3899 lines (3898 with data), 840.0 kB

Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to acute myeloid leukemia (AML) with more than 20% blasts at relapse are not eligible for this trial
Patients must not be known to be refractory to red blood cell or platelet transfusions
Availability of pulmonary function tests (PFTs – spirometry, diffusing capacity of the lungs for carbon monoxide [DLCO], +/- arterial blood gases) within 90 days prior to registration; patients with tracheotomy, etc, who are physically unable to perform PFTs are potentially still eligible if a study credentialed thoracic surgeon documents that the patient’s health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection)
Patients previously untreated or treated with drug therapy for epithelioid hemangioendothelioma (EHE) are eligible; there is no limit on the number of prior regimens used to be eligible
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
Patients must have had histologic verification of malignancy at original diagnosis or relapse\r\n* Parts A & C: patients with recurrent or refractory solid tumors, without central nervous system (CNS) tumors or known CNS metastases, are eligible; note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated\r\n* Part B1: patients with relapsed or refractory neuroblastoma\r\n* Part B2: patients with relapsed or refractory osteosarcoma\r\n* Part B3: patients with relapsed or refractory rhabdomyosarcoma\r\n* Part B4: patients with relapsed or refractory Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET)\r\n* Part B5: patients with relapsed or refractory Hodgkin lymphoma\r\n* Part B6: patients with relapsed or refractory non-Hodgkin lymphoma\r\n* Part B7: patients with unresectable melanoma or metastatic melanoma or relapsed melanoma or refractory melanoma\r\n* Part B8: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without Response Evaluation Criteria in Solid Tumors [RECIST] measurable lesion)\r\n* Once the dose-escalation portion of Part A is completed, cohorts that are open concurrently for eligible patients (including Parts B and C and potential pharmacokinetic [PK] expansion cohorts) may be selected at the treating physician’s discretion pending slot availability; in the event a disease group cohort in Part B is completed after the initial stage of Simon’s optimal two-stage design, for selected disease cohorts, a corresponding cohort in the same disease group for select disease types will be open in Part D:\r\n* Part D1: Patients with relapsed or refractory neuroblastoma\r\n* Part D2: Patients with relapsed or refractory osteosarcoma\r\n* Part D3: Patients with relapsed or refractory rhabdomyosarcoma\r\n* Part D4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET \r\n* Part D5: Patients with relapsed or refractory non-Hodgkin lymphoma\r\n* Part D6: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without RECIST measurable lesion)\r\n* Part E3: Patients with relapsed or refractory rhabdomyosarcoma\r\n* Part E4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET
Patients with a history of any grade autoimmune disorder are not eligible; asymptomatic laboratory abnormalities (e.g. antinuclear antibody [ANA], rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder
Patients with >= grade 2 hypothyroidism due to history of autoimmunity are not eligible; note: hypothyroidism due to previous irradiation on thyroidectomy will not impact eligibility
Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531
Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
Patients must have an acceptable MDS subtype:
Patients with recurrent or refractory solid tumors, including CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria: \r\n* Peripheral absolute neutrophil count (ANC) >= 750/mm^3\r\n* Platelet count >= 50,000/mm^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions)\r\n* Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions, provided they are not known to be refractory to RBC transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
Patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or in patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients must be accessible for treatment and follow-up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.
Patients who plan to receive yellow fever vaccine during the course of the study treatment.
For patients to be treated with a regimen containing bevacizumab:
Patients with carcinomatous meningitis should also be excluded
Patients with known macular degeneration, uncontrolled glaucoma, or cataracts are not eligible
Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Part A: Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors
Part B: Patients with relapsed or refractory neuroblastoma
Part C: Patients with relapsed or refractory medulloblastoma or CNS PNET
Part D: Patients with relapsed or refractory rhabdomyosarcoma
Patients previously treated with irinotecan are eligible for this study
Patients known to have BRCA1/2 gene mutations (testing for gene mutations is not required)
Patients with recurrent or refractory solid tumors, including CNS tumors and lymphoma, for which no standard therapy is available are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients who are receiving any investigational agent other than pevonedistat, including but not limited to androgens, supraphysiologic doses of corticosteroids, erythropoietin, eltrombopag, or romiplostim
Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization
Patients must have pre-treatment blood and tissue specimens submitted for translational medicine as outlined; with patient consent, residuals will be banked for future research
Patients (at National Cancer Institute [NCI] Community Oncology Research Program [NCORP] Institutions only) must be offered the opportunity to participate in the S1207-E01 Behavioral and Health Outcomes study (BAHO); NOTE: patients who have already started endocrine therapy are eligible for the BAHO study
Patients must be enrolled within 1 year after diagnosis
Patients with a prior history of gastric/duodenal ulcers documented on endoscopy can be enrolled as long as the ulcers did not cause bleeding requiring a blood transfusion/major intervention; for patients who are Helicobacter pylori positive, a course of Helicobacter pylori eradication treatment must have been completed
For patients who undergo mastectomy, the margins must be free of residual gross tumor; (patients with microscopic positive margins are eligible as long as post-mastectomy radiation therapy [RT] of the chest wall will be administered)
Patients must have been assigned to S1400F
Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens
Patients are eligible under ONE of the following criteria:\r\n* Patients must have histologically confirmed rare cancer and must be able to submit specimens; NOTE: Subsequent to site’s Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 “National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)” to register to this study\r\n* FOR PATIENTS ENROLLED IN EAY131 “NCI-MATCH” PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 “NCI-MATCH” protocol or who are off protocol treatment on EAY131, “NCI-MATCH” and have no further molecularly-matched treatment recommendations per EAY131, “NCI-MATCH” or who are otherwise unable to receive EAY131, “NCI-MATCH” therapy
Patients that do not qualify for one of the histologic cohorts may be considered for registration in the “Not Otherwise Categorized” Rare Tumors cohort with confirmation of at least one of the study chairs via email
Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
STEP II: Patients must have complete induction without experiencing progression or patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but stopped induction therapy due to adverse events
Patients must not have a clinically relevant hearing impairment >= grade 2
Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization
United States (U.S.) patients who can complete the survey and the interview by telephone or email in English must be offered participation in the S1400GEN survey ancillary study; NOTE: Patients enrolled to S1400 prior to revision #12 are not eligible for the S1400GEN survey ancillary study; study physicians will provide participants with a hard copy of the survey (at the time of informed consent) to improve tracking and comprehension during the interview
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients must be given the opportunity to consent to the optional submission of tissue and blood for future research
Patients must be offered the opportunity to participate in specimen banking
Patients with cutaneous or superficial lesions that do not require imaging guidance for biopsy must be willing to undergo biopsies for tissue submission and blood draws for translational medicine
Patients must be registered to step 2: randomization within +/- 5 days of starting cycle 2; patients MUST NOT be registered prior to the day 56 disease assessment
Patients with rheumatoid arthritis and other arthropathies, Sjogren’s syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
Patients must have completed a minimum of 10 weeks of single agent nivolumab on arm 1 of A091401 to be eligible for re-registration
Patients may be treated with bone modifying agents such as bisphosphonates or RANK-ligand agents (e.g. denosumab) per American Society of Clinical Oncology (ASCO) guidelines; whenever possible, patients requiring bone modifying agents should start treatment >= 7 days prior to study therapy and should continue the same agent throughout study unless clinically compelled to change
Patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive\r\n* NOTE: Any patient with BRAF V600 mutant melanoma (whether cutaneous, acral or mucosal primary) who meets the eligibility criteria is eligible for participation in this trial; patients with uveal melanoma are not eligible for this trial
Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible
Patient who have undergone either a total mastectomy or a lumpectomy are eligible; (patients who have had a nipple-sparing mastectomy are eligible)
Patients must have tissue available and be willing to submit for independent pathologic review in order to classify type I versus type II papillary disease
Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
Patients must have a Ki-67 proliferative index of 20-100% OR at least 10 mitotic figures per 10 high powered fields
Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency will be excluded
Patients with impaired decision making capacity may participate in the study if a legal authorized representative is available to consent
Patients must NOT have absorption issues that would limit the ability to absorb study agents
Patients with tumors with the following molecular alterations must submit testing results via Medidata Rave to determine eligibility to Arm T; the study chair, co-chair, biology co-chair, or a delegate must review the molecular testing and agree that the testing meets eligibility outlined below:\r\n* ROS1 gene rearrangement by fluorescence in situ hybridization (FISH) or deoxyribonucleic acid (DNA) analysis (may have progressed on prior crizotinib therapy)\r\n* MET exon 14 splice mutations on DNA analysis (may have progressed on prior crizotinib therapy)\r\n* MET high amplification by FISH or DNA analysis or other MET mutations predicted to be sensitive to MET inhibitor (no prior targeted therapy allowed)\r\n* RET gene rearrangement by FISH or DNA analysis (no prior targeted therapy allowed)\r\n** Institutions will be notified of the patient’s eligibility status for Arm T within two (2) business days of submission of the molecular testing reports\r\n** If patients do not have tumors with the above molecular alterations noted proceed directly to step 1
For patients with known molecular alterations, institution has been notified that patient is deemed eligible for Arm T per review of molecular testing reports
REGISTRATION STEP 2-RANDOMIZATION: Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy; rationale for clinical determination or notation of patient decision must be made
REGISTRATION STEP 2-RANDOMIZATION: Patients who are transfusion-dependent and patients receiving growth factor support are eligible; patients must discontinue growth factor support prior to initiation of protocol therapy
Patients must have baseline troponin test performed for eligibility; however, no associated values must be met in order for the patient to be eligible
Patients with testing that did not show dMMR (loss of MMR protein) are not eligible to participate; patients whose tumors show MSI-H by polymerase chain reaction (PCR)-based assay are not eligible to participate unless they also have MMR testing by IHC and are found to have dMMR (i.e. loss of one or more MMR proteins)
Patients who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) are eligible to participate
SR1 and SR2 patients:
Patients with multifocal or multicentric invasive disease are eligible as long as all the lesions for which HER2 characterization is available are HER2 negative
Patients with synchronous bilateral invasive disease are eligible as long as all the lesions assessed for HER2 on both sides are negative
Patients must be offered the opportunity to participate in specimen banking
Patients must not be registered to step 2 until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status
Patients may or may not have been treated previously with a nonsteroidal antiandrogen, such as flutamide, bicalutamide or nilutamide; for patients previously treated with an antiandrogen, they must be off treatment for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration and must have shown PSA progression after discontinuing the anti-androgen
Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial
Patients who have met the pre-entry requirements
Patients with postoperative fistula
Patients whose circumstances do not permit completion of the study or the required follow-up
Patients with GOG performance status of 3 or 4
Patients must have resolved any serious infectious complications related to induction
Patients must have resolved any serious infectious complications related to therapy
Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance
Patients with grade 1 NRSTS tumors of any size are not eligible
Patients with active HCV infection should be referred for HCV treatment and standard radiotherapy for the plasmacytoma
Patients must have blood and tissue specimens collected prior to registration and submitted for translational medicine; note that patients without adequate diagnostic specimens will not be eligible; with patient consent, residuals from the mandatory submission will be banked for future research
Patients must have the following components of Follicular Lymphoma International Prognostic Index (FLIPI) available from diagnosis, and collected again at time of registration:\r\n* Age\r\n* Lactate dehydrogenase (LDH)\r\n* Number of nodal groups involved\r\n* Serum or plasma hemoglobin \r\n* Ann Arbor stage\r\nAdditionally, patients must have beta-2-microglobulin collected at time of registration
Patients must have Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
Patients who have met the pre-entry requirements
Patients who have circumstances that will not permit completion of this study or the required follow-up
Patients with GOG performance grade of 3 or 4
Participants may not have a second, clinically active, cancer; patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed
Patients post-prostatectomy with baseline Gleason >= 7 (per prostatectomy pathology)
Patients must be enrolled on AALL08B1 or APEC14B1 (if available for ALL patients) prior to enrollment on AALL1131
Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131
Shortening fraction >= 27% by echocardiogram, or ejection fraction >= 50% by gated radionuclide study \r\n* Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Frederica or Bazett formula\r\n* No major conduction abnormality (unless a cardiac pacemaker is present)
Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction
DS HR B-ALL patients with Induction failure or BCR-ABL1
Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study \r\n* Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131\r\n* Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)\r\n* Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William’s Syndrome, mental retardation)\r\n* Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction: \r\n* Day 29 MRD >= 0.01%\r\n* MLL rearrangement\r\n* Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
Patients with MYCN amplified tumors are not eligible
Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
Patients must be newly diagnosed with histologically confirmed intracranial ependymoma; patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above
Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma are NOT eligible
Patients should be deemed to be potentially eligible and willing candidates for auto-HCT by the enrolling physician
Patients must have no clinical or radiological evidence of distant metastases (M0)
Patients currently enrolled in other clinical trials testing a therapeutic intervention
Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
NOTE: A lumbar puncture is not required in order to be enrolled on study nor are lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms should be deferred until any coagulopathy is corrected; if central nervous system (CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma; if CNS disease is documented, patients are still eligible and will receive protocol directed intrathecal treatments
Patients with secondary APL are excluded; this includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation)
Patients with nodular lymphocyte-predominant HL
Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up.
If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study.
Patients judged capable of tolerating a radical course of chemoradiation therapy
Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population
Patients with a GOG performance status of 0, 1, or 2
Patients with vulvar melanomas or sarcomas
Patients with circumstances that will not permit completion of the study or the required follow-up
Patients with disease limited to the skin are not eligible, regardless of how wide-spread
Female patients who are pregnant are not eligible; pregnancy tests must be obtained in girls who are post menarchal
Patients with undetectable pre-treatment plasma EBV DNA
For patients enrolled on AALL08B1 or APEC14B1 (if open for ALL patients) prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled\r\n* For patients who have not previously enrolled on AALL08B1 or APEC14B1 (if open for ALL patients) prior to enrollment on AALL1631, a baseline diagnostic sample must be available to develop an MRD probe\r\n* In addition, laboratory reports detailing evidence of BCR-ABL1 fusion must be submitted for rapid central review within 72 hours of study enrollment
Patients can not have any neuroendocrine histology in pathology
Patients must not plan to participate in any other clinical trials while receiving treatment on this study or being followed post-protocol therapy
Patients must have had cytology within 21 days prior to registration; cytology for patients with CIS component is not expected to be negative for malignant cells; if the cytology for patients with only Ta/T1 disease is positive for malignant cells, patient must have had a biopsy of the prostatic urethra within the previous six months
Patients must be deemed unfit for radical cystectomy by the treating physician, or the patient must refuse radical cystectomy, which is considered standard of care for these patients; the reason for patients not to undergo cystectomy will be clearly documented
Patients must be offered the opportunity to participate in specimen banking for future studies, to include translational medicine studies
Charlson modified co-morbidity score =< 3 for patients under 60 and =< 4 for patients 60 and over 21 days prior to registration
Patients must be offered the opportunity to participate in specimen banking for future studies to include translational medicine studies
Patients must have a new morphologic diagnosis of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell) based on World Health Organization (WHO) criteria; patients with Burkitt's (L3) are excluded; patients with Ph-positive or Ph-like ALL with dasatinib-sensitive mutations or kinase fusions may have relapsed or refractory diagnoses\r\n* NOTE: Relapsed/refractory Ph-positive patients or Ph-like patients with dasatinib-sensitive mutations or kinase fusions who have previous exposure to either dasatinib or another 2nd or 3rd generation TKI will begin protocol therapy with Cohort 2: re-induction cycle 1
Cohort I, Ph-negative Patients Only
Cohort 2, Ph-positive and Ph-like DSMKF Patients Only
Patients must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing treatment regimen on protocol
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to the site’s preferred CLIA-approved cytogenetics laboratory; BCR-ABL status must be verified in Ph-positive patients by FISH, cytogenetics, and/or PCR prior to enrollment; if a patient is Ph-positive, PCR for both p190 and p210 must be sent
Patients must be offered participation in specimen submission for future research; with patient’s consent, specimens must be submitted as outlined
Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2
Patients must have advanced or metastatic MCC defined as evidence of distant metastasis(es) on imaging\r\n* Patients with locoregionally confined disease are not eligible
Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
A blood pressure (BP) =< the 95th percentile for age, height, and gender for pediatric patients < 18 years old and =< 140/90 mmHg for patients >= 18 years old; patients should not be receiving medication for treatment of hypertension (except patients with Wilms tumor and RCC who may be eligible if on stable doses of no more than one anti-hypertensive medication with a baseline BP =< ULN for pediatric patients and =< 140/90 for adult patients); please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
Patients who are receiving drugs that prolong QTc are not eligible
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in (may receive platelet or packed red blood cells [pRBC] transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive platelet or packed [p]RBC transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients must have a body surface area >= 0.37 m^2 at enrollment while the 120 mg strength tablet supply is available; patients < 0.73 m^2 must follow the dosing nomogram; patients >= 0.73 m^2 at enrollment must follow the dosing nomogram
Patients enrolled after the drug supply of the 120 mg strength has been exhausted must have a body surface area >= 0.73 m^2 at enrollment and follow the dosing nomogram
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in above criteria (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621D based on the presence of an actionable mutation; note that treatment assignment may be to primary cohort A for patients with TSC1 or TSC2 loss of function mutations, primary cohort B for patients with other PI3K/MTOR pathway mutations, a histology specific biomarker positive expansion cohort if the criteria to open such a cohort are met, or a biomarker negative expansion cohort if the criteria to open such a cohort are met
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible
Patients must have sufficient resolution of any surgical side effects (no active wound healing complications). -Patients must either be initiating or have already started adjuvant hormonal treatment. -
Patients crossing over from monotherapy to combination therapy do not have to be fully rescreened; however, they do need to meet performance status, organ function, and blood parameters and not meet any of the exclusion criteria
Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
Shortening fraction of >= 27% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E, and F]), or
Ejection fraction of >= 50% by radionuclide angiogram (for patients on doxorubicin-containing regimens (Groups C, D, E, and F)
Adult patients ? 18 years
Patients with MDS must have been diagnosed as MDS by WHO (4th edition) or French-American-British (FAB) classification
Patients with ocular melanoma.
HER2+ and HER2- patients are eligible
All patients must have diagnostic laparoscopy with diagnostic washings for cytology; both cytology positive and negative patients are eligible for enrollment, but only cytology negative patients will be included in the primary analyses; gross peritoneal disease is not eligible
Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g., *6) will be allowed and treated as in the *28/*28 dosing group
Patients must have a histologic diagnosis of pancreatic adenocarcinoma
Patients taking additional dietary/herbal supplements (excluding Senekot) outside of this protocol and refusing to stop are not eligible
Patients with ? 3 visceral metastases (excluding pulmonary lesions), with no lesions >3.0 cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor.
Patients with tumors to be injected 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 tumor swelling or erosion into a major vessel in the case of necrosis. Patients with lesions in mucosal areas (vulvar, anus, oral cavity, etc.), are eligible, as long as the subject has at least one lesion suitable for injection; consult Medical Monitor for confirmation.
Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less.
Patients previously treated with CVA21.
Patients with biopsy proven locoregional recurrence or second primary SCCHN which is unresectable or the patient is unwilling to undergo resection
Patients who are known to be experiencing an objective partial response to immunotherapy at the time of study enrollment
Patients with porphyria or psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Patients with a known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML) are not eligible
For patients with non-castrate levels of circulating androgen levels (testosterone >= 50 g/dl)\r\n* PSA levels should be increasing on at least two occasions >= 1 week apart\r\n* Patients should not be considered candidates for radiation therapy
Patients with a history of another malignancy within 3 years of the baseline visit. (Patients with cutaneous carcinomas or in-situ carcinomas will be considered for study entry on a case-by-case basis).
Patients planning to undergo radiation therapy for primary or recurrent carcinomas of the lung or oligo-metastatic carcinoma to the lung; Note: this may be delivered by SBRT or standard fractionation, based on the discretion of the treating physician
Patients who are able to tolerate flexible bronchoscopy
Patients able to have bronchoscopic placement of Calypso transponders as confirmed on a recent (within the past 8 weeks) CT scan
Patients with bronchiectasis in the region of the intended implantation sites
Patients who are deemed unable to safely undergo or tolerate flexible bronchoscopy
Patients who are unable to tolerate anesthesia or sedation
Patients enrolled in any other clinical studies the investigator believes to be in conflict with this investigation
Previous treatment with regorafenib AND TAS-102 (this applies to phase II only; if patients have previously received either regorafenib OR TAS-102, they must be able to receive the alternate regimen if randomized to the standard of care arm)
All participants must be prescribed combination antiretroviral therapy with the goal of virological suppression using an acceptable regimen that adheres to national guidelines for treatment of HIV infection; non-suppressed, treatment experienced patients, defined as patients with a viral load > 400 copies/mL who have been on antiretroviral therapy for more than 4 months can be enrolled if an alternative antiretroviral therapy (ART) regimen is available that includes at least two ART drugs that, in the opinion of the site investigator, are expected to have activity based on genotypic testing (if available) and treatment history; patients are not allowed to receive zidovudine (azidothymidine [AZT]) as part of concurrent chemotherapy and ART regimen, since it is myelosuppressive; zidovudine may be discontinued and substituted as clinically indicated prior to or at the time of enrollment
Patients with a rhabdomyosarcoma will be excluded
Patients with uncontrolled hyperlipidemia (total cholesterol > 350 or triglycerides > 300) are NOT eligible for participation
All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole must have sirolimus reduced according to the Standard Practice Antifungal Therapy Guidelines
Patients treated with prior interleukin-2 (IL-2).
Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.
Patients with recurrent brainstem tumors with an atypical presentation who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma WHO II-IV; these patients must undergo Rb1 screening; these patients must have radiographic evidence of progression
Patients with secondary malignant gliomas will be eligible for this study but should conform to all other eligibility requirements; patients with low-grade gliomas are excluded
Patients with recurrent diffuse intrinsic brain stem glioma (DIPG) that has an atypical presentation must also submit the tumor tissue for Rb1 protein status confirmation or provide previous testing results from a CLIA certified laboratory; patients who have been biopsied for atypical DIPG but do not have sufficient tissue for Rb1 screening are not eligible
Body surface area (BSA)\r\n* Patients enrolled on dose level -1 must have BSA >= 0.55m^2\r\n* Patients enrolled on dose level -0.5 must have BSA >= 0.75m^2\r\n* Patients enrolled on dose level 0 must have BSA >= 0.55m^2\r\n* Patients enrolled on dose level 1 must have BSA >= 0.75m^2\r\n* Patients enrolled on dose level 2 and 3 must have BSA >= 0.45m^2
Patients screened for this trial should be expected to meet the criteria for treatment
BSA\r\n* Patients enrolled on dose level -1 must have BSA >= 0.55m2\r\n* Patients enrolled on dose level -0.5 must have BSA >= 0.75m2\r\n* Patients enrolled on dose level 0 must have BSA >= 0.55m2\r\n* Patients enrolled on dose level 1 must have BSA >= 0.75m2\r\n* Patients enrolled on dose level 2 and 3 must have BSA >= 0.45m2
Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (i.e. filgrastim, sargramostim or erythropoietin); 2 weeks must have elapsed if patients received long-acting formulations
Dose Expansion Cohort #1 - Patients will have relapse of CD123+ BPDCN. Patients with prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.
Dose Expansion Cohort #2 - Patients will have first relapse of CD123+ AML.
Dose Expansion Cohort #3 - Patients will have relapse of CD123+ ALL.
For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin
Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
Assessment of HER2 status in patients with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
-  Relapsed or refractory, pathologically proven mantle cell lymphoma. Must have a\n             current or prior tissue sample that is IHC positive for cyclin D 1 or that is positive\n             by FISH or cytogenetics for t(11;14).\n\n          -  Must have been refractory to and/or relapsed/progressed after at least 1 prior\n             therapy.\n\n          -  Prior autologous or allogeneic transplant are allowed. Patients may not have active\n             grade II-IV acute graft-versus-host disease (GVHD) or moderate/severe chronic GVHD by\n             NIH criteria and may not require immunosuppressive medications and/or corticosteroids\n             for the management of acute or chronic GVHD.\n\n          -  Phase I: Prior proteasome inhibitor and/or Bruton's tyrosine kinase (BTK) inhibitors\n             are allowed but patients may not have been exposed to the combination of proteasome\n             inhibitor and BTK inhibitor. Patients who have progressed on ibrutinib that are felt\n             to be at high risk for rapid progression on this study shall not be eligible for the\n             phase I portion of the study. NOTE: Ibrutinib pre-treated patients must meet all\n             eligibility criteria AND must have discontinued prior ibrutinib at least 3 months\n             prior to starting study therapy.\n\n          -  Phase II: Prior proteasome inhibitor and/or Bruton's tyrosine kinase inhibitors are\n             allowed but patients may not have been exposed to the combination of proteasome\n             inhibitor and BTK inhibitor. NOTE: Patients must have tolerated prior ibrutinib (i.e.,\n             not discontinued therapy due to toxicity).\n\n          -  Age ? 18 years.\n\n          -  Eastern Oncology Oncology Group (ECOG) performance status of 0-2.\n\n          -  Ability to understand and willingness to sign Institutional Review Board\n             (IRB)-approved informed consent.\n\n          -  Willing to provide archived tumor tissue and blood samples for research.\n\n          -  Adequate organ function as measured by the following criteria\n\n               -  Absolute Neutrophil Count (ANC) ? 750/mm³\n\n               -  Platelets ?50,000/mm³\n\n               -  Serum Creatinine ? 2x Upper Limit Normal (ULN)\n\n               -  ALT and AST ? 3x ULN\n\n               -  Total Bilirubin ? 1.5x ULN\n\n          -  Patients must not have received systemic treatment for MCL for at least 14 days prior\n             to enrollment, except for steroids which may be used to manage acute symptoms related\n             to disease up to 48 hours prior to starting study therapy. Radiation therapy must be\n             concluded at least 14 days prior to enrollment.\n\n          -  Women must not be pregnant or breastfeeding since we do not know the effects of\n             ixazomib and ibrutinib on the fetus or breastfeeding child. All sexually active\n             females of childbearing potential must have a blood test to rule out pregnancy within\n             2 weeks prior to registration.\n\n          -  Sexually active women of child-bearing potential with a non-sterilized male partner\n             and sexually active men must agree to use 2 methods of adequate contraception\n             (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the\n             duration of study participation, and for 3 months following last dose of study drugs.\n\n          -  Patients must have resolved all prior non-hematologic toxicities assessed as related\n             to prior therapy to ? grade 1.\n\n          -  Patients must have measurable disease (i.e., ? 1.5 cm in largest diameter) by\n             conventional imaging modalities. Patients with spleen or extranodal involvement as the\n             only measurable site of disease must have a discrete splenic lesion ? 1.5 cm in\n             largest diameter.\n\n          -  Patients may not have current/active Central Nervous System (CNS) involvement with\n             mantle cell lymphoma (patients with prior CNS involvement are eligible as long as they\n             have had no evidence of active CNS disease for at least 6 months).\n\n          -  Patients may not have another malignancy that could interfere with the evaluation of\n             safety or efficacy of this combination. Patients with a prior malignancy will be\n             allowed without study chair approval in the following circumstances:\n\n               -  Not currently active and diagnosed at least 3 years prior to the date of\n                  enrollment.\n\n               -  Non-invasive diseases such as low risk cervical cancer or any cancer in situ\n\n               -  Localized disease in which chemotherapy would not be indicated (such as Stage I\n                  colon, lung, prostate or breast cancer). Patients with other malignancies not\n                  meeting these criteria must be discussed with PrECOG prior to enrollment.\n\n          -  Patients requiring long-term anticoagulation must be managed on an anticoagulant\n             besides warfarin. Patients who require warfarin are not eligible.\n\n          -  Patients with a clinically significant bleeding episode as judged by the investigator\n             within 3 months of registration are not eligible, except patients who suffer bleeding\n             due to trauma.\n\n          -  Patients may not have had major surgery within 14 days, or minor surgery within 3\n             days, before registration.\n\n          -  Patients may not have any active infection requiring oral or intravenous antimicrobial\n             therapy at the time of therapy initiation. Patients with a recent self-limited\n             infection that has clinically resolved may complete a prescribed course of\n             antimicrobial therapy after study initiation as long as they are asymptomatic with no\n             clinical evidence of infection for at least 7 days prior to treatment. Patients with a\n             recent serious (grade ? 3) infection requiring hospitalization must have completed all\n             antimicrobial therapy within 14 days of therapy initiation.\n\n          -  Patients may not have evidence of uncontrolled cardiovascular conditions, including\n             uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive\n             heart failure (New York Heart Association (NYHA) class III or higher, unstable angina,\n             or myocardial infarction within the past 6 months. Patients with a history of any\n             significant cardiovascular disease that has been controlled for at least 14 days\n             before registration are allowed (except for patients who have had a myocardial\n             infarction within 6 months).\n\n          -  No systemic treatment, within 14 days before the first dose of ibrutinib with moderate\n             or strong inhibitors of CYP3A (Strong Inhibitors: ketoconazole, itraconazole,\n             voriconazole, posaconazole, clarithromycin, and telithromycin; Moderate Inhibitors:\n             fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir,\n             fosamprenavir, crizotinib, imatinib, verapamil, ciprofloxacin, grapefruit juice\n             products, and Seville oranges) or strong CYP3A inducers for ibrutinib and ixazomib\n             (carbamazepine, rifampin, phenytoin, St. John's wort).\n\n          -  Patients with ongoing or active systemic infection, active hepatitis B or C virus\n             infection, or known Human Immunodeficiency Virus (HIV) positive are not eligible.\n             Testing is not required in absence of clinical suspicion.\n\n          -  Patients with a history of hepatitis B or C must have a negative peripheral blood\n             Polymerase Chain Reaction (PCR) and may not be positive for Hepatitis B surface\n             antigen. Patients with cirrhosis or other evidence of liver damage due to Hepatitis B\n             or C are not eligible.\n\n          -  Patients with any serious medical or psychiatric illness that could, in the\n             investigator's opinion, potentially interfere with the completion of the treatment\n             according to the protocol are not eligible.\n\n          -  Patients with a known allergy to any of the study medications, their analogues, or\n             excipients in the various formulations of any agent are not eligible.\n\n          -  Patients with known gastrointestinal (GI) disease or prior GI procedure that could\n             interfere with the oral absorption or tolerance of ixazomib or ibrutinib including\n             difficulty swallowing are not eligible.\n\n          -  Patients with ? Grade 2 peripheral neuropathy, or Grade 1 peripheral neuropathy with\n             pain on clinical examination during the screening period are not eligible.\n\n          -  Patients may not participate in any other therapeutic clinical trials, including those\n             with other investigational agents not included in this trial throughout the duration\n             of this study.\n\n          -  As ibrutinib will not be provided by the study, the patient must be able to obtain\n             ibrutinib through other means (i.e., commercially or through patient assistance\n             programs). This must be confirmed prior to registration.
Known prior severe hypersensitivity to platinum-related compounds for all cohorts, to pemetrexed for patients enrolled in Cohort A1, and to gemcitabine for patients enrolled in Cohort A2
Patients not able to receive standard-dose cisplatin based on the judgement of the treating medical oncologist
Patients not able or unwilling to travel for proton therapy
Patients whose apheresis product were to be further selected and purified
Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of PT2385
Patients with known unstable angina pectoris
Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
Patients may have received other vascular endothelial growth factor (VEGF) blocking tyrosine kinase inhibitors, provided that they did not progress while receiving one of these agents; patients may not have previously received pazopanib; patients must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria); patients previously treated with irinotecan and/or temozolomide will be eligible for this study provided they did not progress while receiving one of these agents
Patients who are currently receiving enzyme-inducing anti-convulsants are not eligible
Patients receiving drugs with a known risk of torsades de pointes are not eligible; Note: This list includes the prohibition of grapefruit for 14 days prior to enrollment
Patients with unknown BRAF mutation status may enroll so long as mutation testing is planned to be performed within 30 days of Cycle 1 Day 1 First-line NSCLC (pembrolizumab only)
Patients must not have been previously treated with lorlatinib.
Patients who are on hemodialysis.
Patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy; patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine (dose escalation phase)
Patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen; eight patients will participate in the paired biopsy studies; patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy; bone only lesions are not suitable for biopsy; these patients will provide informed consent for the paired biopsy study (dose expansion phase, arm A)
Patients with colorectal adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine; eight patients will participate in the paired biopsy studies; patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy; bone only lesions are not suitable for biopsy; these patients will provide informed consent for the paired biopsy study (dose expansion phase, arm B)
Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo repeat resection and biopsy [inclusive of muscularis propria] if initial biopsy did not include muscularis propria). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
Patients must have an accessible metastatic lesion for pretreatment core biopsy.
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients with a myelodysplastic/myeloproliferative neoplasm
Previous treatment with investigational agents that inhibit MDM2 or MDMX activity (some MDM2-treated patients may be eligible)
Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
Patients with cardiomyopathy and/or LVEF < LLN.
Participants who are receiving other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, or ovarian suppression therapy)
Patients with untreated brainstem metastases are eligible if lesions are small and asymptomatic
Participants who are receiving or will receive other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy)
Patients lacking the capacity to describe their symptoms are excluded
Have biopsiable and evaluable disease. Note: biopsy is optional for patients known to harbor a BRCA1/2 mutation
Patients known to be HIV(+), Hep BsAg(+), or Hep C(+) are excluded as the effect of the agent on immune system has not been assessed
Carcinoid tumors of any site are eligible; patients with pancreatic neuroendocrine tumors are excluded
Patients with symptomatic cholelithiasis
Patients must not have received systemic therapy within 2 weeks of initiating palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain on the drug; no break or washout period required; however, lapatinib, ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out period of 2 weeks is required
Patients who are on any prohibited medication; a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study
Patients taking vitamin E supplements while on study
Patients with a genetic disorder of fat metabolism
SAFETY RUN-IN: Patients known to be carriers of hepatitis virus B and C
Patients must be either:
Patients must be able to travel to one of the study-designated exercise facilities up to three days per week for four weeks during cycle 0, two days per week for cycles 1-8 (32 weeks) and once per week for cycles 9-11 (12 weeks). In addition, patients must be able to attend exercise testing visits as outlined in the Table 1.Required Initial Laboratory Values:
Medical clearance to undergo a symptom-limited cardiopulmonary exercise test (CPET) and vigorous aerobic and resistance exercise training. o Appendix 8: Patients must answer 'No' to all questions. If patients answered 'Yes' to only Questions 8-11, they will be considered eligible upon physician clearance
Currently receiving experimental treatment with non-approved drugs at the time of enrolment. Patients must undergo a 28-day washout between last dose and screening CPET.
Patients with pure seminoma
Patients with pure teratoma
Karnofsky >70% (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 100 where 100 is \perfect\ health and 0 is death.)
Patients must have normal or near normal organ function as defined by their treating institutions BMT program clinical practice guidelines.
Patients who have had more than 12 months of prior therapy; patients outside of this window may be considered for inclusion; please contact the sponsor’s representative in Poland or the lead primary investigator as appropriate on a case-by-case basis
Patients not able to tolerate lenalidomide or carfilzomib or dexamethasone
Patients with pheochromocytoma
Biopsies:\r\n* Cohorts B and C: all patients with disease that is deemed by the treating investigator as safely accessible to biopsy are required to undergo research biopsies as outlined in this protocol\r\n* Cohort A: such biopsies are optional
Patients must be off all colony forming growth factors(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations (e.g. NEULASTA)
Patients with known germline BRCA mutations will be excluded from the study, however testing is not required for inclusion in the study
Patients ? 18 years old
For escalation, subjects must have a pathologically confirmed diagnosis of PPV-MF, PET-MF, or PMF as per the European Hematology Association (EHA) or World Health Organization (WHO) diagnostic criteria (note that all diagnoses must include the presence of at least grade 1 marrow fibrosis according to the European Consensus on Grading of Bone Marrow Fibrosis as well as intermediate-1, intermediate-2, or high risk disease according to the International Working Group for Research and Treatment of Myelofibrosis (IWG-MRT) Dynamic International Prognostic Scoring System; patients with PV may enter the trial if they meet the labeled indication for ruxolitinib (eg hydroxyurea resistant or refractory)\r\n* Escalation Stage 1: patients who have not achieved normalization of splenomegaly, who have ongoing disease related symptoms (as defined by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score [MPN-SAF TSS]), or blood counts with at least 8 weeks of therapy with a steady dose of ruxolitinib\r\n* Escalation Stage 2: patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least 8 weeks of a steady dose of ruxolitinib (patients with exposure to other JAK-STAT inhibitory agents are not eligible); after discussion with the study chair or designee, patients with suboptimal response on at least 8 weeks of a steady dose of ruxolitinib may be allowed to de-escalate ruxolitinib therapy in order to enter a safety cohort which is enrolling patients at a lower dose; patients must receive the lower dose of ruxolitinib for at least 7 consecutive days without event before adding TGR-1202; if the patient completed screening evaluation including bone marrow biopsy/aspirate prior to ruxolitinib de-escalation, it need not be repeated after de-escalation provided that all evaluation occurred within 28 days prior to the first dose of TGR-1202
Patients with 5q del MDS unless failed on Revlimid (lenalidomide)
Inclusion Criteria:\n\n          1. Written informed consent in accordance with federal, local, and institutional\n             guidelines.\n\n          2. Age ? 18 years at the time of informed consent\n\n          3. Histologically confirmed diagnosis, measurable disease and evidence of disease\n             progression of MM, as described below.\n\n          4. Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease as\n             defined by at least one of the following:\n\n               1. Serum M-protein ? 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA\n                  myeloma, by quantitative IgA\n\n               2. Urinary M-protein excretion at least 200 mg/24 hours\n\n               3. Serum FLC ? 100 mg/L, provided that FLC ratio is abnormal\n\n               4. If serum protein electrophoresis is felt to be unreliable for routine M-protein\n                  measurement (e.g., for IgA MM), then quantitative Ig levels by nephelometry or\n                  turbidometry are acceptable.\n\n          5. Any non-hematological toxicities (except for peripheral neuropathy as described in\n             exclusion criterion #24) that patients experienced from treatments in previous\n             clinical studies must have resolved to ? Grade 2 by Cycle 1 Day 1.\n\n          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of ? 2.\n\n          7. Adequate hepatic function within 21 days prior to C1 D1:\n\n               -  For SPd and SRd: Total bilirubin < 2x ULN (except patients with Gilbert's\n                  syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin\n                  of ? 3x ULN) and both AST and ALT < 2.5x ULN)\n\n               -  For SVd, SPVd and SDd): Total bilirubin of ? 1.5x ULN (except patients with\n                  Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total\n                  bilirubin of ? 3x ULN) and both AST and ALT < 2.0x ULN)\n\n          8. Adequate renal function within 21 days prior to C1 D1:\n\n               -  Estimated creatinine clearance of (calculated using the formula of Cockroft and\n                  Gault):\n\n               -  ? 20 mL/min for SVd, SPVd, and SDd Arms\n\n               -  ? 45 mL/min for SPd Arm (as requested by the manufacturer)\n\n               -  > 50 mL/min for SRd Arm\n\n          9. Adequate hematopoietic function within 21 days prior to C1 D1: total white blood cell\n             (WBC) count ? 1,500/mm3, ANC ? 1000/mm3, hemoglobin (Hb) ? 8.0 g/dL, and platelet\n             count ? 75,000/mm3. For expansion cohorts only, platelet counts > 50,000/mm3; for\n             patients in whom ? 50% of bone marrow nucleated cells are plasma cells, platelets or ?\n             30,000/mm3 are acceptable for expansion cohorts. Patients receiving hematopoietic\n             growth factor support, including erythropoietin (EPO), darbepoetin, granulocyte-colony\n             stimulating factor (G-CSF), granulocyte macrophagecolony stimulating factor (GM-CSF),\n             and platelet stimulators (e.g., eltrombopag or romiplostim) may continue to do so.\n             However, patients in the escalation cohorts must be platelet transfusion independent\n             for > 1 week in order to be enrolled in the study.\n\n         10. Female patients of child-bearing potential must agree to use dual methods of\n             contraception and have a negative serum pregnancy test at Screening. Male patients\n             must use an effective barrier method of contraception if sexually active with a female\n             of child-bearing potential. Acceptable methods of contraception are condoms with\n             contraceptive foam, oral, implantable or injectable contraceptives, contraceptive\n             patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is\n             surgically sterilized or post-menopausal. For both male and female patients, effective\n             methods of contraception must be used throughout the study and for three months\n             following the last dose.\n\n             SPd (Arm 1) Only:\n\n         11. Relapsed and refractory MM with:\n\n               1. Documented evidence of PD after achieving at least SD for ? 1 cycle during a\n                  previous MM regimen (i.e., relapsed MM)\n\n               2. ? 25% response (i.e., patients never achieved ? MR) or PD during or within 60\n                  days from the end of the most recent MM regimen (i.e., refractory MM)\n\n               3. Previously undergone ? 2 cycles of lenalidomide and a proteasome inhibitor (in\n                  separate therapeutic regimens [not for maintenance] or in combination)\n\n               4. In the expansion arm at RP2D, patients must not be pomalidomide refractory\n\n             SVd (Arm 2) Only:\n\n         12. Relapsed or refractory MM with\n\n               1. Documented evidence of relapse after ? 1 previous line of therapy\n\n               2. Not refractory to bortezomib in their most recent line of therapy\n\n             SRd in RRMM (Arm 3) Only:\n\n         13. Patients who received ? 1 prior therapeutic regimen (prior lenalidomide is allowed as\n             long as patient's MM was not refractory to prior lenalidomide; patients whose MM was\n             refractory to lenalidomide maintenance regimens will be allowed in this cohort).\n\n             SPVd (Arm 4) Only:\n\n         14. Patients whose MM is relapsing after ? 1 prior therapy with progression on their last\n             therapy.\n\n             SDd (Arm 5) Only:\n\n         15. Patients who received ? 3 prior lines of therapy, including a PI and an IMiD, or\n             patients with MM refractory to both a PI and an IMiD.\n\n         16. Patients must not have received prior daratumumab therapy (Cohort 5.3 ONLY - dose\n             expansion at RP2D).\n\n             SKd (Arm 6) Only:\n\n         17. Patients may have received prior bortezomib or carfilzomib therapy, however their MM\n             must NOT be refractory to carfilzomib.\n\n             SRd in NDMM (Arm 7) Only:\n\n         18. Patients must have symptomatic myeloma per IMWG guidelines with either CRAB criteria\n             or Myeloma Defining Events and need systemic therapy.\n\n         19. No prior systemic therapy for NDMM is permitted other than pulse dose dexamethasone\n             (maximum dose of 160 mg).\n\n        Exclusion Criteria:\n\n        Patients meeting any of the following exclusion criteria are not eligible to enroll in this\n        study:\n\n          1. Smoldering MM\n\n          2. MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and\n             quantitative immunoglobulin levels cannot be used instead\n\n          3. Documented active systemic amyloid light chain amyloidosis\n\n          4. Active plasma cell leukemia\n\n          5. Blood (or blood product) transfusions and blood growth factors within 7 days of C1D1\n             (only for patients enrolling into the Expansion Phase)\n\n          6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ? 2 weeks\n             prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on\n             long-term glucocorticoids during Screening do not require a washout period. Prior\n             radiation is permitted for treatment of fractures or to prevent fractures as well as\n             for pain management\n\n          7. Patients with history of SCC with residual paraplegia (Dose Escalation Phase only).\n\n          8. Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1\n\n          9. Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell\n             transplantation < 3 months prior to C1D1\n\n         10. Active graft versus host disease after allogeneic stem cell transplantation\n\n         11. Life expectancy < 3 months\n\n         12. Major surgery within 4 weeks prior to C1D1\n\n         13. Active, unstable cardiovascular function:\n\n               1. Symptomatic ischemia, or\n\n               2. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with\n                  ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree\n                  atrioventricular (AV) block or asymptomatic left anterior fascicular block/right\n                  bundle branch block (LAFB/RBBB) will not be excluded), or\n\n               3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ? 3, or\n\n               4. Myocardial infarction (MI) within 3 months prior to C1D1\n\n               5. Ejection fraction (EF) < 50% at Screening\n\n         14. Uncontrolled active hypertension\n\n         15. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or\n             antifungals within one week prior to first dose\n\n         16. Known active hepatitis A, B or C\n\n         17. Known HIV infection or HIV seropositivity\n\n         18. Any active gastrointestinal dysfunction that prevents the patient from swallowing\n             tablets or interferes with absorption of study treatment\n\n         19. Currently pregnant or breastfeeding\n\n         20. A serious psychiatric or medical condition which, in the opinion of the Investigator,\n             could interfere with treatment\n\n         21. Hypersensitivity to any of the treatments for the Arm in which the patient is enrolled\n\n         22. In the SVd (Arm 2) only: Prior history of neuropathy Grade > 2, or Grade 2 neuropathy\n             with pain at screening (within 21 days prior to C1D1)\n\n         23. Prior exposure to a SINE compound, including selinexor
Patients with multiple lesions will be eligible as long as there are no overlapping fields of radiation, including at various time frames
New or progressive CNS lesions, as assessed by the patient’s treating physician\r\n* It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one lesion is measurable (>= 10 mm) per RECIST 1.1; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Patients who have had prior cranial surgery are eligible provided that there is evidence of measurable residual or progressive lesions, and at least 3 months have passed since surgery; if a patient has surgical resection followed by whole brain radiation therapy (WBRT), then there must be evidence of progressive CNS disease after the completion of WBRT\r\n* Patients who had had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions that 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\r\n* Patient who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such patients must be asymptomatic or minimally symptomatic from their CNS metastases and not requiring corticosteroids
Patients must be geographically accessible and willing to participate in all stages of treatment
Patients will not be excluded on the basis of sex, racial or ethnic background
Transplant eligible (as determined by referring physician) patients who have failed one prior salvage therapy or transplant ineligible (as determined by referring physician) patients who have failed one prior therapy
Patients with the entity of acute/chronic GVHD overlap syndromes
Biopsy proven MLS (including the reciprocal chromosomal translocation t(12;16)(q13;p11); A the primary sarcoma in case of non-metastatic disease for management is with curative intent (regimen to be chosen = 18 x 2 GY) B in case of oligometastatic patients, the metastasis may also be irradiated to a dose of 36 GY in order to postpone the time interval to next systemic chemotherapy. These patients are usually not operated upon and the total dose may also be reached in 12 times 3 Gy, for convenience purposes (see paragraph 10 for radiobiological considerations).
Anticoagulant medication of any kind; especially Ascal®(and derivates), coumarines (Sintrom® and Marcoumar®), all heparin and heparin-like formulations. (Note: this exclusion criterion only applies for patients consenting to the translational research part of the study; patients on anticoagulant medication as described above may take part in the dose reduction part of the study, but the repeat biopsies may not be taken.)
Patients who receive sirolimus (Rapamune®) as part of their transplant immunosuppression regimen
Patients whose circumstances do not permit completion of the study or the required follow-up
Patients known to have Philadelphia (Ph) positive (+) ALL are not eligible; leukemia cell samples will be obtained from all patients enrolled before starting protocol treatment and submitted for Philadelphia chromosome testing by either karyotyping, or breakpoint cluster region (bcr)/Abelson murine leukemia viral oncogene homolog 1 (abl1) translocation by fluorescent in situ hybridization (FISH) or by PCR; patients who are later found to have Ph+ ALL should have treatment on this trial discontinued and will not be considered in the evaluation
Patients must have histological or cytological evidence of a solid neoplasm
Patients enrolled in the expansion cohort must have at least one measureable lesion as defined by the RECIST 1.1 criteria
Patients must:
No congenital or acquired immune deficiency. These patients are excluded due to the expected intense immunosuppression, increased risk of opportunistic infections, and higher expected septic death rate in this subgroup of patients with this proposed therapy.
Patients with previous malignancies that have been treated with systemic chemotherapy with alkylator or anthracycline therapy. The latter group of patients are excluded due to an expected increase in late effects (eg. late cardiac toxicity, secondary malignancies, sterility, etc.).
Patients with known G6PD deficiency are NOT ELIGIBLE for Rasburicase therapy. Patients with G6PD deficiency should be treated with alkalinization, IV hydration and po and/or IV allopurinol during the reduction phase (COP).
Patients with clinical symptoms or signs of gastrointestinal obstruction
For male patients, agreement not to donate sperm during the study and for 3 months after the final dose of vismodegib; male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with pregnant partners or female partners of reproductive potential during treatment with vismodegib; vismodegib is present in semen
Patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion
In cases of lymphoproliferative disease arising in patients who are pharmacologically immunosuppressed, reduction of immunosuppression (RI) must be attempted prior to or in conjunction with enrollment, with the exception of those for whom RI would pose excessive threat of clinically significant graft rejection (as judged by local investigator)\r\n* NOTE: Patients who are otherwise immunosuppressed (for reasons such as immune dysregulation related to autoimmune conditions, in the absence of pharmacological immunosuppression) may be eligible if, in the opinion of the treating investigator, the risk of immediate treatment with rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) outweighs the benefit for these patients
Patients who have had prior surgical intervention for lymphoma, unless performed for the sake of tissue diagnosis or on an urgent basis for disease-related threat to life, limb, or organ function, are not eligible
Patients must not have known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
Patients who exhibit any other serious concurrent infection or other medical illness which would jeopardize their ability to receive the therapy outlined in this protocol with reasonable safety will NOT be eligible for participation
Patients enrolled in the study will meet standard criteria for whole breast XRT or chest wall XRT for patients who have had mastectomies
Patients with anemia (hemoglobin [HEM] < 10 g/dl) at baseline will be excluded unless otherwise approved by the PI or PI’s designee
Patients will be asked to refrain from having more than one alcoholic beverage per day
ENDOCRINE RESISTANT COHORT: Pre-registration is not required for patients to be enrolled in the endocrine resistant cohort, as PIK3CA mutation status will not be assessed
ENDOCRINE RESISTANT COHORT: Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy; if Ki67 is > 10% by local testing, the Ki67 slide and H&E slide need to be reviewed by the study pathologist to confirm eligibility (discuss with study chair); for patients external to Washington University, please contact the Washington University coordinator by email so that a screening identification (ID)# can be assigned prior to shipment of the slides\r\n* Note that prior neoadjuvant endocrine therapy could include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant) alone or in combination, or endocrine therapy in combination with any investigational agent that is not a Cdk 4/6 inhibitor\r\n* Patients who had a day 17 Ki67 > 10% from the NCI9170 trial are eligible for the endocrine resistant cohort\r\n* Note that enrollment to the endocrine resistant cohort will depend on the funding availability; please contact the study chair before enrolling patients to this cohort
ADJUVANT COHORT: Derived benefit from PD 0332991 in the neoadjuvant setting in this trial; this includes the 26 patients who achieved complete cell cycle arrest only after the addition of PD 0332991 (C1D1 Ki67 > 2.7% and C1D15 Ki67 =< 2.7%) from the main study (PIK3CA WT, mutant, or unknown cohorts) as well as any patients who have a Ki67 =< 10% on C1D15 biopsy in the endocrine resistant cohort
Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
Patients who have received prior treatment with oral or intravenous fenretinide as a single agent are eligible, provided they did not experience severe toxicity related to fenretinide
Patients who have received prior treatment with oral or intravenous fenretinide as a single agent are eligible, provided they did not experience severe toxicity related to fenretinide
Baseline fasting triglycerides > 2.5 IULN or hypertriglyceridemia requiring medication; patients requiring medication for other dyslipidemias (i.e., elevated low-density lipoprotein [LDL] cholesterol) are eligible
Patients with an identified familial hyperlipidemia disorder
Patients unable to have an FDG-PET scan, either through insurance coverage, patient decision or other reason are not eligible for this study
Patients who cannot participate in contributing to the neurocognitive outcomes due to severe neurologic impairment or language barrier will be enrolled at the discretion of the treating physician in consultation with the principal investigator (PI)
Patients must be able to cooperate fully with all planned protocol therapy
Patients with other fibroblastic lesions or other fibromatoses are NOT eligible.
Patients must not be taking medicines known to influence sirolimus metabolism
Patients must be at least 18 years old.
Patients must complete all mandatory tests listed in section 4.0 within the specified time frames.
Patients must have failed a carboplatin-based regimen
Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary
Patients must have a fasting LDL cholesterol within the normal range per institutional guidelines
Incurable advanced solid tumors that are no longer responding to conventional therapy or for which no effective therapy exists; at the RD of Part 1, an extension cohort up to 20 patients with metastatic breast cancer who are known to be BRCA mutation carriers will be enrolled.
Patients must have failed at least 2 lines of stand therapy as outlined for the specific diseases
Patients with evidence of myelodysplasia
Patients for whom paclitaxel (or nab-paclitaxel) is being used in the curative setting, either adjuvant or neoadjuvant, and patients who would receive paclitaxel (or nab-paclitaxel) as first line therapy in a tumor type in which paclitaxel (or nab-paclitaxel) has a proven survival benefit for metastatic disease
Patients cannot have distant metastases and have to be candidates for curative re-irradiation
Patients with salivary gland tumors are excluded (patients with nasopharynx CA or sinonasal cancers can participate)
Patients with carotid artery involvement or encasement will be allowed provided they have no symptoms related to carotid involvement
Patients with primary salivary gland cancers are excluded
For patients with SCCHN or NSCLC, ongoing anticoagulant therapy
Pediatric patients with radiographically recurrent or radiographically progressive non-hematologic malignancies (central nervous system [CNS] or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible
PHASE II: Patients with measurable radiographically recurrent or radiographically progressive disease that is measurable in at least two dimensions on imaging after standard up-front therapy as defined in the following three strata below will be eligible\r\n* Stratum 1: patients with radiographically recurrent or radiographically progressive low-grade gliomas with a BRAF KIAA1549 (or similar) truncated fusion duplication not previously treated with a BRAF or MEK inhibitor\r\n* Stratum 2: patients with NF1 and radiographically recurrent or radiographically progressive LGG (NF1 may be defined clinically or genetically) not previously treated with a BRAF or MEK inhibitor\r\n* Stratum 3: patients with radiographically recurrent or radiographically progressive tumors thought to involve the RAS/RAF/MEK/ERK pathway but not included in Stratum 1 or 2; this includes any radiographically recurrent or radiographically progressive LGG not included in Stratum 1 or 2 (i.e., any LGG without a BRAF truncated fusion in a patient without NF1), any CNS tumor other than LGG in a patient with NF1, and any other CNS or solid tumor (regardless of grade) with a documented activating BRAF, NRAS, or KRAS mutation
Patients with melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary
Patients who are not eligible to receive paclitaxel will be allowed to receive single agent DKN-01.
History of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these hypersensitivities will be eligible to receive single agent DKN-01
Patients currently receiving and unable to stop high doses of supplemental vitamin E
Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder) must be excluded or must stop using the medication.
Patients whose tumour samples have targetable alterations in EGFR and/or ALK are excluded. In addition, patients whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.
Immunocompromised patients
Patients with tumor tissue uptake during NETSPOT PET that is equal to or higher than that in normal hepatic tissue (grade >= 2) will be eligible; at the discretion of the principal investigator, patients with SCLC whose tumors have lower levels of uptake than liver during NETSPOT PET may be eligible for the study
For lymphoma patients only: Participants must have received and relapsed after autologous stem cell transplantation (ASCT), or be ineligible for ASCT (including on the basis of refractory disease), or have declined ASCT
Patients who have active, chronic, or on active treatment for Hep B or Hep C are excluded.
Total bilirubin =< 1.5 x ULN within 28 days of treatment initiation and must be independent of hematopoietic growth factor support\r\n* Note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (eg, Gilbert syndrome) will be eligible at the discretion of the principal investigator
PT/INR ? ULN within 28 days of randomization. Patients receiving therapeutic anti-coagulants are not eligible.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted provided all of following conditions are met: Rash must cover < 10% of body surface area; Disease is well controlled at baseline and requires only low-potency topical corticosteroids; No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
As there is potential for hepatic toxicity with nivolumab or nivolumab non-drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients who are otherwise ineligible to receive the antibiotics in this study
Patients highly unlikely to undergo PD according to the surgeon’s judgment, such as conditions amenable to pancreas enucleation, ampullectomy, etc
Patients receiving hemodialysis or peritoneal dialysis
Any stage HNSCC of the 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx, 5) nasal cavity/paranasal sinuses, 6) unknown primary; patients with resectable or recurrent disease that is amenable to surgery are eligible
Patients taking nitrates
Patients with a secondary condition (sickle cell anemia) that cause priapism
Patients with uveal melanoma will not be eligible as these tumors show low expression of GD3
Patients with leiomyosarcoma must have tumors with intact Rb as documented by protein expression by immunohistochemistry (IHC) for study entry; patients without sufficient archival tissue for testing will not be eligible; in the event that a patient has prior sequencing information (i.e. through commercial testing) suggestive of intact Rb, the patient may be included into the study on a case by case basis as determined by the principle investigators; the patient will still be required to submit tissue for Rb determination by IHC, but will not need to wait for these results for study entry
Patients must have a pathologically confirmed adenocarcinoma of the biliary tract (intra-hepatic, extra-hepatic [hilar, distal] or gall bladder) that is not eligible for curative resection, transplantation, or ablative therapies
Patients with active bacterial infections with systemic manifestations (malaise, fever, leukocytosis) are not eligible until completion of appropriate therapy. Patients taking low-dose antibiotics for biliary obstruction are exempted from this exclusion criterion.
Patients with biliary stents.
Patients previously treated with any intra-arterial regional hepatic therapy such as trans-arterial chemoembolization.
There is no upper age limit but the patients must be able to medically tolerate the regimen
INCLUSION - TREATMENT: The first six (6) patients treated on the study should be adults (? 18 yrs of age); six adolescents (age 12-18) should be treated before children (? 3 yrs of age) are eligible
Participants must have a biopsy proven solid malignancy with untreated (by radiation) intracranial lesions radiographically consistent with or pathologically proven to be brain metastases; patients who have undergone prior systemic therapy are eligible
U.S. ONLY: For all Cohorts, patients who refuse approved therapy for which they are a suitable candidate are not eligible for enrollment on this trial.
Hematologic parameters for patients undergoing biopsy only: patients should have international normalized ratio (INR) =< 1.4 and partial thromboplastin time (PTT) =< 40 seconds (unless due to lupus anticoagulant); in patients not meeting these parameters, clearance by hematology will be required prior to undergoing a biopsy
Patients will be strongly encouraged to participate in 10-C-0086; if a patient does not agree to enroll on 10-C-0086, germline genetic analysis will not be performed
Patients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)\r\n* Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out corrected QT (QTc) prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction should be excluded from the study
Patients receiving steroid treatment exceeding replacement dosing
Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration
Patients with significant edema leading to risk of brain herniation
Patients with midline shift > 10mm
Patients with intractable seizures
History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial.
For patients who have undergone lumpectomy, there are no breast size limitations
Patients receiving drugs with a known risk of torsades de pointes are not eligible.
Part A: Patients with recurrent or refractory solid tumors are eligible, excluding central nervous system (CNS) tumors; patients must have had histologic verification of malignancy at original diagnosis or relapse
Part B: Patients with recurrent or refractory osteosarcoma are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: willingness to undergo mandatory biopsies (day -14, approximately 4 hours post end of irinotecan infusion and day 1, approximately 4 hours post end of irinotecan infusion [= 3 hours post end of VX-970]); patients enrolled to this cohort should have tumors deemed easily accessible for biopsies with low likelihood of complication
Part A: Patients with recurrent or refractory non-CNS solid tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except patients with extra-cranial germ-cell tumors who have elevations of serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); patients in part A cannot have CNS metastases
Part B: Patients with recurrent or refractory CNS tumors will be eligible and must have a histological verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with CNS-germ cell tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-HCG
Patients who are chronically receiving aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs are not eligible
Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial
Patients who are currently receiving belimumab (a monoclonal antibody for systemic lupus erythematosus) are not eligible
Patients who are currently receiving bisphosphonate derivatives are not eligible
Patients receiving corticosteroids are eligible for this trial
Patients must not currently be receiving enzyme inducing anticonvulsants
Patients receiving concomitant medication that may interfere with study outcome; for example, patients cannot be on enzyme inducing anticonvulsants like phenytoin
Patients 18 to 70 years old
Tumors of all locations in the central nervous system, with appropriate histology, are eligible for study; however, patients with intrinsic brainstem tumors of the pons will be excluded from the study; patients with primary spinal cord lesions are allowed; patients with metastatic disease are also allowed
Patients with subependymal giant cell astrocytomas are excluded; patients with intrinsic brain stem tumors of the pons will be excluded from the study
Patients must meet ONE of the criteria outlined in either a, b, c OR d:
Patients with multi-organ involvement by amyloidosis or evidence of amyloidosis-related organ dysfunction
Clinical American Joint Committee on Cancer (AJCC) (AJCC, 7th ed.) II, IIIA or IIIB (with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team within 60 days prior to registration; note: for patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and/or a medical oncologist or pulmonologist \r\n* Patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor are eligible\r\n* Patients who refuse surgery are eligible\r\n* Patients who develop local recurrence after surgery and rendered candidate for definitive concurrent chemoradiation are also eligible\r\n* Patients who have received systemic treatment (up to 4 cycles of induction chemotherapy, or up to 6 months of targeted therapy) are eligible
Patients must =< 25
Patients with active lesions suspicious for keratoacanthomas/cutaneous squamous cell carcinoma (cSCC); patients who have excision of keratocanthomas/cSCC, with dermatologic confirmation of the absence of active disease may become eligible
All patients with known diagnosis of neurofibromatosis type 1 or other known retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS)-opathies are excluded
Must be ? 18 years of age. Due to increased risk of sepsis in patients >80 years old, candidate patients in this age group should be thoroughly evaluated prior to study randomization to ensure they are fit to receive chemotherapy. In addition to all of the inclusion/exclusion criteria listed, clinical judgment should be used regarding patients' susceptibility to infection (including but not limited to presence of ascites or diabetes mellitus increasing risk of infection). Furthermore, the expected stability of their performance status while receiving repeat weekly chemotherapy cycles should be given special attention. Patients in this age group should not be randomized on the study should there be any hesitation on any of these considerations.
Patients must be accessible for treatment and follow up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.
Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
Patients who are unwilling to be transfused with blood components
Patients receiving anticoagulation therapy with Coumadin are not eligible for study; (patients on non-coumadin anticoagulants [Lovenox, Xarelto, etc.] are eligible for study; patients on Coumadin who can be transitioned to Lovenox prior to starting study treatments will be eligible)
Patients allergic to sesame seed oil or cottonseed oil are excluded
Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible; Note: patients that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair
Female patients who:
Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
Patients planned to receive docetaxel with contra-indications to receive docetaxel
History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial
INCLUSION - PROCUREMENT: Any patient, regardless of age or sex, with measurable EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma, (regardless of the histological subtype) or EBV (associated)-T/natural killer (NK)- or B cell lymphoproliferative disease\r\n* The first 3 patients enrolled will be adults; patients <18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or nivolumab\r\n* Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study
Any patients eligible for allogeneic stem cell transplantation (allo-SCT) and willing to undergo allo-SCT as determined at time of screening for trial; patients who are ineligible or not interested in undergoing allo-SCT will be eligible for the trial
Patients with known active cancers who are on therapy for those cancers at time of screening
TREATMENT INCLUSION: Age 16 to 75 for the first three patients on a dose level; thereafter, if no dose limiting toxicity (DLT), patients aged 12 to 75 can be treated on that dose level
Patients taking sertraline at the time of study entry will not be eligible for the study
Patients must consent to the submission of FFPE blocks and/or unstained slides
Patients must not have aspirin sensitive asthma
Patients must be refractory to, or not a candidate for, established therapy known to provide clinical benefit for their malignancy.
