be willing to restrict food intake to a 10 hour period every day (10 am to 8 pm) and wear a smartwatch on their dominant hand
Subjects who work night shifts are not eligible
History of at least one of the following conditions in the previous 12 months:\r\n* Colorectal adenoma(s) >= 1 cm in maximal diameter\r\n* Colorectal adenoma(s) with villous or tubulovillous histology\r\n* Colorectal adenoma(s) with high grade (severe) dysplasia
Presumptive evidence that all adenomatous lesions, including qualifying advanced adenoma, have been completely removed
Willingness to undergo screening tests and procedures
Diagnosis of nonalcoholic steatohepatitis (NASH) and a NAFLD (nonalcoholic fatty liver disease) activity score (NAS) >= 5; NOTES and EXCEPTIONS: NAS is based on findings from a liver biopsy; participants with NAS of =< 2 are eligible for enrollment; participants with NAS of 3-4 must be discussed with the principal investigator and Division of Cancer Prevention (DCP) before enrollment to consider other risk factors (i.e., obesity, alcohol intake); participants with a prior diagnosis of NASH and no available NAS must be discussed with the principal investigator and DCP before enrollment to considered risk factors (i.e., obesity, alcohol intake)
Antinuclear antibody (ANA) test result excludes overt autoimmune disease; note: test result may be reported in any of the following formats: =< 1:160, negative, or < 1.0
African American
Currently smoke at least 5 cigarettes per day
Smoked daily for the past one year
Able to participate in exercise training
Participants in each component (focus groups, surveys and educational programs) will be 18 years of age and over; these men and women are generally healthy, ambulatory and able to participate in events in their community; no women, men, or children of any ethnic or social background will be excluded from the educational program
EDUCATIONAL INTERVENTION:
Self-identify as African American
FOLLOW-UP ASSESSMENTS:
FOLLOW-UP ASSESSMENTS: Must be non-adherent for CRC screening at the time of the educational program
FOLLOW-UP ASSESSMENTS: Self-identify as African American
FOLLOW-UP ASSESSMENTS: Have telephone service (mobile or landline), to participate in the follow up interviews
FOLLOW-UP ASSESSMENTS: Agree to providing consent for release/review of their medical record
Aim 5: Director/leader or program manager/coordinator of organization or organization representative who has been nominated to be interviewed by the organization’s director/leader or manager/coordinator
Aim 5: Organization was contacted to participate in Aim 3
History of 3 or more biopsy confirmed BCCs in the preceding 2 years, calculated from 2 years prior to the screening visit; the number of BCCs found at the screening visit will not be included in the number of BCCs that qualify the subject for the study; if the subject after signing the consent form is found to not have had 3 BCCs prior to the screening visit then they will be a screen failure and will not enter the study
No active skin cancers; any skin cancers found on the screening visit after the subject has signed consent will need to be treated before the subject begins on the study drug at the baseline visit; the skin cancers found on the screening visit will not be included in the total number of skin cancers the subject had 2 years prior to signing the consent
Absence of urothelial carcinoma involving the upper urinary tract (documented by radiological imaging or biopsy) preferably within 12 months from the start of treatment; should the imaging or biopsy be performed outside this window it will be up to the physician's discretion to re-scan/biopsy
Documented diagnosis of MDS (MYELODYSPLASTIC SYNDROMES), classified according to FAB (FRENCH-AMERICAN BRITISH) classification criteria
Any clinical worsening from pre-injectable HMA (HYPOMETHYLATING AGENT) baseline condition, including:
worsening granulocytes should be ? 50% decrease from pre-injectable HMA (HYPOMETHYLATING AGENT) baseline value
worsening platelets should be ? 50% decrease from pre-injectable HMA (HYPOMETHYLATING AGENT) baseline value (untransfused)
meaningful worsening in RBC (RED BLOOD CELL) or platelet transfusion requirement Definition of stable disease is based on modified IWG (INTERNATIONAL WORKING GROUP) 2006 criteria:
Refrain from semen or sperm donation while taking IP and for at least 90 days after the last dose of IP.
Rapidly-progressing MDS (MYELODYSPLASTIC SYNDROMES), defined as:
?100% increase in WBC count (myeloid cell line and monocyte series) within the 8-week period leading to Cycle 1, Day 1
thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag, Interleukin-11)
ESAs (Erythropoiesis stimulating agent) and other RBC (Red blood cell) hematopoietic growth factors (eg, interleukin-3)
hydroxyurea
Serum total bilirubin > 1.5 x ULN (upper limit of normal). Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis). Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs' test or over 50% of indirect bilirubin
Any condition that confounds the ability to interpret data from the study, including known or suspected conditions other than MDS (MYELODYSPLASTIC SYNDROMES), associated with anemia
Subjects with vitiligo or alopecia;
Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting.
Adult (?18 years old)
Adult (aged ? 18 years)
Administration of a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive disease, following discussion with the medical monitor
HbA1c =< 7.0%
Adequate organ system functions as defined below Absolute neutrophil count>=1.0x10^9/L, hemoglobin>=8.0 g/dL, platelet>=50x10^9/L, international normalized ration (INR) <=1.5, Partial thromboplastin time <=1.5xupper limit of normal (ULN), total bilirubin <=1.25xULN, alanine aminotransferase and aspartate aminotransferase<=1.5 X ULN, serum creatinine or calculated creatinine clearance<1.2XULN >=60 mL/min for Part 1;>=50 mL/minute (min) for Part 2 if data supports loosening criteria, Albuminuria<=500 mg/24h, left ventricular ejection fraction >=50%, Troponin<=1xULN, Calcium<=1.1xULN
Known symptomatic acute or chronic pancreatitis.
Persistent diarrhea or malabsorption despite medical management.
Lymphocytes > 500/ mm3
Prior exposure to veledimex
Presence of any contra-indication for a neurosurgical procedure
Typically, pancreatic tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning but final determination of eligibility will be based upon satisfying the radiation normal tissue constraints
Prior thoracic radiation allowed only if there is minimal to no overlap with the treatment area estimated at the time of consultation, and there is no cumulative esophageal dose that exceeds more than 50% of the maximal acceptable dose tolerance
Acute or chronic pancreatitis
Bilateral diffuse lymphangitic carcinomatosis
Both Studies:
Capable of swallowing intact study medication capsules
Willing to be randomized to a no dietary intervention control group or to a low-carbohydrate diet group
Already consuming a carbohydrate-restricted or vegetarian diet
Patient with intermediate risk, early-stage organ-confined prostate cancer (T1a up to T2b, N0, M0) and voluntarily chooses ExAblate thermal ablation as the non-invasive treatment, who may currently be on watchful waiting or active surveillance and not in need of imminent radical therapy.
Largest imaging dimension of cancerous finding < 20-mm
Patient should be eligible for both spinal/epidural anesthesia (planned procedure), and general anesthesia (in case of complication, requiring intervention).
ASA status > 2
Severely abnormal coagulation (INR>1.5)
Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (approximately 3 hrs. sonication time)
Any rectal pathology, anomaly or previous treatment, which could change acoustic properties of rectal wall or prevent safe probe insertion (e.g., stenosis, fibrosis, inflammatory bowel disease, etc).
Identified calcification of 2 mm or more in largest diameter neighboring the rectal wall (in a distance of less than 5 mm) and interfering with the acoustic beam path.
Lower limb musculoskeletal fixed deformities preventing probe insertion or patient positioning during procedure.
Active UTI
Prostatitis NIH categories I, II and III.
Interest in future fertility
Subject has participated in any other clinical investigation that is likely to confound study results or affect study outcome either at the time of IORT or for 3 months prior to IORT.
Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted
Men are excluded from this study
Ability to complete questionnaire(s) by themselves or with assistance
Largest single focus of disease > 5 centimeters by either mammogram or MRI or both; Note: measurement of the largest single focus should include any satellite lesions within 1 centimeter of the index lesion
Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta, Neupogen)
Biopsy proven diagnosis or clinical diagnosis of any benign oral cavity lesion; pre-surgical biopsy will not be required if lesion is suspected to be benign
Biopsy proven diagnosis or clinical diagnosis of premalignant oral cavity lesions (leukoplakia, erythroplakia, lichen planus, dysplasia); pre-surgical biopsy will not be required if lesion is suspected to be benign
All pathology will be reviewed at Memorial Sloan-Kettering (MSK) to confirm diagnosis
Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
Cohort 2 -Positive expression is defined as ?1+ by immunohistochemistry in ?1% cells, but not to exceed 2+ and/or 3+ in ? 50% of cells.
Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
ANC ? 1.0 x 10?/L
Abnormal ECGs (ie, QT prolongation - QTc > 480 msec, signs of cardiac enlargement or hypertrophy, bundle branch block, signs of ischemia or necrosis and Wolff Parkinson White patterns)
Have never had acupuncture for xerostomia
Suspected or known closure of salivary gland ducts on either side
Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma or medulloblastoma.
For neuroblastoma patients only, a positive MIBG (MIBG not required if subject's neuroblastoma is previously determined to not uptake MIBG), abnormal urinary catecholamine levels, or positive bone marrow biopsy/aspirate.
Human Papilloma Virus (HPV) status
Previous enrollment in the present study
Histologically proven primary diagnosis of GBM with unmethylated O6-methylguanine-DNA methyltransferase (MGMT).
Determination of MGMT promoter status by methylation-specific polymerase chain reaction (PCR) per local institutional guidelines is required to assess eligibility for this Arm.
History or presence of myopathy or raised creatine kinase (CK) >5 x upper limit of normal (ULN) on 2 occasions at screening.
Subject has a confirmed diagnosis of myelofibrosis, including PMF, post-PV MF, and post-ET MF.
Persistent or worsening disease-related symptoms, including but not limited to fatigue, pruritus, night sweats, early satiety, and other symptoms as determined by a MPN-SAF TSS score of >20 points; AND
Clinical signs or symptoms of GI obstruction or requirement of routine parenteral nutrition or tube feedings
Have age-appropriate functional performance:
Prior exposure to veledimex
HER2 negative disease based on local testing: American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for assessing HER2 status.
HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status.
Known dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD deficiency must be performed where required by local regulations, using a validated method that is approved by local health authorities.
Subject must have histologically confirmed at last relapse aggressive B-cell NHL according to \The 2016 revision of the WHO classification of lymphoid neoplasms\ defined as:
Epstein-Barr virus (EBV) positive DLBCL, NOS
Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals as detailed in the protocol
Subjects with active auto immune disorders/processes or active neurological or inflammatory disorders
Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week of leukapheresis. Oral chemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks of leukapheresis.
Hypercalcemia (serum calcium greater than [>]0.25 millimoles per liter [mmol/L] [>1 milligram per deciliter {mg/d
Clonal BMPC percentage >=60%
Serum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100 mg/L)
Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis
Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate as indicated for osteoporosis is acceptable
Relapsed after > or = 2 lines of prior therapy that must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where approved and available, a CD38-directed cytolytic antibody in any order during the course of treatment OR refractory to PI, IMiD, and CD38- directed cytolytic antibody,
Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic antibody are eligible to enroll in the study.
Waldenstrom's macroglobulinemia
Amyloidosis
Participants must be designated to undergo reduced intensity allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT); consent will be obtained prior to admission for HSCT; the following HSCT conditions must be planned:\r\n* Donors must be 8/8 HLA-matched (at the allele level) as defined by matching at HLA-A, -B, -DR and –C who pass institutional standard to serve as a peripheral blood stem cell donor\r\n* Donor grafts must be granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells with dose and apheresis logistics at the discretion of institutional standard\r\n* Conditioning therapy will be one of the following 3 options:\r\n** Fludarabine/melphalan where fludarabine is >= 90 mg/m^2 intravenously (IV) total dose and melphalan is 100-140 mg/m^2 IV total dose; exact logistics of administration are at the discretion of institutional standard\r\n** Fludarabine/busulfan where fludarabine is >= 90 mg/m^2 IV total dose and busulfan = 6.4 mg/kg IV total dose; exact logistics of administration are at the discretion of institutional standard\r\n** Fludarabine/busulfan where fludarabine is >= 90 mg/m^2 IV total dose and busulfan is dosed to achieve area under the curve (AUC) of 4000 umol/min based on a pharmacokinetics determined from a test dose; exact logistics are at the discretion of institutional standard\r\n* GVHD prophylaxis is comprised of tacrolimus/short course methotrexate as defined by tacrolimus started prior to day 0 of HSCT and methotrexate given after HSCT on days +1, +3 and +6 +/- +11 at a dose of 5-10 mg/m^2 IV; exact logistics are at the discretion of the treating institution
Have had a prior allogeneic HSCT
Planned use of ex vivo or in vivo T-cell depletion
Premenopausal women
Large waist circumference \r\n* >= 88 cm (>= 35 inches) or \r\n* >= 80 cm (>= 31 inches) for Asian Americans, individuals with polycystic ovary syndrome, or individuals with non-alcoholic fatty liver disease
Premenopausal women with a documented BRCA1 or BRCA2 mutation; menopause is defined as >= 12 months of amenorrhea
Patient choosing PSDO or RRSO must desire permanent sterilization
Presence of at least one fallopian tube; prior tubal ligation is allowed
Willingness to return to the enrolling site for any surgical procedures including pre-operative and post-operative care
Women without a documented BRCA mutation
Prior bilateral salpingectomy; prior unilateral salpingectomy is allowed
Women desiring future fertility except in the screening arm of the trial
Women whose most recent CA125 or transvaginal ultrasound is abnormal; a history of abnormal CA125 or ultrasound is allowed, as long as the most recent testing is normal
BMI >= 50th percentile at time of study enrollment
As this is intended to be a family-based intervention, all family members will be invited to participate, including those living in more than one household, however endpoints will only be assessed formally in the patient and identified primary caregiver; siblings are not required for participation
Subject is a CMV-seropositive HCT recipient
Primary or secondary myelofibrosis
Subject has a modified hematopoietic cell transplant comorbidity index (HCT-CI) score ? 4
Bilateral mastectomy
Women who are receiving endocrine therapy for breast cancer treatment or chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or exemestane at the time of screening
Granulocytes (polymorphs + bands) >= 1.5 x 109/L
Subjects must be accessible for treatment, adverse event tracking and follow-up as determined by the treating physician
Demonstrate hyperinsulinemia with a quantitative insulin sensitivity check index (QUICK I) value =< 0.357
Must have a primary care provider (PCP)
Prior hysterectomy or endometrial ablation
Consent to be contacted for future studies
Participants with known genotype for rs174535 in fatty acid desaturase 1 (FADS1)
Currently taking fish oil supplements
Diagnosis of cirrhosis
Previous partial of total colectomy
Inability to come to Vanderbilt General Clinical Research Center (GCRC) for research procedures
Serum bilirubin > 1.5 x the upper limit of reference range (ULRR)
Serum calcium above the CTCAE grade 1 upper limit; in cases where the serum calcium is below the normal range, 2 options would be available: 1) the calcium adjusted for albumin is to be obtained and substituted for the measured serum value; exclusion is to then be based on the adjusted for albumin values falling below the normal limit; 2) determine the ionized calcium levels; if these ionized calcium levels are out of normal range despite supplementation, then the patient must be excluded
Presence of left bundle branch block (LBBB)
Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea
Post-menopausal at time of diagnosis
Ability to attend clinic visits
Accessible geographically and by telephone
Participants who were eligible for the main trial with the exception of not meeting BMI criteria for obesity
Diabetic neuropathy or other neurological conditions
Inflammatory, metabolic or neuropathic arthropathies
Southwestern Oncology Group (SWOG) performance status of 0 – 2
Clinical diagnosis of asthma
Lymphovascular invasion
In poor health (Karnofsky <60%, ECOG >/-2)
Involved in other experimental protocols (except with permission of the other study PI)
Self-reported inability to walk at least 2 blocks (at any pace).
Insulin requiring diabetes (telephone directed diet and physical activity changes would be difficult in this population without close coordination with the treating physician). Non-insulin requiring diabetics are eligible for the study.
Subject is diagnosed with neuroblastoma, hepatoblastoma, osteosarcoma or extracranial germ cell tumors and has not been previously treated with cisplatin or carboplatin.
Subject has normal baseline auditory function, defined as ? 20 dB from 2000 to 8000 Hz, in both ears and does not have a history of sensorineural hearing loss.
Subject has middle ear effusion upon clinical examination.
Subject is currently participating on a separate otoprotection clinical study.
25-hydroxy vitamin D3 (25[OH]D3) level less than 20 ng/mL prior to study initiation
Willingness to avoid alternative/additional vitamin D3 supplementation for the duration of the trial
Self-reported consumption of more than 4 alcoholic drinks per day
Inability to exercise due to musculoskeletal issue, osteoarthritis or underlying cardiac disease
Subject is using a pre-existing feeding tube for nutritional support at study entry.
Will be receiving stem cell rescue therapy in conjunction with study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant/placebo for fosaprepitant
Has had benzodiazepine, opioid or opioid like therapy initiated within 48 hours prior to study drug administration, or is expected to receive within 120 hours following initiation of chemotherapy except for single doses of midazolam, temazepam or triazolam
Is currently taking, or has taken within 48 hours of Treatment Day 1 the following drugs with antiemetic properties: 5-hydroxytryptamine 3 (5-HT3) antagonists (e.g., ondansetron), benzamides (e.g., haloperidol), cyclizine, domperidone, herbal therapies with potential antiemetic properties, olanzapine, phenothiazines (e.g., prochlorpenzine), scopolamine (this is not an exhaustive list)
Is mentally incapacitated or has a significant emotional or psychiatric disorder
Is allergic to fosaprepitant, aprepitant (MK-0869), ondansetron, or any other 5-HT3 antagonist
Currently enrolled as a first year Ohio State University (OSU) student on the Columbus campus
Self-identifies as being Hispanic or Latino
Previous diagnosis of CRC
Up to date with CRC screening guidelines.
LHW: self-identified as Filipino, Hmong, or Korean Americans
PARTICIPANTS: Self-identified as Filipino, Hmong, or Korean Americans
PARTICIPANTS: Are willing to participate in a study about health behaviors involving nutrition or CRC screening
Medical problems which may prevent them from attending 2 educational sessions
Woman
18-35 years old
Zero CPD for past 4 weeks
Motivated to remain abstinent (7 or higher out of 10)
Established prenatal care
Willing to take Progesterone
Illicit drugs
Pregnancy complications (Diabetes, Anomaly, Fetal growth restriction, HTN, Hx of >2 miscarriages)
Self-report regular smoking
Motivated to quit smoking
Self report of regular menstrual cycles (female only)
Ability to participate fully in research elements for the duration of the trial.
Willing to set a quit date within 2 weeks of enrollment date
Identify as being of Latino heritage, ethnicity, or ancestry
Individuals suffering from any unstable medical condition precluding the use of NRT (identified using the Medical History Questionnaire given at baseline)
Currently using smokeless tobacco, electronic nicotine delivery systems (ENDS), nicotine replacement therapy, or other smoking cessation treatment
Diagnosis of substance dependence other than nicotine (screened using DSM IV TR criteria) Diagnostic and Statistical Manual of Mental Disorders, fourth edition
The CVC consists of a 5.0 French size, Bard, dual-lumen, PowerPICC catheter
Signs and symptoms of localized catheter-related infection (tenderness and/or pain, erythema, swelling, purulent exudates within 2 cm of entry site)
Patients with an occluded (partially or totally) catheter defined as inability to either withdraw blood or instill 3 cc of fluid without resistance through any catheter lumen
Patients who have a short term CVC that have been placed in Intensive Care Unit (ICU) (mainly rigid wall CVCs placed for acute care in ICU)
Diagnosis of any monoclonal gammopathy: monoclonal gammopathy of undetermined significance (MGUS), asymptomatic / active multiple myeloma, asymptomatic / active Waldenstrom macroglobulinemia (WM)
Self-identified African-Americans who are literate and fluent in English
Non-African-Americans
Have preexisting mucositis from other causes.