Patients with ocular, mucosal and unknown primary melanoma will also be eligible
Patients will have close margins
Rochester patients: Willing to sign consent onto Evaluation of cardiac function in patients undergoing proton beam or photon radiotherapy, IRB number 15-007443
Patients must be considered unresectable or inoperable
The patient is refractory to carfilzomib or bortezomib; (refractory is defined as patients who never achieved a response and progressed while on carfilzomib or bortezomib or within 60 days of completing treatment)
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of INC280, and for the duration of the study; patients on non-enzyme-inducing anticonvulsants are eligible
Patients in the Phase 1a dose escalation combination cohorts must have at least 1 tumour lesion amenable to biopsy and must be medically fit and willing to undergo a biopsy during screening and, unless clinically contraindicated, after 2 weeks on monotherapy.
Patients with mCRC must have measurable PSA above normal limits per local ranges.
A minimum of 10 patients with mCRPC, CRC and 'other' tumors will be required to have a site of disease that is safely accessible for biopsy (paired) upon enrollment. Accessible lesions are defined as those which are biopsiable (at screening) and amenable to repeat biopsy (after 2 weeks of monotherapy), unless clinically contraindicated. In the case that the second sample is not taken, the patient will remain in the study and there will be no penalty or loss of benefit to the patient and they will not be excluded from other aspects of the study. The tumor-specific cohorts will be closely monitored to ensure the desired number of biopsiable patients are enrolled. The requirement for biopsies must be made clear to each patient at the time of initial approach by the Investigator.
Patients who require hemodialysis
Patients must be willing and able to undergo study required biopsies.
Patients may have neurofibromatosis type 1 or 2
Participants may have underlying malignant or non-malignant hematologic disease, except for primary immunodeficiency, as the indication for their allogeneic HSCT; patients with immune dysregulation syndromes such as familial or secondary hemophagocytic lymphohistiocytosis (HLH) are eligible
Patients with age =< 10 years undergoing HSCT with a matched sibling donor; these patients are at very low risk of acute GVHD and do not receive gut decontamination per our institutional standard practice
Patients must be eligible for treatment with decitabine
Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in group 1 and 2 in the dose expansion part. Exceptions may be made after documented agreement between Novartis and Investigator.
Histologically proven T1-3N0M0 NSCLC =< 5 cm diameter (patients with tumor size up to 7 cm are allowed if radiation dose/volume histogram constraints for normal tissues can be met); T3 patients with chest wall invasion or 2 nodules within the same lobe are eligible
PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below:\r\n* PID as defined by monogenetic mutation or, in the absence of a PID-associated genetic mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible upon discussion with the principal investigator (PI)\r\n** Mutations should be confirmed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, if such testing is available\r\n** Patients without a mutation must be deemed eligible and appropriate for allo BMT by the PI; some patients may meet the clinical history criteria listed below, but will not be eligible if it is thought that their clinical history is due to a condition apart from an immune defect; in addition, patients with a PID of mild severity, such as those with selective immunoglobulin A (IgA) deficiency, may meet at least two of the clinical history criteria, but may be deemed inappropriate for allo BMT by the PI if it is felt that the risks of the procedure outweigh the severity of the disease\r\n** All mutation testing will be performed on National Institute of Allergy and Infectious Diseases (NIAID) protocols (such as 07-I-0033 – Detection and Characterization of Infections and Infection Susceptibility; PI: Steve Holland, with genetic counseling and education through these established protocols)\r\n* Clinical history of at least two of the following:\r\n** Life-threatening, organ-threatening, or severely disfiguring infection\r\n** Protracted or recurrent infections requiring unusually long or repeated courses of antibiotics\r\n** Infection with an opportunistic organism\r\n** Chronic elevation in the blood (>= 2 documented elevations over a period of 6 months or longer) of a latent virus (EBV, CMV, human herpesvirus [HHV]6, HHV8, etc.)\r\n** Evidence of immune dysregulation, as manifested by autoimmune disease, atopy, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, granulomas, splenomegaly, or lymphadenopathy\r\n*** Patients with hemophagocytic lymphohistiocytosis or macrophage activation syndrome related to an underlying lymphoma with no other clinical history suggestive of a primary immunodeficiency will not be eligible\r\n** Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination\r\n** Hematologic malignancy or lymphoproliferative disorder\r\n*** Tissue diagnosis should be confirmed by National Cancer Institute (NCI) Department of Pathology, if prior biopsies are available\r\n** Virus-associated solid tumor malignancy or pre-cancerous lesion\r\n*** Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available
Consensus among the PI, key assistant investigators (AIs), and consultants (as necessary) that correction of the patient’s immune system through BMT has the potential to improve the patient’s health, quality of life, and/or life expectancy, after taking into consideration the patient’s existing non-hematopoietic, potentially irreversible organ dysfunction
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal (ULN) for patients receiving MAC or ALT and AST =< 10 x ULN for patients receiving RIC, RIC-MMF, or IOC; patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC, RIC-MMF or IOC arms if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with bone marrow transplant
ARM 2 - A: Diagnosis of selected stage III or IVa/b HNSCC; all patients must have T2-T4 primary tumors (patients with T1 tumors will be excluded); although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible
EXPANSION COHORT: There should be a 2- to 4-week break between the patient’s last dose of standard chemotherapy to initiation of the first cycle of study drugs; longer than 4-week break may be permitted at the discretion of the principal investigator (PI)
Patients may not have had prior bevacizumab, based on case reports of tracheoesophageal fistula in patients treated with bevacizumab and radiotherapy
Patients with hospitalization within 4 weeks of treatment initiation date for co-morbid conditions or any complication of disease or therapy that is deemed by the principal investigator as unstable or incompletely treated
Patients with any psychiatric or social condition that leads them to be unlikely to adhere to the study schedule and contribute to the primary objectives
Patients with incurable malignancies, irrespective of 2-year mortality, who, in the opinion of the investigator have no treatment option expected to yield significant clinical benefit
Are pregnant or breast-feeding patients or any patient with childbearing potential not using adequate pregnancy prevention (site-specific criteria applying to Avera only)
Patients with LCH must require systemic therapy according to the Histiocyte Society LCH Evaluation and Treatment Guidelines OR patients with HS requiring systemic treatment as defined by disease that cannot be surgically resected and/or encompassed in a single radiation field
Patients receiving antithymocyte globulin (ATG) or campath within 28 days of infusion
patients with previously treated MDS (with the exception of deletion 5q MDS) (US only)
Patients receiving anti-thymocyte globulin (ATG) or Campath within 28 days of infusion
Patients with phaeochromocytoma
Patients with pheochromocytoma
HPV-positive status ( In HNSCC patients only)
Patients who cannot tolerate pneumocystis jirovecii pneumonia (PJP) prophylaxis (i.e., known Bactrim and pentamidine allergies)
Patients must have a PN amenable to a percutaneous biopsy to participate in the biopsy portion of this study, and must be willing to undergo pre-, and on treatment tumor biopsies; there should be no contraindication for serial biopsies; NOTE: up to 10 patients who meet all criteria, but have PN which cannot be biopsied safely, will be eligible for the treatment portion of the study
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (patients who are wheelchair bound because of paralysis secondary to a plexiform neurofibroma should be considered ambulatory when they are up in their wheelchair; similarly, patients with limited mobility secondary to need for mechanical support (such as an airway PN requiring tracheostomy or continuous positive airway pressure [CPAP] will also be considered ambulatory for the purpose of the study)
Hematologic parameters for patients undergoing biopsy only: patients should have international normalized ratio (INR) =< 1.4 and partial thromboplastin time (PTT) =< 40 seconds (unless due to lupus anticoagulant); in patients not meeting these parameters, clearance by hematology will be required prior to undergoing a biopsy
Patients with pheochromocytoma
Patients known to have a BRCA gene mutation; genetic testing is not required
Patient with breast implants (does not include patients having implants placed AFTER intra-operative radiotherapy)
Patients must have received all approved therapies known to provide clinical benefit for their disease subtype and for which they are eligible or must have refused these treatment options prior to consideration for enrolment. In the case of patients who have lymphomas for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for this study requires that the patient's disease has relapsed after HD-ASCT, that the patient is not eligible for HD-ASCT, or that the patient has refused HD-ASCT.
Patients with a peripheral blood total lymphocyte count of higher than 25,000/mm3 may not be enrolled.
Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (e.g. filgrastim, sargramostim, erythropoietin); 2 weeks must have elapsed for long-acting formulations
Concurrent Illness\r\n* Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, except \r\n** Patients with vitiligo or resolved asthma/atopy\r\n** Patients with hypothyroidism stable on hormone replacement or Sjogren’s syndrome \r\n* History of or ongoing pneumonitis or significant interstitial lung disease\r\nNote: This would include non-infectious pneumonitis that required steroid use\r\n* Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n* Patients with other current malignancies\r\n* Patients with known hypermutated brain tumors including those with CMMRD and Lynch syndrome are ineligible for enrollment in Strata A, B, D and E\r\n* Patients who have received a solid organ transplant
INCLUSION CRITERIA FOR STRATUM C: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (i.e. filgrastim; sargramostim; erythropoietin); 2 weeks must have elapsed for long-acting formulations
Patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy and biopsy
Patients who are HPV-positive by deoxyribonucleic acid (DNA) test
Patients who are immunocompetent
Patients who have the ability to collaborate planned follow-up
Patients with cytologic evidence of glandular dysplasia
Patients with cytologic evidence of adenocarcinoma in situ
ALL PATIENTS
International normalized ratio (INR) =< 2\r\n* If a patient’s bone marrow function falls below the indicated values and it is not thought to be related to prior treatments a hematology consult will be ordered; if hematology deems the patients safe to proceed with treatment they will be allowed to enroll on study; in such cases, the patient’s absolute neutrophil count must be > 1,000/mcl, hemoglobin must be > 7.5 g/dL and the platelet count must be > 75,000 mcL; each patient will also be seen by a medical oncologist at follow-up visits if possible
Patients previously treated with anti-CD19 CAR or other adoptive cell therapies will be eligible if all other eligibility criteria are met but will be evaluated as a separate strata from CAR-naive patients in the expansion phase; circulating CAR T cells must be < 5% in peripheral blood
Patients may receive hydroxyurea or leukopheresis as necessary; hydroxyurea can be continued through induction, as determined by the treating investigator; patients who require hydroxyurea after the 2 induction cycles will be off study
Multifocal gliomas that are bilateral; patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single MLA procedure; also note that corpus callosal tumors are eligible even if they are bilateral as long as they satisfy the size and shape limits of MLA as determined by the performing neurosurgeon
Patients with markedly decreased visual acuity
Patients with sinonasal SCCAs
Body surface area (BSA):\r\n* Patients enrolled on dose level 1 (50 mg/m^2) must have BSA >= 1.20 m^2\r\n* Patients enrolled on dose level 2 (75 mg/m^2) must have BSA >= 0.93 m^2\r\n* Patients enrolled on dose level 3 (95 mg/m^2) must have BSA >= 0.70 m^2
Patients with low grade gliomas and Rb1 negative tumors
Patients who require enzyme inducing anti-convulsants to control seizures
Patients with cataracts on ophthalmologic examination
Patients with mature B-cell ALL will be removed from the protocol as soon as that diagnosis is made and should be treated on a B-cell leukemia (Burkitt’s) protocol; NOTE: patients with T-cell surface markers and a t(8;14)(q24;q11) remain eligible
Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely are excluded
Presence of more than 55% pro-lymphocytes in peripheral blood; patients with Richter's transformation are not excluded
Patients 0-49 years old will be enrolled in Arm A or C (high-intensity)
Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator
Patients on other experimental protocols for prevention of acute GVHD
Patients with a significant other medical conditions that would make them unsuitable for transplant
Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
Patients of Stratum I who have:
Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study
Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.
Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
Patients with isolated \CNS-risk\ or multifocal bone lesions (they are eligible for Stratum I, Group 2)
Patients with primary ocular or mucosal melanoma are excluded
Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult; patients with reversible ischemic changes on cardiac stress test
All patients except cohort 6 must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy; for cohort 5, the second biopsy at progression is mandatory for the responders (PR/CR/stable disease [SD]) >= 4 months
Patients with multifocal tumors must have resectable lesions
Patients with sessile appearing tumors, which may be invasive or high-grade
Any patients taking drugs that are known to have drug interactions with tamoxifen will not be included
Patients must sign a document that indicates that they are aware of the investigative nature of the treatment of this protocol, and the potential benefits and risks; patients unwilling or unable due to cognitive impairment to sign informed consent are excluded from the study
Patients taking valproic acid =< 2 weeks prior to initiation of belinostat therapy (for cohort 2a and 2b [belinostat cohort] only)
Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy; (Note: patients on the standard therapy arm of another GBM trial that otherwise meet eligibility requirements for this trial remains eligible for cohort 1)
Any of the following will exclude patients from the high-dose aldesleukin arm, but may be eligible for the low-dose aldesleukin arm:\r\n* Greater than 2 invasive thoracic procedures\r\n* Poor exercise tolerance\r\n* Greater than 66 years of age
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
Patients may have had multiple primary melanomas.
Patients may have had or may have a metastasis from a cutaneous primary site, mucosal primary site, or unknown primary site.
Patients with melanoma arising from uveal/ocular primary sites.
Patients with known or suspected allergies to any component of the vaccine.
Patients must agree not to donate blood, sperm/ova during the course of taking protocol therapy and for at least 4 weeks after stopping treatment
Patients previously treated on clinical trial with reolysin
Patients should be asymptomatic for jaundice prior to Day 1.
Patients who have had prior therapy with immune checkpoint inhibition or or indoximod are excluded from the trial.
PHASE I: Patients 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; patients that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization
PHASE II: Patients with CNS involvement are eligible provided that they are asymptomatic and in the opinion of the study PI have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion; patients that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization AND
No prior genetically modified cell therapy that is still detectable or virotherapy allowed; patients who are otherwise eligible but have detectable circulating CAR T cells of < 5% will be eligible, but will be evaluated as a separate strata from CAR-naive patients in the phase 2 portion of the study
Patients must be able to tolerate apheresis procedure, including placement of temporary apheresis line if required
Patients with known adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.
Only patients for whom their neuro-oncologist has planned to give bevacizumab and temozolomide 50mg/m^2/day as part of their treatment are eligible for this study
Patients with up to two prior recurrences are allowed
Patients may be potentially resectable or unresectable
Patients enrolling in the expansion cohorts must have disease amenable to biopsy and be willing to undergo pre-and post-treatment biopsies
Patients that have been prescribed sipuleucel-T and have not started treatment
Patients’ tumors will need to tested for the RAS mutation status; only those patients with wild-type or unmutated RAS oncogene are eligible to participate in this study
Patients who have required toxicity related dose reductions of greater than 50% of the original dose of infusional 5-FU and/or irinotecan during the administration of FOLFIRI/bevacizumab
Patients must be off all disease modifying therapy for MDS for 28 days prior to initiation of study treatment; patients may receive hydrocortisone prophylactically to prevent transfusion reactions
Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be >= 20% or a serum ferritin >= 100 ng/100 mL or soluble transferring receptor < 5 mg/L.
Patients with splenomegaly with a spleen size > 16 cm
Patients must be evaluated by a thoracic surgeon, pulmonologist or medical oncologist and deemed medically or surgically unacceptable for resection.
PART II: Patients with breast cancer, gastric, gastroesophageal junction or other caners with 1+ to 3+ HER2/neu expression by IHC or a Vysis FISH result > 2.2
Patients must have serum antibodies directed to human T-cell lymphotropic virus (HTLV)-1
Patients with symptomatic leukemic meningitis, bony or gastrointestinal (GI) tract involvement, serum calcium or lactate dehydrogenase (LDH) > 1.5 X the upper limit of normal will be excluded; however, patients that have both ATL and another HTLV-1 associated disease such as tropical spastic paraparesis (HTLV-I-associated myelopathy [HAM]/tropical spastic paraparesis [TSP]) will be included
No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of >1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies.
COHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Patients must have advanced disease that is not amenable for resection or transplantation, and that is not treatable with liver directed modalities such as radiofrequency ablation or transarterial chemoembolization
COHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Patients with evidence of portal hypertension must have had an esophagogastroduodenoscopy (EGD) within last year with appropriate treatment of esophageal varices as per standard of care
Patients treated with prior Interleukin-2 will be allowed to be in this study
Patients that have undergone Tyrosinase immunotherapy
Patients with sarcomatoid mesothelioma as mesothelin is not expressed in this type of mesothelioma
Patients with diabetic retinopathy
Patients with a diagnosis of MM as defined by the 2014 IMWG diagnostic criteria
Patients should have body Temperature <= 38.0 degrees C.
Patients with indwelling catheters (other than Portacath, Hickman or PICC lines)
Patients with previously documented macular degeneration or diabetic retinopathy are excluded from the trial
Patients must complete all required pre-entry tests listed in section 4.0 within the specified time frames.
Patients must be at least 18 years old.
Tumors of all regions of the CNS, with appropriate histology are eligible for study; however patients with SEGA or tumors intrinsic to the optic nerve and involvement of the optic nerve that cannot be biopsied/resected are eligible without histological confirmation
Patients receiving other experimental immunotherapy
Patients taking folic acid are eligible if the folic acid is discontinued prior to pyrimethamine administration and not taken for the duration of time enrolled on this study
Patients who are in the estimation of the principal investigator (PI), deemed unable or unlikely to adhere to protocol treatment
Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment
Patients with documented history of no response to cladribine, and without 50% improvement in platelets, hemoglobin or granulocytes; this exclusion does not apply to HCLv; these patients are eligible regardless of prior response to cladribine (CDA)
At the investigator’s discretion, receipt of a live vaccine within 4 weeks prior to randomization; efficacy and/or safety of immunization during periods of B-cell depletion have not been adequately studied; it is recommended that a patient’s vaccination record and possible requirements be reviewed; per the investigator’s discretion, the patient may have any required vaccination/booster administered at least 4 weeks prior to the initiation of study treatment; review of the patient’s immunization status for the following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal polysaccharide; varicella; measles, mumps and rubella (MMR); and hepatitis B; patients who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series at least 4 weeks prior to participation in the study
Patients with a known nonmalignant disease that is not clearly defined will need to be discussed with the protocol principal investigator (PI) (Dr. Lauri Burroughs) and potentially the nonmalignant board to determine if they are eligible for HCT on this study
Patients with idiopathic aplastic anemia and Fanconi anemia; (patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria [PNH] or inherited marrow failure syndromes, except Fanconi anemia, will be allowed)
Patients with co-morbidities that would make the use of radiation too toxic to deliver safely, such as serious local injury or collagen vascular disease
Eribulin dose modification necessary in patients with hepatic insufficiency according to United Surgical Partners International (USPI).
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations. Rash must cover less than 10% of body surface area (BSA). 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%). No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
Patients must complete all required pre-entry tests within the specified time frames
Patients from outside of the United States may participate in the study
Patients with newly diagnosed DIPG by magnetic resonance imaging (MRI); defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis. For lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility. Tumors that are biopsied will be eligible if proven to be supportive of the diagnosis of a DIPG. Consensus of diagnosis by the study team must be met.
Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the assessment of mass effect should be made by the study chairs and study neurosurgeons prior to any planned CED treatment.
Patients with evidence of intra-tumoral hemorrhage > 5 mm maximal diameter. These subjects should be discussed with the study chair.
Prisoners or patients who are involuntarily incarcerated
Immunocompromised patients are excluded
Patients who have been treated with prior secondary hormonal manipulations with proposed investigational rationale for having efficacy against AR-V7 splice variants. This includes but is not limited to EPI-002 and AZD5312. (Note: patients previously treated with abiraterone, orteronel [TAK-700], apalutamide [ARN-509], galeterone, or VT-464 will be eligible for this study. Patients who have received prior chemotherapy will also be eligible for this study).
Patients with MDS who transform to AML while on hypomethylator agents or patients with AML who progress on hypomethylator agents could be considered for arm A of this trial if \r\n* They choose not to be treated on or are ineligible for our competing trial of sEPHB4-HSA + hypomethylator (9L-16-6) \r\n* They are appropriate for high dose cytarabine treatment
Patients with Charcot-Marie-Tooth disease or other demyelinating diseases are excluded from the liposomal vincristine containing arm
Patients must have had histologic or flow cytometric verification of the malignancy at relapse
Patients who have previously received bortezomib or other proteasome inhibitors that did not have a response while receiving the inhibitor are not eligible; patients that responded but had a subsequent relapse are eligible
Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant
Asymptomatic mCSPC patients with > 75% PSA decline after 12 weeks of run in period with ADT, abiraterone plus prednisone
Patients with known amyloidosis (AL) subtype amyloidosis
Patients >= 12 years and < 55 years are also included if they are not candidates for myeloablative conditioning regimens due to comorbidities
Patients with significant edema leading to risk of brain herniation
For patients that have refused treatment with sorafenib, the benefits of sorafenib have been discussed in detail with the patient.
Patients must have histologic evidence of relapsed or refractory B-cell ALL
Patients must not be receiving any chemotherapy agents (except hydroxyurea); intrathecal methotrexate and intrathecal cytarabine are permissible
Patients who are eligible for and willing to receive treatment with blinatumomab, inotuzumab ozogamizin, or tisagenlecleucel
Patients currently on Pembrolizumab and achieve a less than complete response
Patients with other active malignancies are ineligible for this study, other than localized malignancies
Patients undergoing pleurodesis for benign disease (e.g., spontaneous pneumothorax)
Patients participating in a clinical trial where prevention of GVHD is the primary endpoint.
Patients must agree to have a biopsy of metastatic tissue at baseline and on-treatment, and there must be a lesion that can be biopsied with acceptable clinical risk (as judged by the investigator)\r\n* Patients with unsuccessful baseline biopsies may undergo an additional biopsy attempt (at the same or a different site, determined by the investigator)\r\n* For patients with an intact primary and no metastatic site that can be safely biopsied, biopsy of the primary is acceptable, but must be approved by the principal investigator
Patients with known contrast allergies requiring pre-medication with steroids
Patients with a histological diagnosis of lymphomas and/or leukemias
Patients with a target lesion located in a previously irradiated field
Symptomatic hypothyroidism without replacement\r\n* Patients may be rescreened after initiating adequate replacement therapy
Patients receiving systemic corticosteroids greater than 2-weeks in duration within 6 months of study entry must have evidence of adequate adrenal function based upon morning plasma cortisol concentration or ACTH (cosyntropin) stimulation test
Cohort B: Patients must have progressed during treatment with enzalutamide or second-generation AR-blocking therapies. Patients progressing on enzalutamide immediately prior to enrolling in this study must be on stable doses of enzalutamide 160 mg once daily (QD). These patients will continue enzalutamide without interruption during the screening period (no wash-out period required).
Patients with prior pneumonectomy
Histologically confirmed myelodysplastic syndrome with positive TET2 mutations (we will test all MDS patients for TET2 mutations using next generation sequencing and only patients with TET2 mutations will be included in our study)
Potassium and magnesium within normal range, patients may receive supplements to meet this requirement
Willingness to have 2 tumor biopsies; the first before and the second while on therapy (optional for all patients and may become mandatory in order to ensure 15 patients at maximum tolerated dose [MTD] have paired biopsies).
Immunocompromised patients with any hematological malignancies.
Patients with criteria of probable or definitive adenoviral diseases.
Patients must have non-target lesion accessible for sequential biopsy (core needle biopsy or excision preferred, fine needle aspiration not eligible)
Patients who are imprisoned or under legal guardianship
Patients must not have had prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload.
Known amyloidosis (MM patients)
Radiotherapy: ?4 weeks (patients who receive palliative radiation for nontarget tumour lesions need not be subjected to this washout period and can be enrolled immediately)
Clinically significant patient history which in the judgment of the principal investigator (PI) would compromise the patients’ ability to tolerate high-dose aldesleukin; (Note: At the discretion of the PI, patients enrolled in cohort 3 may receive low-dose aldesleukin)
Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 (diameter >= 10 mm), percutaneously
Patients with HCL variant (as defined by absence of expression of CD25)
Patients with uncharacterized eye disorders
Patients who had solid organ transplants are not eligible
Patients must have completely resected (as per standard of care) melanoma of cutaneous origin in order to be eligible for this study; patients must be classified as stage IIB or IIC cutaneous melanoma using the American Joint Committee on Cancer eighth edition; patients with melanoma of mucosal or other non-cutaneous origin are not eligible; patients with melanoma of ocular origin are not eligible
Patients with known serious mood disorders
Subjects must have relapsed/refractory DLBCL or relapsed/refractory FL\r\n* For DLBCL, patients must have relapsed after, declined, or considered ineligible for high-dose chemotherapy and autologous stem cell transplantation\r\n* For FL, in addition to relapsed/refractory disease status, patients must have received therapy with CD20 antibody-directed therapy, and must have an indication for treatment; FL eligibility also requires patients have no standard options with curative potential, nor options with more favorable risk/benefit ratio in the judgment of the investigator
Patients with pathologically confirmed MF with cutaneous involvement.\r\n* Patients must have clinically measurable disease of at least 1 lesion on physical (skin) exam.\r\n* If a patient has a prior pathological diagnosis of MF and is clinically diagnosed with a new lesion, the new lesion is eligible for enrollment without additionally biopsy confirmation.
Pregnant patients do not meet inclusion criteria for radiation therapy.\r\n* Patients who subsequently become pregnant may continue follow up within the protocol, but a negative urine pregnancy test will need to be obtained before additional lesions may be enrolled.
Patients with active lupus or scleroderma
Patients must have a confirmed heterozygous TET2 mutations identified by next generation targeted deep sequencing
Patients must have MDS, or MDS/MPN overlap defined by 2016 World Health Organization (WHO) criteria; both newly diagnosed or previously treated MDS or MDS/MPN patients are eligible as long as the patient has never received prior treatment with azacitidine or decitabine
Relapse/refractory is defined as at least 1 course of treatment for AML excluding any patients treated with azacitidine or decitabine
Patients must have normal organ and marrow function as defined at the discretion of the treating physician and principal investigator (PI)
STUDY ENTRY: Confirmation of diagnosis (by surgical excisional/incisional biopsy or imaging-guided core biopsy), and patients for whom the plan of management will include NACT followed by ICS. The decision to proceed with NACT will be at the treating physician’s discretion and include patients with advanced stage disease considered at low likelihood for optimal cytoreduction with primary debulking surgery.
Hospitalized patients (or willing to be hospitalized for 24 hours after Rx) with Modified WHO Grade 1 (subset) or Grade 2 Bleeding Score or at risk for same within 4 weeks of screening. The Grade 1 subset includes patients who have either epistaxis, hematuria, oral petechiae, or bleeding at invasive or other wound sites.
COHORT 3: ENDOMETRIAL CANCER: Patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies
Patients who have previously been treated with any of the agents or same class of agents they are scheduled to receive will be excluded. For example, a patient previously treated with a PD1 or PDL1-based therapy will not be eligible for avelumab+4-1BB or avelumab+OX40 arms. A patient previously treated with an OX40 based therapy will not be eligible for any of the OX40 single-agent or combination arms.
Patients with known congenital or acquired immune deficiency (including those patients who require systemic immunosuppressant drugs for autoimmune disease or organ transplant)
Female patients who intend to donate eggs and male patients who intended to donate sperm during the course of this study or for 4 months after receiving the last dose of study treatment
Patients must be willing and able to check and record daily blood pressure readings when randomized to cediranib containing arm
Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system.
Patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors or lymphoma, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients with a BSA ? 1.17 m^2 at time of study enrollment are not eligible
Patients with a history of allergy to medications that have a benzamide structure (e.g., metoclopramide, procarbazine, domperidone, cisapride etc.) are not eligible
For metastatic colorectal cancers, patients starting maintenance capecitabine after a course of oxaliplatin or irinotecan based chemotherapy are eligible
Diagnosis: Patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.
Patients: Patients of any age and either gender
Patients who are transplanted at non-US transplant centers
Patients must be considered transplant eligible by the treating physician at time of study entry.
Patients with a prior autologous or allogeneic HCT
Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
Known active hepatitis, type B or C; patients on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible
Inclusion Criteria:\n\n        Patients fulfilling the following criteria will be eligible to provide continued long-term\n        follow-up data as part of this study:\n\n          1. Enrolled and randomized on the BMT CTN 0702 protocol.\n\n          2. Alive at the completion of BMT CTN 0702 protocol specified follow-up defined as 4\n             years post-randomization.\n\n          3. Patients without evidence of disease progression at the completion of BMT CTN 0702\n             protocol specified follow up.\n\n          4. Signed Informed Consent Form.\n\n          5. Patients with the ability to speak English or Spanish are eligible to participate in\n             the HQL component of this trial.\n\n        Inclusion Criteria for Optional Long-term Lenalidomide Maintenance Therapy:\n\n        Patients fulfilling the following criteria will be eligible to provide continued long-term\n        follow-up data AND receive long-term lenalidomide maintenance therapy as part of this\n        study:\n\n          1. Enrolled and randomized to BMT CTN 0702.\n\n          2. Completion of 3 years of maintenance therapy on BMT CTN 0702.\n\n          3. Registered in the mandatory Revlimid REMS® program (formerly the RevAssist® for Study\n             Participants (RASP) program), and be willing and able to comply with the requirements\n             of the Revlimid REMS® program, including counseling, pregnancy testing, and phone\n             surveys.\n\n          4. Signed informed consent form.\n\n          5. Patients with the ability to speak English or Spanish are eligible to participate in\n             the HQL component of this trial.\n\n        Exclusion Criteria:\n\n        Patients who meet any of the following criteria will be ineligible to receive long-term\n        lenalidomide maintenance therapy as part of this study:\n\n          1. Patients who have evidence of disease progression prior to enrollment.\n\n          2. Patients who were discontinued from BMT CTN 0702 lenalidomide maintenance therapy, for\n             any reason, prior to the completion of the 3 years of 0702 maintenance.\n\n          3. Female patients who are pregnant (positive - Beta Human Chorionic Gonadotropin) or\n             breastfeeding.\n\n          4. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP\n             unwilling to use contraceptive techniques during the length of lenalidomide\n             maintenance therapy.\n\n          5. Patients who experienced thromboembolic events while on full anticoagulation during\n             prior therapy with lenalidomide.\n\n          6. Patients unwilling to take Deep Vein Thrombosis (DVT) prophylaxis.\n\n          7. Patients who developed a second primary malignancy, excluding non-melanoma skin\n             cancers after initiation of lenalidomide maintenance therapy on BMT CTN 0702.
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
For patients selecting vinorelbine or gemcitabine as the TPC agent, patients may not receive yellow fever vaccine in the 28 days prior to randomization.
Bone only patients during expansion/efficacy portion.
INTRATUMORAL STUDIES PATIENTS:
Patients requiring IV hydration or parenteral nutrition
World Health Organization (WHO)-defined acute lymphoblastic leukemia and either:\r\n* Relapsed after achieving remission\r\n* Refractory to therapy\r\n* Newly diagnosed and ineligible for intensive chemotherapy induction\r\nNote: patients with T lineage and B lineage ALL are eligible for this trial; likewise, patients with Philadelphia chromosome positive (Ph+) (as long as they are not candidate for other therapies for Ph+) and Ph- ALL are eligible
At least 4 weeks away from any previous antineoplastic or investigational agent; patients may receive hydroxyurea or glucocorticoids for suppression of leukocytosis, but these must be stopped at least 24 hours (h) prior to initiation of therapy
Patients with known other active cancers; skin cancers (basal or squamous) are exempted
Patients must have relapsed or refractory cancers for which there is no known curative option or other available therapy proven to prolong survival with an acceptable quality of life
Concomitant medications:\r\n* Growth factors that support platelet or white cell number of function must not have been administered within the past 7 days\r\n* Patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days\r\n* Patients who are currently receiving another investigational drug\r\n* Patients who are currently receiving other anti-cancer agents\r\n* Allergy or intolerance to agents on this protocol: vincristine, irinotecan, temozolomide, or metformin\r\n* Allergy to cephalosporins\r\n* Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection
Patients with histologically diagnosed progressive, recurrent or refractory non NF-1 associated LGG (other than pilocytic astrocytoma or optic pathway glioma); these patients must have BRAF aberrations as documented by the Lindeman and Ligon Labs at Brigham and Women’s Hospital using the same procedures
Patients must have bi-dimensionally measurable disease defined as at least one lesion that can be accurately measured in at least two planes in order to be eligible for this study
Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations
Patients requiring palliative radiotherapy to lesions that are defined as target lesions by RECIST criteria at the time of study entry.
Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
The HBV DNA test will be performed only for patients who have a positive HBcAb test
Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine
Patients with primary nasopharynx or salivary gland cancers are excluded
Patients who discontinued prior trastuzumab or T-DM1 due to progressive or refractory disease are eligible for enrollment; patients who discontinued prior trastuzumab or T-DM1 due to intolerance however are not eligible for enrollment
Patients who have failed bendamustine-based regimen previously
Other medications:\r\n* Patients receiving other anti-neoplastic agents are excluded\r\n* Patients on enzyme-inducing anticonvulsive agents are excluded\r\n* Patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded\r\n* Patients requiring anticoagulation or with uncontrolled bleeding are excluded\r\n* Patients on steroids for symptom management must be on a stable dose for 7 days prior to start of treatment
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\r\n* Rash must cover < 10% of body surface area\r\n* Disease is well controlled at baseline and requires only low-potency topical corticosteroids\r\n* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
Patients with previously documented macular degeneration or diabetic retinopathy are excluded
Patient must currently be receiving systemic PD-1 immunotherapy with pembrolizumab or nivolumab to be eligible; patients who are receiving combination ipilimumab with pembrolizumab or nivolumab are not eligible
Patients with known AL subtype amyloidosis
Inclusion criteria\n\n        1.Provision of informed consent prior to any study specific procedures 2.Patients must be\n        male or female ?18 years of age. 3.Progressive cancer at the time of study entry with a\n        life expectancy of ?16 weeks 4.Histologically or cytologically confirmed TNBC with evidence\n        of metastatic disease as per ASCO-CAP HER2 guideline recommendations 2013 5.Patients must\n        have received at least 1 and no more than 2 prior lines of treatment for metastatic disease\n        with an anthracycline (eg, doxorubicin, epirubicin) and/or a taxane (eg, paclitaxel,\n        docetaxel) unless contraindicated, in either the neo-adjuvant, adjuvant or metastatic\n        setting.\n\n        6.Confirmed presence of qualifying HRR mutation or absence of any HRR mutation in tumour\n        tissue by the Lynparza HRR assay.\n\n        7.At least one measurable lesion that can be accurately assessed at baseline by computed\n        tomography (CT) (magnetic resonance imaging [MRI] where CT is contraindicated) and is\n        suitable for repeated assessment as per RECIST 1.1.\n\n        8.Patients must have normal organ and bone marrow function measured within 28 days prior to\n        randomisation as defined by protocol 9.ECOG PS 0-1 within 28 days of randomisation.\n        10.Patients must be willing to comply with the protocol requirements Exclusion criteria\n\n          1. Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of\n             Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 21 or\n             more days before Cycle 1 Day 1. The patient can receive a stable dose of\n             bisphosphonates or denosumab for bone metastases, before and during the study as long\n             as these were started at least 5 days prior to study treatment.\n\n          2. More than 2 prior lines of cytotoxic chemotherapy for metastatic disease.\n\n          3. Previous randomisation in the present study.\n\n          4. Previous treatment with a PARP inhibitor (including olaparib) or other DDR inhibitor\n             (unless treatment was for less than 3 weeks duration and at least 12 months have\n             elapsed between the last dose and randomisation. Patients that did not tolerate prior\n             treatment are excluded).\n\n          5. Exposure to a small molecule IP within 30 days or 5 half-lives (whichever is longer)\n             prior to randomisation.The minimum washout period for immunotherapy shall be 42 days.\n\n          6. Patients with MDS/AML or with features suggestive of MDS/AML.\n\n          7. Patients with second primary cancer, EXCEPTIONS: adequately treated non melanoma skin\n             cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ\n             (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively\n             treated with no evidence of disease for ? 5 years prior to study entry.\n\n          8. Mean resting corrected QTc interval using the Fridericia formula (QTcF) >470\n             msec/female patients and >450 msec for male patients or congenital long QT syndrome.\n\n          9. Any of the protocol specified cardiac diseases currently or within the last 6 months\n             defined by New York Heart Association (NYHA) ? Class 2:\n\n         10. Concomitant use of known strong cytochrome P (CYP) 3A inhibitors or use of known\n             strong or moderate CYP3A inducers.\n\n         11. Persistent toxicities (? CTCAE grade 2) caused by previous cancer therapy, excluding\n             alopecia and CTCAE grade 2 peripheral neuropathy.\n\n         12. Major surgery within 2 weeks of starting study treatment: patients must have recovered\n             from any effects of any major surgery.\n\n         13. Immunocompromised patients, eg,human immunodeficiency virus (HIV) patients.\n\n         14. Patients with known active hepatitis (B or C).\n\n         15. Patients considered a poor medical risk due to a serious, uncontrolled medical\n             disorder, non malignant systemic disease or active, uncontrolled infection.\n\n         16. Patients with symptomatic uncontrolled brain metastases.\n\n         17. Patients unable to swallow orally administered medication and patients with\n             gastrointestinal disorders likely to interfere with absorption of the study\n             medication.\n\n         18. Patients with a known hypersensitivity to olaparib, AZD1775, AZD6738, or any of the\n             excipients of the products.\n\n         19. Pregnant or breast feeding women.
Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug with the exception of: hydroxyurea (HU) in patients who need to continue this agent to maintain WBC count =< 50,000/mm^3
Patients should not be known to be refractory to red blood cell or platelet transfusions
The hepatic requirements may be waived for patients with grade 1 or 2 elevations of hepatic transaminases clearly due to leukemic infiltration after consultation with a study co-chair
Female patients with infants must agree not to breastfeed their infants while on the study
Diagnosis\r\n* Patients with CNS3 disease\r\n* Patients with isolated extra-medullary relapse involving only sanctuary sites (eg. testicular relapse) but patients with extramedullary disease involving nodal or other non-sanctuary sites are eligible\r\n* Patients with isolated testicular relapse \r\n* Patients with Philadelphia chromosome positive (Ph+) T-ALL/T-LLy\r\n* Patients with Down syndrome \r\n* Patients with pre-existing grade 2 (or higher) peripheral motor or sensory neurotoxicity per CTCAE 4.03 \r\n* Patients with a history of prior veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) or findings consistent with a diagnosis of VOD/SOS, 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
Skin condition\r\n* Patients with pre-existing grade 1 or higher ulcerations, fistulas, mucosal lesions, or skin barrier breakdown
There is no need for steroids and patients have not had steroids at least 2 weeks
Initially only patients who are >= 16 years old will receive HA-1 TCR T cell infusions on the protocol; younger patients may be screened, enrolled in the protocol and monitored for relapse but will not be eligible for infusion until at least one patient >= 16 years old has been treated and discussed with the Food and Drug Administration (FDA)
Patients must have the HA-1(H) genotype (RS_1801284: A/G, A/A)
Patients must agree to participate in long-term follow-up for up to 15 years if they are enrolled in the study and receive T cell infusion
Patients who have relapsed or have MRD after HCT may receive other agents for treatment of disease and remain eligible for the protocol
A specific performance status score is not required for enrolling on the protocol; a delay in infusion of the HA-1 TCR T cells may be required for patients with low performance status
The presence of organ toxicities will not necessarily exclude patients from enrolling on the protocol at the discretion of the PI; however, a delay in the infusion of HA-1 TCR T cells may be required
Patients with contraindications to intravenous (IV) contrast administration are still eligible for this study if the tumor can be delineated clearly without IV contrast (at the discretion of the treating radiation oncologist) but will not participate in the functional imaging studies
Pregnant women; if patients are not status post bilateral salpingo-oopherectomy then pregnancy testing is required
PARPi naive or prior exposure to PARPi therapy (varies depending on Arm 1 and Arm 2)\r\n* Patients in Arm 1 (single agent rucaparib followed by combination upon progression) must be PARPi naive; prior irinotecan is allowed\r\n* Patients in Arm 2 (combination) must have been treated with and progressed on a PARPi previously; prior irinotecan is allowed
PARPi naive or prior exposure to PARPi therapy\r\n* Patients in Arm 1 of the Dose Expansion cohort cannot have prior exposure to PARPi therapy\r\n* Patients in Arm 2 of the Dose Expansion cohort cannot be PARPi naive
Patients must have undergone stem cell mobilization with the combination of G-CSF and plerixafor as per TJUH BMT SOP guidelines
Eligible patients with germline or somatic BRCA mutations must have disease progression after treatment with a PARP inhibitor; patients with unknown BRCA status must undergo testing prior to enrollment; however, non-mutation patients will also be eligible for study
Patients must agree to be randomly assigned to either intervention or control group
Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary; patients must be made aware of their other treatment options
Patients with a known dihydropyrimidine dehydrogenase (DPD) deficiency are ineligible
Patients who are unable to get MRIs due to any reason including pacemakers or automatic implantable cardioverter-defibrillator (AICD) are ineligible
Patients must be CMV seropositive
Patients must have undergone puberty at the time of study entry to allow pre-transplant fertility preservation to occur, if desired; puberty will be defined as Tanner III or more in male patients (typically age >= 13 years) and menarche in female patients
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
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted but patients with psoriasis require a baseline ophthalmologic exam to rule out ocular manifestations; rash must cover less than 10% of body surface area (BSA) and must be well controlled at baseline and only requiring topical steroids
Adult patients who require monitored anesthesia for PET scanning due to claustrophobia
Patients must receive insurance approval for or be willing to pay for commercial gefitinib
Patients with a second, clinically active, cancer; patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients must agree to consent to the companion genomic profiling study MSK IRB 12-245
Patients that have previously been treated with daratumumab or ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients unable to tolerate transrectal ultrasound.
Patients of any gender, race or ethnicity
Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study.
Patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study. 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 agree to tissue collection for correlative studies at the specified timepoints.
Patients between ages 18 and 80
Patients with extrahepatic metastases
Patients with portal vein invasion
Patients whose primary diagnosis was ocular melanoma
Patients who have an active herpetic skin lesion(s) or prior complications of HSV-1 infection
Patients with DLBCL who best fit the criteria of EBV+ DLBCL, NOS are not eligible
Patients taking injections of long-acting SRLs not as indicated in the label
Patients who previously participated in CH-ACM-01 or OOC-ACM-302
If group 1 is not filled, patients may proceed onto treatment without the completion of tests for DNA repair status; once group 1 is filled, patients cannot be enrolled onto the study or start treatment until DNA damage repair status is successfully determined for study group placement\r\n* Patients will be replaced if:\r\n** They have tissues that are not evaluable for mutations or the expression signatures\r\n** They do not have mutations associated with DNA repair and their expression signature is not evaluable
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
Patients must have clinically and radiographically suspected International Federation of Gynecology and Obstetrics (FIGO) stage 3 or 4 epithelial ovarian, primary peritoneal or fallopian tube cancer, high grade, for whom the plan of management will include neoadjuvant chemotherapy (NACT) with interval tumor reductive surgery (TRS); patients will be selected for NACT according to established criteria (Society of Gynecologic Oncology and the American Society of Clinical Oncology Guideline); patients must have undergone core needle biopsy for histologic confirmation prior to start of treatment
Patients who are unwilling to be transfused with blood components
Age greater than or equal to 16 years old; if patients 16-17 years old are enrolled in the trial, they will only be enrolled after 3 patients >= 18 years old have been treated, and the treatment has been shown to be safe
Patients with biliary obstruction or biliary stent are excluded
Patients in Cohort 1 (dose escalation) may have any level of expression
Patients with laboratory evidence of autoimmune disease (e.g. positive antinuclear antibody [ANA] or lupus anticoagulant) without associated symptoms; vitiligo, or mild autoimmunity not impacting the function of organs, such as Hashimoto or psoriasis may be eligible for study
Patients with a known ROS-1-rearrangement must have progressed or been intolerant to treatment with crizotinib or entrectinib
Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< 45ml/minute or creatinine of >= 2 mg/dl) or liver dysfunction (e.g. aspartate aminotransferase [AST]/alanine aminotransferase (ALT) and/or bilirubin >= 2 times upper limit of normal [ULN]) at the time of enrollment that may prevent from safely using chemotherapy; such patients may be allowed to receive low-intensity chemotherapy; patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded; discussion with the principal investigator is encouraged if further clarification is required
Patients with TNBC may be enrolled in dose expansion cohort A with any number of prior lines of therapy (patients will be allowed to enroll in frontline setting)
Patients who require ongoing anticoagulation will be excluded. Only aspirin will be permitted. Pre and post-surgical prophylactic anti-coagulation treatment is permitted
Patients must not require total parenteral nutrition with lipids
Patients with rapidly progressing tumors, as judged by the investigator
Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone)
Patients older than 65 who are deemed fit to receive intensive chemotherapy by the treating physician will be eligible after discussion with the principal investigator (PI).
Patients must be CTC positive (defined as CTCs >= 5)
Patients must have resistant/refractory or recurrent neuroblastoma
Patients are eligible >= 6 weeks after therapeutic 131I-MIBG or stem cell infusion to support 131I-MIBG, whichever is later
Patients who require or are likely to require corticosteroid or other immunosuppressive drugs for intercurrent disease (any other significant medical problem related to or independent from the neuroblastoma or its treatment) while tentatively scheduled to receive treatment on this study are ineligible; the only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product transfusion in order to avoid allergic transfusion reactions
Patients with prior history of ventilator support related to lung injury such as pneumonia, hemorrhagic pneumonitis, capillary leakage are excluded
Patients must have progressed on, been intolerant of or refused prior oxaliplatin- and irinotecan-containing, fluorouracil-based, chemotherapeutic regimen and have disease that is not amenable to potentially curative resection; patients who have a known KRAS wild type tumor must have progressed, been intolerant of or refused cetuximab or panitumumab-based chemotherapy
Patients must have at least one focus of metastatic disease that is amenable to pre- and on-treatment biopsy and be willing to undergo this; ideally the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators
Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis
Patients with secreting tumors must be receiving pharmacologic catecholamine blockade
Patients ?18 years and ?80 years old (The 3 first patients at Dose Level 1 will be < 65 years old. Enrollment of patients ? 65 years old must be approved by the DSMB after the completion of cohort 1).
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 persistent/recurrent following prior treatment for BPDCN. Patients enrolled in the Expansion Phase of the Study:
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients eligible for this trial will be those who have failed carfilzomib either as a single agent as the last form of therapy, or carfilzomib in combination with dexamethasone, or carfilzomib in combination with revlimid and dexamethasone; given the potential for compounding/worsening toxicities with the addition of cabozantinib to carfilzomib, patients eligible for the trial will have to have had very good tolerance to carfilzomib in the context of described regimens, with resolved prior toxicity to grade 1 or better, and no toxicities due to carfilzomib that required dose reductions to less than 27 mg/m^2
Patients with known congenital heart defects
Patients with portal vein thrombus
Must be willing to participate in Gene Therapy Long Term Followup Protocol (15-C-0141), which will follow patients for up to 15 years per Food and Drug Administration (FDA) requirements
Patients residing in prison
Uncontrolled autoimmune disorders. Patients with autoimmune disorders under control on medication may be included. Patients with pure red cell aplasia may be included if hemoglobin levels are relatively stable on transfusions or medication
Patients with major symptoms or impairments related to brain metastases, such as aphasia or severe confusion, will be excluded per principal investigator (PI) discretion when those symptoms preclude proper neurocognitive evaluation during the study treatment
Patients with breast tissue expanders must have those removed before enrollment
Platelets > 100,000/µL. Patients with ? 100,000 platelet count may be allowed into the study on a case-by-case basis after consultation with the Medical Monitor.
Patients enrolled onto the dose-finding phase of the study must have an identified donor and transplant strategy prior to initiation of the lymphodepletion regimen. Patients enrolled in the Expansion Phase of the Study: Relapsed/Refractory Cohort • Patients ?18 years old with relapsed or primary refractory acute myeloid leukemia. Patients Enrolled in the Dose-Escalation Phase of the Study •Patients ?18 years and ?75 years old (The 3 first patients at Dose Level 1 will be <65 years old. Enrollment of patients ? 65 years old must be approved by the DSMB after the completion of cohort 1) Newly Diagnosed Cohort • Patients with newly diagnosed, untreated Acute Myeloid Leukemia (as defined by World Health Organization (WHO) criteria,) who meet criteria for the European Leukemia Net (ELN) Adverse genetics prognostic group. Eligibility criteria for UCART123 administration
Patients voluntarily participate in the clinical trial, understanding they may withdraw participation at any time
Patients with biopsy proven dedifferentiated chondrosarcoma that chose not to pursue neoadjuvant chemotherapy
PRE-CHEMORADIATION SAMPLE COLLECTION: Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4a, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy\r\n* Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation; patients who have down-staged from M1 disease to M0 with prior platinum-based chemotherapy will be eligible\r\n* Staging is determined prior to chemoradiation
STUDY TREATMENT: Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4a, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy\r\n* Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation; patients who have down-staged from M1 disease to M0 with prior platinum-based chemotherapy will be eligible\r\n* Staging is determined prior to chemoradiation
Patients who desire and are candidates for radical cystectomy
Patients with fistula documented radiographically or by EDG/EUS, endobronchial ultrasound (EBUS)
Patients with tumors involving the cerebellum or both cerebral hemispheres
Patients with an active infection requiring treatment or having an unexplained febrile illness
Patients with known brain, spinal or cerebrospinal fluid (CSF) involvement are excluded\r\n* Prophylactic intrathecal therapy is allowed per institutional protocol if deemed necessary
Patients >= 60 years of age with previously untreated Ph-positive ALL [either t(9;22) and/or BCR-ABL positive] (includes patients initiated on first course of hyper-CVAD before cytogenetics known).
Patients whose electrolytes (sodium, potassium, calcium, magnesium) are abnormal or cannot be normalized with standard intervention on the day of treatment with study drug
Patients must have histologically confirmed adenocarcinoma of the colon that has metastasized (stage 4) and is TP53 mutant/deleted by a Clinical Laboratory Improvement Act (CLIA) approved genetic test; only known loss of function TP53 mutation/deletion will be eligible for this study
Patients must be resistant to or intolerant of fluorouracil (5FU), oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab (if RAS wild type)
Patients must have surgically resectable disease in the opinion of the treating physician. For patients with a primary OPSCC, patients must be eligible for TORS (transoral robotic surgery)
Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (There may be certain patients with performance status [PS] 3 in the context of rapidly proliferative/refractory ALL who would benefit from this regimen. We don’t want to exclude such patients who may derive benefit from this salvage regimen)
Patients on prophylactic or full-dose anticoagulation are eligible, provided the treating physician believes it is safe to temporarily withhold anticoagulation
Patients must be eligible to undergo high dose chemotherapy (HDT) followed by ASCT as a form of remission consolidation
Patients may have received any prior therapy deemed necessary for them to be eligible to HDT/ASCT except for patients whom have progressed while on Zydelig. Patients who have responded to Zydelig previously are eligible for enrollment on the protocol
Only patients with R/R ALL will be eligible for cohort C
Patients must have a diagnosis of CLL/SLL and EITHER have high-risk cytogenetic features or molecular features, defined as: del(17p), del(11q), mutated TP53, complex metaphase karyotype (defined as >=3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis) OR have developed a BTK or PLCG2 mutation, detected by sequencing and have not developed disease progression during ibrutinib therapy as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria OR B2M has not normalized after at least 1 year (yr) on ibrutinib therapy\r\n* Note: some patients treated with ibrutinib may no longer have detectable fluorescence in situ hybridization (FISH), karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken within the 3 months prior to starting ibrutinib or at some time during their ibrutinib therapy and analyzed at a Clinical Laboratory Improvement Act (CLIA)-accredited laboratory
Both pediatric and adult patients can be eligible to participate
Patients will not be eligible if they have a history of color vision defects
Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
Patients with contralateral hilar involvement
Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator’s discretion
Patients with tumors that cannot be measured or clinically followed
Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification
Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial
Patients who are carriers of hepatitis B will be included in this study
Consent for tumor biopsies (for patients enrolled in stage 1 only) and blood draws for research purposes (for all patients)
Patients who have had a stent placed for biliary obstruction can be included in the study provided serum bilirubin at time of enrollment is within protocol limits
Patients with evidence of active, non-infectious pneumonia
Patients who have participated in pembrolizumab (MK-3475) Merck studies
Patients with carcinomatous meningitis
Patients >= age 50 must have a comorbidity score (hematopoietic cell transplant-comorbidity index [HCT-CI]) < 4 (Sorror)
Known history of current or recent clinical diagnosis of tuberculosis (within 6 months prior to enrollment). A chest x-ray (XR) will be performed to screen for active tuberculosis (TB) for patients who have a history of treated TB. A chest XR will be performed in all patients to screen for active TB unless there has been a prior chest XR or computed tomography (CT) scan of chest within 1 month of entry
Patients who have undergone a diverting tracheostomy which is either a) traversing directly through tumor, b) has been placed for true airway insufficiency. Patients with a tracheostomy placed preemptively for impending airway compromise remain eligible for enrollment.
Patients requiring treatment with one or more beta-blockers (metoprolol, atenolol, propranolol) or calcium channel blockers with atrioventricular (AV)-nodal blocking activity (verapamil, diltiazem); patients being treated with AV nodal blocker (beta-blocker or calcium channel blocker) are allowed if the agent is being used only for correcting hypertension, and if an acceptable alternative is available (for example, transitioning from a drug such as atenolol to Lisinopril or amlodipine) prior to starting treatment on therapy
Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
Patients must have disease that is not amenable to potentially curative resection; patients must have received, been intolerant of or refused at least one line of chemotherapy
Patients must have at least one focus of metastatic disease that is amenable to pre- and on-treatment biopsies; ideally the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators
However, if the treating physician and diagnostic radiologist strongly suspect PET positivity, the patient should not be enrolled even if the biopsy is negative (to exclude patients with false-negative biopsy)
Female patients who are pregnant or lactating are not eligible (because treatment involves unforeseeable risks to the embryo or fetus)
Patients for whom SABR plans cannot meet the minimum requirement of target coverage and dose-volume constraints of critical structures (see SABR treatment planning section) are not eligible
Patients are known to have contraindications to radiotherapy
Patients with evidence of another malignancy or benign tumor requiring chemotherapy or radiation therapy are excluded; however, those patients with a plexiform neurofibroma requiring treatment will be eligible as selumetinib has documented activity in plexiform neurofibromas
Patients with a diagnosis of NF1 and GIST who do not meet other eligibility criteria may enroll on the NF1 natural history study, and will be followed on this study; should they require therapy for GIST based on evidence of progression, they may then enroll on study
Availability of >= 10 unstained 5 micron slides (to be provided to HTRC at the University of Chicago); patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study
Colorectal patients must have documentation of microsatellite status; immunohistochemistry (IHC) is acceptable
Patients previously treated with regorafenib, lonsurf or capecitabine as the last prior regimen can start on this study as long as there is at least 1 week of period between the last dose of previous treatment and day 1 in this study provided the patients are eligible; patients who were on FOLFOX or FOLFIRI regimens must have at least 2 weeks period between the last dose and the first dose in this clinical study; patients previously treated with Avastin, Zaltrap, cetuximab, pembrolizumab, panitumumab, nivolumab Erbitux, and Vectibix must have at least 4 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study
Patients are included regardless of KRAS/NRAS, BRAF, p53, or microsatellite instability (MSI) status
Patients with phaeochromocytoma
Patients with known sensitivities to either cyclophosphamide and/or sirolimus
Patients with known urinary outflow obstruction
Patients residing in prison
Patients with history of mild autoimmune disorders - including but not limited to - mild psoriasis or Hashimoto's hypothyroidism, may be included at the discretion of the principle investigator.
Female patients who have been on hormone replacement therapy (HRT) for menopausal symptoms for a period of at least 2 months will not be excluded from the study provided the HRT regimen remains unchanged during the conduct of the study.
The first 6 patients must be >= 18 and =< 65 years old. The subsequent patients may include pediatric patients >= 12 and =< 65 years old. Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician.
Patients with options for treatment that are known to be curative are not eligible.
Patients who have had previous radiotherapy in the thorax
Patients must receive a minimum dose of azacitidine of 75mg/(m)(2) dose
Patients can be premenopausal or postmenopausal
Patients with diagnosis of solid tumor with lung metastases and patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Eastern Cooperative Oncology group (ECOG) =< 2 for patients >= 16 years old or Lansky play >= 60% for patients\r\n=< 15 years old
Currently being treated with bronchodilators or corticosteroids or known to have active asthma. This will not include patients who suffered from asthma as a child and outgrew it.
Prisoners or patients who are involuntarily detained
The study is intended to enroll patients with pancreatic and colorectal cancer; patients with other types of solid tumors will require approval by the principal investigator
Nursing patients are not allowed on the study and women must commit to no lactation during the course of the study
Patients with newly diagnosed DIPG by magnetic resonance imaging (MRI); defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis; for lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility; tumors that are biopsied will be eligible if proven to be supportive for the diagnosis of a DIPG; consensus of diagnosis by the study team must be met
Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the assessment of mass effect should be made by the study chair(s) and study neurosurgeon prior to any planned CED treatment
Patients with evidence of intra-tumoral hemorrhage > 5 maximal diameter; these subjects should be discussed with the study chair
Patients must not be on enzyme-inducing anticonvulsants or other drugs that might interact with the cytochrome P450 enzyme system; if previously on an enzyme-inducing antiepileptic drugs (EIAED), patients must be off for at least 10 days prior to CED infusion
Febrile patients
Patients receiving post-transplant cyclophosphamide as GVHD prophylaxis
Patients must have elevated calcitonin levels greater than 40 pg/mL
Patients on systemic steroids (except if solely for adrenal replacement) within two weeks of collection
Patients who previously had any intolerance to lenalidomide 10 mg or who have a contraindication to lenalidomide will not be eligible for concomitant treatment with lenalidomide but will remain eligible for CAR T cell therapy without lenalidomide
Patients who are on corticosteroids or immunosuppressant’s are not eligible; a 2 week wash-out period for is required before registration
Patients have planned invasive dental procedures during the course of the study
Exclude patients with known Kell antibodies
There is no need for steroids and patients have not had steroids at least 2 weeks
Patients may have received chemotherapy or radiation for a previous, curatively treated malignancy provided at least 2 years have elapsed and there is no current evidence of disease (patients with previous or concurrent additional skin cancers will be eligible); patients with chronic lymphoid or leukemic malignancies are eligible with or without active disease as long as they have not had treatment within the past three months
Patients should not be eligible for potentially curative surgical intervention in the case of oligometastatic disease at the time of enrollment or must have actively refused after explicit discussion of potential benefit of this intervention with multidisciplinary team
Patients must be willing to undergo endotracheal intubation, mechanical ventilation, dialysis, cardiopulmonary resuscitation (CPR), and electrical defibrillation; patients must be willing to receive vasopressor drugs and all other standard intensive care unit interventions; any living will must be amended to allow these interventions or the patient will not eligible
Patients who have been treated on other protocols of genetically-modified T cells at the NIH only are potentially eligible under these conditions:\r\n* At least 6 months have elapsed since the last genetically-modified T-cell therapy that the patient received and there is no evidence of replication-competent retroviruses (evidence must be provided from prior NIH gene-therapy protocol principal investigator) and persisting genetically-modified T cells are not detectable in the patient’s blood (evidence must be provided by prior NIH gene-therapy protocol principal investigator)
Patients with lymphoma masses 10.0 cm or larger in longest diameter will not be eligible
Patients that have active hemolytic anemia
Patients currently taking anticoagulants
Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeon
Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (maximum temperature [Tmax] > 99.5 degrees Fahrenheit [F])
Patients who are on dexamethasone receiving > 4 mg/day in the two weeks prior to admission for intra-cerebral delivery of PVSRIPO
Diagnosis of relapsed/refractory advanced malignancies; specifically:\r\n* Patients relapsed refractory acute myeloid leukemia that have failed at least one line of prior therapy, \r\n* Patients with myelodysplastic syndrome that have failed hypomethylating agents, \r\n* Patients with myelofibrosis that have failed or are ineligible to receive ruxolitinib\r\n* Patients that have myelofibrosis on maximal tolerated doses of ruxolitinib, who are unable to discontinue ruxolitinib, are eligible if;\r\n** They have been on stable dose for 1 month and continue to have residual symptoms, splenomegaly or inadequately controlled blood counts
Patients should be previously untreated or have only been treated with single agent ibrutinib therapy for a period of < 3 months and were deemed ibrutinib intolerant
With otolaryngeal cancer receiving surgery with general anesthesia\r\n* Please note we are purposefully including patients with higher predisposition to delirium as we are investigating potential preventive strategies for this diagnosis of multiple etiologies; patients at higher risk of delirium (e.g., advanced age, chronic hypertension) will be included in our study; additionally, other common risk factors that exist in this patient population (e.g., alcohol or nicotine use) are thought to contribute to delirium postoperatively
Patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Patients with previously documented macular degeneration or untreated diabetic retinopathy (stable retinopathy is allowed)
Patients with prolactinomas
Patients with active inflammatory processes including T max > 101 or active tissue inflammation are excluded up to and including the day of admission
Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of their treatment regimen
All patients must be able to lie supine
All patients must have a vertebral body site to be treated located from T1 to L5
Patients unable to lie flat comfortably for 2 hours
Patients must have radiographic and/or CSF cytological evidence of LMD
Patients who have previously received a-PD-1 and/or anti-CTLA-4 will be eligible, unless they have ongoing > grade 2 adverse event (AE) side effects of such therapy. Ongoing physiologic replacement doses for adrenal and thyroid insufficiency are allowed on protocol
Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the ophthalmologist
As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment; however, adequate recovery of blood counts will be required to receive subsequent cycles)
Patients must have stable cardiovascular, neurovascular and neurological status, and be considered surgical candidates, as determined by any relevant pre-operative assessments, at the neurosurgeon’s discretion.
Patients must not have previously undergone an intracranial LITT procedure.
Patients with progression of multifocal tumors or tumors involving the posterior fossa (brainstem and cerebellum) will be excluded, as will patients where the anticipated treatment margin will be within 5 mm of critical intracranial structures (e.g., primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).
Patients at risk of brain perfusion problems, e.g., carotid stenosis • Uncontrolled hypertension requiring clinical intervention
Immunocompromised patients
Hyperleukocytosis (leukocytes ?25 x 109/L) at study entry. These patients may be treated with hydroxyurea according to routine practice, and enroll in the study when the leukocyte count falls below 25 x 109/L.
Patients known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.
Patients with equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are allowed, as long as the clinician has determined that they should be treated as HER2 negative
Patients with multifocal or multi-centric disease are eligible if the treating clinician has determined the patient should be treated as ER+ and HER2- negative
Patients with a history of ipsilateral or contralateral ductal carcinoma in situ (DCIS) are eligible
Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). Patients with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
Patients with active ? grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
Steroids: patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary
Patients must have progressed on imatinib, sunitinib, and regorafenib or have documented intolerance to any of these treatments.
Patients must discontinue antiandrogen therapy (i.e., flutamide, bicalutamide, nilutamide) for at least 4 weeks prior to registration with no evidence of a falling PSA after washout
Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. prostate cancer [PC]- hope [spes (Latin)], saw palmetto, St John’s wort, etc.) must be discontinued before starting protocol treatment; hormonal-acting agents such as diethylstilbestrol (DES) are forbidden during the trial and must be stopped starting protocol treatment; no washout period will be required; patients on megestrol acetate for hot flashes are allowed to continue therapy
Patients must stop taking ritonavir, idinavir, saquinavir, telithromycin, clarithromycin and nelfinavir 1 week prior to registration; Note: topical ketoconazole is permitted
Patients must have relapsed or refractory cancers for which there is no known curative option
Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
Patients who were intolerant of a gemcitabine containing regimen.