Have a known sensitivity to any of the constituents of the test product including sensitivities to sandalwood oil, fragrances or any member of the Compositae family of vascular plants (e.g., sunflowers, daisies, dahlias, etc.).
BMI ? 85 percentile for age and sex (overweight or obese) OR at risk for obesity (BMI between the 50th and 85th percentile and at least one overweight parent (BMI ? 25 kg/m2)
Comorbidities of obesity that require immediate subspecialist referral
Smoked at least 100 cigarettes in lifetime
Currently smoking 5 or more cigarettes per day
Willing to make a quit attempt within 1 week of enrollment
Enrolled in another smoking cessation study
Colonoscopy within the last three years that found >= 1 adenoma
Smoked regularly in the past year
Dietary restrictions substantially limiting compliance or vegetarian or vegan diet
Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)
Patient with active Hepatitis B or C determined by serology and/or nucleic acid amplification tests (NAAT)
Able to read, understand, and complete questionnaires and diaries
Has evidence of CMV viremia (if tested) at any time from either signing of the Informed Consent Form or the HSCT procedure, whichever is earlier, until the time of randomization.
Received the following within 7 days before screening or plans to receive during the study: ganciclovir, valganciclovir, foscarnet, acyclovir, valacyclovir, or famciclovir
Received the following within 30 days before screening or plan to receive during the study: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent or biological therapy
Requires mechanical ventilation or is hemodynamically unstable at the time of randomization
Has previously participated in a MK-8228 (letermovir) study
Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
Gastric intolerance attributable to ASA or NSAIDs
Adult asthma
Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
Urine cotinine level, if collected at screening, does not confirm active smoking status
Postmenopausal women. Postmenopausal status is defined either by:
Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
Patient has been assessed by treating physician to be appropriate candidate for everolimus plus exemestane therapy as treatment of advanced or metastatic breast cancer and plans to prescribe everolimus 10mg PO QD in combination with exemestane 25mg PO QD
Willingness to self-report level of oral pain using Visual Analog Scale (VAS) and the Normalcy Diet Scale (NDS) throughout each stomatitis event, as required in the patient diary. At baseline, patient's self-reported oral pain level, using VAS, must be 0 and the normalcy diet scale score should ? 60
Legal lower age limitations (country specific) Indication for therapeutic-dosed anticoagulants Indication for antiplatelet therapy or a conventional non-steroid anti-inflammatory drug (NSAID) Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk Calculated creatinine clearance < 30 mL/min
In poor health (Karnofsky <60%, ECOG >2)
Involved in other experimental protocols (except with permission of the other study PI)
Documented history of advanced adenomas (>= 1 cm in maximal diameter, >= 3 in total number, villous morphology, or high?grade dysplasia) or colorectal cancer
Irritable bowel syndrome, chronic constipation, functional bowel disorders, or colonic motility disorder
Sigmoidoscopy finding requiring clinical intervention
Normal volunteers, either male or female
Participants may not be taking lipid lowering agents
Ability to complete questionnaire(s) and dietary food logs
Willingness to consume meals/snacks provided for 28 consecutive days
Drink less than or equal to one alcoholic drink/day
Self identified as a smoker
Non-Hispanic African American or non-Hispanic White
Smoke 3-20 cigarettes per day (cpd)
Functioning telephone
Interested in quitting smoking
Renal impairment
Another household member enrolled in the study
Subject who has been diagnosed with one or more haematologic malignancies prior to the first vaccination and who is receiving, is scheduled to receive or has just finished immunosuppressive cancer therapy to treat this condition.
Has baseline neutrophil counts of > 1500 cells/mm3 within 72 hours prior to registration
Has serum calcium less than or equal to ULN (for patients with an albumin lower than 3.0, a corrected calcium serum calcium = serum calcium +[0.8][3.5-serum albumin]) within 72 hours prior to registration
Patients that indicate they have significant hair breakage or hair damage and associated hair loss from hair over-processing within the last 30 days due to peroxide applications, permanent hair coloring, bleaches, streaking, perms, relaxers and/or hair oxidative dyes.
anticipated to be severely immobilized for at least 24 hours after randomization
acute respiratory failure,
acute infection without septic shock,
acute rheumatic disorders
acute ischemic stroke with lower extremity hemiparesis or hemi paralysis
a condition requiring prolonged anticoagulation or anti-platelets
general conditions in which subjects are not suitable to participate in the study
Inclusion Criteria (adult):\n\n          -  Age 18 years or older\n\n          -  Female\n\n          -  Smoked ? 1 cigarettes per day for at least the past 6 months\n\n          -  Smoked on 20 days or more in the last month\n\n          -  Smoking status confirmed via cotinine verification strips\n\n          -  Resides with a child ? 10 years of age in the role of the child's parent or caregiver\n\n          -  Will agree to provide a urine sample at study enrollment\n\n          -  Will also agree to the child providing a urine sample at study enrollment and at\n             follow-up visits (for children who are not toilet trained, a diaper sample will be\n             collected in lieu of the urine sample)\n\n          -  Has a home address\n\n          -  Has a functioning home phone or cell phone\n\n          -  Provides written informed consent\n\n        Inclusion criteria (child):\n\n          -  < or = 10 years of age\n\n          -  Non-smoker -no cigarette use within prior 30 days to enrollment; however\n             experimentation with smoking (a puff) will not exclude the child\n\n          -  Lives in the primary home with the adult study participant at least 5 days a week\n\n        Exclusion criteria (adult):\n\n          -  Current or past 7 day use of Nicotine Replacement Therapy (NRT) or pharmacotherapy for\n             smoking cessation\n\n          -  Planning to move outside of Minnesota within the next 3 months\n\n          -  Have complete home smoking restrictions currently in place verified by the nicotine\n             dosimeter\n\n          -  Currently pregnant
Subjects must have at least two atypical nevi of >= 4 mm diameter and prior diagnosis of melanoma
Subjects should not have known allergies to cruciferous vegetables
Subject must not be a tobacco user or quit at least 6 months prior to the first administration of the BSE-SFN as tobacco has been found to interfere with the measurement of sulforaphane (SFN) metabolites
Potassium (K) within 2 x ULN
Chlorine (Cl) within 2 x ULN
Carbon dioxide (CO2) within 2 x ULN
Blood urea nitrogen (BUN) within 2 x ULN
Calcium within 2 x ULN
able to eat at least soft solids
Men with a history of at least one male sexual partner            \r\n* “Men” is defined as those documented “male” at birth (including male-to-female transgendered persons)
Normal anal cytological result, low-grade intraepithelial lesions (LSIL)/condyloma or atypical squamous cells of undetermined significance (ASCUS) result within 90 days prior to entry, and no by high-grade anal intraepithelial neoplasia (HGAIN) on biopsy
Anal cytological result of HSIL, atypical squamous cells suggestive of HSIL (ASC-H), or suggestive of invasive carcinoma at screening; or history of these results
HGAIN (e.g., anal intraepithelial neoplasia [AIN] 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3) or invasive carcinoma at pre-entry on biopsy, or participant has a history of invasive carcinoma or any prior anal cytology result of HSIL or ASC-H
It is encouraged that standard of care vaccinations are not offered during the 2 weeks preceding plasma HIV-1 RNA measurements, and that standard of care vaccinations are not administered at the same time as the study vaccine; routine vaccinations other than influenza vaccine that are administered after enrollment in the study should be given 1 month before or after HPV vaccination (or any visit where antibody titers are measured) during the study period. Influenza vaccination may be given within 1 week before or after HPV vaccination visits
Subject is currently receiving anticoagulation therapy other than acetylsalicylic acid
Prior splenectomy
Hemophilia
Prior receipt of Gardasil or other HPV vaccine
Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than that foreseen in the protocol.
if they test positive for oncogenic HPV infection, but display normal cervical cytology at their concluding HPV-015 study end visit;
if they are pregnant so that no cervical sample can be taken at their concluding HPV-015 study end visit;
Previous administration of any components of the vaccine.
Inclusion criteria:\n\n        Initial from phone interview:\n\n          -  Currently smoking 10-45 cigarettes per day for the past year;\n\n          -  Between the ages of 21 and 70 years;\n\n          -  In apparently good physical health with no unstable medical conditions including\n             seizures or cancer;\n\n          -  In stable and good mental health, i.e., currently do not experience unstable or\n             untreated psychiatric diagnosis, including substance abuse, as determined by the\n             DSM-IV criteria, during the past six months;\n\n          -  Not using any other tobacco or nicotine-containing products;\n\n          -  Not on methadone maintenance or stimulants such as ephedra; not a regular user of\n             street drugs and if uses occasionally, willing to abstain during the study; not taking\n             any drugs known to be P4501A6 substrates such as phenobarbital, rifampicin,\n             dexamethasone, ketoconazole, methoxsalen, pilocarpine, or tranylcypromine due to their\n             role in NNK metabolism;\n\n          -  Does not average more than 21 alcoholic drinks per week;\n\n          -  Willing to perform study activities such as having blood sample drawn, urine\n             collection, multiple clinic visits;\n\n          -  For female subjects of child bearing potential, not known to be pregnant or nursing,\n             or planning to become pregnant within next 12 months.\n\n        For enrollment in the Short-Term Trial:\n\n          -  Subjects who are generally healthy with liver enzyme and blood count values within the\n             ranges shown below based on blood samples drawn at the second screening visit.\n             Specifically:\n\n               -  White blood cells ? 3,000/mL\n\n               -  Total bilirubin ? 1.5 x upper limits of normal (ULN)\n\n               -  AST (SGOT)/ALT (SGPT) ? 2.5 x ULN\n\n               -  BUN and serum creatinine ? 1.5 x ULN\n\n        For enrollment in the Long-Term Trial:\n\n          -  Participated in the short-term trial and invited to participate in the long-term\n             trial;\n\n          -  Possess the GSTM1 null-null genotype;\n\n          -  Smoke 20 or more cigarettes/day with a cumulative smoking history of 20 or more\n             pack-years (one pack-year equals to smoking a pack of cigarettes a day for one year);\n\n          -  Normal liver enzymes based on blood sample drawn during 1 month wash-out;\n\n          -  Determined to be a good candidate for the bronchoscopy procedure by a primary care\n             physician.\n\n        Exclusion Criteria:\n\n          -  Subjects with uncontrolled hypertension, uncontrolled diabetes mellitus, unstable\n             coronary artery disease, history of cancer other than non-melanoma skin cancer, and\n             pregnant or lactating women will not be eligible.
Must be a former or current smoker
Must meet Eastern Cooperative Oncology Group (ECOG) performance status criteria of 0-1 (0 = fully active, must be able to carry out all pre-disease activities without restriction; 1 = restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature)
If patients are routinely taking a multivitamin supplement, they will be asked to continue the supplement as long as the amount of vitamin D in the supplement is not in excess of the RDA (recommended daily allowance); if they are not taking a multivitamin supplement, they will be asked to not start supplementation while on study
Subjects taking thiazides (which can decrease urinary excretion of calcium)
No known allergies to tree nuts (i.e. almonds)
18-40 years old,
current smoker
currently minimally active,
ambulatory,
willingness to attend weekly exercise intervention sessions at a SNAP Fitness location within 10 miles of the University of Minnesota campus,
abnormal electrocardiogram or V02 test results,
acute myocarditis or
pericarditis,
dissecting aneurism,
First allogeneic HSCT
Hypo- (calcium [Ca] < 8.5 mg/dL) or hyper-calcemia (Ca > 10.5 mg/dL)
Meets Mini International Neuropsychiatric interview (MINI) criteria for major depression, schizophrenia, bipolar illness, delirium or psychosis
Has moderate to severe depression according to Quick Inventory of Depressive Symptomatology-Self Rated 16 (QIDS-SR-16) scores of >= 11 AND a Hospital Anxiety and Depression Scale (HADS) Depression subscale score of >= 8
Korean American immigrant women
Aged 40-79
Residence in Minnesota
Possession of mobile phone with text-message function
Possession of active email account
Mammogram receipt within the past 2 years
Patients with operable focal or multifocal (T1-T3, stage II and IIIA invasive ductal carcinoma [all receptor phenotypes]), and who have completed neoadjuvant chemotherapy with a clinical complete response (by clinical examination)
Patient must be able to undergo stereotactic-vacuum-assisted breast biopsy with clip placement after completion of neoadjuvant chemotherapy
Patients with one or more of the following imaging criteria from any of the 3 imaging modalities after completion of neoadjuvant chemotherapy (NCT) are not eligible:\r\n* Mammogram with malignant appearing calcifications or mass > 1 cm; or\r\n* Ultrasound with a hypoechoic area > 2 cm; or\r\n* Breast MRI demonstrating a residual mass with rapid rise and washout type III kinetics.
Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram; women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial; for patients who have neoadjuvant therapy, eligibility for BCT is determined at completion of therapy; repeat mammogram +/- ultrasound (US) will be required at completion of neoadjuvant chemotherapy to determine eligibility for BCT
For patients with intratumoral hemorrhage (acute, subacute, or chronic) seen on hemosiderin-sensitive (gradient-echo) MRI, there must be at least 10 x 10 x 10 mm \measurable enhancement\ that is not obscured or distorted by magnetic susceptibility blooming artifact
The imaging abnormality must have been categorized as Breast Imaging-Reporting and Data System (BIRADS) level 1-4 lesion
There is documented concordance* between the initial breast imaging finding and the core biopsy pathology report; the core needle biopsy must contain FEA or IPWA, according to the local pathologist; (it is possible that the central pathology review which is done after the patient is registered on this protocol will have a diagnosis discrepant from that made by the original institution’s pathologist; in that case, the study team will communicate this to the original institution’s site investigator within one week of the date of the central pathology review having been finalized); patients may have a personal history of prior or concurrent fibroadenoma and a prior history of proliferative breast lesions with or without atypia\r\n* Concordance is a determination by the radiologist (or his or her covering provider) performing an image-guided core needle biopsy that the pathology report from this procedure corresponds to the imaging appearance of a given lesion and that the said lesion’s most representative portion has been sampled
Pathologic nipple discharge associated with IPWA (spontaneous bloody or clear persistent single duct discharge)
A BIRADS 5 lesion
Discordance between the initial breast imaging finding and the core biopsy pathology report
The presence of atypical ductal hyperplasia (ADH) on core biopsy
Sufficient leukemia or MDS specimen available for profiling from diagnosis or recurrence OR bone marrow aspirate or blood draw planned for clinical care anticipated to allow collection of minimum specimen for testing; OR clinical tumor profiling using rapid heme panel available in the medical record
Insufficient leukemia or MDS specimen available for profiling from diagnosis or recurrence; or bone marrow evaluations NOT planned for clinical care; or peripheral blast percentage < 20% AND clinical blood draw not planned; or patient sample did NOT already complete rapid heme panel leukemia profiling clinically
Patient is a postmenopausal woman, man, or premenopausal woman for whom standard endocrine therapy alone (tamoxifen, aromatase inhibitor [AI], with or without ovarian suppression or fulvestrant) is planned after FES-PET/CT is completed
The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN (or current ACRIN) approval
Patient has already had molecular profiling and patient has not yet started matched targeted therapy based on the report; approved molecular profiling include: \r\n* Foundation Medicine FoundationOne\r\n* University of California, San Francisco (UCSF) 500 Cancer Gene Panel\r\n* University of Washington OncoPlex Cancer Gene Panel\r\n* Children's Hospital of Philadelphia (CHOP) Comprehensive Solid Tumor Next Generation Sequencing (NGS) Panel\r\n* Other pre-approved molecular profiling test by study principal investigator (PI)
The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN approval as outlined
Capable of making informed decisions regarding his/her treatment
Liver nodule previously treated with trans-arterial or thermal ablation
Scheduled or planned radical prostatectomy with PLND. Cohort B Only: [Enrollment is complete; No longer recruiting subjects]
Scheduled or planned percutaneous biopsy of at least one amenable lesion.
Has lesions involving chest wall
Renal dysfunction for which cisplatin dose would be considered unsafe
Willing to come to MSK main campus for baseline and follow-up MP-MRIs
Gynecologic Oncology Group (GOG) performance status =< 2
Participation in other research protocols does not exclude a patient from participation in this study
Renal insufficiency with plasma creatinine > 1.6
Patient is incontinent of urine or stool (which would make them unable to tolerate lying still for 60 minutes)
Claustrophobia
No indication of distant metastases (M0)
Cancer located on a site that may not be convenient or accessible for imaging with the current version of the RCM device (gingivobuccal region, back of the oral cavity, back of the tongue, floor of the mouth, deep under the tongue, etc.)
ADULTS
CHILDREN
ADULTS
CHILDREN
Those with GBM but suspected to have pseudoprogression at any time after completion of chemoradiation can enroll in cohort C
For cohort C, patients with GBM who have completed standard temozolomide + radiation and have suspected pseudoprogression can enroll; there is no time frame from completion of chemoradiation as pseudoprogression is increasingly recognized at later time points
High or mixed affinity binders (alanine [Ala]/Ala or Ala/threonine [Thr]) based on genotyping result from PBR affinity test; this blood test will be performed as part of the screening process after consent has been obtained
Negative technetium 99-m methylene diphosphonate (MDP) or F-18 PET bone scan for skeletal metastasis
Concurrent radiotherapy prior to the performance of both CMR studies, however consolidative radiotherapy after the completion of DOX and after the acquisition of the second CMR study is acceptable
T1, T2, T3, or T4 primary
Conventional chest abdomen and pelvis CT images demonstrating recurrent tumor must be submitted within 21 days from acquisition to the American College of Radiology (ACR) Core Lab
The patient is ?21 years old,
The patient has a lung nodule identified on chest CT and is a candidate for elective EMN bronchoscopic evaluation as determined by the treating pulmonologist,
The size of the target nodule, as measured at its greatest diameter, is between 1-3cm,
There is a predetermined plan to pursue stereotactic body radiation therapy (SBRT) in the event of a nondiagnostic study procedure in patients with a nodule within SPiNPerc range (i.e. The patient would not go on for a CT guided TTNA), OR There is a predetermined plan to pursue stereotactic body radiation therapy (SBRT) in the event of a nondiagnostic study procedure in patients where the target nodule is within a region considered to be not accessible to a percutaneous approach as determined by the radiology core lab and thus would prevent a confirmatory tissue diagnosis before SBRT.
Participants must have a pre-operative standard mammogram with or without ultrasound; these may be performed at outside institutions but must be reviewed at Brigham and Women's Hospital/Dana-Farber Cancer Institute (BWH/DFCI)
Participants must be candidates for neoadjuvant therapy (NAT) upfront
Participants with a known BRCA 1 or 2 mutation
Previous exposure to OTL38
Known sensitivity to fluorescent light
Patient capable of making informed decisions regarding his/her treatment
Enrolled in study part #1
Diagnosis must be documented by histology or cytology from brushings, washings, or needle aspiration of a defined lesion but not from sputum cytology
Able to produce 45mL of urine
Women undergoing colposcopy for an abnormal Pap test, positive HPV test or history of cervical dysplasia (cervical intraepithelial neoplasia [CIN] or adenocarcinoma in situ [AIS])
Minimum of at least three discrete metastatic lesions in the bone and/or soft tissue amenable to whole body PET imaging per the judgment of study radiologist
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Participants must have a pre-operative standard mammogram with or without ultrasound; these may be performed at outside institutions
Subjects with evidence of iron overload with a pre-study ferritin level greater than 370 ng/ml and percent saturation of transferrin level greater than 40%; patients with lab values above these limits may be included in the study if documented hematology consultation rules out hemochromatosis, idiopathic or iatrogenic iron overload
Occlusive main portal vein thrombosis
Presence of biliary-enteric anastomosis
Very young children who need sedation or anesthesia will be excluded from the study; there will be no gender or race-ethnic restrictions
Need of sedation or
Claustrophobia
Hemosiderosis/hemochromatosis
Patients of all ethnic and gender groups will be included; protocol accrual will be reviewed annually to include a determination of minority and gender representation; if accrual demonstrates under-representation of any group with comparison to disease incidence in that group, appropriate measures will be undertaken to increase participation of patients of that minority or gender group
Symptomatic osteonecrosis (ON) of the femur or proximal tibia with MR signal abnormalities that involve more than 50% of the respective joint surface, but no evidence of epiphyseal collapse
There will be no gender/race-ethnic restrictions
Need for sedation or anesthesia
Claustrophobia
Undergoing colposcopy for the diagnosis of cervical cancer and LEEP or cervical biopsy for the treatment of premalignant cervical dysplasia
Location: supratentorial
Individuals with plasma creatinine > 180 umol/L
Individuals who are unable to comply with photosensitivity precautions
Patients undergoing :\r\n* Surgical laryngeal, esophageal, and tracheal endoscopy (“panendoscopy”)\r\n* Fiberoptic esophagoscopy\r\n* Intubation\r\n* Office-based nasal or laryngeal endoscopy
Planned SRT for recurrence after primary prostatectomy.
Willingness to undergo radiotherapy.
Female participants of childbearing age must not be lactating due to theoretical potential harm to the infant from exposure to radiation
Patients with peripheral lung lesions 1-5 cm in size identified on chest CT with the intention to undergo bronchoscopic evaluation and biopsy; the decision to pursue biopsy will be made by the treating physician and agreed upon by the patient
Are physically unable to tolerate flexible bronchoscopy or moderate sedation as determined by the bronchoscopist
Subjects must be eligible for resection as determined by the operating surgeon
Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
With current diagnosis of major axis I psychiatric disorder (Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV), major depression, bipolar disorder, or schizophrenia, as per medical records or patient report
With evidence of visual or auditory impairment that would preclude completion of the assessments, as per medical records or patient report
Patient with either a single focus or multiple foci (multi-isocentric planning) of disease in the thorax amenable to SBRT with at least one focus with at least 1.5 cm or larger in its largest diameter
Patients with minimal FDG-avidity localized to the planned treatment target (e.g. maximum standardized uptake value [SUV] < 4.0)
Patient would require anesthesia for the study
Unmanageable claustrophobia
The patient is found to have unfavorable anatomy to indicate that stereotactic biopsy could not be safely performed.
Ability to lie still for PET scanning
Subjects who require sedation to participate will be excluded
Presence of erosive esophagitis
Unable to tolerate sedation due to medical comorbidities
Prisoner
Cannot receive furosemide
Cannot receive furosemide
Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy including focal ablation techniques (high-intensity focused ultrasound ablation [HiFu])
Individuals with known or suspected substance abuse, obtained by self-reporting.
Currently receiving immunotherapy
Be capable of understanding the investigational nature of the study and all pertinent aspects of the study
Have metallic hardware in the lower extremity which is MR compatible however would create too much artifact for MR examination
Are unable to lay still in the MR scanner for length of examination
Contraindication to furosemide administration including prior allergy or adverse reaction to furosemide or sulfa drugs; (Note: This exclusion criteria can be removed if furosemide is omitted as part of the PET imaging protocol if a second-generation scatter correction is available for the used PET device)
Claustrophobia
Histological diagnosis of NET
Planned administration of any NET therapy between scan 1 and 2, except for short acting octreotide
Ability to undergo MR imaging, tolerate breath hold procedures and follow direction during the imaging process
HEALTHY CONTROLS: No contraindications for MR or PET imaging
HEALTHY CONTROLS: Scheduled to undergo a hysterectomy and/or salpingo-oophorectomy
Do not fit age criteria
Prisoners
Patients with known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts
Patients with a history of anaphylactic allergy to Definity, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock
Patient may be of any race/ethnicity
Capable of complying with study procedures and communicating with study personnel
Subjects who lack fitness for flexible bronchoscopy as determined by the physician performing the bronchoscopy before the procedure
Subjects on anticoagulation (other than aspirin) whom cannot have their anticoagulation held for the procedure due to other clinical reasons (i.e. recent cardiac stent placement)
Subjects must have neurological findings (i.e. loss of consciousness, paresis, cranial neuropathy, etc.), and/or radiological abnormalities in the brain (neoplastic or non-neoplastic in nature)
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Referred to the Washington University School of Medicine for conditions necessitating surgery to include at least a unilateral oophorectomy
Members of all races and ethnic groups are eligible for the study
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
SUB-STUDY I: No prostatectomy scheduled more than 12 hours post imaging
Confirmed presence of somatostatin receptors (type 2) on technically evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired within 6 months prior to screening (Visit 1) and showing minimally two lesions in at least one of the key organs; these images shall be available to be sent to the imaging core lab electronically to ascertain quality and admissibility
Subject who have received treatment of any somatostatin analogue, including Somatuline® Autogel® /Depot®, Sandostatin® LAR within 28 days, and Sandostatin® within 24 hours prior to first 68Ga-OPS202 administration
Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration; those that have had iodinated intravenous contrast for CT imaging within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration
Subjects weighing > 350 pounds (lbs.) (weight limit for scanner table), or unable to fit within the imaging gantry
Women with renal failure or insufficiency
Presence of a thyroid nodule that is amenable to ultrasound guided fine needle aspiration
Subjects weighing > 350 lbs; (weight limit for scanner table), or unable to fit within the imaging gantry
Lactation should be suspended for at least two days following the administration of [18F] FAZA to the mother, because of the unknown but potential risk for adverse events in nursing infants secondary to administration of the radionuclide to a lactating woman.
Able to remain motionless for up to 30-60 minutes per scan
Lack of availability for follow-up assessments
Subject must have a suspected SCLC or NSCLC
Subject is a pregnant or nursing female; exclude the possibility of pregnancy:\r\n* By testing (serum or urine betaHCG) within 24 hours before contrast agent administration, or\r\n* By surgical sterilization, or\r\n* Post-menopausal, with minimum one (1) year history without menses
Subject has an acute psychiatric disorder or is cognitively impaired
Subject is using or is dependent on substances of abuse
Clinical symptoms of peripheral neuropathy noted in medical record and suspected to be secondary to taxane-based therapy
Localized SCCHN.
>18 years old.
Minors will be excluded
Prisoners and members of other vulnerable populations will be excluded from this study as these populations will not provide any additional unique information or uniquely benefit from the study
Claustrophobia
Patient is capable of complying with study procedures
Be willing to be injected with 11C-methyl-L-tryptophan (C11-AMT)
Has had prior monoclonal antibody (mAb) targeting immune checkpoint proteins, for distant metastatic melanoma and have progressed or have developed intolerable side effect
TOBACCO PRODUCT USERS
Inability to place an IV catheter or draw blood for any reason
Must not have had an injection of a radioisotope 24 hours prior to exam
Patient who require reduced intravenous contrast dose based on the Department of Radiology contrast policy
Any ethnic group
Patient with metastatic disease (from primaries other than lung) who have suspicious mediastinal or hilar LN that require sampling
Cutaneous melanoma with Breslow depth > 1 mm or melanoma Breslow depth of 0.76 – 1.00 mm in setting of ulceration, extensive regression
Mitotic rate >= 1/mm^2
Presence of angiolymphatic invasion
Deep positive margin
No known allergies to contrast material
No known allergies to contrast material
Known allergies to contrast material
Current enrollment in a therapeutic clinical trial
HER2 immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) ordered on core biopsy, if biopsy indicates invasive cancer; Oncotype DX or other deoxyribonucleic acid (DNA) testing performed on core biopsy or not requested
Any systemic neoadjuvant (or preoperative) therapy between the core biopsy and lumpectomy
Risk of poor cosmetic outcome after initial lumpectomy and possible additional excision, as assessed by Dr. Sharma
Recommendation for mastectomy based on radiology
Presence of visual impairment to an extent that the patient is unable to complete the computer testing
PART B ONLY
Intracoelomic primary tumors or tumors expected to drain to an intracoelomic SLN
Subjects with risk factors for esophageal malignancy including Barrett’s esophagus and gastroesophageal reflux disease (GERD)
Subjects with known or suspected esophageal varices
Cases without prior biopsy will be chosen based upon consensus of a MD Anderson faculty neuroradiologist and neurosurgeon for high probability of representing a glioblastoma
Children
Definitive/gross total lesion resection
Able and willing to undergo anal cytology, anal molecular testing, and high resolution anoscopy with targeted anal biopsies
Highly suspicious pulmonary nodule(s), defined as distinct nodule with a diameter of ?8mm in its largest dimension
Willing to participate in all aspects of study protocol for duration of study
Untreatable life-threatening arrhythmias
Acute respiratory failure with hypercapnia (unless the patient is intubated and ventilated)
Bullae >5 cm located in vicinity of target nodule or tunnel
ASA class > 3
Ability to lie still for PET scanning
Already scheduled to undergo biopsy
Active prostatitis
pT3 (seminal vesicle invasion or extraprostatic extension), or
Radical prostatectomy within one year of enrollment
Good operative candidate
Previous exposure to OTL38
In the case of cryotherapy, external beam radiation, or high-intensity focused ultrasound therapy (HIFU) the procedure will have occurred at least one year in the past; in the case of brachytherapy, treatment will have occurred at least 2 years in the past to eliminate patients with so-called “prostate-specific antigen (PSA) bump”
Less than 1 year since cryotherapy, external beam radiation therapy, or HIFU, or 2 years since brachytherapy; does not meet above criteria of suspicious PSA elevation
Individuals who are considered to be mentally disabled will not be recruited for this study
Subjects who have difficulty lying flat on their back for extended periods of time
Patient is being considered for SBRT
Patient's malignancy is consistent with well differentiated neuroendocrine (carcinoid) histology
Individuals who are considered to be mentally disabled will not be recruited for this study
Women, children, fetuses, neonates, or prisoners are not included in this research study
Good operative candidate as determined by the treating physician and multidisciplinary team
Main or segmental portal vein thrombosis
Inability to lay flat for at least 2 consecutive hours
Are in good health (other than having breast cancer) and can lie still in a prone position for 45 minutes inside MRI scanner
Have engaged in occupations or activities which may cause accidental lodging of ferromagnetic materials (e.g. iron), or have embedded metal fragments from military activities
Claustrophobic (i.e. feeling very anxious in a confined small space)
Willingness to participate in collection of pharmacokinetic samples
Is in an intensive care setting
Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives such as:\r\n* Mental illness\r\n* Drug abuse
Obesity that limits obtainment of acceptable images
HEALTHY VOLUNTEER: Be able to comprehend the full nature, purpose and risks of the study
HEALTHY VOLUNTEER: A history of chest wall trauma or surgery, or dermatologic disorders, which could be expected to disrupt lymphatic drainage of the chest wall
HEALTHY VOLUNTEER: Lymphedema or chronic edema
HEALTHY VOLUNTEER: Patients with a history of anaphylactic allergy to eggs or egg products, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock
HEALTHY VOLUNTEER: Significant axillary, supraclavicular, or other chest wall palpable adenopathy
Suspected but pathologically unconfirmed diagnosis of Erdheim-Chester disease or Langerhans cell histiocytosis or other histiocytic disorder on the basis of clinical diagnosis, radiologic features, or findings from prior biopsies OR
Confirmed diagnosis of Erdheim-Chester disease or Langerhans cell histiocytosis or other histiocytic disorder and requiring additional diagnostic imaging and biopsy to determine mutational status in order to determine therapeutic options
Known sensitivity to 18F FSPG or components of the preparation
Investigator precludes participation for scientific reasons, for reasons of compliance, or for reasons of the patient’s safety
Patient must be seen at the St. Louis Children’s Hospital Neurofibromatosis (NF) Clinic
Diagnosis of NF1
Normal tone on clinical exam
Poor kidney function defined as a known renal disease or elevated blood urea nitrogen (BUN) and creatine
Requiring intubation for anesthesia
Patient scheduled to undergo thoracic RT at Duke University to a dose of at least 20 gray (Gy)
Subject cannot hold his/her breath for 15 seconds
Healthy volunteers for the Dosimetry Studies Arm must not\r\n* Have a history of cardiopulmonary conditions requiring any treatment or medical intervention\r\n* Be a current smoker
An indeterminate pulmonary nodule (IPN) (7–30 mm diameter) on CT, or an indeterminate lung mass (> 30 mm diameter), without prior examinations that establish that the lesion has been stable for two or more years
Untreated; OR
For patients who do not have a tissue diagnosis:\r\n* Non-oncologic severe co-morbidities suggesting a life span of less than two years if not treated, as determined by the potential subject’s treating physician\r\n* If severe co-morbidities are present, the treating physician should indicate that a life span of 2 years is expected if treatments are effective\r\n* This exclusion is to prevent loss of the needed 2 year CT follow-up to establish a benign diagnosis for lesions lacking tissue diagnosis if extremely fragile subjects are enrolled and then experience an untimely, unrelated death
Subject weighs more than 450 pounds or otherwise cannot be safely fit into the imaging system
Treatment with Sandostatin long-acting release (LAR) within 4 weeks, subcutaneous (SQ) Octreotide within 12 hours, or Lanreotide injection within 8 weeks of Ga-68 DOTATOC PET/CT (+/-5%)
Able to have bronchoscopic placement of Calypso transponders as confirmed on a recent (within the past 8 weeks) CT scan
Able to breathe regularly for gated treatment, as measured with the Varian Real-time Position Management (RPM) system
Bronchiectasis in the region of the intended implantation
Deemed unable to safely undergo or tolerate flexible bronchoscopy as per institutional guidelines
Unable to tolerate anesthesia or sedation
Enrolled in any other clinical studies the investigator believes to be in conflict with this investigation
Posterior lesions that would be > 19 cm distance from Calypso detector plate
Willingness to undergo biopsy
Willingness to travel to National Institutes of Health (NIH) for follow-up visits
Any condition that would preclude the subject from getting the required biopsy as stated in the protocol
Participants/volunteers from the vulnerable population, as defined by 45 Code of Federal Regulations (CFR) 46
Patient is judged by the investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
Hemorrhagic cystitis or active prostatitis
Subject is hospitalized in the intensive care unit
CHILD: If applicable, willingness of the patient to shave axillary (armpit) hair
CT scans showing involvement of 1 or more clearly demarcated lesions with a long axis > 1.5 cm and short axis >= 1.0 cm
Uncontrollable claustrophobia
Both sporadic desmoid tumors and those associated with familial adenomatous polyposis (FAP) syndromes will be included
Known or suspected diagnosis of intracranial glioma with substantial non-enhancing regions as assessed by contrast enhanced MRI; for the purposes of this study, gliomas with substantial non-enhancing regions are defined as having contrast-enhancing volumes of less than 80% of the total estimated tumor volume; gliomas that do not have any contrast-enhancing regions are eligible for this study
Any race
Has lesions involving chest wall
The patient must report persistent cognitive problems following the initiation of chemotherapy, defined as impairment being one or more standard deviations above normative data on our two scales of subjective cognitive dysfunction; this is defined as a total score of 45 or higher on the Cognitive Failure Questionnaire, and a T-score of 60 or higher on the Frontal System Behavioral Scale Questionnaire
Patients must agree to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database, as evidenced by signing the informed consent form
Current or past major psychiatric illness (e.g., schizophrenia, bipolar affective disorder)
Color blindness (cannot complete Delis–Kaplan Executive Function System [D-KEFS] Stroop test)
Prior development of positive human anti-mouse antibody response (HAMA) or human anti-human antibody response (HAHA)
Positive human anti-hu3F8 antibody titer
Although not mandated by the protocol, the results of the computed tomography (CT) scans and labs (complete blood count [CBC], comprehensive metabolic panel [CMP]) that are performed as part of the standard work up should be available and should have been done within 2 months prior to study entry
Any patient who has had exposure to mouse or chimeric (human/mouse) immunoglobulin and has antibody to the M5A
Patient must be status post near total thyroidectomy for differentiated thyroid cancer without known distant metastases and who are planning to undergo routine remnant thyroid tissue ablation with I-131
Participants with persistent asthma as defined by the National Heart, Lung, and Blood Institute
Participants with actively treated thyroid disease who still have a portion or all of their thyroid gland
Participants with a history of Graves disease, goiter, thyroid nodules, Hashimoto’s thyroiditis, post-partum thyroiditis, type 2 amiodarone-induced thyrotoxicosis, or subacute thyroiditis who still have a portion or all of their thyroid gland
Participants who are taking a beta blocker at the time of the investigational exam are excluded
Biopsy reviewed by a University of Miami pathologist
Greater than 4 cores positive, of any Gleason score, on the University of Miami (UM) review
Bilateral hip replacement
Prisoners
For the clinical diagnosis of NF1 all study subjects must have at least two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):\r\n* Six or more cafe-au-lait spots (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in postpubertal subjects)\r\n* >= 2 neurofibromas or 1 plexiform neurofibroma\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Subjects must have:\r\n* Diagnosis of NF1 with a lesion concerning for MPNST\r\n** Criteria include pain, growth of a known plexiform neurofibroma, abnormality on functional imaging study (FDG-PET) or change in clinical exam OR\r\n* Diagnosis of NF1 with a histologically confirmed MPNST
Subjects must be eligible for and willing to participate and sign consent for National Cancer Institute (NCI) protocol 08-C-0079: Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type 1, for the clinical evaluation necessary for this study
Eastern Cooperative Oncology Group (ECOG) =< 3; subjects who are wheelchair bound because of paralysis will be considered “ambulatory” when they are up in their wheelchair; subjects have to be able to travel to the NIH for evaluations
Any woman with a confirmed preoperative diagnosis of cervical AIS, including co-existing squamous cervical intraepithelial neoplasia (CIN) and/or microinvasive cancer
Women undergoing cold knife cone (CKC) of the cervix at MD Anderson
No serious associated psychiatric illnesses
Center of suspicious lesion is not deeper than 1.5 cm
Institutionalized subject (prisoner or nursing home patient)
Patient is judged by the investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
Any patient with tachycardia defined as heart rate (HR) of 100 or higher at the day of SPECT will not be eligible for this study
Second- or third-degree atrioventricular (AV) block
Adult (age ? 18 years) subjects with peripheral lung lesions that are <1.5 cm in size who are planning to undergo percutaneous image guided lung biopsy as part of their routine medical care.