Patients must be undergoing surgery that is clinically indicated as determined by their care providers; patients must be eligible for surgical resection with the expectation that the surgeon is able to resect at least 400 mg of tumor with low risk of inducing neurological injury
Patients must consent to undergo biopsies of externally visible CSCC lesions (Group 2 only)
Arm A 14-patients expansion cohort: patients with histologically or cytologically proven chemotherapy naive unresectable malignant pleural or peritoneal mesothelioma
Arm B (first stage of phase II of TRC102 and pemetrexed): patients with malignant pleural or peritoneal mesothelioma who had progressed while being treated with or had recurred within 6 months of being treated with pemetrexed and cisplatin or carboplatin frontline; intervening treatment is allowed
Patients with known disorders associated with hemolysis
Patients with a prior cumulative cisplatin dose > 300 mg/m^2 (pertains to Arm A only)
Patients may not have current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
Patients should not be on antibiotics for any infection but post operative antibiotics are allowed if used prophylactically but should be completed prior to starting RT
Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy
Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study
Patients must be either refractory to or relapsed after 1 line of therapy; exception: in the expansion cohort only, no BV refractory patients will be allowed
Patients with HCL must be intolerant of or not candidates for purine analog-based therapy, or failed to achieve response (CR or partial response [PR]) or relapsed within 2 years of such therapy, AND meet the standard treatment initiation criteria (absolute neutrophil count [ANC] =< 1000/uL, hemoglobin [Hgb] =< 10 g/dL, platelet count =< 100,000/uL); patients with indolent lymphoma (FL, LPL, MZL) and patients with B-cell prolymphocytic leukemia must have an indication for treatment in the opinion of the investigator; patients with MCL and patients with CLL in Richter’s transformation should have previously received or not be candidates for high dose chemotherapy/autologous stem cell transplant
Patients with chronic GVHD requiring systemic therapy are eligible
Patients who would have otherwise been eligible to receive routine post-RP care
Participation in a different trial that increases a patient’s risk of VTE
Patients should have been identified by their respective physicians as candidates for radioembolization and scheduled to undergo such a procedure
Patients should agree to serial liver metastases biopsy pre-treatment, post-radioembolization, and post-combination immunotherapy
Patients should not be deemed candidate for curative hepatic resection
Patients with symptomatic extrahepatic metastases
Acceptable haematological function defined as (Patients can be transfused to meet the haemoglobin entry criteria):
No hematologic parameters for inclusion; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm^3 throughout cycles 1 and 2
Patients with nasopharynx or salivary gland primary site
Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
Patients with undetectable anti-tetanus toxoid IgG
Patients must be actively receiving treatment for their CML with a TKI: imatinib, dasatinib, nilotinib, or bosutinib\r\n* Patients must be on a stable dose of their TKI for at least 1 year prior to enrollment onto trial
Patients who have failed nilotinib or not tolerated nilotinib in the past
Patients must be considered appropriate candidates for LITT
Has a diagnosis of immunodeficiency; note that patients should not receive steroids during pembrolizumab administration
Patients with inherited syndromes associated with hypersensitivity to ionizing radiation, specifically patients with known history of ataxia-telengiectasia, Nijmegen breakage syndrome
Candidate for fulvestrant therapy – patients who have started fulvestrant may enter this trial if within 3 months of starting fulvestrant
Patients with thyroid dysfunction if not adequately controlled
Patients may agree to provide optional paired biopsies.
Patients who are scheduled to undergo therapeutic or prophylactic mastectomy with immediate placement of tissue expanders and have a strong family history or hereditary cancer
Pancreatic ductal adenocarcinoma: 1) pancreatic ductal adenocarcinoma patient with KRAS point mutation at codon G12 or G13; in addition to the above inclusion criteria, first 5 patients from both non-small cell lung cancer and pancreatic ductal adenocarcinoma patients will need to agree to mandatory pre- and post-treatment tumor biopsies
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
In the case of women, both pre/perimenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.
Patients with histologically confirmed classical HL that is relapsed or refractory after at least one prior therapy are eligible\r\n* Patients with lymphocyte predominant Hodgkin’s are eligible
Patients who are currently taking Coumadin or Coumadin derivatives
Patients with T315I mutation will not be excluded, but their response will be analyzed separately.
Patients who have been treated with chemotherapy or radiation within two weeks of planned study enrollment; this does not include hydroxyurea, which may be continued until start of conditioning therapy; ruxolitinib may be continued at principal investigator's discretion during conditioning
Patients with prior selective internal radiation are candidates are eligible as long as they are candidates for repeat procedures and they have demonstrated progressive disease.
Patients requiring beta blockade are disqualified from participating in this study
Patients with contraindications to general anesthesia, as determined by the treating physician or surgeon
Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; for patients in whom surgery is feasible, maximal surgical resection must have occurred
Patients aged 70-75 with hematopoietic cell transplant-co-morbidity index (HCT-CI) of 0-1 are eligible
Patients must have refused or have evidence of intolerance to or progression on imatinib
Failure to one induction course of chemotherapy (these patients will be analyzed separately); patients who require steroids, ara-c or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
Patients who are not candidates for, or who cannot tolerate intensive chemotherapy or blinatumomab, sources for the determination of clinical significance by the treating physician will be included in the subject’s medical record
Patients in which iodine contrast is contraindicated
Patients must be CMV seropositive
Patients with comorbidity score > 3; the principal investigator is the final arbiter of eligibility for comorbidity score > 3
Patients must have substantial cutaneous neurofibroma burden causing distress to the patient by disfigurement or itching; patients must have >= 9 measurable cutaneous neurofibromas; for the purpose of this study measurability will be defined for each of the lesions selected as target lesions as a neurofibroma with a longest diameter >= 4 mm in the longest diameter
Hematologic parameters for patients undergoing biopsy only: patients should have international normalized ratio (INR) =< 1.4 and prothrombin time (PT) =< 40 seconds (unless due to lupus anticoagulant); in patients not meeting these parameters, clearance by hematology will be required prior to undergoing a biopsy
Since there is no standard effective chemotherapy for patients with NF1 and cutaneous neurofibromas, patients may be treated on this trial without having received prior medical therapy directed at their plexiform neurofibromas (PN)
Registered patients with an active infection or with a fever of ? 38.5 Celsius degrees (C) within 24 hours of the first scheduled day of protocol initiation will be excluded until their infection and/or fever resolves
Patients with renal failure currently requiring dialysis of any kind are not eligible
Patients with exposure to prior immunotherapy are not eligible
Patients must not have elevated lung shunting precluding treatment with Y-90
Patients with prior transplant of any kind are not eligible
Patients with Fanconi anemia; at a minimum, the diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients younger than 30 years of age; (additional mutational testing may have been performed in a clinical or research capacity on a per patient basis but is not considered an exclusion criteria)
Patients on androgen deprivation therapy (ADT) are allowed
Decision impaired patients
Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation; HCC patients must have progressed on, been intolerant to, or refused prior sorafenib therapy; patients with BTC must have received, been intolerant of or refused at least one line of chemotherapy
Patients must agree to research blood sampling to participate in study
Patients with the following high-risk features who are not candidates for traditional neoadjuvant chemotherapy will be included for this trial: micropapillary, sarcomatoid and plasmacytoid features; 3-dimensional (3-D) mass on exam under anesthesia (EUA); lymphovascular invasion; hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); high grade (grade 3) tumors of the ureter, renal pelvis, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by computed tomography (CT) or magnetic resonance imaging (MRI) imaging; direct invasion of the prostatic stroma or the vaginal wall (i.e. cT4a disease); patients who are candidates for but refusing conventional chemotherapy may be considered eligible; for patients in whom eligibility is unclear, final arbitration will be determined by the principal investigator
Patients must be registered within 6 weeks of most recent resection
Moribund patients not expected to survive up to 48 hours
Patients with ARDS resulting from trauma
Patients with prior pneumonectomy
All patients with 1-4 metastatic brain lesions who are considered eligible for single-fraction, frame-based SRS, who are unable or unwilling to undergo frame-based SRS
Patients with exposed carotid artery preoperatively requiring sacrifice or bypass intra-operatively
Patients with active pharyngocutaneous fistula
Patients must agree to biospecimen submission for tissue and serum processing and storage for secondary biomarker studies
Patients with an outside primary site biopsy showing perineural or perivascular invasion
Patients residing in prison
Patients should have demonstrated resistance, intolerance or treatment discontinuation for any other reason of at least 2 FDA-approved TKIs (other than bosutinib) if in CP (cohort 1), or at least 1 Food and Drug Administration (FDA)-approved TKI (other than bosutinib) if in AP (cohort 2); resistance will be defined as meeting the criteria for failure or warning by the European Leukemia Net (ELN); no prior therapy is necessary for patients in BP (cohort 2); patients in CP who have failed < 3 TKIs, but are ineligible to receive other FDA-approved TKIs, may also be enrolled in cohort 1; at least 10 CP patients with the T315I mutation affecting the kinase domain of Bcr-Abl will be enrolled in cohort 1, as well as in the phase II portion of cohort 2
Patients receiving anticoagulants that are unable to be discontinued
Patients must be willing to accept blood product transfusions
Patients with a diagnosis of Philadelphia chromosome (Ph)+ ALL are not eligible
All patients with unhealed wounds or fistulas should not be given vascular endothelial growth factor (VEGF) inhibiting TKIs
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma (resected or management deferred), who are eligible
At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator’s discretion
Patients receiving systemic corticosteroids are NOT eligible for either Stratum
Patients who are currently receiving other anti-cancer/devices agents are NOT eligible for either Stratum
Additionally, patients treated in stage 1, cohort #3 must be EBV seropositive, given the inclusion of T cells derived from an EBV-specific subset in this group
mCRPC EXPANSION COHORT: All patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy
mCRPC EXPANSION COHORT: Patients who were treated for metastatic castrate-sensitive prostate cancer with docetaxel and androgen deprivation therapy who progress on docetaxel treatment or who progress within one month of the last docetaxel dose are eligible
Patients residing in prison
Patients must be vulnerable or frail by Balducci Criteria or the patient is refusing breast surgery; vulnerable patients are defined as those with dependence in some instrumental activities of daily living, well controlled co-morbidities, and early symptoms of geriatric syndrome; frail patients are defined as those with three or more co-morbidities, dependence in one or more activities of daily living, or a clinically significant geriatric syndrome; geriatric syndromes include: dementia, delirium, incontinence (fecal and/or urinary), osteoporosis or spontaneous fractures, polypharmacy, visual/hearing impairment, sarcopenia and neglect or abuse
Patients with a relapsed/refractory peripheral T cell lymphoma; patients must have received at least one prior standard cytotoxic regimen such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP), or etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (EPOCH) OR
Patients must be entered within 12 weeks of diagnosis
Patients must have disease that is amenable to biopsy and be willing to provide the same; NOTE: Patients in whom a baseline biopsy is attempted, but is not successful, will still be considered eligible for the study; in addition, if the primary oncologist has a concern regarding the feasibility of a biopsy, it may be omitted after consulting with the protocol chair
Female patients must either:
Immunocompromised patients
Patients previously treated with taxanes are excluded, unless the taxane therapy was part of an initially curative regimen (e.g. adjuvant) and was completed > 12 months from study enrollment; patients with previous intolerance to ramucirumab
Treatment-naive systemic ALK-positive ALCL patients
Patients with options for treatment that are known to be curative are not eligible
RESEARCH SAMPLE COLLECTION: Myeloma patients who are not candidates for high-dose melphalan followed by autologous HCT based on institutional standards
Patients must be ? 18 years old.
Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the PI
Willing to defer definitive surgery for one week while taking DSF and Cu; patients who declined the optional pre-operative pharmacokinetic study or enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion
Patients who do not have other options of treatment, based on consensus recommendation of the multidisciplinary SSRS tumor board; patients will have an appropriate medical oncologist for their disease
Patients must not have any active infectious process.
Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood obtained by phlebotomy and/or consent to leukapheresis for DC generation.
Patients with HM who have undergone myeloablative systemic therapy are ineligible to participate in this study.
Patients with contraindications to CYP and/or GM-CSF.
Patients with preexisting known or suspected radiation sensitivity syndromes will be excluded
Patients who may receive the injections endoscopically should be eligible for sedation.
Resectable primary lesion (patients with pre-existing metastasis will be included if their primary is still going to be resected)
MPNST for which standard therapy is not curative, including patients with surgically unresectable lesions, progression (WHO criteria) or recurrence of an MPNST in a previously radiated field (if it has been at least 4 weeks prior to registration since the last dose of radiation); Note: patients with metastatic disease also are eligible for participation
Previous pathologic confirmation of a tumor treated with radiation to the brain completed at least 6 months prior to the start of planned reirradiation, except for patients with tumors that are routinely diagnosed without biopsy, including germinoma and optic pathway glioma; patients with a history of cranial irradiation for leukemia are eligible
In the first 5 patients enrolled in treatment groups on part B of this study (receiving combination ipilimumab and nivolumab), patients may have had 1-0 prior lines of systemic therapy after being diagnosed with metastatic disease; this restriction will be lifted in all subsequent cohorts of patients treated on part B
Patients with smoldering and lymphomatous ATL
Patients with active, uncontrolled psychiatric disorders include: psychosis, major depression, and bipolar disorders
Patients may have either metastatic lesions from another primary site or primary hepatocellular carcinoma; patients with one histologically confirmed metastatic lesion of the liver who are presenting for local therapy for lesions concerning for metastases that cannot or should not be biopsied will also be considered for enrollment on a case by case basis; patients can simultaneously receive treatment for multiple hepatic lesions meeting the prior two requirements, at the discretion of the treating radiation oncologist
Taking warfarin sodium; patients on other blood thinners should be monitored for thrombocytopenia
Patients with active hemoptysis
Family history: one or more close blood relative with ovarian carcinoma at any age or breast cancer age 50 or younger or two relatives with breast, pancreatic or prostate cancer (Gleason 7 or higher) at any age, or patients with Ashkenazi Jewish ancestry; however, patients with previously identified genetic aberrations that are associated with homologous recombination deficiency (HRD) will be eligible even in the absence of family history [e.g. somatic BRCA mutation, Fanconi anemia gene, ATM or RAD51 mutations]
Patients must be germline BRCA 1 or 2 negative; (Note: if BRCA status was previously determined, that result is acceptable but documentation of status must be available; subjects with unknown status will be referred to genetic counselling for BRCA testing as per standard of care) and/or patients with previously identified genetic aberrations that are associated with HRD will be eligible even in the absence of family history [e.g. somatic BRCA mutation, Fanconi Anemia gene, ATM or RAD51 mutations]
Patients must complete all screening assessments as outlined in the protocol
Patients may not be on an inhibitor of breast cancer resistance protein (BCRP)\r\n* NOTE: AZD1775 is an inhibitor of breast cancer resistance protein (BCRP); the use of statins including atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives
Patients >= 70 and =< 75 years of age may be eligible if they have a Hematopoietic Cell Transplantation- Comorbidity Index (HCT-CI) Co-Morbidity score =< 2
Patients who have been treated on other protocols of genetically-modified T cells at the NIH only are potentially eligible under these conditions:\r\n* At least 6 months have elapsed since the last genetically-modified T-cell therapy that the patient received and there is no evidence of replication-competent retroviruses (evidence must be provided from prior NIH gene-therapy protocol principal investigator) and persisting genetically-modified T cells are not detectable in the patient’s blood (evidence must be provided by prior NIH gene-therapy protocol principal investigator)
Patients that have active hemolytic anemia
Highly active antiretroviral therapy (HAART) for HIV+ patients:\r\n* All HIV+ patients must be willing to be compliant with HAART\r\n* Group I – on HAART for 1 month with stable disease; however, no minimum time restriction for patients with progressive and/or end-organ threatening disease\r\n* Group II – no minimum time restriction on prior HAART, patients may be HAART naive
All patients must be surgical candidates for complete hysterectomy and bilateral salpingo-oophorectomy and pelvic and aortic lymphadenectomy
Patients must have Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
Patients who have circumstances that will not permit completion of this study or the required follow-up
Patients with GOG performance grade of 3 or 4
Patients must have unresectable cutaneous, mucosal or ocular metastatic stage III/IV melanoma, and in the opinion of the institutional principal investigator (PI) is an acceptable candidate for adoptive cell therapy (ACT) with high dose interleukin-2 (IL-2); patients with ocular or mucosal metastatic melanoma may be included, as our prior experience indicates that TIL can be successfully propagated from these subtypes of melanoma metastases
Patients with cytopenias below these thresholds deemed to be the result of disease will be considered eligible
Patients must be willing to consent for protocol #12-245 for IMPACT testing
Patients with performance status of =< 3 (3 only allowed if decline in status is deemed related to\r\nlymphoma and felt potentially reversible by the treating physician)
Patients with unmutated (=< 2% homology with germ line) IGHV
Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.
Patients previously treated with bevacizumab.
Patients on EIADs are not eligible, unless the antiepileptic drug can be safely tapered and discontinued before C1D1.
Patients may have single or multinodular tumors
Patients may receive concurrent capecitabine or sorafenib at the discretion of the treating physicians
Please note that tumor samples for patients with MF or SS can be CD30 negative and do not have to be CD30 positive on either flow cytometry or immunohistochemistry for patients to be eligible
Patients must be willing and able to undergo biopsy according to the institute’s own guidelines and requirements for such procedures
Patients must be irinotecan refractory; patients must have progressed on prior irinotecan therapy but must be able to tolerate standard irinotecan doses
Patients taking high-dose vitamin D supplementation (50,000 IU weekly) prior to enrollment
Patients with vitamin D total 25-hydroxy level above 66 ng/ml at baseline testing
Patients with hypercalcemia and/or any condition resulting in malabsorption
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients must have metastatic pancreatic ductal adenocarcinoma (PDA) or metastatic colorectal cancer (CRC) to be eligible; (PDA patients with an elevated tumor marker following a primary pancreatic surgery would be eligible)
ENTRECTINIB INCLUSION CRITERIA: Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed; the use of seizure prophylaxis is allowed as long as patients are taking non enzyme-inducing anti-epileptic drugs (non-EIAEDs); if patients were previously on EIAEDs and these have been discontinued, they must have been discontinued for at least 2 weeks prior to the start of entrectinib treatment; if patients require an anti-epileptic medication, a CYP3A4 non-EIAED can be used such as levetiracetam, valproic acid, gabapentin, topiramate, or lacosamide; moderate inducers of CYP450, such as dexamethasone or other glucocorticoids, may be used at the discretion of the investigator; patients requiring steroids must be at a stable or decreasing doses for at least 2 weeks prior to the start of entrectinib treatment
CAPMATINIB EXCLUSION CRITERIA: Known symptomatic brain metastases requiring increasing doses of steroid to manage CNS symptoms within 2 weeks prior to study entry\r\n* Patients with asymptomatic brain metastases may be enrolled at the discretion of the sponsor as long as the patient is stable and has not required increasing dose of steroids to manage CNS symptoms for at least 2 weeks prior to study enrollment\r\n* Patients requiring seizure prophylaxis must be taking non-enzyme-inducing anti-epileptic drugs (non-EIAED); if patients were previously on EIAEDs and these have been discontinued, they must be discontinued for at least 1 weeks prior to capmatinib administration; if patients require an antiepileptic medication, then a CYP3A4 non-EIAED can be used such as levetiracetam, valproic acid, gabapentin, topiramate or lacosamide
Patients receiving chronic steroids and or immunosuppression
Patients with solid tumors or lymphoma must have 1 or more tumors accessible to biopsy or resection, including biopsy allowing multiple cores from at least 1 lesion (fine needle aspiration is excluded), incisional or excisional biopsy, and/or resection. Note: Patients with resectable brain metastases must be undergoing planned resection. Patients with rHGG must be undergoing planned subtotal or gross total resection.
Patients with KPS < 70 and/or unable to tolerate potentially longer treatment times
HCT-CI/age score =< 5 points (patients with greater than 5 points will be allowed for trial with approval of the PI and the co-PI or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points
HCT-CI/age score > 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator and the co-principal investigator or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points
Patients who are or are not receiving bisphosphonates or denosumab are eligible; bisphosphonates or denosumab should not be initiated after registration and during active treatment
Patients currently receiving active therapy for other neoplastic disorders
Patients with disease only in the bone previously treated with radium-223 will not be eligible
Patients with malignant solid tumors must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
Patients must have serum 25-hydroxyvitamin D (25[OH]D) drawn at time of enrollment; (NOTE: subjects currently taking vitamin D supplements are eligible for screening)
The patient is eligible for TSEBT
Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for at least 2 weeks; NOTE: Vitamin supplements are acceptable
Patients with electronic pacemakers or defibrillators.
FLT3-ITD and/or FLT3-D835 mutated patients with relapsed/refractory AML (any number of relapses) including patients who may have been previously exposed to one or more FLT3-inhibitor therapies will be eligible for the phase I portion of this study
Patients with MDS (up to 20% blasts) of any risk as defined as:\r\n* Previously untreated\r\n* Previously treated with hypomethylating agent (HMA) agent; patients need to have relapsed or progressed after any number of cycles of HMA therapy; patients that do not respond to HMA therapy will also be allowed in the study; relapse or progression will be measured by International Working Group (IWG) 2006 criteria; no response will be lack of clinical benefit after at least 6 cycles of HMA therapy
Patients with malignant celiac nodes are eligible if the primary lesion is in the mid-thoracic or distal thoracic esophagus or it is involving the gastroesophageal junction
Numerical rating pain scale within 1 week prior to registration; documentation of the patient’s initial pain score is required; patients taking medication for pain at the time of registration are eligible
Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca • Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
Patients will have no more than 4 distinct lesions within the brain; at least 1 lesion has been recommended for surgical removal based on size, symptomology, or regional mass effect on the brain
Female patients with infants must agree not to breastfeed their infants while on the study
Patients taking drugs leading to significant QT prolongation where the interaction is too great to proceed with romidepsin
Patients who have had only segmentectomies or wedge resections
Cohort 1: Pre-treated patients with cMET GCN ? 6 or
Cohort 2: Pre-treated patients with cMET GCN ?4 and < 6, or
Cohort 3: Pre-treated patients with cMET GCN < 4, or
Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or
Cohort 5: Treatment-naïve patients with cMET dysregulation
Patients with characterized ALK-positive rearrangement
Patients receiving treatment with any enzyme-inducing anticonvulsant
Patients with advanced/metastatic, symptomatic, visceral spread, at risk of life-threatening complications in the short term by investigator assessment
New onset acute GVHD Ann Arbor score 3 following allogeneic bone marrow transplantation (BMT); any clinical severity (Glucksberg grade I-IV) is eligible; patients with prior or existing diagnosis of GVHD without any treatment are eligible; patients given only topical corticosteroids for skin GVHD are eligible
Biopsy of acute GVHD target organ is strongly recommended but not required; enrollment should not be delayed for biopsy or pathology results; patients who do not enroll within 3 days of initiation of systemic steroid treatment for acute GVHD are not permitted to participate
Patients with chronic GVHD only; patients diagnosed with overlap syndrome are still eligible
Patients on dialysis
Patients requiring ventilator support
Patients with cytologically or histologically confirmed locally advanced or metastatic pancreas adenocarcinoma with a BRCA1 or 2 or PALB2 mutation confirmed by report from Myriad Genetics (United States of America [USA]); reports from other molecular diagnostic companies can be used to confirm mutations as well; BRCA 1 or 2 or PALB2 mutation can be confirmed locally for all international sites\r\n* For Part I, non-randomized, lead-in portion, patients with a known BRCA 1 or 2 or PALB2 mutation are eligible along with patients who potentially may have a likelihood of having a BRCA mutation (e.g., personal or family history of breast, pancreas, ovary, endometrial, prostate or other likely related malignancy); for Part I, randomized portion, a known BRCA 1 or 2 or PALB2 mutation is required
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to molecular analysis for therapy choice (MATCH) to APEC1621E based on the presence of an actionable mutation\r\n* Note: patients with BRAF V600 actionable mutations of interest (aMOIs) will be preferentially assigned to APEC1621G (vemurafenib) if that study is open and they are otherwise eligible for it
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Criteria:\n\n          -  Histologically and/or cytologically confirmed malignant pleural mesothelioma.\n\n          -  Unresectable disease (defined as the participant not being a candidate for curative\n             surgery).\n\n          -  Measurable disease, defined as at least 1 lesion (measurable) that can be accurately\n             assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI)\n             and is suitable for repeated assessment (modified RECIST for pleural mesothelioma).\n\n          -  Available unstained archived tumor tissue sample in sufficient quantity to allow for\n             analyses. At least fifteen unstained slides or a tumor block (preferred). NOTE: A fine\n             needle aspiration sample is not sufficient to make the patient eligible for\n             enrollment. Given the complexity of mesothelioma pathological diagnosis and that these\n             will be newly diagnosed patients it is expected that they will have a core needle\n             biopsy or surgical tumor biopsy as part of their initial diagnostic work up.\n\n          -  Age ? 18 years.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n\n          -  Ability to understand and willingness to sign Institutional Review Board\n             (IRB)-approved informed consent.\n\n          -  Willing to provide archived tumor tissue and blood samples for research.\n\n          -  Adequate organ function as measured by the following criteria, obtained ? 2 weeks\n             prior to registration:\n\n               -  Absolute Neutrophil Count (ANC) ? 1500/mm³\n\n               -  Hemoglobin ?9.0 g/dL\n\n               -  Platelets ?100,000/mm³\n\n               -  Serum creatinine clearance (CL)>60 mL/min by the Cockcroft-Gault formula or by\n                  24-hour urine collection for determination of creatinine clearance. NOTE:\n                  Patients with a creatinine Cl ? 45 mL/min however ? 60 mL/min may be considered\n                  for enrollment provided they fulfill all other eligibility criteria, these\n                  subjects will receive pemetrexed carboplatin concurrent with durvalumab during\n                  the combination phase of treatment. Patients with a creatinine CL<45 mL/min\n                  should not be enrolled.\n\n               -  Albumin ? 2.8 g/dL\n\n               -  Total Bilirubin ? 1.5x Upper Limit of Normal (ULN)\n\n               -  Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ? 2.5x ULN (? 5x\n                  ULN in patients with liver metastases)\n\n          -  Women must either be of non-reproductive potential or must have a negative serum\n             pregnancy test upon study entry.\n\n          -  Women must not be pregnant or breastfeeding.\n\n          -  Patient is willing and able to comply with the protocol for the duration of the study\n             including undergoing treatment and scheduled visits and examinations including\n             follow-up.\n\n          -  Patient must not have involvement in the planning and/or conduct of the study. No\n             previous enrollment in the present study.\n\n          -  Patients may not have participated in another clinical study with an investigational\n             product during the last 4 weeks.\n\n          -  Patients must not have any prior systemic therapy (chemotherapy, immunotherapy,\n             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal\n             antibodies, and other investigational agent) for mesothelioma.\n\n          -  No previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or any other\n             agent targeting immune checkpoints.\n\n          -  Patients must not have non-pleural mesothelioma e.g. mesothelioma arising in\n             peritoneum, tunica vaginalis or any serosal surface other than the pleura.\n\n          -  Patients must not have an active second malignancy other than non-melanoma skin cancer\n             or cervical carcinoma in situ.\n\n          -  Patients must not have mean QT interval corrected for heart rate (QTc) ?470 ms\n             calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.\n\n          -  Patients must not have symptomatic or uncontrolled brain metastases requiring\n             concurrent treatment, inclusive of but not limited to surgery, radiation and/or\n             corticosteroids (prednisone >10 mg or equivalent). Surgery, radiation and/or\n             corticosteroids (any dose >10 mg prednisone equivalent) must have been completed ? 2\n             weeks prior to registration.\n\n          -  Patients must not have uncontrolled seizures.\n\n          -  Patients must not have current or prior use of immunosuppressive medication within 28\n             days before the first dose of durvalumab, with the exceptions of intranasal and\n             inhaled corticosteroids or systemic corticosteroids at physiological doses, which are\n             not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Standard\n             steroid premedication given prior to chemotherapy or as prophylaxis for imaging\n             contrast allergy should not be counted for this criterion.\n\n          -  No active or prior documented autoimmune or inflammatory disorders (including\n             inflammatory bowel disease, diverticulitis with the exception of diverticulosis,\n             celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years.\n             Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic\n             treatment (within the past 3 years) are not excluded.\n\n          -  No history of primary immunodeficiency.\n\n          -  No history of allogeneic organ transplant.\n\n          -  No history of hypersensitivity to durvalumab, cisplatin, carboplatin, pemetrexed or\n             any of their excipients.\n\n          -  No uncontrolled intercurrent illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable\n             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active\n             bleeding diatheses including any subject known to have psychiatric illness/social\n             situations that would limit compliance with study requirements or compromise the\n             ability of the subject to give written informed consent.\n\n          -  No active infection including tuberculosis (clinical evaluation including: physical\n             examination findings, radiographic findings, positive PPD test, etc.), hepatitis B\n             (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human\n             immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA\n             test). Patients with a past or resolved HBV infection (defined as the presence of\n             hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients\n             positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction\n             is negative for HCV RNA. HIV testing is not required in absence of clinical suspicion.\n\n          -  No known history of leptomeningeal carcinomatosis.\n\n          -  Patients must not have received live attenuated vaccination within 30 days prior to\n             study entry or within 30 days of receiving durvalumab.\n\n          -  Patients must not have any condition that, in the opinion of the investigator, would\n             interfere with evaluation of study treatment or interpretation of patient safety or\n             study results.
Unable or unwilling to take any prophylaxis; patients with history of or new/active deep vein thrombosis/embolism/thrombophilia are allowed to participate if they are on appropriate therapeutic anticoagulation during the treatment on the trial; these patients would not need the aspirin with the lenalidomide unless clinically indicated; therefore, patients must be able and willing to receive anticoagulation (prophylaxis versus therapeutic as clinically indicated)
All potential patients must undergo a tuberculosis (TB) test prior to study entry (either purified protein derivative [PPD] or QuantiFERON-TB Gold, whichever is preferred and available at the Institution); patients with a history of TB (even if treated), or evidence of active or latent TB, are excluded; the diagnosis of active TB is defined per current guidelines; patients with a positive TB test (e.g. PPD or QuantiFERON-TB Gold) will be excluded; patients with history of Bacille-Calmette-Guerin (BCG) vaccination will be tested with QuantiFERON-TB Gold test in order to rule out exposure to TB
A large soft tissue mass or other disease involving an area outside of the defined pertrochanteric anatomic region; (patients excluded based on intra-operative findings will be replaced on the study)
Patients with advanced hip arthritis on radiographic imaging
Requirement for constant administration of proton-pump inhibitor, histamine 2 (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed while patients are on dexamethasone; we strongly recommend that patients who require gastric protection to receive only antacids starting 24 hours before the first dose until 24 hours after the last dose of alisertib
Patients with progressive synchronous/metachronous AT/RT and MRT will be eligible for stratum A3
Female patients with infants must agree not to breastfeed their infants while on this study
Patients refractory to red blood cell or platelet transfusions
Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective\r\n* Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment\r\n* Patients with the following tumor types will be excluded from the normal and mild cohorts:\r\n** Pancreatic cancer patients\r\n** Colorectal cancer patients \r\n** BRAF V600E melanoma patients who have failed BRAF inhibitors\r\n*** Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist
Patients with active hemolysis should be excluded
Patients must be healthy enough to undergo a general anesthetic
Patients with a history of a prior malignancy who have undergone potentially curative therapy with no evidence of that disease for five years, or patients who are deemed low risk for recurrence by his/her treating physician are permitted to enroll
Patients must have histologically confirmed advanced RCC (any histology); collecting duct tumors and tumors originating from the renal pelvis or upper urinary tract are considered of urothelial origin and are excluded from this protocol
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients must be eligible for TACE
Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:\r\n* Class I – patients with no limitation of activities; they suffer no symptoms from ordinary activities\r\n* Class II – patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion
Patients must have recurrent OS; OS must be verified by histopathology review by the site's Department of Pathology; (patients registered at Memorial Sloan-Kettering Cancer Center [MSKCC] must have pathology confirmed by MSKCC Department of Pathology)
Surgical Stage IVA includes patients with bladder or bowel mucosal involvement, but no spread outside the pelvis.
Patients with a GOG Performance Status of 0, 1, or 2.
Patients with carcinosarcoma.