Uncorrectable coagulopathy prohibiting biopsy. (INR > 1.5 and/ or platelets < 50,000)
Subjects of all races and ethnic origins will be recruited
The study population may include illiterate persons and University Hospital (UH)/Case employees if they meet other inclusion criteria; the consent process for these potential participants will be conducted according to Institutional Review Board (IRB) guidelines
Prisoners and members of other vulnerable populations will be excluded from this study; the subject selection population will not regularly include prisoners and other vulnerable population members as these populations will not provide any additional unique information to or uniquely benefit from the study; non-English speaking population will be excluded from the study
Presenting with one of the four conditions specified below
Fludeoxyglucose F 18 (FDG) avid cancers
Neurologic disorders (dementia)
Inflammatory disease (for example fever of unknown origin, vasculitis, osteomyelitis)
GROUPS 1, 2, AND 3: \All participants” described above
Participants with concurrent clinical diagnosis, evidence of suspected hemochromatosis, or other diseases of iron metabolism (i.e., iron overload)
Pregnant women are excluded from this study because there is an unknown, but potential risk, for adverse events, as small animal trials have linked ferumoxytol administration (at very high doses) to birth defects (e.g., soft-tissue malformations and decreased fetal weights); it is not known whether ferumoxytol is present in human milk; breastfeeding, however, should be discontinued if the mother receives ferumoxytol while nursing
Participants with any contraindications to gadolinium-based contrast agents
Skeletal x-ray film or MRI confirmation of absent skeletal metastases if bone scan findings are equivocal
Patients with known sensitivity or contraindication to any of the component of 89Zr-DFO-trastuzumab (89Zr or desferrioxamine [DFO] or trastuzumab)
Planned craniotomy and resection or biopsy
Willing to sign release of information for any radiation and/or follow-up records
Unable to undergo an 18F-DOPA PET scan (e.g. Parkinson’s disease, taking anti-dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists; NOTE: other potentially interfering drugs: amoxapine, amphetamine, benztropine, buproprion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline; if a patient is on any of these drugs, list which ones on the on-study form
Ability to hold the breath for 10 seconds
Ability to complete questionnaire(s) by themselves or with assistance
Unable to undergo an 18F-DOPA PET scan (e.g. Parkinson’s disease, taking anti-dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists); NOTE: other potentially interfering drugs consist of: amoxapine, amphetamine, benztropine, bupropion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline; if a patient is on any of these drugs, list which ones on the on-study form
Clinical instability
Asthma, wheezing or breathing problems
Medical condition\r\n* Renal transplant\r\n* Active or ongoing kidney disease or kidney failure, including but not limited to: functioning renal transplant, solitary kidney, proteinuria, multiple myeloma, acute and chronic nephropathies\r\n* Myasthenia gravis\r\n* Thyroid cancer or overactive thyroid\r\n* Severe congestive heart failure
Ventilator
Unable to stand without assistance
Mentally/physically impaired/unresponsive
Participants must have clinical characteristics consistent with IBC, characterized by a rapid onset of clinical findings exemplified as diffuse edema and erythema of the breast, often without a palpable mass
Healthy volunteers
Evidence of prostate cancer recurrence (biochemical relapse by the Phoenix definition, enlarging palpable prostatic abnormality, imaging evidence strongly suggestive of local failure)
GENERAL POPULATION:
Patient is judged by the investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
Females with tattoos on either or both breasts
Females with nipple piercings on either or both breasts
Females with skin piercings (aka microdermal anchor surface or microdermal piercings) in either or both breasts
Symptomatic distal rectal stenosis
Prisoners are not eligible
Claustrophobia
Preexisting language or developmental disorder that would limit ability to cooperate with testing (as determined by the P.I. or treating physician after interviewing potential subject and his/her family; for example, a child may be excluded if he/she has confirmed or suspected autism spectrum disorder, dysarthria, dyslexia, lisp, hypotonia, or other age inappropriate speech development)
Ability to exercise on a treadmill or stationary cycle
Claustrophobia
Inability to exercise on a treadmill or stationary cycle
Breast size per visual inspection to fit within the ultrasound tomography (UST) ring array
Subjects with any type of ferromagnetic bioimplant that could potentially be displaced or damaged
Subjects with permanent tattoo eye liner (may contain metallic coloring)
Subjects that exhibit noticeable anxiety and/or claustrophobia
Subjects who cannot adhere to the experimental protocols for any reason, or have an inability to communicate with the researcher
Acute renal dysfunction due to the hepato-renal syndrome or in the perioperative liver transplantation period
The patient has an orbital mass which needs further diagnostic evaluation before treatment or for monitoring
Known right to left cardiac shunt, bidirectional or transient
Claustrophobia
The patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained, in accordance with institutional policies approved by the US Department of Health and Human Service
Willingness to comply with required follow up perometer and BIS measurements and completion of LEFT-BC questionnaire
Any patient who will not be returning routinely for follow-up at Massachusetts General Hospital (MGH) or Dana-Farber/ Harvard Cancer Center (DFHCC)
Any patient with a current case of cellulitis
Primary or secondary brain tumor (enhancing mass lesion +/- nonenhancing abnormality), known or suspected, located near (< 2 cm) any portion of the motor cortex, motor pathway, language cortex, or language pathway, or other clinically relevant brain areas, as determined on anatomical images
Lesions of 5 cm or less in maximum diameter
Less than 5 mm distance to a structure (gastrointestinal [GI] or biliary tract), that cannot be protected from the ablation injury with technical modifications such as hydro or air dissection\r\n* This will not be considered exclusion when IRE is used
Patient with more than 3 tumors treated with any percutaneous ablation
Known hyperthyroidism
Abnormal thyroid function, such as untreated clinical diagnosis of hypothyroidism, hyperthyroidism, or other thyroid disease
Claustrophobia
Urinalysis abnormalities will not preclude the patient from being enrolled and studied
Gamma-glutamyl transpeptidase (GGT) less than 4.0 times below or above the upper or lower limit range
Lactate dehydrogenase (LDH) less than 4.0 times below or above the upper or lower limit range
Urea nitrogen less than 4.0 times below or above the upper or lower limit range
Complete blood count (CBC) with platelets less than 4.0 times below or above the upper or lower limit range
Blood urea nitrogen (BUN) less than 4.0 times below or above the upper or lower limit range
Adult subjects with brain, head and neck, and skull base tumors receiving external beam proton radiotherapy on gantry at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (MGH)
Any condition conflict based on the investigation’s clinical judgment that would prevent the patient from completion all trial assessments and visits
Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the MR
Physical exam, complete blood count (CBC) and multiphasic (including electrolytes, blood urea nitrogen [BUN], creatinine, total bilirubin, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) must be done within 28 days of PET imaging, but eligibility is not restricted by these results; the CBC and multiphasic may be drawn at the time of imaging
The medical monitor, Dr. Lois Ayash, at minimum, may discuss the research protocol with the investigators, interview human subjects, and consult with others outside of the study about the research, shall have authority to stop a research protocol in progress, remove individual human subjects from a research protocol, and take whatever steps are necessary to protect the safety and well-being of human subjects until the Institutional Review Board (IRB) can assess the monitor’s report; shall have the responsibility to promptly report their observations and findings to the IRB or other designate official and the Human Research Protection Office at the Department of Defense; the monitor may also observe recruitment and enrollment procedures and the consent process for individuals, groups or units overseeing study interventions and interactions, reviewing monitoring plans and reports; overseeing data matching, data collection and analysis
All participants under the care of St. Jude physicians with known or suspected neoplastic disease are eligible for participation
Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Ability to understand and carry out subject instructions
Members of all races and ethnic groups will be included
Subject agrees to complete follow up visit
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness
Subjects with known hepatic insufficiency or cirrhosis
NORMAL ADULT VOLUNTEERS
Ability to lie motionless for up to 5 minutes
PATIENT VOLUNTEERS
Diagnostic findings from prior mammography highly suggestive of breast malignancy (Breast Imaging-Reporting and Data System [BI-RADS] [R] category 4) or known biopsy-proven malignancy (BI-RADS [R] category 5)
Patient Volunteers: Ability to lie motionless for up to 5 minutes
PATIENT VOLUNTEERS/CONTRAST ENHANCEMENT SUB-GROUP
Suspected or known biopsy-proven malignancy (BI-RADS [R] category 4 & 5)
Patient Volunteers/Contrast Enhancement Sub-group: Ability to lie motionless for up to 5 minutes
NORMAL ADULT VOLUNTEERS:
PATIENT VOLUNTEERS:
PATIENT VOLUNTEERS/CONTRAST ENHANCEMENT SUB-GROUP:
Patient Volunteers/Contrast Enhancement Sub-group: Positive urine pregnancy test or currently breast-feeding
Patient Volunteers/Contrast Enhancement Sub-group: Inability to understand the risks and benefits of the study
Claustrophobia
Known reaction to gadopentetate dimeglumine (Gd-DTPA)
Subjects with premalignant lesion, or potentially premalignant lesion, of the oral cavity mucosa (leukoplakia or erythroplakia)
Persons with any other condition (such as lichen planus, Fanconi anemia, heavy tobacco use, etc) making them at higher risk for oral cancer development
Aged 18 to 65 years inclusive
Be in good general health
5 or more decayed, untreated dental sites (cavities)
Non-smoker
Appear to be in general good health
Less than 20 teeth (excluding third molars)
An interval of > 6 weeks between the biopsy and MRSI
Metals or any conditions (e.g. hip prosthesis) that can distort the local magnetic field
Radiographic diagnosis: Patients must have a brain tumor (including, but not limited to high grade gliomas, low-grade gliomas, primitive neuroectodermal tumors, ependymomas) or residual abnormality (e.g. post-operatively or post-radiation) that is measurable or evaluable on standard MRI or computed tomography (CT)
Any patient with permanent braces, permanent retainers or nonferrous implant that, in the judgement of the principal investigator, would interfere with obtaining spectroscopy in the area of the tumor
African-American or white men (Hispanic or non-Hispanic)
Have an undiagnosed suspicious solid or mostly solid thyroid nodule.;
Have received recommendation for and are scheduled for an ultrasound guided FNAB, ultrasound guided core biopsy, excisional biopsy, lobectomy or complete thyroidectomy of at least one thyroid nodule.
Are prisoners;
Have a condition or impediment (i.e., insect bites, poison ivy, open sores, chafing of the skin, scar, tattoos, moles, etc.); that could interfere with the intended field of view (within one probe length or 4 cm of the nodule),
Nodule to be biopsied is greater than 3.0 cm in maximum diameter;
Have an acute or a chronic hematoma and/or acute ecchymosis of the thyroid;
Is experiencing photo-toxicity or photo-sensitivity or is undergoing treatment for a photo-sensitive condition such as porphyria or lupus erythematosus;
Patient has previously participated in this study.
Prisoners and members of other vulnerable populations will be excluded from this study; non-English speaking population will be excluded from the study
Minors will be excluded
Enrollment into this study may occur in tandem with other clinical therapeutics trials occurring at Vanderbilt University Medical Center (VUMC) as long as this trial does not violate protocol or inclusion criteria of that study
Before the administration of Lymphoseek, has received any radiopharmaceutical within 7 radioactive half-lives of that radiopharmaceutical
Patient is ? 18 years old at the time of the drug administration (Patient may be male or female of any race / ethnicity.)
Patient is capable of complying with study procedures
Patient is able to remain still for duration of imaging procedure (about one hour)
confirming the subject is post menopausal, with a minimum 1 year without menses
Any known psychiatric disorder other than mild depression or anxiety that may affect adherence to the study requirements.
Individuals weighing more than 300 lb; (this is the weight limit of the scanner table)
Subject enrolled into the protocol BDS-USHPV and identified as eligible for the longitudinal protocol • Subjects enrolled into protocol BDS-USHPV with a baseline colposcopy and biopsy procedure and not treated.
Subjects with prior complete or partial hysterectomy involving removal of the cervix
Evidence of calcifications on mammogram
have implanted prosthetic heart valve,
neurostimulator,
have engaged in occupations or received orthodontic work which may have caused lodging of ferromagnetic materials in the body;
are claustrophobic;
are diabetic;
Incarcerated or otherwise institutionalized at time of enrollment
Refusal to have an IV placed for injection
Gamma-glutamyltransferase (GGT) > 2.5 x ULN
Magnesium or potassium lower than the normal institutional values
Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
Members of all races and ethnic groups will be included
Medical contraindications to low anterior resection or abdominoperineal resection
Subjects with concurrent clinical diagnosis of evidence of active iron overload defined by the following 1) ferritin >= 250 ng/mL in men or >= 200 ng/mL in women AND 2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as percent, >= 45%
Subjects with known hepatic insufficiency or cirrhosis as determined by either a prior diagnosing physician or at review at initial consultation; these disease entities do not have formal associated lab values and are thus a clinical diagnosis by the prior aforementioned physician
Evaluated by radiation oncologist to be appropriate SBRT candidate and scheduled to undergo SBRT as part of their care
Adult patients who have a presumed diagnosis of advanced stage epithelial ovarian, fallopian tube, or peritoneal\r\n* Pelvic mass and/or omental caking with Ca-125:carcinoembryonic antigen (CEA) ratio 25:1
Packed cell volume (PCV) >= 30 (with or without transfusion)
Patients will be deemed not candidates for surgical resection and therefore ineligible for this study based on imaging criteria alone, if CT chest, abdomen, pelvis demonstrates:\r\n* Any disease in the thoracic cavity >= 1 cm\r\n* Any suprarenal lymphadenopathy >= 1 cm\r\n* Liver metastases >= 1 cm\r\n* Disease in the porta hepatis or gallbladder fossa >= 1 cm\r\n* Pleural effusion >= 50% volume of the chest cavity on chest x-ray\r\n* Omental extension to the stomach, spleen, or lesser sac\r\n* Extension to the pelvic sidewall (this criteria may also be assessed on physical examination\r\n* Involvement of the root of the mesentery
Patient declines procedures that might be necessary for optimal primary cytoreduction (i.e. colostomy or splenectomy)
Subjects with cervical or Siewert 3 esophageal carcinoma, that are recommended by the multi-disciplinary tumor board to have treatment other than tri-modality chemo-radiation therapy (RT) followed by esophagectomy
Medical contraindications to esophagectomy
Subjects with evidence of iron overload
Subjects with known hepatic insufficiency or cirrhosis
Has a known hypersensitivity to indocyanine green (ICG), methylene blue and Technetium TC-99m colloid (99mTc-colloid)
Not currently on ADT
Patient is capable of complying with study procedures
Normal volunteers
Children will be excluded from this study
Subjects found to have any constitutionally present non-MR compatible ferromagnetic materials will be excluded from this study
Neurofibromatosis type 1 (NF1) status will be determined by clinical exam or genetic testing
Major psychiatric diagnosis prior to neuro-oncological diagnosis
Ability to lie still for PET scanning
Adults with intraocular tumors (melanoma, metastasis, retinal tumors) who are going to undergo enucleation diagnosed in the Emory Eye Center Ocular Oncology Service; patients will be assessed by a cardiologist or cardiology fellows
Patient with right-to-left, bi-direction, or transient right-to-left cardiac shunts
Respiratory failures marked by signs and symptoms of carbon dioxide (CO2) retention or hypoxemia
Off Sandostatin (octreotide acetate)-long acting release (LAR) > 4 weeks and off immediate release (subcutaneous) for 12 hrs prior to 68Ga-DOTATOC PET-CT
No therapy other than Sandostatin since last Octreoscan + diagnostic CT
Fresh frozen (recommended) or paraffin fixed (required) specimen of primary or metastases available for ribonucleic acid (RNA) and immunohistochemistry (IHC)
Weight more than 400 pounds (subjects who weigh more than 400 pounds will not be able to fit inside the imaging machines)
Gleason =< 3+3
=< 3 total cores positive
No evidence on biopsy of extracapsular extension
The subject is able and willing to abide by the study protocol or cooperate fully with the investigator or designee
Conditions which make repeat TRUS biopsies not feasible
Patient must have been valuated by a thoracic radiation oncologist within the past 4 weeks and deemed an appropriate candidate for stereotactic ablative radiotherapy (SABR)
Patient is capable of complying with study procedures
Patient is able to remain still for duration of imaging procedure (about one hour)
Patient is participating in other research protocols at the time of the NaF/FDG PETMRI scan
Preexisting medical conditions or claustrophobic reactions, and any greater than normal potential for cardiac arrest
Active or history of major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder in mid-life, or treatment with electroconvulsive therapy (ECT) (mild depression that is well treated with stable dose of selective serotonin reuptake inhibitor [SSRI] antidepressants may be allowed)
Patient with salivary gland malignancies
Patient with thyroid cancers
Serum potassium >= 3.5 mmol/L
Lactate dehydrogenase (LDH) less than 4.0 times below or above the upper or lower limit range
Complete blood count (CBC) with platelets less than 4.0 times below or above the upper or lower limit range
Blood urea nitrogen (BUN) less than 4.0 times below or above the upper or lower limit range
Urinalysis less than 4.0 times below or above the upper or lower limit range; urinalysis abnormalities will not preclude the patient from being enrolled and studied
Intention to enroll in a blinded therapeutic clinical trial
Subjects will be selected on the basis of their willingness and ability to participate and on their likelihood of completing the study
Claustrophobia
Any racial or ethnic origin
Any patient under age 18 may only participate in 3T imaging
Patient must have a histologic diagnosis of gastric or gastroesophageal junction adenocarcinoma
Presence of atrial fibrillation
Have measurable disease in their skin by direct visualization (visible lesion typically > 0.5 cm in maximal diameter); to perform a microscopic observation, the lesion will have to be visible by the naked eye, lined-up visually, and be able to interface with the microscope objective; a melanoma lesion that is smaller than 0.5 cm in diameter would present several obstacles to obtaining a reliable microscopic observation in the operating room; therefore, a visible lesion, at a minimum of 0.5 cm in diameter, is proposed for this study
To determine any sensitivity to fluorescein, subject must have a skin prick test preoperatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given); a negative skin prick test to fluorescein is an inclusion criteria
Melanoma deposit is deemed inaccessible to microscopic observation during the operative procedure (i.e., lesion is less than 0.5 cm or is not clearly visible to the naked eye)
In the case of cryotherapy, external beam radiation, or high intensity focused ultrasound (HiFU) the procedure will have occurred at least one year in the past; in the case of brachytherapy, treatment will have occurred at least 2 years in the past to eliminate patients with so-called “PSA bump”
Ability to lie still for PET scanning
All men undergoing robotic prostatectomy or cystoprostatectomy at City of Hope will be eligible for the study
Men who undergo neoadjuvant treatment with androgen deprivation therapy (ADT) or salvage prostatectomy including those who have had brachytherapy will be excluded
Unacceptable hemogram: hematocrit < 34%
No other active cancers
Subjects who lack fitness for flexible bronchoscopy as determined by the physician performing the bronchoscopy before the procedure
Subjects on anticoagulation (other than aspirin) whom cannot have their anticoagulation held for the procedure due to other clinical reasons (i.e. recent cardiac stent placement)
Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
Patient scheduled for TRUS-guided prostrate biopsy with or without MR TRUS Fusion determined based on standard of care requirements
Prostrate volume ? 20cc and height at least 22mm (at the area(s) to be biopsied) as verified by ultrasound or prostrate MRI
Contraindications to TRUS prostrate biopsy
Acute painful perianal disorder
Previous prostrate surgeries
Symptomatic acute prostatitis
Actively taking blood thinning agents (with the exception of low dose aspirin [81 mg] Plavix, Coumadin, etc.) or severe comorbidity prohibiting halting of anticoagulation therapies or history of bleeding disorder (e.g., coagulopathy
Patient is mentally incompetent or a prisoner
Those with contraindications for exercise tolerance test (ETT) testing, including unstable angina or inability to exercise on a treadmill or stationary cycle
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nScheduled for partial nephrectomy of renal mass
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nEastern Cooperative Oncology Group (ECOG) =< 1
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nECOG =< 2
Known sensitivity to fluorescent light
AIMS 1 AND 2: Healthy individuals with pigmented lesions or a partially biopsied melanoma or cutaneous melanoma metastasis whose treatment plan includes excision
Subjects enrolled on the University of Pennsylvania/Abramson Cancer Center (UPCC) 13413 CART-19 autologous T-cell trial with relapsed or refractory DLBCL and FL
Subjects who are pregnant or lactating; subjects will be co-enrolled in this study and UPCC 13413 and therefore must comply with the UPCC 13413 requirements pertaining to pregnancy, lactation, conception and contraception use throughout their participation in both studies
Women presenting for mammographic evaluation of an undiagnosed palpable mass found either by self examination and/or examination by referring physician
Lack fitness to undergo flexible bronchoscopy as determined by the bronchoscopist prior to procedure
Presence of suspicious lesion of the pancreas consistent with pancreatic adenocarcinoma; cytological confirmation is not required
Prior resection for pancreatic adenocarcinoma
Presence of a biliary stricture
Presence of altered anatomy (Billroth II or Roux-en-Y reconstruction)
Intrahepatic biliary strictures or strictures within 2 cm of the ampulla
No stricture
Patients with history of histologically-confirmed neoplasm of any of the following classifications: solid malignancy, myeloid neoplasm, lymphoid neoplasm
Patient must be available for follow-up
Patient must be a candidate for SLNB
There are no ethnic restrictions
Able to tolerate supine position
HEALTHY VOLUNTEERS: Able to tolerate supine position
Pain in supine position
Previously untreated participants must have a measureable lesion on an imaging study
After entry into the study, participants agree to be followed for up to 6 weeks after the final infusion of ferumoxytol
Participants with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Participants with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations, are not eligible; participants with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator’s discretion
Participants with known hepatic insufficiency or cirrhosis
Lesions and/or clip targetable with image guidance
Clinically unstable, severely ill, or moribund
Contraindication to furosemide administration including prior allergy or adverse reaction to furosemide or sulfa drugs; (Note: This exclusion criteria can be removed if furosemide is omitted as part of the PET imaging protocol if a second-generation scatter correction is available for the used PET device)
Negative for BRCA1 and BRCA2 mutations
Healthy volunteers
Prisoners are not eligible
Able to remain still for duration of each imaging procedure (about one hour)
Women with Breast Imaging-Reporting and Data System (BI-RADS) 4 or 5
Subjects who have had a needle biopsy of the suspicious area within the last 6 weeks
If an initial biopsy demonstrates neoplasm other than GBM
Other serious illness (es), which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
Off Sandostatin (octreotide acetate)-long acting release (LAR) > 4 weeks and off immediate release (subcutaneous) for at least 12 hours (hrs) prior to 68Ga-DOTATOC PET-CT imaging
The clinician/patient has made the decision as to whether the patient will proceed to wide local excision or mastectomy or patient has been diagnosed with invasive disease\r\n* NOTE: if surgical decision is delayed greater than 10 weeks after the MRI or patient is diagnosed with invasive disease, the patient should register to Step 2, arm B, and proceed to follow-up to capture all relevant data
The Oncotype DX Patient Report of the DCIS Score from the Oncotype DX Breast Cancer Assay performed by Genomic Health on the excision tissue have been uploaded by the site into the Rave electronic case report forms (eCRF)\r\n* NOTE: Prior to registration to Step 3, the institution must upload a redacted copy of the first page of the “Oncotype DX Patient Report” to the ‘DCIS Score’ eCRF in Rave; after submission of the Oncotype DX Patient Report, the institution may proceed to register the patient to Step 3
Patient must have biopsy-proven cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage-Ib2-IVb)
Patient must be planning to receive chemoradiation therapy with cisplatin
Patient may be part of other clinical trials (as long as no other local treatments beyond GK such as WBRT or other local therapy are indicated to the brain) or imaging studies
Patient must not have melanoma
Patient must not have hemorrhagic lesions
PRE-ENROLLMENT BIOPSY PARAMETERS: minimum of 12 biopsy cores
PRE-ENROLLMENT BIOPSY PARAMETERS: Gleason 6 (3+3) or 7 (3+4)
FINAL ENROLLMENT BIOPSY PARAMETERS: Gleason 6 (3+3) or 7 (3+4)
Histology other than adenocarcinoma
History of TURP (transurethral resection of prostate) or other similar procedures (transurethral microwave thermotherapy [TUMT], transurethral needle ablation [TUNA])
Physician recommendation of ADT
Physician prescription of androgen receptor antagonist therapy (examples: bicalutamide, flutamide, or enzalutamide) during time of protocol scans
Other serious illness(es) which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
Participants who are not considered candidates for ado-trastuzumab-emtansine
Patient would require anesthesia for the study
Unresolved bowel obstruction
Patients unlikely to be optimally debulked at surgery (tumor implants in difficult to reach places [i.e. falciform ligament or porta hepatitis], suprarenal retroperitoneal lymphadenopathy)
Prisoners
Evolving brain lesions post SRS requiring neurosurgical resection (whether for symptomatic control or to establish pathology)
Subjects who have difficulty lying flat on their back for extended periods of time
Patient must not require sedation for imaging purposes
Patient must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia, or antiphospholipid antibody syndrome); testing is not required in patients without a thrombophilic history
Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
Determination by the surgeon that the neoplasm is non-palpable; a patient with a palpable hematoma from core biopsy, but a non-palpable neoplasm, will be eligible for study
Subjects must be deemed eligible for resection by a surgeon who is listed as an Investigator in this study
Subjects will have had standard care computed tomography (CT), MRI, or ultrasound, and a fine-needle aspiration biopsy demonstrating PTC or MTC with nodal metastases or recurrent/persistent nodal disease in a patient with known PTC or MTC
Subjects with sickle cell disease, hemoglobinopathy, hemochromatosis or other clinical conditions that may lead to iron overload
If planning therapeutic systemic therapy, willing to undergo biopsy for research purposes only after drug dosing in LCCC1214
Surgeon and medical oncologist agree one week window trial is appropriate/safe for the patient and that surgery appointment/initiation of therapeutic systemic therapy can accommodate treatment schedule as outlined in the study schema
Inability to tolerate imaging procedure (i.e., remain relatively still for multiple short durations of 3-4 minutes) over a total time of 20 minutes
Participants with any extent of resection are eligible
Participants with multifocal or recurrent glioblastoma
Participants with glioblastoma involving the brainstem or posterior fossa, cerebrospinal fluid dissemination
Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib
Superficial bladder tumors (Ta, Tis, T1) OR
Must be:
Phenotypic studies (obtained within 8 weeks prior to study drug administration) from peripheral blood showing CD3+, CD57+ cells >400/mm³ or CD8+ cells >650/mm³.
Note: Complete blood count (CBC) and differential should be reported for the phenotyped sample.
Histopathologically confirmed mycosis fungoides or Sézary syndrome (CTCL stage IIB or greater according to the European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas [EORTC-ISCL] consensus classification) at study entry with progressive, persistent, or recurrent disease who have no available remaining standard therapeutic options (i.e., Refractory) as determined by the Investigator.
Requires therapy with agents that have a predisposition for hepatoxicity
Subjects must have solid tumors with malignant lesions in the thorax, abdominal cavity, head and neck region, or extremities (any histology) likely to benefit from palliative radiotherapy; subjects requiring palliative RT for lesions in the spine or lesions adjacent to the spinal cord are excluded from this study
Prior RT to the same region that would be irradiated in this study
Subjects must complete all baseline screening assessments
Dose Escalation Segment
or c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4
or mutation, including any deletions and any met fusions
c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4
or mutation, including any deletions and any met fusions
Part 2: Subjects will be enrolled into 1 of 3 cohorts:
Cohort C: cholangiocarcinoma, esophageal, nasopharyngeal or serous ovarian cancers (regardless of FGF/FGFR status), or other solid tumor malignancies with documented FGF19/FGFR4 alteration.
Note, the line of therapy limit does not apply to the biopsy substudy cohorts.
Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring medication
Creatine phosphokinase (CPK) =< 2.5 x ULN
Pathologically confirmed MCL (in tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen.
Documented systemic light chain amyloidosis.
Symptomatic ischemia, or
Subjects enrolled into Part 1 must have metastatic lesions where repeated IT injections are not feasible and in whom SC injection is the only viable route of CMP-001 administration, based on Investigator judgment. Subjects with injectable lesions are NOT eligible to participate in Part 1. Subjects enrolled into Part 2 must have metastatic lesions that are amenable to repeated IT injections.
Histopathologically confirmed diagnosis of metastatic or unresectable malignant melanoma arising from skin. Ocular melanoma subjects are not eligible.
Capable of understanding and complying with protocol requirements.
LDH ?2.0 times the ULN range of each institution
Acyclovir resistant mucocutaneous HSV infection based on clinical failure (no improvement after at least 5 days with FDA approved high doses with acyclovir, valacyclovir or famciclovir) requiring switch to foscarnet treatment.
Lesion accessible for size measurement and photography.
Willingness to abstain from the application of lotions and/or creams to the area with HSV lesions. Wet/dry saline dressings or bandages at lesion site are allowed.
monogamous relationship with vasectomized partner
ACV-resistant and foscarnet-resistant/intolerant mucocutaneous HSV infection based on clinical failure (no improvement after at least 5 days of foscarnet therapy or intolerance to foscarnet requiring cessation of foscarnet treatment) or result from genotypic/phenotypic testing.
Need to use drugs that have a narrow therapeutic index and are substrates for CYP2B6, CYP2C8, CYP2C9, CYP2C19, OATP1B1, OATP1B3, and OCT1 (organic cation transporter 1), ie warfarin, digoxin, phenytoin, paclitaxel, S-mephenytoin
Documentation of a TP53 gene mutation by next generation sequencing (NGS) based on central or local evaluation
Participants with a clinical diagnosis of neurofibromatosis type 2 (NF2) (either by National Institutes of Health [NIH] or Manchester criteria) or with a molecular diagnosis of NF2
Exposure to specific substrates of the drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within the appropriate wash-out period (a minimum of 5 x reported elimination half-life) before the first dose of study treatment
At least 2 doses of fusion vaccine were produced (Arm A only)
Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), and herpes zoster (varicella zoster virus [VZV]) at start of treatment
ECOG 0 or 1 at enrolment.
Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS
?18 years old
Washout period prior to Day 1 Cycle 1:
>1 week since palliative RT
Prior exposure to CBT-1
Previously untreated sarcomas
Sustained platelet count ?50,000/µL, and/or sustained Hgb ?8 g/dL and/or sustained ANC ?1000/mm3, which is considered by the Investigator as related to the nature of the graft (higher transient levels following occasional blood product transfusions are allowed).
No other known etiology of the thrombocytopenia (such as infection, medication, etc.) or anemia (such as blood loss, iron deficiency, etc.).
Ability to complete patient medication and blood pressure diaries by themselves or with assistance
Cohort 2 only: discontinued lenvatinib due to toxicity
Active hemoptysis (bright red blood > 1 teaspoon on more than one occasion) =< 3 weeks prior to registration
Histopathological evidence of glioblastoma (WHO grade IV) on a progressive tumor specimen after treatment with temozolomide or PCV chemotherapy; the diagnosis of glioblastoma must be confirmed on central review by a study-designated neuropathologist at New York University Langone Medical Center (NYULMC) at screening; exceptions to this eligibility include the following:\r\n* Any progressive glioma with IDH1 or IDH2 mutation, regardless of WHO grade, histopathological diagnosis, or prior therapy, will be eligible if the progressive tumor specimen is found to have one of the genetic alterations below:\r\n** >= 20 somatic mutations per Mb by whole-exome sequencing\r\n** High mutation burden or microsatellite instability (MSI) identified by Foundation Medicine panel next-generation sequencing (FoundationOne, FoundationOne CDx); Foundation Medicine's threshold for high mutation burden (HMB) in their panel next generation sequencing (NGS) assays is >= 20 somatic mutations per megabase (Mb); Foundation Medicine's panel NGS assay has been validated by whole-exome and whole-genome sequencing to correlate tightly with tumor mutation burden (R^2 = 0.94)\r\n** Mutation in a mismatch repair gene or other genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MSH2, MSH6, MLH1, POLE, PMS2, POLD as determined by validated methods\r\n** Microsatellite instability as identified by polymerase chain reaction (PCR) or other validated methods\r\n* Progressive oligodendroglioma (with 1p/19q codeletion) that has hallmark histopathological features of glioblastoma (i.e. necrosis, pseudopalisading necrosis, or microvascular proliferation) is eligible as IDH1/2 mutant, 1p/19q codeleted oligodendrogliomas that have progressed after chemotherapy have been shown to develop hypermutation phenotype
Must have, or accept to have, an acceptable central catheter for infusion of melflufen
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
Waldenstrom's macroglobulinemia.
M/F at least 18 years old
Serum potassium, calcium, magnesium, phosphorus within normal limits (may be supplemented)
Advanced low or intermediate grade gastroenteropancreatic or lung or thymus neuroendocrine tumor (NET), or NET of unknown primary, progressed after at least 1 line of anticancer therapy (unless no standard treatments available or such treatments are deemed not appropriate)
Subject is considered an adult according to local regulation at the time of obtaining consent form (ICF).
Subject consents to allow access to subject's diagnostic bone marrow aspirate or peripheral blood sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic test that is being developed in parallel with gilteritinib.
Subject will not proceed with transplantation as either a decision not to proceed with transplantation has been made either on the recommendation of the treating physician or by the patient or a suitable donor could not be identified.
Female subject must either:
Be of nonchildbearing potential:
Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
Subject with hypokalemia and hypomagnesemia at screening (defined as values below LLN).
Subject has progressing infection defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Ability to travel to appointments and willingness to participate in this study
The patient is not a candidate for robotic assisted hysterectomy and lymphadenectomy
The patient has known or suspected allergies to iodine, indocyanine green (ICG) or isosulfan blue (ISB)
Primary or secondary iron overload
Clinically documented or risk of primary or secondary iron overloading (e.g. history of thalassemia, sickle cell anemia, hereditary hemochromatosis, multiple transfusions with any reason), anemia not caused by iron deficiency
Able to remain still for duration of each imaging procedure (about one hour)
STEAP1 antigen positive tissue known from prior IHC testing or if STEAP1 status is not known archival sample will be sent to Genentech for IHC; samples needed to be positive, when feasible metastatic lesions will be tested preferentially rather than primary
Patients with history of hypersensitivity reaction to any component of 89Zr-DFO-MSTP2109A, including DFO
TREATMENT GROUP: Premenopausal or peri-menopausal, defined by having regular menstrual cycles that are regular but may have > 7 days variability in the length of consecutive cycles (irregularity caused by hormonal contraceptive use is acceptable if the subject is 45 years of age or younger)
NORMAL GROUP: Premenopausal or peri-menopausal, defined by having regular menstrual cycles that are regular but may have > 7 days variability in the length of consecutive cycles (irregularity caused by hormonal contraceptive use is acceptable if the subject is 45 years of age or younger)
Have engaged in occupations or activities which may cause accidental lodging of ferromagnetic materials, or have imbedded metal fragments from military activities
Are claustrophobic
Medically unstable
Does not meet histologic criteria
Baseline creatinine (necessary for imaging studies)
Subject weighs more than 400 pounds; (subjects who weigh more than 400 pounds will not be able to fit inside the imaging machines)
Prior exposure to murine proteins or chimeric antibodies
Ability to lie still for PET scanning
Be a female diagnosed by x-ray mammography (performed within 90 days prior to the study procedure) as having a solid breast mass or abnormal area without a mass
Be scheduled for a biopsy (core/excisional/lumpectomy) of the mass or region of abnormality or for mastectomy within 30 days after this study procedure
Renal insufficiency
Patient must be enrolled or being considered for enrollment on protocol 2010-0085
Must have been listed on the regional OPTN/UNOS liver transplant wait list with HCC-exception Model for End Stage Liver Disease (MELD) points prior to enrollment in this trial OR \r\n* Site principal investigator (PI) or designated site co-investigator determines whether patient is likely to meet all criteria for being listed on the regional OPTN/UNOS liver transplant waitlist with HCC-exception MELD points, but has not yet been listed with UNOS UNet\r\n* Investigator has completed and signed the Declaration of Intent to List source document declaring that the patient will likely meet all wait list criteria\r\n* Participants listed with the intent to undergo either deceased donor transplant or live donor adult liver transplantation (LDALT) are eligible for this trial
Renal insufficiency at the time of enrollment, as determined by eGFR 30 to 60 mL/min/1.73 m^2 by the MDRD model based on a serum creatinine level obtained within 28 days prior to enrollment, unless permitted by the institution’s policy and/or American College of Radiology (ACR) guidance for risk reduction strategies
Known allergy-like reaction to contrast media (iodinated or extracellular gadolinium that does not have dominant hepatobiliary excretion) or moderate or severe allergic reactions to one or more allergens as defined by the ACR, and unwillingness to undergo pre-treatment as defined by the institution’s policy and/or ACR guidance
Subjects may be excluded at the discretion of the principal investigator or study team members
Ureteral stint present or removed within six weeks
Claustrophobia
Unable to hold a breath
Ascites or other clinical or radiographical signs of portal hypertension
Previously untreated subjects must have a lesion on an imaging study
Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2012); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known hepatic insufficiency or cirrhosis
Has the following International Federation of Gynecology and Obstetrics (FIGO) IA2-IIA1staging. Subjects with a single enlarged/suspicious node on PET/CT will still be considered eligible as consistent with FIGO guidelines.
Before the administration of Lymphoseek, has received any radiopharmaceutical within 7 radioactive half-lives of that radiopharmaceutical
Subjects must be eligible for resection as determined by the operating surgeon
Subjects who have a serious reaction with the test/loading cetuximab dose for which they were not able to receive the full dose
Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
Abnormal digital rectal exam (i.e. palpable nodule, induration or firm area to the prostate)
Contraindications to TRUS/prostate biopsy (BX)\r\n* Currently on blood thinning agents (Plavix, Coumadin etc.) or bleeding disorder\r\n* Active urinary tract infection\r\n* Acute painful perianal disorder (i.e. rectal abscess)
GROUP A (painful neuropathy group): Must have subjective symptoms of painful peripheral neuropathy (burning, stabbing, throbbing, painful tingling, aching in the fingers and/or toes) that is greater than or equal to 10 on a scale of 0 to 100 in the neuropathic pain questionnaire
GROUP B (no pain group): Must either have subjective symptoms of painless neuropathy (loss of sensation, worsening balance, strange sensation in fingers and/or toes) or no complaints related to neuropathy
Has pain rated 50 or higher on a scale of 0-100, with 0 = no pain at all and 100 = worst pain imaginable on the day of the first DLss test
Confirmation of pathology as glioblastoma
Diagnosed with mCRPC and painful bone metastases, referred for Xofigo (radium Ra 223 dichloride)
Able to remain still for duration of the imaging procedure (about one hour)
PART A: Healthy volunteers enrolled from within the Department of Radiology at University of California San Francisco (UCSF)
No clinically relevant deviations in renal function (Serum Creatinine > Grade 2 CTCAE v4.0.). Maximal interval between confirmation and injection of 18F-FSPG is one week.
evaluation of 18F-FSPG safety and tolerability will not be confounded by the other investigational PET or SPECT tracer
a minimum of two days (or longer as necessary based on radiological half-life) have elapsed between investigational PET or SPECT tracer administrations to allow acceptable clearance of the tracer
the investigational PET or SPECT tracer administration was well tolerated by the patient.
At least one of the brain lesions must measure 5 mm (or more) in short axis diameter in the axial plane
Locally advanced disease as determined by endoscopic rectal ultrasound (ERUS) or pelvic MRI; endoscopy reports should clearly state both the T and N stage
Neoadjuvant chemoradiation prior to resection is planned
Weight in excess of limitations of the scanner or girth that prohibits entry into the bore of the PET/CT scanner due to size
Able to remain still for duration of each imaging procedure (about 20 minutes)
Transaminases =< IULN
Elevated LDH levels are permissible if transaminases are =< IULN
Subjects must be scheduled to undergo transarterial chemoembolization (TACE)
Subjects must have at least 1 lesion being targeted by TACE that is > 2 cm in the longest cross-sectional (axial plane) diameter
Subjects who have undergone prior radioembolization
Subjects who exhibit noticeable anxiety, claustrophobia, or vertigo when moved into the scanner
Subjects incapable of giving informed written consent, for the following reasons:\r\n* Inability to adhere to the experimental protocols for any reason\r\n* Inability to communicate with the research team\r\n* Mental disability, altered mental status, confusion, or psychiatric disorders\r\n* Prisoners or others susceptible to coercion
Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the magnet bore
Women who are planning to undergo hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for the management of their endometrial cancer
Women with a history of prior loop electrosurgical excision procedure (LEEP) or cone procedures performed on their cervix
Women may also be excluded at the discretion of their surgeon if he or she feels that the patient is not an appropriate candidate
Breast size and epithelial integrity adequate to allow NIR imaging exams
No serious associated psychiatric illnesses
Intolerance of hyperoxia or hypercarbia as delivered by the RespirAct™ breathing circuit
has the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
Hematocrit < 22%
Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced
Subjects who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the magnet bore
Enrolled in the National Institutes of Health (NIH) phase II clinical protocol evaluating FdCyd with THU (National Cancer Institute [NCI] protocol # 09-C-0214 [Cancer Therapy Evaluation Program (CTEP)# 8351]) or NCI protocol #12-C-0066 (CTEP# 9127) with target lesion measured as >= 10 mm with spiral CT scan
Subjects weighing > 400 lbs (weight limit for scanner table), or unable to fit within the imaging gantry
The subject is unable to lie still for ~75 minutes
Children, pregnant women, Stanford employees or students, or prisoners will be excluded from this study
Any person with a lesion of the oral mucosa; persons with changes in existing lesions or those who develop new lesions can be re-evaluated, but it is not required
Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
Subject presenting, at the time of inclusion, with known or highly suspected focal areas of disrupted BBB (e.g., primary and secondary tumors, focal inflammatory or demyelinating disorders) including at least one expected enhancing lesion of minimum 5 mm (long axis). This lesion must have been detected on a previous imaging procedure (computerized Tomography (CT) or MRI).