Patients must have a lesion amenable to resection for the generation of TIL on MD Anderson protocol 2004-0069
Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability
Patients must sign the treatment consent document before Turnstile II screening procedures; before the treatment starts and at each visit, the patient will be asked to complete two quality of life questionnaires; It should take about 15 minutes to complete the questionnaires (Functional Assessment of Cancer Therapy General [FACT-G], FACT-Melanoma); patients must fulfill all of the following criteria to be eligible for Turnstile II of the study
Patients must have adequate TIL that were previously harvested and then cryopreserved on MD Anderson Cancer Center (MDACC) protocol 2004-0069
Patients must have at least one biopsiable measurable metastatic melanoma, lesion > 1 cm and must be amenable to undergoing serial biopsies through the course of therapy; this lesion must not be documented as one of the target lesions
Patients must be willing and able (in the opinion of the treating physician) to undergo two research biopsies for the investigational component of this trial
Patients must be willing to undergo two leukapheresis procedures for the investigational component of this trial
Patients who have undergone splenectomy
NOTE: There is no exclusion for prior immune-based therapy; this includes patients previously treated on Arms 1 or 2 who are otherwise eligible for treatment on Arm 3 or 4
Patients are allowed to receive, but are not required to receive, biologic/targeted therapy as part of their primary treatment regimen; patients are allowed to receive, but are not required to receive, up to 5 biologic/targeted therapies as part of their treatment regimen for recurrent disease (either alone or in combination with chemotherapy)
ARM A COHORT 1: Patients must not have prior nab-paclitaxel exposure
ARM B COHORT 2: Patients must not have prior exposure to docetaxel
ARM B COHORT 3: Patients must not have prior exposure to docetaxel
ARM B COHORT 3: Patients must not have a central lesion with radiologic evidence of arterial involvement
ARM C COHORT 4: Patients must not have prior cisplatin exposure
Patients with pre-existing retinopathy
Patients with active lupus or scleroderma are ineligible
Patients must be considered unresectable or inoperable
Patients with untreated MCL should be asymptomatic or minimally symptomatic from their MCL and without aggressive clinicopathological features that would otherwise warrant immediate intensive therapy; these will generally be patients who qualify for an initial period of “watch and wait” per clinical discretion
Patients who are currently receiving treatment with cidofovir, leflunomide, or other antiviral therapy with no response, will be eligible for CTL infusion
Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the principal investigator (PI)
Patients with recurrent/relapsed AA will be eligible for the trial as long as they were not previously refractory to hATG-based therapy and the relapse occurred > 3 months after response.
Patients with Hypoplastic MDS defined as MDS with marrow cellularity of:
< 20% for patients ? 60yrs.
Any major medical illnesses or psychiatric impairments that in the treating physician’s opinion will prevent administration or completion of protocol therapy (which may include patients who are elderly, debilitated, or malnourished persons and/or those with renal, hepatic or adrenal insufficiency)
Patients currently on beta blockers
Known HIV-positivity on combination antiretroviral therapy because of the unknown potential for pharmacokinetic interactions with indoximod, or docetaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy.
Patients must complete all screening assessments
Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
Have had second-line hormonal therapy (abiraterone, ketoconazole, and/or Tak-700, etc.) within two weeks prior to the first dose of study drug; patients require a two-week wash out; patients may continue standard supportive dosing of prednisone and hydrocortisone for abiraterone and ketoconazole, respectively, as needed
Patient’s tumor must be deemed resectable by the study team prior to registration; borderline resectable patients will be excluded
ADDITIONAL CRITERIA FOR STUDY CONTINUATION: Have a surgically resected (R0 or R1) American Joint Committee on Cancer (AJCC) pathologic stage I or stage II adenocarcinoma of the head, neck, or uncinate of the pancreas; (following study treatment #1, if the patient’s tumor is found intraoperatively to be limited to the distal portion (body or tail) of the pancreas and is resected by distal pancreatectomy, the patient may continue to receive study treatments but will be considered non-evaluable for the primary and efficacy endpoints and will be followed for additional endpoints;) the patients with an R2 resection will not be eligible for the continuation of the study; patients with intraoperative findings of metastatic disease will not be eligible for the continuation of the study
Patients treatment history may not include anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)
Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
Patients who are on immunosuppressant medication
No active infection: patients should be afebrile; if present, pulmonary infiltrates or other sites of infection must be improving on antibiotics; patients should not require oxygen; study chair will be the arbiter of this criterion
Male patients
Patients must agree to appropriate clinical monitoring to receive the study regimens
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0 or 1
Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies
Patients whose tumors are positive for the sensitizing ALK fusion
Patients whose tumors are positive for the sensitizing ROS-1 fusion
Note: Patients positive for hepatitis B and C will be evaluated on a case by case basis
Patients whose primary therapy was changed due to suboptimal response or toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
Phase I: patients are eligible with any number of prior regimens regardless of what those regimens contained (i.e. prior bortezomib or combination gemcitabine and adriamycin is acceptable)
Patients with other malignancies will not be eligible for stratum I or II; patients with disseminated disease including to the spine will not be eligible for stratum 1 but will be eligible for stratum II
Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
Patients who are less than 4 weeks from CRS/HIPEC or have insufficient recovery from surgical-related trauma or wound healing as determined by the patient’s surgeon
Incarcerated patients
Patients whose tumors are deemed unresectable by clinical/imaging criteria
Patients with LVEF =< 40% from treatment with anthracyclines for all malignancies at any dose without evidence of other causes of cardiomyopathy
Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab
Patients who have previously been treated with nivolumab and/or ipilimumab in combination with 5-azacytidine will be excluded
Patients taking sorivudine or brivudine must be off of these drugs for 4 weeks prior to starting capecitabine; patients taking cimetidine must have this drug discontinued; ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine if necessary; if patient is currently receiving allopurinol, must discuss with principal investigator (PI) to see of another agent may substitute for it
Patients with multiple lesions, which by size criteria would be enrolled in a cohort which is full at the time of enrollment and the 12-16 week dose-limiting toxicity (DLT) period has not yet been reached
Patients who completed induction treatment followed by autologous stem cell transplant as initial therapy for symptomatic myeloma as per IMWG criteria and are considered for single agent lenalidomide (Revlimid) maintenance or initiated single agent Revlimid maintenance\r\n* Patients will be eligible for enrollment in the first 0-4 months of lenalidomide maintenance provided that lenalidomide maintenance has been initiated on days 60 - 120 after transplant\r\n* Patients must be receiving lenalidomide 10 mg or 15 mg and be able to tolerate dose escalation to 25 mg daily\r\n* Patients receiving lenalidomide maintenance cannot exceed 4 months of lenalidomide post-transplant
Patients who have already started or received multi-drug consolidation regimen post-transplant expect for patients receiving up to 4 months of single agent  lenalidomide maintenance
Anticonvulsants: patients on enzyme inducing anticonvulsants (EIAED) will be excluded; if patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for >= 2 weeks prior to initiation of dasatinib
A documentation of diagnosis of hemophagocytic lymphocytosis, either newly diagnosed or relapsed/refractory by the treating physician and the principal investigator (PI) in the patients chart; it must be noted that no diagnostic criteria have been established for diagnosis of HLH in adult patients as this was a hitherto poorly identified and considered to be a very rare disease in adults; adult HLH seems to occur more frequently post malignancy and has a more fulminant course than pediatric HLH; in the absence of standard diagnostic guidelines if the patient's symptoms are highly suspicious for HLH and after an adequate work-up to rule out alternate potential alternate etiologies is performed we will treat the patient for HLH as missing the diagnosis is associated with high mortality; these patients will be discussed with the PI (Dr. Daver) prior to enrollment in all such cases
If organ dysfunction is thought to be related to the HLH process this must be clearly documented in the chart and the patients may be enrolled on study irrespective of creatinine and bilirubin levels
Patients should have no evidence of immune dysfunction as listed below
Patients must have a diagnosis of neuroblastoma verified at diagnosis, or at the time of relapse by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with non-neuroblastic MIBG avid tumors are also eligible including but not limited to paraganglioma and pheochromocytoma
Platelets > 50,000/cu mm (transfusion allowed - however patients must not require more than two platelet transfusions per week)
Patients who are on hemodialysis
Patients with an active infection requiring intravenous antivirals, antibiotics or antifungals; patients on prolonged antifungal therapy are still eligible if they are culture negative and biopsy negative in suspected residual radiographic lesions have stabilized or regressed and they meet other organ function criteria
Patients with intolerance to compounds similar to pegylated interferon alpha-2b
Patients must either:
Patients with HbA1c > 8.5% at Screening
Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible
Patients who are currently receiving and responding to a different course of anti-neoplastic therapy, within the limits of acceptable toxicity per standard clinical practice, may not be enrolled to this study
Patients with HER2(-) status
Patients with relapsed or refractory solid tumors (excluding primary central nervous system tumors) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
Patients actively receiving insulin are excluded unless approved by the investigational new drug (IND) medical monitor, IND sponsor, and the study principal investigator (PI)
Patients with neurofibromatosis are eligible
Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by P.I.)
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The patient’s life expectancy is =< 90 days even with aggressive treatment and/or supportive care, as determined by the treating hematologist/oncologist
Patients are required to meet criteria for initiation of therapy for their B-NHL according to published guidelines by the National Comprehensive Cancer Network (NCCN)
Patients with diabetes on a different agent or patients with rheumatoid arthritis taking hydroxychloroquine (Plaquenil)
Patients on antipsychotic medication
Patients must be ineligible for, refused or having failed at least one previous salvage regimen
Patients with persistent grade 3 or higher prior vincristine (VCR) (vincristine sulfate)-related neuropathy
Serum bilirubin =< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI
Patients must have untreated or relapsed SCCS that is considered to be aggressive and locally advanced by the following criteria: tumors 2 cm or more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes; patients may have had prior surgical interventions or been treated with investigational agents with residual or recurrent disease
Patients with distant organ metastases will not be included in this study
For dose expansion cohort: patients with stage IIIB or IV ALK + NSCLC who have failed at least one line of therapy and are progressing on an ALK inhibitor; for dose expansion, patients who have ROS1 rearrangement testing by either next generation sequencing (NGS) or fluorescence in situ hybridization (FISH) will be eligible
Patients with porphyria are not eligible
Patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Patients with previously documented macular degeneration or untreated diabetic retinopathy (stable retinopathy is allowed)
Patients previously exposed to bosutinib are eligible unless they carry T315I
Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort)
For patients undergoing SABR, both early stage primary lung cancer patients and those with limited metastatic disease to the lungs are eligible; however, patients with oligometastatic disease should have a controlled primary and no more than one other involved organ system
We will carefully consider the inclusion of patients with severe artifacts in 4D CT images, which deteriorate the accuracy of ventilation computation
Patients previously treated with gemcitabine or Abraxane
Breakpoint cluster region-Abelson positive (BCR-ABL +) patients will be excluded from the study
Patients must have radiographic evidence of malignancy in the spine or cauda equina region (L2 to sacrum) which is suitable for radiation therapy
Patients receiving Anti-thymocyte globulin (ATG), Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-A.
Patients with multiple malignancies remain eligible
Patients with acute hematological malignancies
Patients who are incarcerated are not eligible
Patients must be considered unresectable or medically-inoperable
Patients with contralateral hilar involvement (greater than 1.5 cm on short axis or positive on PET scan, or biopsy-proven)
PART 2: Meeting criteria for 1st phase as above, at time of initiation of JAK inhibitor, including ability to understand and willingness to sign a written informed consent; patients arriving to our institution for transplant and not enrolled in Part 1 may still be enrolled in Part 2 if Part 1 criteria met; these patients will have Part 1 endpoints transcribed from medical records
Patients must have high-risk neuroblastoma as defined by the Children's Oncology Group (COG) Risk Stratification Schema\r\n* Patients with International Agreement on Staging (INSS) stage 4 are eligible with the following:\r\n** MYCN amplification, regardless of age or additional biologic features OR\r\n** Age > 18 months, regardless of biologic features OR\r\n** Age 12-18 months, with any of the 3 following unfavorable biologic OR features: MYCN amplification, unfavorable pathology, and/or deoxyribonucleic acid (DNA) index = 1\r\n* Patients with INSS stage 3 are eligible with the following:\r\n** MYCN amplification, regardless of age or additional biologic features OR\r\n** Age > 18 months with unfavorable pathology, regardless of MYCN status\r\n* Patients with INSS stage 2a or 2b are eligible with the following:\r\n** MYCN amplification, regardless of age or additional biologic features\r\n* Patients with INSS stage 4s are eligible with the following:\r\n** MYCN amplification, regardless of additional biologic features
Patients that have previously progressed on immunotherapy such as ipilimumab will be eligible
Patients with macular degeneration with markedly decreased visual acuity, patients with markedly decreased visual acuity (no specific etiology) or uncontrolled glaucoma
Patients with prior receipt of brentuximab vedotin
Patients with a histologic diagnosis of adenocarcinoma of the esophagus located distal to the carina
Patients with primary tumors exceeding 8 cm in length or 5 cm in width
Patients with primary tumors located at or above the carina
Patients who require ongoing anticoagulation will be excluded; only aspirin will be permitted; pre and post-surgical prophylactic anti-coagulation treatment is permitted
Patients must not require total parenteral nutrition with lipids
Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study
Patients with any type of autologous or allogeneic HSCT with CMV infection will be included
Patients with active acute GVHD grades II-IV
Patients receiving anti-thymocyte globulin (ATG), or Campath within 28 days of CMV reactivation
Patients who are unable to perform the breath hold scan
Patients must be anticipated to complete 2 cycles of therapy in the opinion of the treating physician
Patients that previously were treated with ibrutinib for > 7 days
Patients with gynecologic malignancy of low-grade serous or borderline histology
Patients who refuse to receive blood transfusions
Female patients of any ethnic group; female patients must be surgically sterile, postmenopausal (no menses for at least one year), or using medically approved method of contraception (excluding rhythm, withdraw or abstinence)
Patients with pathology demonstrating mucinous, carcinosarcoma or low malignant potential tumor histology are excluded; in addition, non-ovarian malignancies, malignant germ cell or stromal tumors are also excluded
Patients currently taking warfarin, tamoxifen, phenytoin, diclofenac, tolbutamide, or ibuprofen are excluded secondary to potential inhibition of cytochrome P450 2C9 (CYP2C9); in addition patients that consume grapefruit juice and Seville orange juice must not consume these during the study
Patients with known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration
Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
Patients enrolled in the expansion cohort must have biopsiable disease; there will be preferential enrollment of patients with pancreatic neuroendocrine tumors or ovarian cancer during the dose expansion cohort
Patients on bisphosphonates, denosumab, and/or endocrine therapy are eligible
Patients presenting with lesions that may harbor an occult infectious source
Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone)
Patients will be staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria
Patients with histologically confirmed peritoneal surface malignancies, including malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) from presumed appendiceal and colorectal primary tumors; most patients will have received extensive prior treatments, due to the recurrent nature of PC; prior therapies involve previous CRS, local and systemic chemotherapy, and their different numbers; none of these prior treatments disqualifies the patient from receiving the protocol-mandated experimental treatment
Patients who are moribund
Patients must be no taller than 1.9 m (6 feet 4 inches), and no wider from elbow to elbow in the supine position than 60 cm
Hematopoietic Cell Transplantation-Specific Comorbidity Index score (HCT-CI) =< 4 for patients in Cohort 1 and > 4 for Cohort 2
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) or patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM- IV]) are not eligible; Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug\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 (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)
Patients receiving anti-thymocyte globulin (ATG), Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment
Patients who are not candidates for, intolerant, or relapsed/refractory to ruxolitinib
Patients with history of activating RAS mutation positive tumors regardless of interval from current study; however, patients may have concurrent BRAFV600 and RAS mutations in the tumor to be treated with protocol therapy
Patients with other active malignancies are ineligible for this study, other than localized malignancies
Inclusion Criteria\n\n        -Male or female patients ?18 years of age who present with one of the following:\n\n        LGH447 monotherapy arm\n\n          -  Refractory/Relapsed AML following no more than 2 prior therapies, or in previously\n             untreated AML patients who are not candidates for standard therapy.\n\n          -  High and very high risk MDS according to the revised International Prognostic Scoring\n             System (rIPSS) who have failed prior therapies, such as azacitidine and decitabine\n\n          -  Patients with rIPSS score of > 4.5\n\n        LGH447 and midostaurin combination arm\n\n          -  Refractory/Relapsed AML following no more than 2 prior therapies, or in previously\n             untreated AML patients who are not candidates for standard therapy. AML patients may\n             have either FLT3 wild type or FLT3-ITD/TKD mutant disease, and FLT3 mutation status\n             needs to be defined at study entry.\n\n               -  For AML patients, peripheral blast counts < 50,000 blasts/mm3\n\n               -  For MDS patients;\n\n          -  Platelet count > 25,000/mm3\n\n          -  Neutrophils > 500/mm3\n\n          -  Blood transfusions are allowed to maintain clinically adequate hemoglobin and\n             hematocrit levels\n\n               -  Patients with active central nervous system (CNS) disease are eligible to\n                  participate and may be treated concurrently with intrathecal (or intra Ommaya)\n                  chemotherapy\n\n               -  Patients who are maintained on prophylactic antibiotics are eligible to\n                  participate as long as agents comply with the list of approved concomitant\n                  medications\n\n               -  Performance status ? 2\n\n               -  Meet other lab criteria\n\n        Exclusion Criteria\n\n          -  Systemic antineoplastic therapy (including unconjugated therapeutic antibodies and\n             toxin immunoconjugates) or any experimental therapy within 7 days or 5 half-lives,\n             whichever is longer, before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Radiotherapy with a wide field of radiation within 28 days or radiotherapy with a\n             limited field of radiation for palliation within 7 days of the first dose of LGH447\n             monotherapy or LGH447 in combination with midostaurin\n\n          -  Patients who received CNS irradiation for meningeal leukemia, except if radiotherapy\n             occurred > 3 months previously\n\n          -  Major surgery within 4 weeks before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Ongoing therapy with corticosteroids greater than 10 mg of prednisone or its\n             equivalent per day. Inhaled and topical steroids are permitted\n\n          -  Patients who are currently receiving hydroxyurea to control peripheral blood leukemic\n             blasts and cannot be discontinued for at least 48 hours prior to obtaining PD\n             biomarkers at screening/baseline and during the study\n\n          -  Patients who are currently receiving treatment with prohibited medication and that\n             cannot be discontinued at least one week prior to the start of treatment with LGH447\n             monotherapy or LGH447 in combination with midostaurin\n\n          -  Active infection requiring systemic therapy or other severe infection, including\n             pneumonia, within 2 weeks before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Known human immunodeficiency virus (HIV) positive\n\n          -  Corrected QT interval (QTc) of > 450 milliseconds (ms) in males and > 470 milliseconds\n             (ms) in females on baseline electrocardiogram (ECG) (using corrected QT interval using\n             Fridericia [QTcF] or local standards).\n\n          -  Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias,\n             congestive heart failure, angina, or myocardial infarction within the past 6 months\n\n          -  Pregnant or nursing
Patients must be at least 4 weeks from last cytotoxic chemotherapy (including alkylating, anthracyclines, epipodophyllotoxins, and platinum drugs), or immunomodulatory drugs (including lenalidomide or pomalidomide, or related derivatives) at time of treatment on this protocol
Patients with known urea cycle disorders (i.e.: ornithine transcarbamylase deficiency)
Patients who are taking antiplatelet or anticoagulant agents - patients taking 81 mg of aspirin will be allowed with close observation
Patients who are currently taking or plan to take curcumin during the study
Patients do not need a histologically proven diagnosis of brain mets
Patients having previously undergone splenectomy.
Patients with sickle-cell anemia or thalassemia major.
Patients must have:
Patients enrolled in the dose-expansion part of the trial must have at least one lesion that may qualify as a target lesion based on the RECIST 1.1 criteria.
Patients who require coumadin administration.
Patients who are in-patients.
Patients may not be on an enzyme-inducing anti-epileptic drug (EIAED); if previously on an EIAED, patient must be off for at least 10 days prior to CED infusion
Patients who are currently receiving a beta-blocker for another medical condition will be excluded from this study; patients with extremes of blood pressure (e.g., systolic blood pressure [SBP] > 150 or < 100) may be excluded from participation if the treating physician feels that this medical condition has not been adequately addressed by the patient’s primary care physician
Patients with worsening depression that has not been addressed clinically will be excluded from this study
Patients on nonsteroidal anti-inflammatory drugs (NSAIDs) will be eligible only when they are off NSAIDs for 14 days
Patients must have a minimum expected duration of survival of 8 weeks as determined and documented by the attending surgeon or medical oncologist
Patients must not have any systemic illness which precludes them from being an operative candidate
For patients with a new diagnosis of melanoma treated in cohort 2 who have a cutaneous primary, the primary site may be addressed surgically (wide local excision; skin grafting) prior to the initiation of ipilimumab and radiation at the discretion of the treating surgeon
Patients must agree to blood sampling to participate in study
Patients must have pathologically confirmed GIST
Patients with porphyria are ineligible
Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist who agrees to monitor the patient for exacerbations
Patients with previously documented macular degeneration or diabetic retinopathy are excluded
Patients must have at least one site of disease that is accessible for intratumoral injection percutaneously (e.g. inguinal, axillary, cervical, or subcutaneous)
Patients who are actively receiving steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) on a chronic basis and who are unwilling and/or unable to discontinue while on study therapy are NOT eligible for participation; NOTE: patients must have discontinued steroids or NSAIDs for 1 week prior to registration to be considered eligible for participation
Although rare, the only exception to this would be patients with Hashimoto’s thyroiditis who ARE eligible for participation
Note: patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies
Patients must have at least one lesion which can be biopsied with acceptable clinical risk as judged by the clinical services who perform the biopsy
Patients must be entered no more than 12 weeks post operatively
Patients must have a lesion amenable to resection for the generation of TIL (Turnstile I)
Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability (Turnstile I)
Patients must have at least one biopsiable measurable metastatic melanoma, lesion > or = to 1 cm (Turnstile II)
Patients may have brain lesions =< 1 cm each; the PI or designee will approve the treatment (Turnstile II)
Patients being treated with certain drugs not acceptable while receiving CFI-400945 fumarate.
Patients treated with simple cystectomy with macroscopically negative margins are eligible for this study
Patients with a ?20mm non-pedunculated colon polyp
Patients with ulcerated depressed lesions (as defined by Paris Classification type III)
Patients who are receiving an emergency colonoscopy
Patients with coagulopathy with an elevated INR ?1.5, or platelets <50
Patients with any number of recurrences are allowed
Patients treated on any other therapeutic clinical protocols within 3 weeks of registration
Inclusion criteria at the time of Procurement:\n\n          -  Patient with malignant or nonmalignant diseases who are candidates for transplant.\n\n          -  Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA\n             class I (serological) and II (molecular) antigens.\n\n        Inclusion criteria at the time of CTL infusion:\n\n          -  Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions\n             (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with\n             CMV/Adenoviral disease or reactivation.\n\n          -  Lansky/Karnofsky scores >60\n\n          -  Absolute neutrophil count (ANC) greater than 500/ul.\n\n          -  No evidence of GVHD > Grade II at time of enrollment.\n\n          -  Life expectancy > 30 days\n\n          -  Absence of severe renal disease (Creatinine > x 3 normal for age)\n\n          -  Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x\n             upper limit of normal.\n\n          -  Patient must be at least 30 days post transplant to be eligible to receive CTL\n\n          -  Written informed consent and/or signed assent line from patient, parent or guardian.\n\n          -  Patient not on Fi02 of >60%\n\n        Exclusion criteria at the time of Procurement\n\n          -  Pregnant or lactating\n\n          -  Patients with active central nervous system disease\n\n          -  Patients with Karnofsky performance status <70%\n\n          -  Patients with grade 3 or 4 or primary myelofibrosis\n\n          -  Patients with suitable related donors\n\n        Exclusion criteria at the time of CTL infusion\n\n          -  Pregnant or lactating\n\n          -  Unable to wean steroids to ?0.5 mg/kg/day prednisone.\n\n          -  Patients with other uncontrolled infections (except CMV and/or adenovirus and/or\n             EBVemia).\n\n          -  Patients with less than 50% donor chimerism in either peripheral blood or bone marrow\n             or patients with relapse of original disease.
Allogeneic patients if: i. patients had engrafted donor cells (i.e., > 20% donor T-cell from peripheral blood [PB]/polymerase chain reaction [PCR]); and, ii. patients NOT in complete remission (CR) after their allogeneic transplant, and off tacrolimus and/or mycophenolate mofetil for at least 3 to 4 weeks with no signs of GVHD; or, iii. patients had evidence of relapse after their transplant who are off tacrolimus and/or mycophenolate mofetil or other immunosuppressants for GVHD for 3 to 4 weeks with no signs of GVHD (prednisone doses =< 10 mg are permitted as stated previously)
Patients with tumors primarily of the tail of the pancreas requiring a distal pancreaticoduodenectomy would be excluded; tumors of the body that require a surgical approach similar to pancreatic head tumors are acceptable
Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age 2-17 years old may be enrolled after at least 4 adults (ages 18-65 years old) have been treated without toxicity
DIAGNOSIS REQUIREMENT FOR PHASE I PATIENTS: Myelodysplastic syndrome (MDS) with excess blasts (> 5%) and progressive disease at any time after initiation of deoxyribonucleic acid (DNA) hypomethylator treatment during the past 2 years, OR failure to achieve complete or partial response or hematological improvement after at least six cycles of azacytidine or four cycles of decitabine administered during the past 2 years, OR intolerance to azacytidine or decitabine; MDS patients with isolated 5q- abnormalities that meet these criteria after lenalidomide therapy and DNA hypomethylator therapy are also eligible
Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]) are eligible; tamoxifen therapy or other SERMs should be discontinued at least 1 week before the patient is enrolled on this study
Patients with any number of metastatic site are allowed to enroll; however, only up to six sites will be selected for SBRT treatment, at the discretion of the treating radiation oncologist
Urinalysis; abnormalities on urinalysis (i.e. proteinuria) will not exclude patients from participation on study
Patients with allergies to any component of the vaccine will be excluded from the protocol
Patients 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
Relapsed/refractory MCL: Absolute neutrophil count (ANC) >= 500/mm^3; (patients who have bone marrow infiltration by MCL are eligible if their ANC is >= 500/mm^3 [growth factor allowed]; these patients should be discussed with either the principal investigator [PI] or Co-PI of the study for final approval)
Patients who have been treated with vemurafenib will be allowed in this study
Bradycardia defined as heart rate < 50 beats per minute; patients with a pacemaker and heart rate >= 50 beats per minute are eligible
Patients who are currently taking omega-3 fatty acids
Patients must not be receiving growth factors
Patients who have uncontrolled infection are not eligible; patients must have any active infections under control; fungal disease must be stable for at least 2 weeks before study entry; patients with bacteremia must have documented negative blood cultures prior to study entry
Patients with:\r\n* CLL who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody or who were not eligible for such therapy; patients with CLL for whom ibrutinib is now standard first line therapy, must have progressed on ibrutinib; patients with fludarabine refractory disease are eligible; patients may be treated following allogeneic hematopoietic cell transplant (HCT); for the concurrent ibrutinib cohort, patients must agree to continue on or be restarted on ibrutinib and must not have had prior intolerance to ibrutinib that would prevent this; patients managed with prior dose reductions for toxicity will continue at the reduced dose for the remainder of this study\r\n* Indolent NHL or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy or who were not eligible for such therapy; patients who have relapsed following autologous or allogeneic HCT are eligible\r\n* Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL), who have relapsed or have residual disease following treatment with curative intent; patients should have relapsed following, or not be eligible for high-dose therapy and autologous HCT; patients with chemotherapy refractory disease or marrow involvement or comorbidities precluding successful autologous HCT are eligible; patients may be treated following allogeneic HCT\r\n* Patients with CD19 expressing, relapsed or refractory ALL\r\n* Patients with one of the above diagnoses whose disease state does not qualify but who have prognostic indicators that suggest a high risk of progression of disease may be screened and undergo leukapheresis; enrollment for T cell therapy would require meeting the full disease state eligibility
Patients with resectable primary NSCLC who are undergoing surgery to resect T3 to T4 lesions OR any patients with clinical NI or N2 disease regardless of T-stage
Hemoglobin >= 8.0 g/dL with transfusions allowed if stem cells available; patients with stem cells available are excluded if they require two platelet transfusions per week to maintain the minimum required platelet count; a bone marrow examination is not medically indicated for patients diagnosed with metastatic pheochromocytoma
Patients who are on hemodialysis
Subjects will be recruited from patients who are potential candidates for SRS treatment at Dartmouth Hitchcock Medical Center (DHMC) for brain metastases
Previously untreated patients with locoregional-only disease are not eligible
Patients receiving SRS to resection bed
Patients who have had a positive SLNB but decline completion ALND are not eligible
Breast implants; (patients who have implants removed are eligible)
Patients with primary or secondary immunodeficiencies
Pediatric patients (age 7-18 years) will be entered only after 3 adult patients have been entered without dose limiting toxicity
Primary HLH patients
Patients treated with biologics within a specific timeframe
Patients on chronic nitrate therapy or alpha-blockers
Previous therapy:\r\n* It is expected that patients will have received upfront standard of care therapy for their respected disease\r\n* Patients who relapse after either single or tandem autologous BMT are eligible (> 6 months must have elapsed from start of last BMT)\r\n* Patients must be recovered from the acute toxicities of any prior chemo/radio/immunotherapy or BMT
Patients will not be excluded on the basis of sex, racial or ethnic background
Tumor types – tumor type/location:\r\n* Stratum A: Patients with a recurrent ependymoma with the primary site in the posterior fossa; patients may have non-bulky asymptomatic, metastatic disease; patients may have undergone surgical resection or debulking prior to enrollment\r\nStratum B: Patients with a recurrent ependymoma with the primary site outside the posterior fossa; patients may have non-bulky asymptomatic, metastatic disease; patients may have undergone surgical resection or debulking prior to enrollment
Patients with a known immune deficiency
Patients previously treated with RUX or AZA (only applicable for the MF and MDS/MPN arms)
Patients for whom endoscopic techniques are contraindicated
Patients with baseline troponin levels greater than the institutional limit of normal
Patients aged 60 to 65 years must have a KPS of >= 80% and an HCT-CI score of 4 or less
Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
Patients must have high-risk NB (including v-myc myelocytomatosis viral related oncogene [MYCN] amplified stage 2/3/4/4S of any age and MYCN-non-amplified stage 4 in patients greater than 18 months of age) AND:\r\n* Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy; for NB standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response\r\n* Phase II: Patients must have primary or secondary refractory disease in BM, defined as morphologic evidence of NB in BM and/or abnormal 123 iodine (I)-MIBG uptake in osteomedullary sites, OR patients are in >= 2nd CR/VGPR
Patients may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
Patients with known sensitivity to any immunomodulatory drugs (IMiDs)
Patients with primary systemic amyloidosis
Patients must be on continuous TKI therapy for management of their CML. Any commercially available and FDA- approved TKI can be used, i.e., imatinib mesylate (IM), nilotinib (NIL) or dasatinib (DAS). Patients may be receiving TKI at entry in the frontline or salvage setting, including patients currently on imatinib after alpha-interferon failure or on dasatinib or nilotinib after failure to prior therapy including imatinib.
Patients who relapse after receiving a one or more courses of fludarabine, bendamustine, cytoxan, rituxan, chlorambucil, or campath based therapy
Patients with MDS must be transplant candidates by current clinical standards
Patients who have been treated with hypomethylating agents prior to entering the study are eligible
Stage IIIB/C patients must have refused, be ineligible for, or have failed at least one standard of care regional therapy (isolated limb perfusion or infusion) or one non-vaccine based systemic therapy (such as, high dose interleukin [IL]-2, dacarbazine/temozolomide, ipilimumab, or participation in a clinical trial); patients who are BRAF V600E mutation positive need to have failed, refused, or be ineligible for at least 2 lines of therapy (vemurafenib plus one other regimen)
Stage IV patients must have refused, be ineligible for, or have failed at least one non-vaccine based systemic therapy (such as, high dose IL-2, dacarbazine/temozolomide, ipilimumab, or participation in a clinical trial); patients who are BRAF V600E mutation positive need to have failed, refused, or be ineligible for at least 2 lines of therapy (vemurafenib plus one other regimen)
Patients must have a lesion amenable to resection for the generation of TIL (Turnstile I)
Patients must have adequate TIL available (Turnstile II)
Patients must have at least one biopsiable and measurable metastatic melanoma lesions >= 1 cm (Turnstile II)
Patients may have brain lesions which measure =< 1 cm each (Turnstile II)
For dose escalation study, patients must have histological confirmation of solid tumors that is metastatic or unresectable. For expansion cohorts, patients must have metastatic or unresectable GIST, melanoma, or uncategorized tumors with tumor biopsies that are positive for c-KIT mutations by polymerase chain reaction (PCR) or immunohistochemistry (IHC). For patients enrolled in the melanoma expansion cohort, only select KIT mutations will be eligible. Patients with mutations in exon 13 V654X, 14 T6701, 17 D816X and all exon 18 mutations will not be eligible for enrollment.