Patients unable to tolerate a SPECT/CT 99mTc-MAA and 99mTc-DTPA scan
No significant esophagitis (LA grade < B, C and D).
Significant esophageal stricture requiring dilatation.
Fit to undergo all procedures listed in protocol
Previous hip replacement surgery, metallic hip replacement or extensive pelvic orthopaedic metal work
Unfit to undergo any procedures listed in protocol
Lesion can be visualized with EUS and is ?1 cm in size
Purely cystic lesions
Female or male adult patient (patient having reached legal majority age)
Patient with national health insurance (according to local regulatory requirements)
Patient having received any contrast agent within 48 hours prior to first study contrast agent injection scheduled for the study and patient expected to receive any other contrast agent within 24 hours of the last study contrast agent injection
Patient already included in this trial
Pathology reviewed by Moffitt pathologist
Less than ten biopsies obtained at time of diagnosis
Pathology not reviewed by Moffitt pathologist
Primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, bronchus intermedius, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
Direct evidence of regional or distant metastases after appropriate staging studies
Any non-surgical local treatment such as previous cryotherapy, external beam radiation, or HiFU (Ultrasound) must have occurred at least 1 year in the past.
Clinically referred for portal vein embolization
Patients with peripheral lung lesions 1-7 cm in size identified on chest CT with the intention to undergo bronchoscopic evaluation and biopsy; the decision to pursue biopsy will be made by the treating physician and agreed upon by the patient
Are physically unable to tolerate flexible bronchoscopy or moderate sedation as determined by the bronchoscopist
Prior diagnosis of cancer treatment induced left ventricular dysfunction (CILVD) with recovered LVEF (i.e. improved to > 50%) for at least 6 months with recommended HF medications (ACE-I or ARB and/or beta [B]-blocker)
Absence of other causes of cardiomyopathy (e.g. ischemia, hypertension, amyloidosis, or hemochromatosis) per chart review of the clinician’s documentation
Residence within the United States
Exhibiting HF symptoms (e.g. shortness of breath, edema)
Able to remain still for duration of each imaging procedure (about one hour)
Hemosiderosis/hemochromatosis
Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology
Currently treated for hyperthyroidism
NORMAL VOLUNTEERS: Be using more than one antihypertensive drug
NORMAL VOLUNTEERS: Currently treated for hyperthyroidism
Subjects aged 18 years or more at the time of consent.
Prior SLN dissection
Negative nodal basin clinical exam
Patient is being evaluated or receiving treatment by the pediatric oncology division at the University of Kentucky
Heart rate < 60 prior to propranolol
Currently on dialysis
Referred to University Hospitals Case Medical Center (UHCMC) Nuclear Medicine for methylene diphosphonate (MDP) bone scintigraphy
Patients who cannot tolerate imaging up to 120 minutes of total imaging (breaks of several minutes between imaging will be available)
Healthy volunteers
Subjects weighing >= 350 lbs or are unable to fit within the imaging gantry
Patients with (any one of the following):\r\n* Suspicion of NET on axial imaging (CT/magnetic resonance imaging [MRI]/fludeoxyglucose [FDG] PET) and/or\r\n* Biochemical evidence of neuroendocrine tumor (serum/urinary) based on elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-hydroxyindoleacetic acid [HIAA]), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), glucagon and/or\r\n* Familial predisposition to NET in patients with multiple endocrine neoplasia type 1 (MEN1) and Von Hippel-Lindau (VHL) (symptomatic and/or asymptomatic cases; with biochemical or anatomic imaging evidence of disease)
Women with symptoms such as palpable mass or nipple discharge
Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed
HER2/neu positive by IHC and/or another FDA approved HER2 testing method
No vulnerable populations will be enrolled (prisoners, children, pregnant females or institutionalized individuals)
Able to remain still for duration of each imaging procedure (about 30 minutes)
An upper GI endoscopy is scheduled to check upper abdominal symptoms.
Inclusion criterion for PC suspicious cohort * A EUS or ERCP is scheduled to suspected pancreatic disorder.
Subject is judged by the investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
Anticipated survival less than 5 years, as per the treating physician
Hematocrit < 22%
Right-hand dominance
Presence of pain that developed or worsened since breast cancer diagnosis (not specifically due to an identifiable trauma [eg fracture or injury]) and has been present for at least 3 months; average pain must be at least 4 on a 0-10 scale over the past 7 days
Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or artificial nails) that are likely to alter pain perception during testing
The principal investigator determines that the patient is acting in ways that would lessen their chances of completing the study
Prior diagnosis of fibromyalgia
Prior craniotomy for resection of deep seated tumors in thalamus and brain stem
At least one lesion that can be accurately measured in two dimensions utilizing mammogram, ultrasound, or MRI images to define specific size and validate complete pathologic response.
The patient must be considered legally capable of providing his or her own consent for participation in this study
Patient must agree to receive standard or dose-dense adriamyacin, cyclophosphamide, and taxane-based\r\nchemotherapy given preoperatively
The patient is male
Planned treatment with standard agents or investigational agents that can potentially activate herpesvirus TK, including but not limited to the following; concurrent radiation therapy is permissible:\r\n* Platinum compounds (for example, cisplatin, carboplatin)\r\n* Anthracyclines (for example, doxorubicin or pegylated doxorubicin)\r\n* Tubulin disrupting agents (for example, vincristine, vinblastine)\r\n* Rituximab\r\n* Gemcitabine\r\n* Cytarabine\r\n* Histone deacetylase inhibitors\r\n* Bortezomib; Note: patients who would not receive bortezomib as part of their usual care may receive a one-time dose of bortezomib for the purpose of imaging with 124I-FIAU and FIAU-PET-CT
Chronic renal insufficiency requiring dialysis
Patient has contraindication to either endobronchial ultrasound or mediastinoscopy such as: history of bleeding diathesis, latex allergy, mediastinoscopy, mediastinal nodal resection, tracheostomy
Patient has two separate same histology lung tumors (where the question of two separate primaries or metastatic disease makes definitive clinical staging inaccurate)
An intact cervix.
Willing and able to undergo colposcopy and biopsy and endocervical curettage within 8 weeks after study Visit 1.
Presenting for colposcopy at study Visit 1.
Subject must be a patient undergoing diagnostic bronchoscopy and/or thoracoscopy at University of California Irvine Medical Center (UCIMC)
Patient who presents to clinic with a history of hoarseness and voice changes and are noted to have changes to their vocal folds that are concerning for the possibility of dysplasia or early stage malignancy
Patient will have vocal fold leukoplakia or other abnormal epithelial changes
Patient must not have a documented reaction to fluorescein (fluorescein sodium)
Have had stereotactic or ultrasound-guided biopsy with marker placement
Have a lesion or biopsy marker that is visible under ultrasound
Have a lesion in which the center/focal area is defined
Require more than one localization needle for localization of the surgical target (bracket localization)
Urine culture positive for significant urinary tract infection (UTI)
Subjects who are willing to participate
Expected lifespan of 12 weeks or less
Serum iron, total iron binding capacity, and serum ferritin within normal institutional limits; patients are eligible even if they are taking an iron supplement
Receipt of any other iron-oxide based nanoparticle therapy or IV iron within 4 weeks of scans
A known diagnosis of hemochromatosis, mitochondrial disorder, or iron overload
Cohort A: Screening visit peripheral blood must be available for retrospective analysis of spliceosome mutations of interest.
Cohort B and Expansion: Screening visit peripheral blood must be submitted for central analysis at a sponsor-designated laboratory to identify spliceosome hotspot mutations in SF3B1, SRSF2, U2AF1, mutations in ZRSR2, and SRSF2 deletion including amino acid P95.
Family history of Leber Hereditary Optic Neuropathy, Autosomal Dominant Optic Atrophy, Late-Onset Retinal Degeneration, Familial Dysautonomia or other hereditary mitochondrial disease, unless the causative mutation(s) in the family have been determined and the participant has tested negative for the mutation(s).
Known prior or current retinal or optic nerve disease (eg, Retinitis Pigmentosa, diabetic retinopathy, optic neuritis) based on screening ophthalmology assessment for eligibility.
Corrected vision is worse than 20/40 unless due to cataracts.
Significant symptom burden from presumed diagnosis including large volume ascites, pain requiring narcotic medication, or shortness of breath on exertion
The lesion is suitable for repeat measurement
Nonhepatic lesion
Non-nodal lesion that measures ?1.0 cm in the longest diameter ii.Participants with ICC:
No evidence of biliary duct obstruction unless obstruction controlled by local treatment or, the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to ?1.5×ULN
Current evidence of corneal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, or keratoconjunctivitis
Participants with genetic diseases of the liver that may complicate review of safety data
Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or selective pan-FGFR inhibitor 14. Use of any vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy 15. Presence of gastric or esophageal varices requiring active treatment 16. A clinically significant ECG abnormality, including a marked baseline prolonged QTc interval (eg, a repeated demonstration of a QTc interval >500 ms) 17. Significant cardiovascular impairment or any other major illness, medical condition 19. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria 20. Hypersensitivity to the study drug or to any of the excipients 21. Intolerance or hypersensitivity to both CT and MRI contrast material that would preclude the ability to acquire the triphasic liver imaging required by the protocol 22. Participants with inorganic phosphorus > upper limit of normal for the institution 23. Participants with total or ionized serum calcium > upper limit of normal for the institution 24. Participants with endocrine changes that may result in increases in calcium or phosphate, including but not limited to hyperparathyroidism and tumoral calcinosis 25. Participants with past medical history and/or current evidence of tumoral calcinosis or tissue calcification 26. Participants who take calcium, vitamin D or systemic corticosteroids
Radiographically resectable PDAC as adjudicated by Memorial Sloan-Kettering Cancer Center (MSKCC) surgical oncologist without evidence of distant metastases by computed tomography (CT) or by laparoscopy, if performed at the discretion of the surgeon*
* Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion of the study are exempt from these criteria
Active infection, with the exception of resolving cholangitis, will preclude enrollment on the study; preoperative interventions can only be initiated when acute cholangitis has resolved*
* Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion are exempt from these criteria
Any chronic medical condition requiring daily corticosteroids or other immunosuppressants (e.g. tacrolimus, sirolimus, cyclosporine, azathioprine, mycophenolate mofetil, etc.)
Untreated/unstabilized pathologic long bone fractures
Willingness to travel to National Institutes of Health (NIH) for follow-up visits
Castration-resistant PCa
Evidence of biochemical recurrence
Self-identify as African American or Black
Smoke at least five cigarettes daily for the past year
Recent unstable or untreated psychiatric diagnosis including substance abuse, as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria
Labs required for enrollment (prior to microinjection):
Hematocrit > 25%
Tumors near critical structures such as those located near or in the brain or spine. This assessment will be determined by the treating clinician.
Current or former smoker by self-report
Willing to abstain from cruciferous vegetable consumption other than the study vegetables during the study period
History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect gastric absorption
Vegetarians
Ambulatory and possessing all four limbs
Participants not capable of keeping moderately still for the imaging portion of the study session (~1 hour for imaging)
Prior exposure to idelalisib
Known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
Pregnancy or active nursing of an infant
Are currently taking a statin or have taken a statin in the past 6 months or have a history of an allergic reaction or intolerance at any time to a statin
Are taking a drug that may significantly interact or influence the metabolism of atorvastatin
Healthy adults who reside within the greater Twin Cities area
Diagnosis of dementia
Able to remain still for duration of each imaging procedure (about one hour)
Able to eat a full range of solid food and liquids and tolerate seeds/nuts
Maintain a consistent general diet without significant variation
Able to recollect dietary intake for the prior 24 hours in order to complete a one-day food record with assistance from a dietician at each study visit
Willing to complete the food frequency questionnaire (FFQ) at baseline and at 16 week visits with assistance from a dietician
On prophylactic antibiotics, such as trimethoprim-sulfamethoxazole for pneumocystis prophylaxis or post-transplant penicillin prophylaxis
Only individuals who can understand and give informed consent will be eligible to participate in this study; individuals who are considered to be mentally disabled will not be recruited for this study; all subjects must understand and be able to give informed consent; we will not be using specific methods to assess decisional capacity; all individuals will be told that their choice regarding study participation will in no way change their access to clinical care; this should negate any undue influence or coercion; children, fetuses, neonates, or prisoners are not included in this research study; women of child-bearing potential will have a urine pregnancy test at the time of screening
Aim 1 only: 1) smokers who smoke at least 10 cigarettes per day with a stable smoking pattern of at least 6 months and no prior e-cig use within one year; smoking status will be confirmed by salivary cotinine; subjects with at least 10 ng/ml cotinine in their saliva being considered smokers; 2) e-cig users who report using e-cigs daily for 3 months with at least one nicotine-containing cartridge/day or 1 ml of liquid/day; they should have not smoked a cigarette for at least one year; 3) non-smokers who have smoked less than 100 cigarettes in their lifetime and not for at least 1 year, and not have used an e-cig for at least 1 year; lack of regular smoking will be confirmed by salivary cotinine
Able to read adequately to complete the survey and related study documents or give consent
General anesthesia within one year
Bronchoscopy or any other lung procedure for any reason within the previous year
Unable to read for comprehension or completion of study documents
Cachexia
Any NSAIDs or omega-3 free fatty acid supplementation within the last 14 days
Cancer/testis antigen 1B (NY-ESO-1) specific T cell therapy within 1 year of starting on the trial
Willing to avoid cruciferous vegetable intake during the study period (2 weeks)
Intolerance to broccoli/ITC-BSE taste
Current ingestion of broccoli sprout extract, which may confound study results
Known prosthetic devices that would prohibit imaging of lesion of interest due to radiographic artifact
Participants must have a mammographic breast composition category (density) of c or d
Participants cannot be taking the following medications because of major pharmacokinetic interactions with celecoxib while being enrolled in the study: abciximab, argatroban, bivalirudin, cilostazol, dabigatran, etexilate, dipyridamole, fondaparinux, heparin, lepirudin, pemetrexed, protein C, rivaroxaban, sibutramine, Ticlopidine, tirofiban, vilazodone and warfarin
No daily NSAIDs intake within the past 4 weeks; intermittent non-daily NSAIDs is allowed under principle investigator (PI) discretion
Creatine phosphokinase (CPK) =< 2.5 x ULN
Subjects with a smoking history of at least 5 cigarettes daily for at least 1 year (carbon monoxide [CO] > 8 parts per million (ppm); if CO =< 8 ppm, then Nic Alert test =< level 3) and no serious quit attempts in the last 3 months (to ensure stability of smoking)
Immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data
Use of > 25% of cigarettes in the form of roll-your-own cigarettes unless they are machine rolled and include a filter
If does not have a way that the research team can communicate with them by phone or e-mail
If is neither a citizen of the United State nor a Permanent Resident Alien (Green Card holder) (to facilitate compensation of participants)
Metabolic acidosis, acute or chronic; acidosis will be defined a blood pH < 7.35; acidosis will be suspected if serum bicarbonate is < 22 mEq/L; in such cases, venous blood pH would be checked to confirm or exclude acidosis
Participant must be a non-Hispanic white or non-Hispanic black (self-reported race) woman 45 to 80 years of age and postmenopausal; postmenopausal will be defined as no menstrual cycle in the past 12 months; women with a hysterectomy but with intact ovaries will be included if aged >= 55 years
Self-reported race other than non-Hispanic white or non-Hispanic black
Gastric bypass
Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 centimeters (cm) unless they are previously irradiated
Subject must have histologic or cytologic confirmation of advanced melanoma
Other concomitant malignancies (with some exceptions per protocol)
Patient is a candidate for radical prostatectomy
Any non-adenocarcinoma histologic component
Any evidence of lymphatic or hematogenous metastases
Unwillingness to engage in adequate contraception
Non-diabetic and obese
Willing and able to participate in clinic visits, group sessions, and telephone and Internet communications at specified intervals
Able to provide data through questionnaires and by telephone
Willing to allow blood collections
Capable of performing a simple test for assessing cardiopulmonary fitness
Minimum of one 3cm area of non-ulcerated columnar-lined esophagus or squamous-lined tissue suitable for ablation
Serum magnesium and corrected serum calcium within the institution’s normal reference range
Patients with a history of excessive alcohol intake which is defined in accordance with Centers for Disease Control and Prevention (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men; this definition is referring to the amount consumed on any single day and is not intended as an average over several days; a standard drink is equal to 13.7 grams (0.6 ounces) of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey)
Study Arm 1: primary diagnosis of a pelvic or adnexal mass of presumed gynecologic origin who is scheduled for operative resection
Known sarcomatous histologies
Greater than 1.5 x the ULN for blood urea nitrogen (BUN)
Chronic or acute pancreatitis as evidenced by clinical or pathologic diagnosis
Significant symptom burden from presumed diagnosis including large volume ascites, pain requiring narcotic medication, or shortness of breath on exertion
Aged at least 18
Is MMR-proficient [selected by the site based on microsatellite instability assay (MSI) and/or immunohistochemistry (IHC) for MMR proteins]
Has met protocol-specified criteria for qualification and contraception
the analysis of results
Current smoker of >= 5 cigarettes daily, determined by self-report
Willingness to take kava supplement as instructed
History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect the absorption of kava
May continue ongoing antiestrogen
Patients undergoing unilateral SLNDs either levels I-III, I-IV, II-III, or II-IV for oral cavity, oropharynx (if the resection does not connect to the neck), thyroid, salivary gland, parotid, and skin carcinoma
No restrictions based on gender or racial/ethnic background
Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography (CT) scan with contrast).
The presence of at least one lesion, measuring ? 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.
Uncontrolled ascites that is not stable with medical management (i.e., on diuretics and salt restriction) as defined by requiring therapeutic paracentesis more than once every 4 weeks.
Active hemolysis or evidence of biliary sepsis.
Subject enrolls into LCCC9819
Surgeon and medical oncologist agree one week window trial appropriate/safe for trial candidate and that surgery appointment can accommodate a 7 day (one week) treatment schedule
(STEP 2) - SECONDARY GENETIC COUNSELING SUBSTUDY:
Agree not to take a daily dosage of a non-steroidal anti-inflammatory drugs (NSAID) except 81 mg cardioprotective aspirin for the 6-week intervention period; (higher doses of an NSAID on an ‘as needed’ basis for acute pain management are permitted but should not exceed more than 1000 mg on any given day)
Have the approval of their treating physician to receive the 6 week ibuprofen/placebo regimen (200 mg twice a day and doses 8 hours apart); (physician must sign eligibility checklist prior to registration)
Be colorblind
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of Institutional Review Board approval for this study has been entered in the system
Minimum provider participation requirements met; this includes participation in the study intervention of a minimum of the following: Site Coordinator and Site Clinician Investigator/study champion
Site Coordinator identification and contact with as many as possible of the site’s relevant healthcare providers and staff regarding participation in the study intervention; relevant providers may include physicians, nurse practitioners, physician assistants, patient navigators, nurses and other staff who interact directly with breast cancer patients
On-site genetics professionals as defined by the Commission on Cancer
Received HBOC genetic counseling or mutation testing prior to diagnosis; if the patient was previously tested only for a variant of uncertain clinical significance (i.e., not for known familial mutation, Jewish ethnicity panel/multisite 3 or comprehensive sequencing) and documentation is provided, they remain eligible
The SunCoast Community Clinical Oncology Program (CCOP) Research Base does not exclude patients who are participating in other investigational studies; refer to the local Institutional Review Board (IRB) guidelines
Patient must have malignant bowel obstruction (MBO) as evidenced by all of the following:\r\n* Clinical evidence of a small bowel obstruction (via history, physical, and radiographic examination)\r\n* Bowel obstruction below (distal to) ligament of Treitz\r\n* Intra-abdominal primary cancer with incurable disease
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Patients must consent and provide both their contact information and that of their representative for a monthly 24-hour dietary recall phone call to be conducted by the Arizona Diet, Behavior and Quality of Life Assessment Lab
Has a study site-specific nurse available to act as a PN or has a (study site-specific or shared) nurse available to act as a “clinical consultant” to a study site-specific, non-nurse navigator\r\n* Study sites randomized to the Intervention Arm are not eligible to register subjects (nor administer the protocol intervention), until the site’s identified PN(s) has/have completed the protocol-specific navigation training
African American or Black race
Recently diagnosed (i.e., within 70 days of enrollment) with clinically suspicious or biopsy-proven early stage (i.e., stage I-II) NSCLC; the inclusion criteria will be operationalized as follows:\r\n* Recently diagnosed (i.e., within 70 days of definitive tissue biopsy) biopsy-proven NSCLC\r\n* Recently diagnosed (i.e., within 70 days of clinical diagnosis) probable NSCLC where \probable NSCLC\ is defined as a suspicious lung nodule for which the patient was referred for\r\n** Invasive diagnostic procedure (i.e., bronchoscopy or image-guided biopsy), OR\r\n** Surgical or radiation oncology consultation and \date of clinical diagnosis\ is defined as (whichever comes first)\r\n** Date of referral for invasive diagnostic procedure (i.e., bronchoscopy or image-guided biopsy), OR\r\n** Date of referral for surgical or radiation oncology consultation\r\n* Study sites should enroll patients that meet either of the above inclusion criteria as early as possible during the diagnostic work-up (i.e., if the patient meets the criteria for recently diagnosed, clinically suspicious NSCLC, definitive tissue biopsy is not required for eligibility)
Evaluated/treated for NSCLC at an eligible study site
Currently in hospice care
Scheduled to receive an allogeneic HCT at the Dana-Farber Inpatient Hospital or Brigham and Women's Hospital (BWH) under the care of a DFCI physician
Residence in New York, Maine, New Hampshire, Vermont, Connecticut, Rhode Island, or Massachusetts
Referred from one of the above six centers, or chooses to receive care at one of the six centers
Scheduled to receive an autologous HCT
Did not receive an allogeneic HCT at Dana-Farber
Does not live in New York, Maine, New Hampshire, Vermont, Connecticut, Rhode Island, or Massachusetts
Registered Nurse (RN) or Doctor of Medicine (MD) degree.
Unable to undergo the informed consent process and the study interview in English per the judgment of the primary urologist.
PHASE I: Women who have “dementia” (of any kind) or memory problems listed in their problem list
PHASE II: Women who have “dementia” (of any kind) or memory problems listed in their problem list and we will exclude women that score > 10 on the OMC test (indicative of dementia)
Patient is expected to see their physician or another member of their care team at least 3 times annually
Members of other ethnic minorities will not be included
CLINICIAN: MSK medical oncology HCPs - specifically identified as attendings, fellows, or advance practice professional (APP) – either a nurse practitioner (NP) or physician assistant (PA) from gastrointestinal (GI), genitourinary (GU) oncology, lymphoma, or bone marrow transplant (four services with a large number of geriatric patients)
CLINICIAN: Willingness to be audio-recorded as per self-report
PATIENT: Willingness to be audio-recorded as per self-report
CAREGIVER: Accompanying an MSK patient undergoing treatment for cancer by one of the consented HCPs as per the HCP and/or EMR
Children will not be included in the study. The pattern of disease and symptoms are different in children than in an adult population. The web-based tool was designed based on the symptom experience of adults with cancer
Is medically or otherwise unable to participate (as determined by a physician or study principal investigator [PI])
Enrolled in hospice
Patient: Female
Considering a mastectomy
AIM 2: Having a short message service (SMS) capable mobile phone that is not shared with anyone else
AIM 1: Difficulty reading due to poor eyesight (i.e., reporting more than “only a little difficulty”)
AIM 1-3
Willing to provide access to medical records, insurance and billing data, biospecimens and respond to questionnaires, typically by phone, but possibly to include online or in-person surveys
AIM 3 ONLY
Household members must be current smokers, defined as smoking at least one cigarette most days per week
Hearing and vision impairments that would prevent ability to complete consent, interviews, or sample collection
Altered cognition (as assessed routinely in the Supportive Care Clinic using the Memorial Delirium Assessment Scale [MDAS], with a score of >= 7/30)
Patient must have ongoing oncologic needs and plan to receive all care at the study institution and not already be in hospice or home-care
Have not previously viewed the Pathways decision aid
For clinical provider participants: Clinical provider at a Houston Area Location of MD Anderson assigned to the intervention
MEDICAL CHART REVIEW
Post-intervention: 200 patient records receiving care beginning six months post training are subject to review; the first 50 records with a diagnoses of head and neck, lung, prostate, or breast will be utilized
PROVIDER TRAINING
OHSU Radiation Medicine department has agreed to participate as pilot department for this project; all active Radiation Medicine providers are requested to participate in the training; providers have the option to not participate
TOBACCO CESSATION COACHING
Willing to consider quitting smoking
Patients who meet this criteria will be referred to OHSU Health Promotion Sports Medicine researcher, Carol DeFrancesco, to complete assessment using stages of change tobacco use readiness ruler and question set
Patient smoking status will be documented in their electronic health record, per routine care
Vulnerable Populations\r\n* The following groups will be excluded from participation:\r\n** Children\r\n** Decisionally impaired adults\r\n** Prisoners\r\n** Pregnant women
PATIENTS: Significant uncontrolled psychiatric disorder (psychotic disorder, bipolar disorder, major depression) or other co-morbid disease (dementia, cognitive impairment), which the treating clinician believes prohibits the ability to participate in study procedures
CAREGIVERS: A relative or a friend upon whom the patient relies for help and who will be likely to be present during hospitalization, or willing to participate by phone
All diseases that are indications for allogeneic BMT at Stanford University will be eligible for participation in this study
Prior allogeneic BMT
Board-certified oncologists who practice in any setting in the United States and have a smartphone
Dana Farber Cancer Institute (DFCI) oncologists are excluded from this study; this includes DFCI satellite sites, non-DFCI Dana Farber (DF)/Harvard Cancer Center (HCC) sites, and other non- DF/HCC sites that are under the DFCI Institutional Review Board (IRB)
Patient samples will be identified from among those receiving care in one of 28 Henry Ford Health System (HFHS) primary care clinics
Average-risk patients due for colorectal cancer (CRC) screening at the time of a primary care appointment who initiate a portal session within the two-week period following their visit
Pennsylvania or New Jersey residents\r\n* Telehealth visits for New Jersey residents will only be performed by physicians with a current medical license issued by the state of New Jersey
KPS < 60%
Staff of the Department of General Internal Medicine (usability test)
Diagnosis of rheumatoid arthritis by a rheumatologist (randomized controlled trial [RCT])
Adequate cognitive status as determined by a research coordinator at recruitment; to assess the participant‘s capacity to take part in the interview, the interviewer will note and comment on the participant's spontaneous speech and capacity to write date at the time of consent; participants should be oriented to person, place, date, time, and events (RCT)
Living in the community (not institutionalized, etc) (RCT)
Familiarity with and participation in social media (e.g. Facebook) (usability test and RCT)
Participants not willing to complete interviews or survey instruments (usability test and RCT)
Hospitalized (RCT)
Agreed to receive home healthcare
Members of all races and ethnic groups are eligible for this trial
Located in the New York City (NYC) Borough of Manhattan, Queens, Brooklyn, or the Bronx
Has a roster of at least 100 drivers
Affiliated with a NYC garage
Owns a cell phone that can receive text messages and is willing to receive text messages for this study
Does not have a usual primary care provider (PCP) at baseline
TIPs INCLUSION: Licensed taxi driver for at least two years
TIPs INCLUSION: Affiliated with a NYC garage
TIPs INCLUSION: Willing and able to attend in person TIPs training sessions
TIPs INCLUSION: As per study team judgment, based upon the TIPs screening tool, is socially active among fellow taxi drivers, cares about health issues, and wants to help others improve their health
Does not agree to holding screening health fairs on location (e.g. does not sign enrollment form, or send email confirming agreement, or verbally agree to study team management)
Part-time driver (drives fewer than 35 hours per week); although it is highly unlikely for NYC taxi drivers to work for multiple garages at study baseline, drivers may switch jobs and/or their garage base affiliation while participating in this study; new jobs and/or garage base affiliations will be tracked during follow-up assessments and noted for potential limitations with study retention and intervention contamination; drivers will be allowed to continue the study even if they are no longer working with the initial garage base
Newly diagnosed with colorectal adenocarcinoma at Ohio State University (OSU) (or a participating Ohio hospital) with sufficient tumor available to perform the microsatellite instability (MSI) test, regardless of age at diagnosis or family history
First-degree relatives of the cases who test positive for LS
First-degree relatives of the cases who test negative for LS
Prisoners
Individuals who are cognitively impaired
Lives in the Houston area (Harris county or a contiguous county) (Pre-pilot phase)
Eastern Cooperative Oncology Group (ECOG) status of 0 - 2, or self-reports being up and about more than 50% of waking hours and able to provide self-care (Arm 1)
Has a valid home address and functioning home telephone number (Arm 4)
Lives in the Houston or surrounding area, or resides in this same area during the time period that coincides with this study (Arms 1-4)
Patients who will undergo curative pancreatectomy for pancreatic adenocarcinoma, pancreatic neuroendocrine tumors, or pancreatic cysts (malignant or benign) (PCS study)
Self-reports hypertension that is not being monitored by a physician and is not being managed with either medication, observation, or lifestyle change (Pre-pilot phase, Arms 1-3)
Overt cognitive difficulty demonstrated by not being clearly oriented to time or person or place (Arms 1-4)
Orthopedic, neurologic, or musculoskeletal disability that would interfere with the functional task of standing on a weight scale (Pre-pilot phase, Arm 2)
Zubrod performance status > 2, or self-reports either not being up and about more than 50% of waking hours or unable to provide self-care (Arms 2 and 3)
History of current oropharyngeal dysphagia unrelated to cancer diagnosis (e.g. dysphagia due to underlying neurogenic disorder) (Arm 3 only)
Currently enrolled in protocol 2014-0712 (PCS study)
No home WiFi connection (PCS study)
Recent fracture or acute musculoskeletal injury that precludes the ability to fully bear weight on all 4 limbs in order to participate in an exercise intervention (PCS study)
Poorly-controlled pain with a self-reported pain score of 7/10 at the time of enrollment (PCS study)
Mothers self-identified as primary caregivers to minor-age children ages 8-17 years old participating in genetic counseling and testing for BRCA 1/2 mutations
Mothers need to be free of serious mental illness (e.g., cognitive and psychotic disorders) or developmental disability that would limit participation or preclude informed consent
Have at least one of 10 pre-defined anatomic mucosal subsites on view
Presence of mucosal ulceration at baseline
Oncology providers and staff at Moses Cone Health System (MCHS)
African American or White patients who reside in Guilford County, NC or Allegheny County, Pennsylvania (PA)
Uninsured or Underinsured
Colonoscopy not completed in the last 10 years
Sigmoidoscopy not completed in the last 5 years
Fecal Occult Blood Test (FOBT) or fecal immunochemical test (FIT) not completed in the last year
Complete contact information on file
Not incarcerated or homeless
Insured but not underinsured
Colonoscopy completed within the last 10 years
Sigmoidoscopy completed within the last 5 years
FOBT or FIT screening completed within the last year
Incomplete contact information (i.e., no address or phone number on file)
Incarcerated or homeless
Be interventional trials
Set monthly accrual target >= 1/ and annual accrual target >= 12
Missouri residents
Calling for themselves
Not in acute crisis
Willingness to receive calls from others (i.e., coaches, navigators) to help them quit smoking and address barriers to cessation
Willingness to provide multiple contacts (i.e., phone numbers, addresses of close others) if not reached for follow-up assessments
Do not own a smart phone
Unable to respond to text messages and questions or unable download the study app
Unable to see the app and study materials and videos (i.e., are blind, deaf)
RETROSPECTIVE STUDY POPULATION
Patient on the gynecologic oncology service
Admitted to Seidman 6th floor of the Seidman Cancer Center
Diarrhea or clinical concern for C. difficile infection
PROSPECTIVE STUDY POPULATION
Residents covering the gynecologic oncology service
Those who do not wish to participate
Individuals who are prisoners
Patient of the Internal Medicine Clinic at University of North Carolina (UNC) Health Care
Coughed up blood from lungs (also called hemoptysis) within the past year prior to enrollment
FOCUS GROUP SUBJECT SELECTION
Half of the participants will be overdue for CRC screening and the remaining half will be current on their screening, as defined by national published guidelines
RANDOMIZED-CONTROLLED TRIAL SUBJECT SELECTION
Scheduled to see a primary care provider for a routine (i.e., non-urgent care) visit
Specific CRC risk factors, including:\r\n* First degree relative with CRC\r\n* Personal history of adenomatous polyps\r\n* Recent blood in stools\r\n* Currently taking medication for a diagnosis of dementia
Part 2 only: did not complete part 1 of the study
Short portable mental status questionnaire (SPMSQ) score of less than \intact mental functioning\ (3 or more errors)
Significant psychiatric or cognitive disturbance sufficient, in the consenting professional's or investigator's judgment, to preclude providing informed consent or participating in the interventions (i.e., acute psychiatric symptoms which require individual treatment)
Outpatients (either new referrals or follow ups) seen in the supportive care clinic
Patients with normal cognitive status (Memorial Delirium Assessment Scale [MDAS] =< 6/30) who are able to understand the nature and purpose of the study and have the ability to complete the consent process
Altered cognitive status as determined by the interviewer based on the ability to understand the nature of the study and consent process
Documented cirrhosis
Undiagnosed cirrhosis
Any Parkland outpatient visit during study period
Inclusion and exclusion criteria for the ETRIC randomized study will be the same as the\n        eligibility criteria for the BMT CTN parent studies. Please refer to BMTCTN0901\n        (NCT01339910) Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or\n        Myelodysplastic Syndrome, BMTCTN1101 (NCT01597778) Double Cord Versus Haploidentical,\n        BMTCTN1203 (NCT02208037) Novel Approaches for Graft-versus-Host Disease Prevention Compared\n        to Contemporary Controls, and BMTCTN1301 (NCT02345850) Calcineurin Inhibitor-Free\n        Interventions for Prevention of Graft-versus-Host Disease for detailed eligibility\n        criteria.\n\n        Notes: Enrollment on the BMT CTN 0901 trial (NCT01339910) was closed to further accrual on\n        April 18, 2014. Enrollment on the BMT CTN 1203 trial (NCT02208037) completed accrual on May\n        13, 2016.\n\n        Additional inclusion criteria specific for the ETRIC study will include:\n\n          1. Adult patients (? 18 years)\n\n          2. Speaking and reading proficiency in English (as most of this study's instruments have\n             not been translated and validated in languages other than English)\n\n          3. Willing and able to provide informed consent\n\n          4. Stated willingness to comply with study procedures and reporting requirements\n\n        Exclusion Criteria: N/A
Undergoing routine oncology care and surveillance at the chosen site (defined as receiving follow-up care with FCCC or FCCCP site health care providers and have an active medical chart)
Health care providers at the participating site must be willing and able to participate in the educational initiative
Charts eligible for audit after completion of the educational initiative will be for those CRC and NSCLC survivors presenting for follow-up after the initiative has been completed by site health care providers
Fox Chase Cancer Partners sites who do not agree to chart audit procedures or providers are unable or unwilling to participate in the educational initiative
Participants will be patients scheduled to visit the Barnes-Jewish Hospital (BJH)/Washington University (WU) Department of Otolaryngology clinic for management of thyroid disorders (ranging from benign to cancerous nodules or masses) that will involve surgical interventions of complete or partial thyroidectomies
Have not participated in a clinical trial before
Reasonably able to read a newspaper or book (without sight impairment)
Reasonably able to listen to radio, television (without hearing impairment)
CLINICIANS:
Displays ability to use and understand the PMSA as evidenced by successful response to alarm and successful entries while monitored by the principal investigator (PI)
Smoking cigarettes for at least 3 years (so that smoking is expected to be reasonably established)
Smoking, on average, 4-27 days per month (the lower limit avoids including intermittent smokers [ITS] whose smoking is so sparse that it cannot be stably observed or assessed over a 2-week period; the upper limit avoids recruiting people who are essentially daily smokers.)
Smoking non-daily for the previous one year
Willingness to try novel cigarettes
Willingness and ability to come to the University of Pittsburgh’s Smoking Research Group lab for 11 visits over a 12-week period, and to report on smoking behavior via an IVR telephone system during that time
Active plans to quit or actively seeking smoking cessation treatment in the next 3 months. (Subjects are permitted to quit during the study, and this will be assessed and analyzed, but those with stated active intention to quit at the time of screening will not be included.)
Exclusive use of roll-your-own cigarettes (since the study uses manufactured cigarettes); and cannot be currently smoking more than 1/3 of roll your own cigarettes
Night and/or ‘swing’ shift work (which complicates phone-based reporting system)
Other household members are participating or have participated
At first session, reporting smoking 28 or more days of the past 30, or registering a carbon monoxide (CO) reading of 15 or above
Only women considering mastectomy will be eligible; that is, women who have definitely selected lumpectomy will not be approached
All patients who have received anti-CD19 directed CART therapy and completed or discontinued early from a Novartis sponsored treatment protocol that utilized CD19-directed CART cells or from any CD19 CART trial sponsored by the University of Pennsylvania with which Novartis has a contractual agreement to co-develop the CAR technology.
Recipients with AML will be recruited by personnel at the transplant centers (TC) who are candidates for URD HCT
Thrombocytopenia < 150 x 10(9)/L (< 150,000/µL) at baseline evaluation.
Current treatment with lithium. Drug interactions between filgrastim and lithium, which may potentiate the release of neutrophils, have not been fully evaluated.
Be scheduled to receive one of 3 myeloablative conditioning regimens (defined in population) followed by allogeneic SCT for hematological malignancy.
Be willing and capable of completing the assessments and adhering to protocol requirements.
Subjects receiving pre-transplant conditioning/GVHD prophylaxis regimens other than those defined, herein.
Candidate for bronchoscopy
Abnormal blood results
Implantable cardioverter defibrillator.
Cardiac pacemaker with heart rate (HR) set at a fixed rate and treatment with concomitant medication that may limit increase in HR in response to hypotension (example, high-dose beta blocker).
Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. Entry Criteria for Continuation to Optional Part B: After completing Part A of the study, participants may choose to enter the optional Part B of the study. To be eligible for the optional Part B, participants must have completed Part A and be reassessed to determine if they meet the entry criteria for optional Part B. Only participants who meet the following criteria may enter into Part B:
Patient scheduled for radical retropubic prostatectomy
Actively taking blood thinning agents (with the exception of low dose aspirin {81 m
Patient is mentally incompetent or a prisoner
Individuals who are unable to complete study materials
Fever (> 38° Celsius [C]), chills or rigor
Fatigue or lethargy
Cachexia or edema
Cough, dyspnea, airway hyperreactivity, or nasal inflammation
Nausea, anorexia, abdominal pain or altered bowel habit
Arthralgia or myalgia
Hyponatremia (sodium < 135 mmol/L)
RADIOGRAPHIC ABNORMALITIES
Pathologic lymphadenopathy (at least five discrete nodes each > 1cm in their longest dimension)
Splenomegaly (> 12 cm in the longest dimension)
Hepatomegaly (> 17cm in the longest dimension)
Body cavity effusions not caused by primary effusion lymphoma nor chylous effusions directly related to lymphatic infiltration by KS
Exposure risk for KSHV infection (including being a first or second generation immigrant from an endemic area, or male-to-male sexual activity) or evidence of KSHV infection demonstrated by one of:\r\n* Molecular evidence of KSHV in whole blood, confirmed by testing at Focus Laboratories, CA (human herpes virus-8 [HHV-8] quantitative polymerase chain reaction [PCR], Focus Unit Code 45700)\r\n* Immunohistochemical evidence of KSHV in tissues (for example by staining for latency\r\nassociated nuclear antigen [LANA] or viral [v] IL-6) confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI)\r\n* Presence of KS or primary effusion lymphoma (PEL) (KSHV-associated malignancies), confirmed in the Laboratory of Pathology, CCR, NCI
Biopsy proven KSHV-associated multicentric Castleman disease (MCD), confirmed in the Laboratory of Pathology, CCR, NCI
Any abnormality that would be scored as NCI Common Terminology Criterial (CTC) grade 4 toxicity that is unrelated to HIV, its treatment, or to KICS that would preclude the use of all of the study treatments or the ability to monitor the natural history of KICS untreated
Personal phone with SMS text messaging capability
Currently fasts 12 hours or more (on either of two 24 hour diet recalls, conducted during interim 1)
Unable to fast due to medical reason such as pregnancy
Willingness to travel to National Institutes of Health (NIH) for follow-up visits
A personal email address
Men who have contraindications to exercise based the American College of Sports Medicine 2016 Exercise pre-participation screening criteria and who do not receive a physician clearance to participate in the moderate intensity physical activity with one or more of the following self-reported conditions:\r\n* heart attack\r\n* heart surgery, cardiac catherization, or coronary angioplasty\r\n* pacemaker/implantable cardiac defibrillator/rhythm disturbance\r\n* heart valve disease \r\n* heart failure \r\n* heart transplantation \r\n* congenital heart disease \r\n* diabetes \r\n* kidney (renal) disease\r\n* chest discomfort with exertion \r\n* unreasonable breathlessness \r\n* dizziness, fainting or blackouts \r\n* ankle swelling \r\n* unpleasant awareness of forceful, rapid or irregular heart rate \r\n* burning or cramping sensations in your lower legs when walking short distance
Food or beverages containing grapefruit, Seville oranges, or Star fruit within 5 days before the first dose of study drugs. Note that food and beverages containing grapefruit, Seville orange, or Star fruit are not permitted during the study.
Have not recovered from adverse events due to other pharmaceutical or diagnostic agents.
Criteria 3, There is invasion by cancer into the main blood vessels such as the portal vein, hepatic vein or the vena cava
Biliary tract adenocarcinoma.
Concomitant diseases/conditions:
Adequate coagulation defined as:
Corticosteroids: no restrictions
Photosensitizing drugs, medications which might generate fluorescence or according to label, might generate photochemical reaction. These include hematoporphyrin derivatives and purified fractions; Photofrin®; and precursors of protoporphyrin IX (5-Aminolevulinic acid) used in Gliolan or Hexvix
Acuity of surgical needs: Subjects with acute neurologic compromise, symptoms of impending cerebral herniation, or other condition(s) necessitating urgent or emergent neurosurgical intervention to be planned within 2 hours not eligible. NOTE: If subject is enrolled on study, receives study medication and subsequently condition worsens such that urgent surgical intervention is felt to be in best interest of subject, best interest of subject should always take precedence over timing between study medication and surgery
A plan to treat with radiotherapy
N0 and M0 at the time of study entry.
Diffuse tumors or multiple malignant tumors in the breast.
Patient dosed with UCART19 who completed or discontinued early from a sponsored or from any investigator-initiated study that tested UCART19, or patients who were administered UCART19 under a special access scheme (compassionate use);
Individual test orders; defined as single biomarker assessment
Due to the complexity of state and federal requirements governing the participation\n             of prisoners in research, prisoner-patients shall not be approached for participation\n             in the Registry.
Positive Coombs tests at screening.
The patient must be able to communicate and understand/complete forms/instructions, and be able to provide informed written consent prior to enrollment; patients may have the assistance of an interpreter or surrogate when completing forms/surveys as needed
Sedentary baseline lifestyle, with an average of < 180 minutes/week of moderate-intensity aerobic activity
Attending surgeon clearance to undergo a supervised exercise training program
Contraindication to exercise training, such as skeletal metastases, symptomatic coronary artery disease, severe anemia, or any condition limiting their ability to participate in an exercise training program
Daily smoker;
Generally good health;
Unable to read for comprehension or completion of study documents.
At least 1 but no more than 2 prior systemic anti vascular endothelial growth factor (anti-VEGF) treatments
Target Population
Men and women diagnosed with CP-CML, on treatment with dasatinib for a minimum of 2 years at the time of enrollment and in dasatinib-induced complete molecular remission ongoing for at least 1 year prior to study entry.
Patients who have not achieved a 1-log reduction in BCR-ABL transcript levels compared with baseline as determined by local standards or > 10% IS [International Standard]) documented at 3.0-6.5 months since the initial start of dasatinib therapy.
Sex and Reproductive Status
Prisoners or subjects who are involuntarily incarcerated
Any patient who has lost MMR and is eligible for re-starting dasatinib therapy must not have developed a condition that precludes dasatinib use.
Active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis).
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV-1 induced complications (eg, immunosuppressed individuals, HIV-positive individuals, pregnant women, or children under the age of 1 year) during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
current smoker of at least 5 cigarettes per day for at least 1 year
at least some concern for health effects of smoking
having an easily accessible email address
lifetime ever purchase of any e-cigarette
The patient is at least 18 years old.
The patient has serum electrolytes (including calcium, magnesium, phosphorous, sodium and potassium) within normal limits (supplementation to maintain normal electrolytes is allowed).
The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids.
The patient is receiving colony stimulating factors (CSFs) that cannot be held during the monitoring period for dose-limiting toxicities (DLT).
Only subjects previously participating in two specific studies are eligible to enroll into this study. Enrollment is not open to subjects if not previously enrolled in studies B1871006 or B1871008.
All subjects are excluded unless previously participating in studies B1871006 or B1871008.
Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification\
Patient in MR4.5 at prescreening at Novartis designated lab
Potassium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
Magnesium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
Previous anticancer agents for CML other than nilotinib except for cytoreduction after CML diagnosis until up to 4 weeks after first dose of nilotinib
LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher)
Complete left bundle branch block
Right bundle branch block plus left anterior or posterior hemiblock
poor cytogenetics
adenocarcinoma of the colon or rectum
synchronous tumors
Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab)
SCLC or PAC that is advanced or has spread to other parts of the body
Minimal limitations on activities of daily living as measured by Eastern Cooperative Oncology Group (ECOG) score of 0-1
no CHR by 12 weeks (whether lost or never achieved)
no partial cytogenetic response by 24 weeks (ie, 1 to 35% Ph-positive) (whether lost or never achieved) no major cytogenetic response by 52 weeks (ie, ?35% Ph-positive) (whether lost or never achieved)
Other criteria may apply, please contact the investigator for additional information
Other criteria may apply, please contact the investigator for additional information
Adequate baseline hematological and organ function, assessed by laboratory values prior to study treatment as follows: absolute neutrophil count (ANC) > 1.0 x 109/L; hemoglobin > 7 g/dL; serum creatinine < 2 x institutional upper limit of normal (IULN); aspartate transaminase (AST) < 2.5 x IULN; alanine transaminase (ALT) < 2.5 x IULN; (if liver metastases are present, ALT and AST < 5 x IULN); total bilirubin < 1.5 x IULN.
Patient must be willing and able to undergo the imaging studies outlined in the protocol.
Known bladder outlet obstruction.
Subjects with a known current condition of substance addiction.
Subjects who will have administration of methylene blue or any blue dye used for sentinel node mapping procedures.
Subjects with prior reduction mammoplasties or breast reductions performed less than 2 years prior to enrollment to this study.
able to stand independently
not experiencing psychiatric neurological disorders (assessed through clinical team members) that would prevent obtaining consent.
currently experiencing psychiatric or neurologic disorders that would prevent their ability to provide consent.
Known or suspected sensitivity to diagnostic imaging contrast agents.
Known or suspected sensitivity to indocyanine green (ICG).
Specific serum electrolyte levels
Heart rhythm disturbances
Previous exposure to OTL38
Known sensitivity to fluorescent light
recruited through primary care sites aligned with study
Relapsed or progressive advanced malignancies (solid tumors or hematologic malignancies)
Clinical diagnosis of chronic hepatic impairment that is stable with no acute worsening of liver failure within one month prior to enrollment. Hepatic impairment will be assessed as per National Cancer Institute Organ Dysfunction Working Group Criteria (NCI-ODWG) schema and will fall into one of the following three categories:
Cohort 3 (moderate): ? 1.6-3 × ULN; any AST
Significant neurotoxicity (Grade 2 with pain or higher) at the time of enrolment
Waldenström Macroglobulinemia
Inclusion:\n\n        A parent trial must :\n\n          -  have a coordinating Center willing to allow their Clinical Sites to participate;\n\n          -  be studying be studying a condition that requires community or health system physician\n             referral\n\n          -  be studying an intervention where the recruitment approach cannot be made directly to\n             minority community members\n\n          -  need to increase recruitment of racially/ethnically diverse participants* to the trial\n             as demonstrated by current trial progress or historical data from other trials in the\n             same disease;\n\n          -  be a Phase II or Phase III trial\n\n          -  be conducted in at least six multiple sites;\n\n          -  expect each Clinical Site to recruit at least 10 participants;\n\n          -  be funded by a sponsor (NIH or pharmaceutical company or other) that has a strong\n             commitment to recruiting racially/ethnically diverse subjects;\n\n          -  be willing to have investigators and coordinators attend a special training meeting\n             (at RECRUIT expense);\n\n          -  require randomization to intervention or control (could be best medical care or active\n             control or placebo or other type of control);\n\n          -  provide transportation costs for trial participants who need assistance in getting to\n             trial sites or use some RECRUIT reimbursement for this purpose.\n\n        The clinical site must\n\n          -  be a funded Clinical Site in the parent trial;\n\n          -  be located in an area where at least 20% of the population within 30 miles in the age\n             group under study in the parent trial are from diverse populations.\n\n        Exclusion Criteria:\n\n          -  site does not agree to be randomized;\n\n          -  investigator or coordinator is under 18 years of age.
Patient agrees to the collection and testing of their blood and is willing and able\n             to provide approximately 40mL blood draw(s) at:
Baseline (prior to the initiation of new ET), and;
Patients whose lung tumors are being monitored with MR imaging (MR imaging of the anchored transponders is safe but yields an image artifact around the anchored transponders).
Inclusion Criteria:\n\n          1. age 18 or older\n\n          2. former smoker who quit during pregnancy as assessed via self-report\n\n          3. smoked an average of greater than or equal to 1 cigarette per day during the year\n             prior to the current pregnancy\n\n          4. gestational age < 33 weeks and ability to attend an in-person visit at University of\n             Texas MD Anderson Cancer Center (UTMDACC) between 30-33 weeks of gestational age\n\n          5. can speak, read and write in English.\n\n          6. must have a functioning home or personal cell phone\n\n        Exclusion Criteria:\n\n        1) high-risk pregnancy or known negative birth outcome
Inclusion Criteria:\n\n          1. age 18 or older\n\n          2. former smoker who quit during pregnancy as assessed via self-report\n\n          3. smoked an average of greater than or equal to 1 cigarette per day during the year\n             prior to the current pregnancy\n\n          4. gestational age < 33 weeks and ability to attend an in-person visit at University of\n             Texas MD Anderson Cancer Center (UTMDACC) between 30-33 weeks of gestational age\n\n          5. can speak, read and write in English.\n\n          6. must have a functioning home or personal cell phone\n\n        Exclusion Criteria:\n\n        1) high-risk pregnancy or known negative birth outcome
The patient or legal designate must be able to complete study tools by the BMT social workers. Interpreters will be provided by UMMC for non-English speaking pt's and BMT social workers will assist patients who cannot read.
Patients who do not have any identified any potential legal needs, or whose legal needs are beyond those covered in the I-Help model.
Patients who are not residents of Minnesota as CALL attorneys are only licensed to practice law in Minnesota.
Subjects who cannot adhere to the experimental protocols for any reason, or have an inability to communicate with the researcher
Prisoners
Any medical conditions that would impose excessive risk to the patient, or would adversely affect his/her participation in the study
Patient is currently undergoing AML-like intensive induction, re-induction/salvage, or consolidation chemotherapy, or planned to start such therapy within 1 week
Willingness to have close follow-up and treatment at the Clinic at the Seattle Cancer Care Alliance (SCCA) or at a local facility; typically, patients will be seen at least 3 times per week as per standard practice, including at least once weekly at the SCCA
Permanent or temporary housing available within a 60 minute (min) commute from the SCCA
Available caregiver
Cognitive impairment
Scheduled for endoscopic screening and/or evaluation of Barrett’s esophagus
Symptoms of dysphagia
All subjects or legally appointed representatives/caregivers, must personally sign and date the IRB/IEC approved consent form before initiating any study specific procedures or activities.
Positive test for HbsAg, or positive test for HBcAb (unless serology is positive due to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if HBsAb is present.
For those enrolled in Adjuvant Treatment with Optune™, patients are excluded if they are < 22 years of age, have an active implanted medical device, a skull defect, bullet fragments in the head, sensitivity to conductive hydrogels, a scalp condition that might interfere with wearing the device, or GBM that is not supratentorial.
Women ? 18 years old
Non-epithelial ovarian cancers, including malignant mixed Müllerian tumors.
Ovarian tumors with low malignant potential (i.e. borderline tumors).
Selected electrolytes within normal limits or correctable with supplements.
Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP)
Female participants who:
Are postmenopausal for at least 1 year before the Screening visit, or
To be enrolled in the TNBC expansion cohort, participants must have:
To be enrolled in the NSCLC expansion cohort, participants must have:
To be enrolled in the HNSCC expansion cohort, participants must have:
Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/college of American Pathologists (ASCO/CAP) guidelines.
Serum albumin <25 gram per liter (g/L)
Gleason score (GS): 8-10
Gleason score (GS) 4+3=7
Absolute Neutrophils > 1.5 x 109/L
Males have undergone sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate, or
History of colorectal surgery, or repeated endoscopic examinations/interventions related to anorectal diseases or proximal urethral stricture requiring dilatation
Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC (Centers for Disease Control) definition
Subjects with congenital long QT syndrome or subjects taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. subjects with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events
Presence of bilateral hip replacement prostheses
CRITERIA FOR PLASMA GENOTYPING
Tissue must be available for genotyping or biopsy planned to obtain tissue for genotyping; biopsy requirement may be waived if not technically feasible and plasma genotyping reveals an eligible EGFR mutation (exon 19 del/L858R); determination of technical feasibility must be made independently of plasma genotyping results
Participants must possess at least two of the following clinical characteristics which enrich for EGFR mutations:\r\n* Smoked less than 10 pack years\r\n* Asian race\r\n* Adenocarcinoma (including adenosquamous carcinoma) on histology or cytology
CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).
In France, a subject will not be eligible when under legal protection.
Primary ocular or mucosal melanoma.
Active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis).
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV-1 induced complications (immunosuppressed individuals, HIV-positive individuals, pregnant women, or children under the age of 1 year) during talimogene laherparepvec treatment and through 28 days after the last dose of talimogene laherparepvec.
No ongoing requirement for dexamethasone or anti-epileptic drugs.
Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS)
Hysterectomy, or vasectomy of the partner (provided that partner is the sole sexual partner of the woman of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success) In addition, the use of condoms for patients or their partners is required
BPDCN
Absolute blast count ?10,000/mm3 or symptoms of leukostasis
Follicular variant
Hurthle cell
Insular
One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan.
Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies or any ongoing treatment for RR-DTC other than TSH-suppressive thyroid hormone therapy.
Women without histologic confirmation of nodal involvement
Active collagen vascular disease, specifically dermatomyositis with a creatine kinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
Women must have newly diagnosed histologically confirmed ER positive (+) DCIS scheduled to undergo surgical therapy; the pathology report (signed pathology report from attending pathologist) from each individual institution will be used to determine eligibility\r\n* Note: After the patient has completed the study and the slides have been sent to Northwestern University (NU), our pathologists will review the slides to confirm the diagnosis\r\n* Note: DCIS suspicious for micro invasion is eligible on core biopsy
DCIS must be >= 5 mm of DCIS on one single core; can be < 5 mm if DCIS is identified on multiple cores (at least 2 cores)
Women presenting after excision with positive margins are eligible; Ki-67, cyclooxygenase 2 (Cox-2), cyclin-dependent kinase inhibitor 2A (P-16), expression in immediately adjacent tissue is similar to what is found in DCIS\r\n* Note: Positive margins are defined as DCIS present at the inked margin or DCIS < 1 mm from the margin
Current hormone replacement therapy (HRT), selective estrogen receptor modulator (SERM) or aromatase inhibitor (AI) use; if yes, the wash-out period is 30 days before diagnostic core needle biopsy\r\n* Note: local therapy (i.e. estrogen cream) will be permitted due to low systemic absorption of estrogen\r\n* Note: if patient is registered prior to completed washout, diagnostic core needle biopsy date will need to be provided
Unexplained/undiagnosed abnormal uterine bleeding (concern for undiagnosed endometrial cancer)
Has completed or scheduled to begin 4-6 cycles of platinum-based induction chemotherapy that does not include a taxane\r\n* Induction may contain, but is not required to contain bevacizumab or cetuximab; induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina (UNC) principal investigator (PI) that there is no additional risk to the subject\r\n* Day 1 (D1) of treatment on LCCC1516 must be 21-42 days from the last day of induction, consistent with timing of standard of care maintenance
Had inadequate home environment or social support to safely complete the trial procedures
Has responded (achieved a CR or PR) to BV or BV-containing regimens, if previously treated with BV.
Isolated extramedullary relapse.
Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)
Pregnant or actively breastfeeding without intention to discontinue prior to initiation of study
Unable to take drugs orally
At least 2 distinct measurable metastatic sites, which are 1 cm or larger
has a substantial probability to cause an irreversible injury to any tissue and/or
Positive HBs Ag or positive HBV viremia, Positive HCV viremia.
Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy
Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
Serologic status and/or polymerase chain reaction (PCR) testing reflecting active hepatitis B or C infection
Ineligible for high dose cisplatin therapy; the reason for ineligibility must be defined; acceptable reasons for ineligibility include the following:\r\n* Abnormal renal function (glomerular filtration rate [GFR] < lower limit of institutional normal (< lower limit of institutional normal [LLN])\r\n* Abnormal hearing (patient or audiology defined)\r\n* Pre-existing tinnitus\r\n* Neuropathy (bilateral paresthesias or loss of deep tendon reflexes in upper and/or lower extremities)\r\n* Diabetes mellitus\r\n* Oncologist-certification that patient would not be considered eligible for high dose cisplatin when given as standard of care (for example, due to age or another medical problem); reason should be documented\r\n* Patient refusal for high dose cisplatin
Has inadequate home environment or social support to safely complete the trial procedures