Patients in the expansion cohort must also agree to participate in the biomarker study. However, patients in the Melanoma KIT positive mutant subgroup, patients must agree to participate in the biomarker study and biopsies.
Patients with an organ confined renal mass planning to undergo a robotic assisted partial nephrectomy (RAPN)
Patients with bilateral synchronous renal masses
Patients with transfusion-dependent anemia.
Patients must have cytologic or histologic confirmation of carcinoma arising in the pancreas; patients with neuroendocrine tumors are excluded
Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not required for patients with a genetic mutation consistent with DC)
Patients residing in prison
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects must be aged 2-50 years
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects must be co-enrolled in NIH protocol 08-HG-0059
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects must have a primary care provider
COHORT 3: ATOPIC DERMATITIS PATIENTS: All subjects and/or their legally authorized representative (LAR) must have the ability and agree to participate fully and comply with the procedures of the protocol and provide informed consent; pediatric patients will be included in age appropriate discussions and age appropriate assent will be obtained in accordance with NIH guidelines
COHORT 3: ATOPIC DERMATITIS PATIENTS: Subjects with known primary or acquired immunodeficiency
COHORT 3: ATOPIC DERMATITIS PATIENTS: Pregnancy or lactating
Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
Patients with measurable inoperable, histologically confirmed primary lung and esophageal carcinomas, thymic neoplasms, germ cell tumors, malignant pleural mesotheliomas or chest wall sarcomas, as well as patients with gastric, colorectal or renal cancers and sarcomas metastatic to the thorax are eligible
Patients with cerebral metastases
All patients must be eligible to have all lesions treated with SRS (i.e. maximum diameter of largest lesion < 3.5 cm) as determined by the radiation oncologist
Patients will be excluded if they have had prior whole brain radiotherapy (WBRT) or prophylactic cranial irradiation (PCI); prior SRS or gamma knife radiosurgery to 1-3 metastases with minimum of (6) weeks to the most recent scan are allowed on protocol
Patients will be excluded if they have < 4 lesions, or > 15 lesions at enrollment or > 20 lesions at the time of treatment (note: patients who qualify for enrollment based on having 4-15 lesions, but who are discovered to have up to 20 lesions on the volumetric MRI used for treatment planning will be allowed to continue on study)
All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority
All patients (dose escalation and dose expansion phases) must be willing to undergo pre- and post-treatment biopsies
Patients whose circumstances do not permit completion of the study or the required follow-up
Patients with a radiosurgery boost or fractionated stereotactic boost as a part of their treatment plan are not eligible
Patients assessed at presentation as requiring interstitial brachytherapy treatment
Patients willing and able to complete the questionnaires
Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
It is expected that five types of patients afflicted with EBV-associated lymphomas, lymphoproliferative disease or malignancies will be referred and will consent to participate in this trial; these are:
Patients developing aGvHD after ablative or non-myeloablative or reduced intensity conditioning will be eligible
Patients with renal dysfunction or veno-occlusive disease are eligible
Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by PI)
Prophylactic use of lamivudine in patients that have antibody positive (+), but no active infection will be up to the treating physician
Patients with cerebral or systemic vasculopathy:
Patients taking immunosuppressants (corticosteroids to prevent/treat brain edema are permitted).
Patients who are unable to receive MRIs will be excluded from the study
Patients may not have previously failed treatment with salvage temozolomide
Patients must have an Easter Cooperative Oncology Group (ECOG) score equal to or less than 2
Patients with the following histologies are excluded: melanoma, other soft tissue or bony sarcomas, giant cell tumor, aneurismal bone cyst or metastatic lesions from other histologies
Patients is on an enzyme inducing anti-convulsants; if patients were previously on enzyme inducing antiepileptic drugs (EIAEDs) and these have been discontinued, patients must have been off the agent for at least 2 weeks prior to first study drug administration; for patients who need to start an antiepileptic drug (AED) or the AED needs to be changed, it is strongly recommended that all efforts should be made to use a non-EIAED
Patients who are not able to swallow the lenalidomide capsule as a whole are excluded from this study; (capsule cannot be opened, chewed, or crushed)
Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient’s ability to endure known side effects of cytokine release syndrome or neurological toxicity
Corneal epitheliopathy or any eye disorder that may predispose the patients to this condition
Patients must have minimum head circumference of 44 cm
Patients with major skull defects (such as missing bone without replacement) are not eligible
Patients with prior Whipple's procedure.
Patients that have previously been treated with ixazomib, or who participated in a blinded study with ixazomib (whether treated with ixazomib or not)
Bulky disease patients - tumors encompassing >50% of the liver volume and / or inferior vena cava invasion
Patients with lymphomas: prior allogeneic SCT
Patients with del(17p) confirmed by FISH in >= 20% of cells or on stimulated karyotype
Patients of Asian descent
INCLUSION CRITERIA\n\n        -Patients must be greater than or equal to 12 months and ? 21 years of age at the time of\n        study enrollment.\n\n        Patients must have one of the following:\n\n        Leukemia\n\n          -  Bone marrow involvement defined as ALL ? 25% blasts (M2 or M3) with or without\n             extramedullary involvement.\n\n          -  Refractory bone marrow involvement defined as MRD ? 0.1% blasts done at a COG-approved\n             MRD testing lab after most recent treatment regimen. in the bone marrow (M23) and any\n             CNS status. OR\n\n          -  Newly diagnosed patients (T or B-cell ALL) with refractory bone marrow involvement\n             after Consolidation therapy are eligible.\n\n          -  First relapse B-cell ALL patients are eligible with refractory disease.\n\n          -  Second or greater relapse B-cell patients are eligible at time of relapse or with\n             refractory disease.\n\n          -  First or greater relapse T-cell ALL patients are eligible at time of relapse or with\n             refractory disease.\n\n          -  Isolated CNS 2 or 3 patients with < 0.1% MRD bone marrow involvement are not eligible.\n\n        Lymphoma\n\n          -  Patient must have relapsed or refractory lymphoblastic lymphoma or peripheral T-cell\n             lymphoma.\n\n          -  Patient must have histologic verification of disease at original diagnosis.\n\n          -  Patient must have evaluable or measurable disease documented by clinical or\n             radiographic criteria or bone marrow disease present at study entry.\n\n          -  Patients may have CNS 2 or 3 disease\n\n        Karnofsky greater than or equal to 50% for patients > 16 years of age and Lansky greater\n        than or equal to 50 for patients ? 16 years of age.\n\n        Patients must have fully recovered from the acute toxic effects of all prior anti-cancer\n        chemotherapy.\n\n        Patients with leukemia or lymphoma who relapse while receiving maintenance chemotherapy\n        will not be required to have a waiting period before enrollment onto this study.\n\n        At least 14 days must have elapsed after the completion of cytotoxic therapy, with the\n        exception of hydroxyurea.\n\n        Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth\n        factor (e.g. Neulasta) or 7 days for short-acting growth factor.\n\n        Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent.\n        For agents that have known adverse events occurring beyond 7 days after administration,\n        this period must be extended beyond the time during which adverse events are known to\n        occur. The duration of this interval must be discussed with the study chair\n\n        Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g.\n        tumor vaccines. or chimeric antigen receptor T cell (CART) therapy or tumor vaccines.\n\n        Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the\n        last dose of a monoclonal antibody. (ie: Rituximab = 66 days, Epratuzumab = 69 days).\n        Patients must have been off blinatumomab infusion for at least 4 days and all drug-related\n        toxicity must have resolved to grade 2 or lower as outlined in the inclusion and exclusion\n        criteria\n\n        XRT: At least 14 days after local palliative XRT (small port); At least 84 days must have\n        elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of\n        pelvis; At least 42 days must have elapsed if other substantial marrow radiation.\n\n        Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84 days must\n        have elapsed after transplant or stem cell infusion.\n\n        Adequate Bone Marrow Function Defined as: Blood counts are not required to be normal prior\n        to enrollment on trial. However, platelet count must be greater than or equal to 20,000/mm3\n        to initiate therapy (may receive platelet transfusions). Patients should not be known to be\n        refractory to red blood cell or platelet transfusions.\n\n        Adequate Renal Function Defined as:\n\n          -  Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2 or\n\n          -  Normal serum creatinine based on age and gender.\n\n        Adequate Liver Function Defined as:\n\n          -  Total bilirubin (sum of conjugated + unconjugated) must be less than or equal to 1.5 x\n             normal per institutional normal values for age.\n\n          -  SGPT (ALT) and SGOT (AST) must be less than 3 x institutional upper limit of normal\n             (Grade 1 or less per CTCAE 4).\n\n             --GGT must be less than 2.5 x institutional upper limit of normal (Grade 1 or less per\n             CTCAE 4).\n\n          -  Serum albumin greater than or equal to 2 g/dL.\n\n          -  The hepatic requirements may be waived for patients with elevations clearly due to\n             leukemic infiltration after consultation with the Study Chair or Vice Chair.\n\n          -  Fasting or non-fasting serum triglyceride level ? 300 mg/dL and serum cholesterol\n             level ? 300 mg/dL.\n\n        Adequate Cardiac Function Defined As:\n\n          -  Shortening fraction of ? 27% by echocardiogram, or\n\n          -  Ejection fraction of ? 50% by gated radionuclide study.\n\n        Adequate Pulmonary Function Defined as:\n\n          -  Pulse oximetry > 94% on room air (> 90% if at high altitude)\n\n          -  No evidence of dyspnea at rest and no exercise intolerance.\n\n          -  Baseline chest x-ray with no evidence of active infectious disease or pneumonitis.\n\n        Reproductive Function\n\n          -  Female patients of childbearing potential must have a negative urine or serum\n             pregnancy test confirmed prior to enrollment.\n\n          -  Female patients with infants must agree not to breastfeed their infants while on this\n             study.\n\n          -  Male and female patients of child-bearing potential must agree to use an effective\n             method of contraception approved by the investigator during the study.\n\n          -  Random or fasting glucose within the upper limits of normal for age. If the initial\n             blood glucose is non-fasting and above normal limits a fasting glucose can be obtained\n             and must be within the upper limits of normal for age.\n\n        EXCLUSION CRITERIA\n\n          -  Corticosteroids: Patients receiving corticosteroids who have not been on a stable or\n             decreasing dose of corticosteroid for at least 7 days prior to enrollment are not\n             eligible.\n\n          -  Investigational Drugs: Patients who are currently receiving another investigational\n             drug are not eligible. The definition of \investigational\ for use in this protocol\n             means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods\n             Administration to be sold in the countries they govern. (United States, Canada and\n             Australia)\n\n          -  Anti-cancer Agents: Patients who are currently receiving or may receive while on\n             therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible\n             [except leukemia patients receiving hydroxyurea, which may be continued until 24 hours\n             prior to start of protocol therapy]. Intrathecal chemotherapy (at the discretion of\n             the primary oncologist) may be given up to one week prior to the initiation of study\n             therapy.\n\n          -  Anti-GVHD or agents to prevent organ rejection post-transplant: Patients who are\n             receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host\n             disease post bone marrow transplant or organ rejection post transplant are not\n             eligible for this trial. At least 3 half-lives must have elapsed after the last dose\n             of GVHD meds.\n\n          -  Anticoagulants: Patients who are currently receiving therapeutic anticoagulants\n             (including aspirin, low molecular weight heparin, and others) are not eligible. At\n             least 3 half-lives must have elapsed after the last dose of anticoagulants.\n\n          -  Angiotensin-converting enzyme (ACE) inhibitors: Patients who are currently receiving\n             ACE inhibitors are not eligible due to the development of angioneurotic edema-type\n             reactions in some subjects who received concurrent treatment with temsirolimus + ACE\n             inhibitors. At least 3 half-lives must have elapsed after the last dose of ACE\n             inhibitors.\n\n          -  Calcium Channel Blockers: Patients who are currently receiving Calcium Channel\n             Blockers are not eligible due to the development of angioneurotic edema-type reactions\n             in some subjects who received concurrent treatment with temsirolimus + Calcium Channel\n             Blockers. At least 3 half-lives must have elapsed after the last dose of Calcium\n             Channel Blockers.\n\n          -  Enzyme inducing Anti-convulsants: Patients who are currently receiving enzyme inducing\n             anticonvulsants (ie phenytoin, phenobarbitol, or carbamazepine) are not eligible.\n             Stabilizing on a non-hepatic inducing metabolizing anti-convulsant (ie: gabapentin or\n             levetiracetam) prior to study entry is acceptable. At least 3 half-lives must have\n             elapsed after the last dose of enzyme inducing anti-coagulants.\n\n          -  Patients receiving treatment with azoles such as fluconazole or voriconazole which are\n             potent inhibitors of temsirolimus metabolism. At least 3 half-lives must have elapsed\n             after the last dose of azoles.\n\n          -  Patient with Burkiett's leukemia and /or lymphoma are not eligible.\n\n        Infection Criteria\n\n        Patients are excluded if they have:\n\n          -  Positive blood culture within 48 hours of study enrollment;\n\n          -  Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection.\n             Fever that is determined to be due to tumor burden is allowed if patients have\n             documented negative blood cultures for at least 48 hours prior to enrollment and no\n             concurrent signs or symptoms of active infection or hemodynamic instability.\n\n          -  A positive fungal culture within 30 days.\n\n          -  Active fungal, viral, bacterial, or protozoal infection requiring IV treatment.\n             Chronic prophylaxis therapy to prevent infections is allowed.\n\n        Patients with Down syndrome and Fanconi Anemia are excluded.\n\n        Patients will be excluded if they have significant concurrent disease, illness, psychiatric\n        disorder or social issue that would compromise patient safety or compliance with protocol\n        treatment or required observations, interfere with consent, study participation, follow up,\n        or interpretation of study results.\n\n        Patients with known optic nerve and/or retinal involvement (because it may not be possible\n        to safely delay irradiation) are not eligible. Patients presenting with visual disturbances\n        by history or physical exam should have an ophthalmological exam and, if indicated, an MRI\n        to determine optic nerve or retinal involvement.
Patients undergoing preoperative chemoradiotherapy
Patients must have recurrent or refractory intracranial ependymoma (including myxopapillary, clear cell, papillary, tanycytic, and anaplastic ependymoma) or subependymoma; patients with primary diagnosis of intracranial ependymoma with spinal cord metastases or relapse are eligible; the diagnosis must be confirmed by the Collaborative of Ependymoma Research Network (CERN) enrolling site's pathologist on tissue from either the initial presentation or time of recurrence prior to registration; for central pathology review and trial biological studies, submission of a paraffin block with tumor measuring at least 1 cm x 1 cm in area is preferred, but 15 x 5 micro molar (m) unstained sections on slides may be provided by the referring laboratory instead; tissue must be submitted within 60 days after enrollment for central processing and analysis
Patients may have had any number of prior treatment regimens (including biologic) before or after radiotherapy; patients may not have previously been treated with bevacizumab or lapatinib. Gliadel wafers must be approved by CERN Principal Investigator (PI) (Project Leader, Co-Leader and Protocol PI)
Patients may not have previously been treated with bevacizumab or lapatinib
Patients on enzyme inducing anticonvulsants
Patients undergoing extrapleural pneumonectomy
Patients with clinical or radiological evidence of bone (>= 3 sites, or predominantly lytic if < 3) or other extranodal metastasis
Patients with any infectious process that, in the opinion of the investigator, could worsen or its outcome be affected as a result of the investigational therapy
Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early)
Patients must have adequate Karnofsky performance status (KPS) and hematopoietic cell transplantation comorbidity index (HCT-CI) scores:\r\n* Patients < age 60 years must have a KPS of >= 80% and an HCT-CI score of 5 or less\r\n* Patients aged 60 to 65 years must have a KPS of >= 80% and an HCT-CI score of 4 or less\r\n* Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less\r\n* Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
Patients who require or likely to require corticosteroids or other immunosuppressives for intercurrent disease are NOT eligible
Splenectomized patients
Patients who have developed anaphylactic responses to other vaccines
Patients with previously untreated ALL of pre-B, Philadelphia chromosome (Ph-) negative ALL; minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed
Patients with refractory-relapsed ALL of any age are eligible, provided they are not eligible for regimens of higher priority
Patients must be entered no more than 12 weeks post operatively
Patient’s will have no evidence of gross vascular invasion
Patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists
Patients must have at least one unresected VS
Patients with clinical symptoms of gastrointestinal obstruction and who require parenteral hydration/nutrition
Patients are eligible if, based on the postoperative CT scan, partial breast irradiation (PBI) is judged to be technically deliverable
Men are not eligible for this study
Patients with previous history of irradiation at any dose to thoracic-spine, ribs or >= 20% of bone marrow cannot undergo TMI and will be eligible for bortezomib, fludarabine, and melphalan regimen (Stratum II); patients can be enrolled on Stratum II at their physician's discretion or if patients decline radiation therapy
Patients in Stratum A, B, and E must have received standard involved field radiation therapy (RT) defined as fractionated external beam radiotherapy with total doses between 5000-6000 centigray (cGy); patients in these strata must be registered within 4-12 weeks of completing RT
Presence of metastatic disease for patients in Stratum A, B, D and E; patients with metastatic high grade gliomas diagnosed at < 1 year of age are eligible for Stratum D at the time of recurrence; patients with low grade gliomas (Stratum C) may have tumor spread within the CNS; patients in Stratum F must have tumor spread within the CNS
Patients may be of either gender or any ethnic background
Patients with clinically suspected dense intraperitoneal adhesions preventing adequate IP distribution
Patients previously treated with murine monoclonal antibodies will be excluded if they have a human anti-murine antibody (HAMA) level of > 1000 U/ml
Patients must undergo a peritoneal scan documenting at least one working intraperitoneal port prior to receiving chemotherapy
Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment
Receipt of a live vaccine within 4 weeks prior to randomization; efficacy and/or safety of immunization during periods of B-cell depletion have not been adequately studied; it is recommended that a patient’s vaccination record and possible requirements be reviewed; the patient may have any required vaccination/booster administered at least 4 weeks prior to the initiation of study treatment; review of the patient’s immunization status for the following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal polysaccharide; varicella; measles, mumps and rubella (MMR); and hepatitis B; patients who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series at least 4 weeks prior to participation in the study
Patients with primary idiopathic myelofibrosis
Patients with stored autologous stem cells will be allowed
Multiple myeloma (MM): patients who\r\n* Have received induction therapy for a minimum of 4 cycles\r\n* In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft): \r\n** Any abnormal karyotype by metaphase analysis except for isolated t(11,14),\r\n** Fluorescent in situ hybridization (FISH) translocation 4:14,\r\n** FISH translocation 14:16,\r\n** FISH deletion 17p,\r\n** Beta2 (B2)-microglobulin > 5.5 mg/ml,\r\n** Cytogenetic hypodiploidy\r\n** Plasmablastic morphology (>= 2%)\r\n** Recurrent or non-responsive (less than partial remission [PR]) MM after at least two different lines of conventional chemotherapy\r\n** Progressive MM after a previous autograft (provided stored autologous cluster of differentiation [CD]34 cells are available)
Patients must have absolute lymphocyte counts (ALC) of more than 5,000 cell/mm^3
patients with high grade cervical intraepithelial lesions (CIN2/3)
patients whose lesions are HPV16+
patients who are immunocompetent
patients who are not pregnant, committed to using adequate contraception if of childbearing age
Patients with cytologic evidence of glandular dysplasia
Patients with cytologic evidence of adenocarcinoma in situ
Patients with any evidence of damaged skin, or moles, scars, tattoos or marks at the proposed site(s) of administration that might interfere with the interpretation of local skin reactions.
Patients with non-healed wounds.
Patients with collagen vascular diseases, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis
Patients with instability of the spine requiring instrumentation as judged by a neurosurgeon are not eligible
Patients must have localized spinal metastasis; this includes patients with a solitary lesion, a lesion that spans two contiguous levels, a lesion with a para-spinal component, and up to three separate single vertebral levels
Patients with loss of normal vertebral height, due to for example compression fracture or other process, prior to treatment are not allowed; patients with normal height and compression fracture are allowed
Pre-existing bilateral sensorineural hearing loss at >90dB at any frequency from 250-8000Hz as assessed by a comprehensive audiometric evaluation for patients receiving cisplatin. This criteria will not apply to patients receiving carboplatin.
Patients must be consulted to avoid impregnating partner
Patients with cytogenetic abnormalities suggesting an improved prognosis [t(8:21), t(15;17) and inv(16)] will be eligible for transplantation in first remission
Patients can also be deemed not eligible for transplant because of specific organ toxicity; specifically, patients with pre-existing compromise to the heart, lungs, kidney, central nervous system (CNS) or liver may be excluded
Patients and donors must be able to sign consent forms; partially mismatched (at least haploidentical) first degree relative should be willing to donate
Patients must be geographically accessible and willing to participate in all stages of treatment
Patients will not be excluded on the basis of sex, racial or ethnic background
Patients must have adequate TIL available (Turnstile II)
Patients may have brain lesions which measure =< 1cm each; lesions that are > 1 cm that have been treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or his designee no longer represents active disease will also be allowed (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria)
Patients in Cohort A will be randomized to receive either TIL alone or TIL plus dendritic cells
Patients with rapid decline in neurological function as documented on exam and/or as per clinical judgment of treating physician (Cohort D)
Previous Therapies\r\n* Patients who are currently being treated with intrathecal (IT) IL-2 for LMD are eligible; no wash out period is required\r\n* Patients who have been previously treated with other IT therapies are eligible, as long as there is at least a 2 week wash out period\r\n* Patients who have previously received therapy with systemic TIL therapy are eligible\r\n* Patients with ventriculo-peritoneal (VP) shunts must have VP shunts with on/off valves and must be expected to tolerate VP shunt valve off for more than 6 hours; patients who have received CNS irradiation, including whole brain radiation or stereotactic radiosurgery, are eligible, if they are at least 1 weeks post CNS-irradiation (Cohort D); patients who are currently being treated with IT IL-2 for LMD are eligible; no wash out period is required. (Cohort D)
Other Requirements\r\n* Patients must be able to give informed consent\r\n* Patients must have ECOG performance status 0, 1 or 2 and/or Karnofsky performance status (KPS) > 50\r\n* Patients must be able to swallow\r\n* Patients must be able to sit up with or without assistance\r\n* Patients must be able to undergo contrast-enhanced MRI (Cohort D)
Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately); for patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
Alpha feto protein (AFP) < 50 ug/L (for non-hepatitis B or C patients); alpha fetoprotein > 50 ug/L is allowed for patients with hepatitis B or C cirrhosis
Patients must demonstrate the ability and willingness to eat solid food and SV/placebo.
Patients must demonstrate the ability and willingness to follow the study requirements.
Patients must have no rapidly progressing or deteriorating neurologic examination
Patients with stored stem cells will be treated at the escalating dose while patients with no stem cells will be treated at the 50 mCi dose; neuroblastoma patients can be treated at the 50 mCi dose with or without stored stem cells
Patients with obstructive or symptomatic communicating hydrocephalus
Severe major organ toxicity; specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than grade 2; patients with stable neurological deficits (because of their brain tumor) are not excluded; patients with =< 3 hearing loss are not excluded
Inclusion Criteria:\n\n          -  Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma,\n             or other EBV-associated malignancy OR\n\n          -  Severely immunocompromised patients who develop blood levels of EBV DNA exceeding 500\n             copies/ml DNA, and are therefore at high risk for developing an EBV LPD\n\n        It is expected that five types of patients afflicted with EBV-associated lymphomas or\n        lymphoproliferative diseases will be referred and will consent to participate in this\n        trial. These are:\n\n          1. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders\n             following an allogeneic marrow transplant.\n\n          2. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders\n             following an allogeneic organ transplant.\n\n          3. Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a\n             consequence of the profound acquired immunodeficiency induced by HIV.\n\n          4. Patients who develop EBV lymphomas or lymphoproliferative diseases as a consequence of\n             profound immunodeficiencies associated with a congenital immune deficit or acquired as\n             a sequela of anti-neoplastic or immunosuppressive therapy.\n\n          5. Patients who develop other EBV-associated malignancies without pre-existing immune\n             deficiency, including: EBV+ Hodgkin's and Non- Hodgkin's disease, EBV+ nasopharyngeal\n             carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma.\n\n        Exclusion Criteria:\n\n        The following patients will be excluded from this study:\n\n          -  Moribund patients who, by virtue of heart, kidney, liver, lung, or neurologic\n             dysfunction not related to lymphoma, are unlikely to survive the 6-8 weeks required\n             for in vitro generation and expansion of the EBV-specific T cells to be used for\n             therapy and the subsequent 3 weeks required to achieve an initial assessment of the\n             effects of infusions of EBV-specific T cells.\n\n          -  Pregnancy does not constitute a contraindication to infusions of EBV-specific T cells.
Previously untreated and treated patients are eligible
FGFR testing of patients will be performed at the investigators' discretion up to a max. of 90 days prior to start of screening. Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment within this timeframe.
Patients with relapsed/refractory CMML.
Providers and patients must be willing to defer new systemic or cutaneous topical treatment of aGvHD for at least 36 hours after administration of Neihulizumab.
Patients are eligible unless their treatment is to be guided by a higher priority protocol
Other leukemia subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy; this effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes; therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee
Patients previously treated with TLR-7/8 agonist treatment.
Must be accessible for treatment and follow up. Patients registered on this trial must be treated with chemotherapy and followed at the enrolling centre.
Patients with known dihydropyrimidine dehydrogenase deficiency
Patients must have either:
Patients must have measurable metastatic disease amenable to biopsy; patients who decline to undergo a biopsy for this trial will be ineligible
Patients able to complete study and within geographical proximity allowing for adequate follow up
Patients with just one measurable or evaluable tumour lesion that has been resected or irradiated prior to their enrolment in the study
Patients whose tumors harbor a ROS1 rearrangement must have demonstrated progression on or intolerance to crizotinib
Patients whose tumors harbor an ALK rearrangement must have demonstrated progression on or intolerance to an FDA-approved first-line TKI; if the first-line TKI was crizotinib, then they also must have demonstrated progression on or intolerance to an FDA-approved second-line TKI; patients who received alectinib or ceritinib as first-line therapy and have demonstrated progression or intolerance will be eligible for this trial
Patients whose tumors harbor the BRAF V600E mutation, must have demonstrated progression on or intolerance to the combination of dabrafenib and trametinib
1. Confirmed diagnosis of HCC by imaging criteria per American Association for the Study\n             of Liver Diseases (AASLD) criteria.\n\n          2. Patients with single or multiple HCC who are unsuitable for surgical resection or RFA,\n             but suitable for embolization.\n\n          3. ECOG score 0-1. Child-Pugh score up to B7.\n\n          4. Patients should have measurable tumor lesion(s) by contrast MRI.\n\n          5. Patients have adequate normal organ function and suitable laboratory criteria.\n\n          6. Men and women of child-bearing age need to commit to using two levels of contraception\n             simultaneously to avoid pregnancy.\n\n        Exclusion Criteria:\n\n          1. Patients who have had a liver transplantation.\n\n          2. Patients who have uncontrolled major medical problems such as cardiac, pulmonary (COPD\n             requiring constant oxygen), renal (creatinine over 2.0) diseases, active infectious\n             diseases (except chronic Hepatitis B or C), or non-healing ulceration.\n\n          3. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on\n             room air.\n\n          4. Patients with evidence of arterial insufficiency or microangiopathy in any organ due\n             to any reason, which could lead to distal extremity hypoxia, as evidenced by any\n             gangrenous change in distal limbs or requiring resection for this reason.\n\n          5. Patients with poorly controlled HBV infection.\n\n          6. Patients on interferon treatment need to have at least 2-week washout period from Day\n             1.\n\n          7. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment or\n             known diagnosis of cancer other than HCC.\n\n          8. Pregnant or lactating women.
patients participation in other pharmaco therapeutic program with an experimental therapy that is known to effect the coagulation system;
Patients with an active infection or with an unexplained fever during screening or on the first scheduled day of dosing;
For Cohort A:\n\n          1. Prior history of diagnosis of SAA\n\n          2. Diagnosis of relapsed/refractory SAA or recurrent AA following IST for SAA at the time\n             of enrollment. Patients with recurrent AA (e.g., losing their response) are exempt\n             from meeting the diagnostic criteria for relapsed SAA at the time of enrollment, but\n             must have been previously diagnosed with SAA.\n\n          3. Agree to concurrent eltrombopag treatment with appropriate, investigator-selected IST\n             with either hATG + CsA or CsA.\n\n             For Cohort B:\n\n          4. Diagnosis of SAA at the time of enrollment\n\n          5. Patients must not have been previously treated for SAA\n\n          6. Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.\n\n             For all patients, regardless of cohort:\n\n          7. Age 1 to <18 years\n\n          8. Where appropriate, assessments to rule out congenital/inherited bone marrow failure\n             syndromes and other causes of immune-mediated pancytopenia, which may be treated with\n             transplant, must be completed prior to enrollment.\n\n          9. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a\n             treatment option or has been refused by the patient. (Candidacy for HSCT will be\n             determined as per local practice.)\n\n         10. Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of\n             eltrombopag\n\n         11. Normal karyotype with FISH for chromosomes 7 and 8\n\n         12. Performance status score: Karnofsky ?50 or Lansky ?50 (depending on age)\n\n         13. Serum creatinine ?2.5 × ULN\n\n         14. Total bilirubin ?1.5 × ULN\n\n         15. Written informed consent signed by a parent or legal guardian prior to initiation of\n             any study specific procedure.\n\n        Exclusion Criteria:\n\n          1. Prior and/or active medical history of:\n\n               -  Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry)\n\n               -  Other known underlying congenital/inherited marrow failure syndromes\n\n               -  Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of\n                  PMN or RBC at time of enrollment\n\n               -  Any cytogenetic abnormalities, including but not limited to chromosome 7 or\n                  myelodysplasia, in bone marrow within 4 weeks of study enrollment\n\n               -  Myelodysplastic syndrome (MDS)\n\n               -  Other known or suspected underlying primary immunodeficiency\n\n               -  Any malignancy\n\n          2. Active infection not responding to appropriate therapy\n\n          3. Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at\n             least 2 months and a lack of response.\n\n          4. Any out of range lab values Creatinine >2.5 × upper limit of normal (ULN), Total\n             bilirubin >1.5 × ULN Aspartate aminotransferase (AST) or alanine aminotransferase\n             (ALT) >2.5 × ULN
Patients with Portal-caval shunts
Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
Patients receiving unstable or increasing doses of corticosteroids
Patients receiving treatment with any enzyme-inducing anticonvulsant
Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
Patients who receive post-transplant high dose cyclophosphamide
Female patients who are post-menopausal or surgically sterile.
Patients who tolerated previous administration with TMZ
Patients at least eighteen (18) years of age with histologically proven, progressive and/or refractory SM.
Patients must not have any active infectious process.
Patients must be willing to provide at least 250 mL, and up to 500 mL, of whole blood obtained by phlebotomy and/or consent to leukapheresis for DC generation.
Patients with contraindications to CYP and/or GM-CSF.
Patients receiving any statin except pravastatin or rosuvastatin
Treatment with concurrent enzyme-inducing anti-epileptic drugs (EIAEDs); patients previously treated with EIAEDs may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of mibefradil (mibefradil dihydrochloride)
Male patients must agree not to donate semen or sperm while they are taking carfilzomib and 28 days after the last carfilzomib dose.
Patients with markedly decreased visual acuity in the opinion of the treating investigator after completion of screening ophthalmologic exam
For Stage 2 only, mixed histology i.e. patients with >10% non-endometrioid malignant cells in provided histopathology samples.
Patients who have received at least 1 transfusion per year in the last 2 years and who are expected to have a continuing requirement (based on Investigator's judgement) during the duration of the trial
Patients with MEN 2b (since these patients may have megacolon)
Patients must have histological confirmation of a cutaneous T-cell lymphoma (CTCL) of any histology; confirmation of histological diagnosis must be completed prior to enrollment by the lead site (Northwestern)\r\n* Patients will be stratified by mycosis fungoides (MF) and Sezary syndrome (SS) (report diagnostic or consistent with MF/SS), stage IA-IVB according to TNM blood (TNMB) classification versus other CTCL histologies
Patients with sodium, potassium, or creatinine serum electrolytes > grade 2.
Patients must have KPS >/=70
Patients with CEA plasma levels > 1000 ng/mL are excluded during dose escalation, but may be included after the MTD is determined.
Patients with active ? grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
Patients with evidence of high-grade symptomatic duodenal obstruction
Candidates for a Whipple resection; candidates of the Whipple resection will be excluded based on the written recommendations by surgery, oncology, and/or the patient’s primary care physician
Patients who are unable to swallow the medication in its prescribed form are not eligible; the drug cannot be administered via gastric feeding (G)-tube; there will be no exceptions for this criteria
Patients who are suffering from symptoms of bone metastases
Patients who either
Patients on dialysis
Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study.
Patients on anti-arrhythmic drugs
Patients with persistent undistinguishable pain (pain source unidentifiable)
Patients must receive a myeloablative preparative regimen containing busulfan targeted to an area under the curve (AUC) of 1000/ dose for 16 doses combined with fludarabine 40 mg/M2 daily for 4 days
Patients must not have any significant organ system compromise except hematopoiesis as defined in the UAB eligibility checklist including, a Karnofsky performance status > 70% and a life expectancy assuming control of primary disease > 8 weeks
Patients must have failed prior therapy with either a hypomethylating agent (e.g., azacytidine, decitabine) alone or in combination with other agents. Patients with abnormalities in chromosome 5q, should have failed either a hypomethylating agent or lenalidomide.
Patients intolerant or unable to receive these agents will be considered eligible.
Coagulation: INR < 1.5 times normal, aPTT < 1.5 times normal. Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible for the trial if INR and aPTT are within the acceptable therapeutic limits for the institution.
Patients with OPA > 2 (moderate to intolerable general handicap)
Patients who require or are likely to require any strong modifier of CYP450 activity to be taken prior to milataxel administration
Patients who will require APR or hand-sewn colo-anal anastomosis
Patients or their representative who are unable to understand the conditions and objectives of the study
Patients, who are participating in a previous Bayer/Onyx sponsored study that has reached its endpoint (statistical and regulatory or study end), and who are, in the opinion of the Investigator, expected to continue to have an overall positive benefit/risk from continuing treatment.
Patients who are receiving concurrent combination with sorafenib (Nexavar) and capecitabine in their originating Study 12444 (RESILIENCE) will be eligible.
Demonstrated refractoriness or intolerance to standard approved therapy (lenalidomide in del(5q) MDS patients & azanucleosides in non-del(5q)patients).
Patients with gliomatosis cerebri type 1 or 2
Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
205 For Part 2 (Expansion in patients with DLBCL): fluorodeoxyglucose non-avid patients.
Patients whose circumstances do not permit completion of the study or the required follow-up
Patients with chronic HCV infection with less than 4 weeks between completion of HCV therapy and start of study drug. Note: patients with chronic infection with HCV who are untreated or noncuratively treated HCV are allowed on study.
Patients must have one of the histologically advanced solid tumors harboring CCNE1 amplification: their diseases are refractory to, or do not have, standard-of-care therapy; or they declined standard-of-care therapy; patients with triple negative breast cancer or small cell lung cancer are not eligible since there is an ongoing phase Ib study of AZD1775 as a single agent targeting these patients; CCNE1 amplification is defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE1 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent PGM; or CCNE1 amplification on alternate CLIA platforms such as Foundation One, UW-OncoPlex – Cancer Gene Panel, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to be treated after principle investigator (PI) approval; patients with known CCNE1 amplification on local or commercial platforms can start treatment after planned biopsy or submission of recent archival sample; central next-generation sequencing (NGS) CCNE1 and fluorescence in situ hybridization (FISH) testing will be performed to confirm the result
Drugs that affect the CYP3A4 systems are allowed and essential for cancer patients, including anti-fungals but should be used with caution.
Patients must be willing to undergo additional radiologic imaging while on study
Patients who cannot hold instillation for 2 hours
Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation
Patients must have progressed on abiraterone and/or enzalutamide; there must be at least a 3-week washout period after stopping the most recent approved therapy for mCRPC (i.e., abiraterone, enzalutamide, Ra-223, sipuleucel-t); if applicable, patients should be weaned off steroids at least 1 week prior to starting treatment
Patients who have never smoked, defined as smoking ?100 cigarettes in a lifetime
Patients who are on hemodialysis.
Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation.
Patients with a history of having to discontinue anti-GD2 antibody therapy due to toxicity are not eligible.
Patients with a coexisting skin condition such as scleroderma, psoriasis, or eczema in the skin areas to be treated with PDT, that might interfere with response assessment
Patients with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.
Patients with active ? Grade 3 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
Patients who can only receive pentamidine therapy for PCP prophylaxis are excluded, since this drug prolongs the QT interval
Patients with other ongoing serious medical issues must be approved by the study chair prior to registration
Patients who are on hemodialysis
Patients with an active or uncontrolled infection; patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria
Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation
A patient weight that would require exceeding a maximum total allowable dose of 131I-MIBG at the assigned dose level; the study committee will discuss treating such patients at a lower dose level if six patients have not yet been treated at that lower dose level
AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations; Rash must cover less than 10% of body surface area (BSA); 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%, alclometasone dipropionate 0.05%); No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
Patients whose clinical biopsies are found to be insufficient for the planned translational studies must be willing to undergo a research biopsy.
Pre/perimenopausal women must be amenable to be treated with goserelin. All patients will be rendered post-menopausal secondary to concomitant administration of goserelin.
Part 1: patients will be excluded if (1) have clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of ? 13 at baseline
Part 2: patients with Cut Down, Annoyed, Guilty and Eye Opener-Adapted to Include Drugs (CAGE-AID) ? 2
Patients who are not candidates for, or decline, intensive therapy
Patients requiring therapeutic anticoagulation with drugs requiring INR monitoring or anti-platelet therapy, except for acetylsalicylic acid (aspirin) ? 325 mg per day, are not eligible
Patients with low grade ovarian/fallopian tube/peritoneal cancers
Patients must be treated within 6 weeks of most recent resection.
Patients with MCL underwent >= 1 chemoimmunotherapy-based regimen; patients with FL and MZL underwent >= 1 prior chemotherapy-based and/or immunotherapy-based regimen; patients with DLBCL and CLL in Richter’s transformation underwent >= 1 chemoimmunotherapy-based regimen and are not transplant-eligible; patients with CLL, B-PLL and LPL underwent >= 1 chemotherapy-based, or immunotherapy-based or targeted therapy regimen (e.g., PI3K inhibitors [idelalisib], venetoclax, ibrutinib or an investigational agent, including an investigational BTK inhibitor); all regimens must have been administered for >= 2 cycles, and patients must have had either documented disease progression or no response (stable disease) to the most recent treatment regimen
RENAL COHORT: Patients with an outside biopsy within 12 months is allowed for entry requirements; during the screening phase, patients without a tissue diagnosis may undergo a renal biopsy for histologic confirmation on PA13-0291
Patients who are cognitively impaired and unable to consent for the study
Patients with risk of broncho-aspiration based on documented swallowing test by a speech pathologist (if available)
Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy
Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition as judged by an ophthalmologist\r\n* Note: Low grades of superficial punctate keratitis, within the range seen in the normal population, should not lead to the exclusion of the patient
Patients with tumors that are not curable by salvage approaches including resection and/or re-irradiation.
Patients with HRD identified by one of the following criteria: a) Tested positive for BRCA 1 or 2 germline deleterious mutation, b) Previously identified genetic aberrations that are associated with HRD (e.g., somatic BRCA mutation, PALB2, Fanconi anemia gene or RAD51 mutations), c) Patients with somatic ATM loss as identifiable with immunohistochemistry or with ATM mutation, d) Pancreatic ductal adenocarcinoma (PDAC) patients with family history of 2 or more first-degree relatives with BRCA-associated cancers (stomach, breast, ovary) or 1 or more first-degree relative with PDAC
Patients > 45 to =< 65 years: Karnofsky >= 70 or ECOG 0-1 and non-age adjusted comorbidity index =< 5
No specific hematologic parameters for study entry are required; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm^3
Patients must have cHL that has not been previously treated (patients who have received one dose [day 1 cycle 1] of standard doxorubicin hydrochloride [adriamycin], bleomycin, vinblastine and dacarbazine [ABVD] or doxorubicin hydrochloride, vinblastine, dacarbazine [AVD] may be enrolled as long as they completed all the required standard of care baseline studies before enrollment and initiate study therapy by day 15 cycle 1)
Patients with active sepsis or pneumonitis
Hepatocellular carcinoma cohort specific criteria:\r\n* Patients must have a histologically proven diagnosis of hepatocellular carcinoma that is not amenable to curative surgical therapeutic options\r\n* Patients must not be good candidates for locoregional therapy as determined by the investigator (ie diffuse multifocal disease, vascular involvement, etc)\r\n* Patients must have had evidence of radiologic progression on sorafenib or have had intolerance to sorafenib as defined by the recurrence of clinically significant toxicities despite a minimum of one dose reduction and appropriate supportive care; patients who refuse sorafenib are eligible with documentation of refusal by the treating physician\r\n* Patients may have received other treatment for HCC such as embolization, chemoembolization, intra-arterial chemotherapy, ethanol injection, ablative therapy, cryosurgery, or other locoregional or targeted therapy\r\n* Patients must have a Child Pugh score of 7 points or less \r\n* International normalized ratio (INR) =< 2.3 or prothrombin time =< 6 seconds above control\r\n* Patients with hepatitis B infection must be on appropriate anti-viral therapy
Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.
FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Patients must have relapsed/progressed after any therapy for MCL.
FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH STANDARD OF CARE (PART 2): Patients must have adequate organ function for drugs(s) or combination being utilized (dependent on the drug (s) being given).
Patients with angle-closure glaucoma
Patients must have a minimum expected duration of survival of greater than 6 weeks as determined and documented by the attending surgeon or medical oncologist
Progression during or within 6 months after fluoropyrimidine, irinotecan, and oxaliplatin; for oxaliplatin-based therapy, failure of therapy will also include patients who progressed within 12 months of adjuvant therapy and patients who had oxaliplatin discontinued secondary to toxicity or allergic reaction; patients with a known history of Gilbert’s disease who cannot receive irinotecan or patients who are intolerant of irinotecan or fluoropyrimidine are eligible
Ultimate progression through previous treatment with cetuximab, with documented clinical progression; patients who discontinued cetuximab for any other reason, such as decline in performance status, hypersensitivity, or other adverse effects of therapy, are not eligible
Patients must have consented to the MD Anderson ATTACC protocol prior to inclusion
Patients are eligible if they are going to receive TMZ as part of the standard adjuvant treatment regimen following concomitant TMZ/radiation therapy (RT)
Patients with LVEF =< 40% documented from treatment with anthracyclines for any malignancy at any dose at any time without evidence of other causes of cardiomyopathy
Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab
Patients actively receiving insulin are excluded unless approved by the investigational new drug (IND) medical monitor, IND sponsor, and the study principal investigator (PI)
Enrolled in another clinical trial with a targeted endpoint of treating the patient’s cancer (observational trials are acceptable)
Only patients with tumors that score positive in the in vitro organoid bio-assay will be enrolled in the clinical trial; patients with tumors that score negative in this bio-assay will be considered screening failures and will not be enrolled in the clinical trial
Patients with tumors that score negative in the in vitro organoid bio-assay will be excluded
Patients who are taking or anticipate taking any maintenance therapy while actively being treated on protocol or while being followed on protocol will be excluded; an example of this would be maintenance therapy with a Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor such as olaparib
As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment; however, adequate recovery of blood counts will be required to receive subsequent cycles
Patients with extracranial metastases
Previously diagnosis of alpha- or beta-thalassemia since these patients may have significantly higher PK levels than patients without these disorders
Patients on a medication or herbal therapy known to inhibit cytochrome P450 (CYP)2A6, UGT1A9, or UGT2B7
Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment
Patients with pheochromocytoma
Active intracranial metastases; patients with previously resected intracranial disease and/or previously irradiated intracranial metastases that have been clinically stable for four weeks are eligible
In the case of malignant glioma patients, they must have previously undergone standard-of-care treatment including surgery, radiation, and first line adjuvant chemotherapy prior to the experimental treatment (WP1066); in the case of melanoma patients with brain metastasis, they may have previously undergone a resection (with radiographic evidence of progression), have undergone gamma knife radiosurgery (with radiographic evidence of progression), or have been treated with other systemic therapies that failed
Patients with stable seizures (e.g., no seizures for >= 14 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible
Patients who are receiving any other investigational agents require a 4 week washout period; patients who have received cellular or gene therapy at any time are not eligible
It will be at the Principal Investigator's (PIs) discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients with treatment related myeloid neoplasms with cumulative anthracyclines greater than 230 mg/m^2 doxorubicin equivalents
Stratum 2: Newly diagnosed DIPG patients (on-hold until pediatric recommended phase 2 dose [RP2D] has been established in Stratum 1)\r\n* Patients with diffuse intrinsic pontine gliomas (DIPGs) will be eligible 6 to 14 weeks post-completion of radiation therapy if they do not have any evidence of progression; patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of 2/3 or more of the pons, are eligible without histologic confirmation; patients with pontine tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors have been biopsied and (1) are proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma or fibrillary astrocytoma or (2) have a histone mutation typically seen in DIPG; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (i.e., filgrastim, sargramostim or erythropoietin); 2 weeks must have elapsed if patients received polyethylene glycol (PEG) formulations
All patients must be deemed by investigator to have the initiative and means to be compliant with the study protocol (treatment and follow-up)
Pathologically confirmed advanced, unresectable, or metastatic colon or rectal cancer who have had intolerance to or progression after a fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab or panitumumab in the event of wild-type RAS/BRAF tumors\r\n* Of note, prior bevacizumab or regorafenib exposure is not mandated as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents
PART 1 PATIENTS (SURGICALLY ELIGIBLE RECURRENT GBM)
Part 2 patients must have recovered from the immediate post-operative period
Part 2 patients must show evidence of wild-type (WT) p53 as assessed by central deoxyribonucleic acid (DNA) sequencing
Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of AMG 232
Drugs known to be CYP3A4 substrates with narrow therapeutic windows (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfanide) or CYP2C8 substrates are not allowed; patients must be switched to alternative drugs at least 14 days prior to receiving the first dose of AMG 232; those patients who cannot switch to alternative drugs will be excluded from the study
Melanoma patients with an LDH ? 3 x ULN.
Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer (NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories rather than specific diagnoses, specific guidance on eligible tumor types is provided below
Patients must have been pretreated for advanced disease - the number of prior systemic therapy/regimen depends on which origin for NET and for GEP-NEC
Patients must have biopsy-proven adenocarcinoma of the small bowel at any site (duodenum, jejunum, ileum), excluding ampullary and appendiceal tumors
Patients with prosthetic heart valves
Mandatory submission of H&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients
Patients with uveal/ocular melanoma are excluded
Pediatric patients ? 1 day old on Cycle 1 Day 1 (C1D1)
Adequate hepatic function: Bilirubin (sum of conjugated + unconjugated) ? 2.5 upper limit of normal (ULN) for age (patients with documented Gilbert's Disease may be enrolled with Sponsor approval).
NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation treatment
Patients must have resolved any serious infectious complications related to consolidation cycle 2
Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance
For expansion cohort patients, the profiling must reveal at least one mutation in the following selected DNA repair genes involved in cell cycle arrest signal transduction, BRCA1 pathway, Fanconi’s proteins pathway, and RAD51 pathway: (ATR, ATM, CHEK1, CHEK2, BRCA1, BAP1, BARD1, FANCD2, FANCE, FANCC, RAD50, FANCA, RAD51, BRCA2, PALB2, CDK12 [ENSG00000167258, also known as CRK7, CRKR, CRKRS], POLE, POLD1, BRAC2, PRKDC, ERCC2, POLQ, MRE11A, NBN [MBS1]), or at least one gene amplification in FANCD2, FANCE, FANCC, FANCA, C11orf30 (EMSY)\r\n*NOTE: Tissue or blood cell free DNA are allowed for genomic profiling of tumor; profiling should have been performed at a Clinical Laboratory Improvement Act (CLIA) certified lab =< 1 year prior to registration\r\n* NOTE: Patients in the dose escalation phase are not required to have such mutations; although genomic profiling is not required for dose escalation patients, it is encouraged in these patients prior to or after study registration if feasible
Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for >= 14 days\r\n* NOTE: Vitamin supplements are acceptable
Patients must have histologic diagnosis of osteosarcoma at original diagnosis
Patients must have had at least one episode of disease recurrence in the lungs without limitation on number of episodes of recurrence as long as they meet the following criteria:\r\n* Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment**\r\n* Pathologic confirmation of metastases from at least one of the resected sites\r\n** For patients with bilateral pulmonary metastases, resection must be performed from both lungs and the study enrollment must be within 4 weeks from date of the last lung surgery\r\n* Note: If surgery related changes such as atelectasis are seen on the post-operative computed tomography (CT) scan, patients will remain eligible to enroll as long as the operating surgeon believes that all sites of metastases were resected; patients with positive microscopic margins will be eligible to enroll
Patients with distant bone metastases at original diagnosis or relapse (patients with only skip lesions will be eligible)
Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary within 60 days prior to step 1 registration; submission of hematoxylin and eosin (H&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch biopsy of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non- oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H&E and p16 stained slides to the biospecimen bank at UCSF for central review is also required prior to step 2 registration\r\n* Note: fine needle aspirates (FNA) samples are not acceptable since they do not provide enough material for PD-L1 and p16 testing
Patients must have recovered from the immediate post-operative period
Patients who have been previously treated with inotuzumab ozogamicin
Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
Patients must have at least one of the following high risk pathologic features:\r\n* Extracapsular nodal extension\r\n* Invasive cancer at the primary tumor resection margin (tumor on ink); Note: Patients who have a positive margin and undergo re-resection with final negative margin are eligible only if they can be enrolled within 63 days of initial gross total resection AND extracapsular nodal extension was also present; patients who have a positive margin and undergo re-resection with final negative margin and do not have extracapsular nodal extension, are NOT eligible
Patients with feeding tubes are eligible for the study
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma, who are eligible
The presence of radiographically measurable disease immediately prior to start of Phase I immunotherapy is not an eligibility requirement in the following situations:\r\n* In patients with NB who have documented bone marrow (BM) involvement;\r\n* In patients with NB who have MIBG-positive bony lesion(s);\r\n* In patients with OST who had to undergo resection of the pulmonary lesion(s)
T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project:EveryChild (APEC14B1, if open for the classification of ALL patients) prior to treatment and enrollment on AALL1231
Diagnosis of relapsed or refractory AML and not candidate for standard consolidation treatment after daunorubicin and cytosine arabinoside OR diagnosis of APL relapsed after tretinoin (ATRA) and arsenic trioxide therapy or APL with persisting or rising blasts, and no other comparable or satisfactory alternative therapy available (including patients not eligible for, or who have access to, investigational therapies via a clinical trial)
Patients must have cluster of differentiation (CD)33 positivity of >= 30%
Patients currently being treated with quinacrine or drugs related to quinacrine
Patients with documented glucose-6-phosphate dehydrogenase deficiency
Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency
TREATMENT: Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients who have a history of seizures are not eligible to receive veliparib, but patients who have either not had seizures or who have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks will be eligible for other study agents; enzyme-inducing anticonvulsants are contraindicated
Patients with feeding tubes are eligible for the study
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors located in the suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible; tumors present in the above mentioned locations and with unifocal parenchymal extension are eligible\r\n* Stratum 1(NGGCT): Patients must have one of the following criteria:\r\n** Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional normal are eligible, irrespective of biopsy results\r\n** Patients with any of the following elements on biopsy/resection are eligible, irrespective of serum and/or CSF hCGbeta and AFP levels: endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma, and mixed GCT with malignant GCT elements\r\n* Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained (unless obtaining CSF is medically contraindicated) and must have one of the following criteria to be eligible:\r\n** Patients with institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) AND hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically contraindicated) (only 1 is required to be elevated) are eligible; no histologic confirmation required\r\n** Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus (D1) AND hCGbeta =< 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible; no histologic confirmation required\r\n** Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGbeta =< 100 mIU/mL in serum and/or CSF and institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible
Patients must not be in status, coma, or assisted ventilation prior to study enrollment
Patients with mature teratoma or completely resected immature teratoma with normal tumor markers are not eligible
Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible
Male patients unless they are using condoms as contraception starting on the day of transplantation up until one week after infusion
Patients who have received yttrium (Y)-90 ibritumomab (Zevalin) or iodine (I)-131 tositumomab (Bexxar), as part of their salvage therapy are not eligible for myeloablative UCB transplant
Patients with all degrees of renal dysfunction are allowed including patients on hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined below:
For patients with a recently placed biliary stent, patients should have consistent results within a hepatic group from two laboratory readings within 3 days apart, taken at least 10 days following biliary stent placement; for patients with a biliary stent placed over 2 months ago, no obstruction or blockage can have occurred within the last 2 months
Consultations: all patients should be evaluated by a surgeon prior to study entry
Drugs with predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients with abnormal hepatic function will be eligible and will be grouped according to criteria; patients with active hemolysis should be excluded; no distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes; this data will be captured in the case report form (CRF); registration laboratory investigations will be used to assign a patient to a hepatic function group; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients’ group assignment being altered if different to registration test results
Patients must be willing to undergo extra blood sampling for correlative studies
Drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients with solitary plasmacytoma
Patients requiring hemodialysis
Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic KRAS G12R mutation as determined by sequence analysis of matched normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual; patients must provide tumor sample for KRAS analysis or be willing to undergo mandatory screening biopsy
Patients must be willing and able to check and record daily blood pressure readings if receiving cediranib
Patients with cerebral metastases
Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up
Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial
Patients 18-54 years of age with “good risk” AML defined as the presence of t(8;21), inv(16), or t(16;16) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or fluorescence in situ hybridization (FISH) (patients with t(8;21), inv(16), t(16;16) who are unable to receive anthracycline based induction will be allowed to enroll provided the medical reason they are unable to receive anthracyclines is clearly documented and provided they fulfill all other eligibility and criteria)
Patients must have had histologic verification of AML at original diagnosis
To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016) \r\n* Relapsed patients\r\n** Patients must be in first relapse, and\r\n** Patients must not have received prior re-induction therapy\r\n* Refractory patients\r\n** Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example\r\n* Treatment-related AML (t-AML)\r\n** Patients must be previously untreated for secondary AML
Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded; pre-registration testing for G6PD is at the investigator’s discretion and is not required for study enrollment
Patients with melanoma of mucosal or ocular primary
Patients must be lenalidomide failures: disease progression on a prior lenalidomide-based therapy or progression within 60 days of the last dose of a lenalidomide; patients should have received at least 2 cycles of a lenalidomide-based regimen at standard doses to be evaluable for refractoriness; prior intolerance to lenalidomide does not exclude participation in the study except in cases of severe allergic reaction
Patients unable to receive adequate thromboprophylaxis in combination with pomalidomide
Patients must not be eligible for curative liver resection or has refused resection
Patients for whom there is a plan to receive ipilimumab, vemurafenib, or other treatment for advanced melanoma
Patients with untreated AML and the presence of FLT3 mutation (Cohort A only); untreated AML patients > 60 years who are not candidates for intensive chemotherapy and patients with relapsed or refractory FLT3-mutated AML may enroll to Cohort B
Patients with core-binding factor AML (inv[16], t[8;21]) or t(15;17) (Cohort A only)
Full anti-coagulant therapy Coumadin; patients may be receiving therapeutic Lovenox, Fragmin, or other heparin product that does not require laboratory monitoring
Patients with carcinomatous meningitis should also be excluded
Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided CT scans are obtained and are of sufficient quality; patients without non-compatible devices may not have CT scans performed to meet this requirement
All patients will be previously or simultaneously enrolled in the natural history ECD protocol #11-HG-0207, “Clinical and Basic Investigations into Erdheim Chester disease”; eligible patients must have been diagnosed with Erdheim Chester disease, confirmed by pathological evaluation of the affected tissue with adequate staining; affected tissue must harbor the BRAF V600E or V600K mutation
Patients with wild type BRAF gene molecular results on ECD affected tissue
Patients already using topical sirolimus therapy
Patients ?18 year old
Patients with uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis is not an exclusion)
Patients with known Richter's transformation which is progressive and is deemed to require immediate chemotherapy (history of Richter's transformation is not an exclusion); patients with prolymphocytic leukemia (prolymphocytes in blood >55%)
An adverse prognosis, documented by persistent signs and symptoms of CD that have failed to respond satisfactorily to medical and surgical therapies in the past, including but not limited to systemic immune suppressive drugs and biopharmaceuticals; to be considered as refractory to medical and surgical therapy, there must be clinical, endoscopic, and histologic evidence of active inflammatory Crohn's Disease that has either persisted or recurred despite exhaustive treatment with available pharmaceutical and surgical therapies; exhaustive treatment is defined as prior exposure to the following, without durable improvement:\r\n* Systemic glucocorticoids at or above a prednisone equivalent of 40 mg/day for at least 2 weeks, or until drug toxicity or intolerance develops\r\n* Methotrexate (25 mg per week for at least 3 months, or until drug toxicity or intolerance develops) and/or a thiopurine antimetabolite (either 2.5 mg/kg azathioprine or 1.5 mg/kg 6-mercaptopurine in patients homozygous wild-type for the thiopurine-S-methyltransferase [TPMT] gene, or either 1.5 mg/kg azathioprine or 1 mg/kg 6-mercaptopurine in patients heterozygous for TPMT, or doses of these drugs capable of producing a 6-thioguanine nucleotide level of 230-400 without producing a 6-methylmercaptopurine nucleotide level above 5700 for at least 3 months, or until drug allergy, intolerance or toxicity develops); if a patient is homozygous mutant for the TPMT gene, thiopurines would be contraindicated and their use would not be a requirement for enrollment in this protocol\r\n* Use of at least two anti-tumor necrosis factor (TNF)-alpha therapies, that is, infliximab (at least 5 mg/kg every 8 weeks for at least 3 months, or until drug allergy, toxicity or intolerance or anti-infliximab antibodies develop) and/or adalimumab (at least 40 mg subcutaneously [SQ] every 2 weeks for at least 3 months, or until drug allergy, toxicity or intolerance develops) and/or certolizumab pegol (at least 400 mg SQ every 4 weeks for at least 3 months, or until drug allergy, toxicity or intolerance develops)\r\n* Due to the serious risk of progressive multifocal leukoencephalopathy (PML) and the reluctance of some patients to agree to therapy that carries such risk, prior exposure to natalizumab is not required to meet the definition of exhaustive pharmaceutical treatment; neither will use of natalizumab among patients who are John Cunningham (JC) virus antibody seronegative be an exclusionary criterion\r\n* Exhaustive surgical treatment will be defined as indicated operations for complications of Crohn's Disease up to the point where the risks of surgery (for example, mortality or post-operative morbidity such as short bowel syndrome or extensive adhesions with high risk for inadvertent enterotomy) are deemed by patients and their physicians to be unacceptably high; indicated operations for complications of Crohn's Disease include, but are not limited to, surgical resection of involved intestine, stricturoplasty, drainage, curettage, or adhesiolysis of tissues affected by Crohn's disease\r\n* Exposure of patients to investigational drug therapies for Crohn's Disease, that is, to drugs that are not Food and Drug Administration (FDA) approved for this indication, will not be a criterion for either inclusion or exclusion
Other patients\r\n* Patients who do not have biopsy-accessible disease are not required to undergo a biopsy as part of study participation\r\n* In addition, patients who are being treated with therapeutic doses of anticoagulant(s), are not required to undergo a biopsy as part of study participation; if it is felt clinically appropriate despite anticoagulation (i.e. a skin punch biopsy, etc) by the treating physician, a biopsy is allowed, it is simply not required\r\n* The sites of metastatic disease and reason that the disease is not biopsy-accessible should be documented in the medical record and case report form(s)\r\n* Patients who do not undergo baseline biopsy must have their study participation approved by the overall primary investigator (PI) before start of protocol therapy; only patients who have biopsy inaccessible disease may enter the study without the requirement for baseline biopsy
Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy (HAART) treatment
Patients with stage I or smoldering myeloma, isolated plasmacytoma, or benign monoclonal gammopathy are not eligible
Patients who have undergone therapeutic debulking surgery for independent clinical indications and have tissue frozen and stored under sterile conditions as part of protocol 07-319 (Study of Primary Tumor Harvest for the Purpose of Possible Use in a Future Clinical Trial in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer)
Newly diagnosed, previously untreated: (1) M0 medulloblastoma with > 1.5 cm^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor\r\n* As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued\r\n* All patients with M4 disease are not eligible
Patient must be willing to undergo mandatory research biopsy and blood draw; prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding
Patients with other ongoing serious medical issues must be approved by the study chair prior to registration
Patients with a paraben allergy cannot take isotretinoin preparations containing this compound (i.e. Accutane, Sotret) but are eligible if they can take an alternate preparation without paraben; (applicable only for entry onto dose levels receiving isotretinoin)
Serious comorbidities (as determined by the investigator) such as, but not limited\n             to, active congestive heart failure or recent myocardial infarction. Patients who\n             require antifolate therapy for the management of comorbid conditions (e.g.,\n             rheumatoid arthritis) will be excluded from the trial.
Patients with fully resected stage IIb through IV melanoma, with melanoma validated by histology or cytology, who have NOT received prior therapy\r\n* Patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site\r\n* Tissue should be submitted for evaluation of NY-ESO-1 expression and T-cell infiltrates; however, availability of tissue and/or positivity for NY-ESO-1 is not mandatory
Inclusion Criteria:\n\n          -  Patients having histologically and/or cytologically confirmed non-haematological\n             malignancy that is metastatic or unresectable and for which standard\n             curative/palliative treatment does not exist or is no longer effective or is not\n             tolerated by patient.\n\n          -  Patients of either sex, of all races and ethnic groups, and more than 18 years of\n             age.\n\n          -  ECOG (Eastern Cooperative Oncology Group) performance status less than 2.\n\n          -  Patients with life expectancy of at least 4 months.\n\n          -  Patients with measurable or evaluable disease per Response Evaluation Criteria In\n             Solid Tumors (RECIST) version 1.1.\n\n          -  Patients must have adequate organ and marrow function as defined below:\n\n          -  Absolute neutrophil count more than equal to 1500/cmm\n\n          -  Platelets more than equal 100,000/cmm\n\n          -  Total bilirubin within normal limits of the institution.\n\n          -  AST/ALT less than equal 2.5 X institutional upper limit of normal (ULN) or less than\n             equal 5 X institutional upper limit of normal (ULN) in the presence of liver\n             metastases\n\n          -  Creatinine less than equal 1.5 X institutional upper limit of normal (ULN)\n\n          -  Women of childbearing potential and men willing to agree to use adequate\n             contraception (hormonal or barrier method of birth control; abstinence) prior to\n             study entry, during the duration of study participation and for at least 4 weeks\n             after withdrawal from the study, unless they are surgically sterilised.\n\n          -  Ability to understand and the willingness to provide a written informed consent\n             document.\n\n        Exclusion Criteria:\n\n          1. Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted\n             anti-cancer therapy or surgery within 4 weeks (3 months for monoclonal antibodies,\n             radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before\n             study drug administration and have not recovered (to < Grade 1) from the toxic\n             effects from any prior therapy.\n\n          2. Patients having received any other investigational agents within 4 weeks prior to the\n             date of enrolment and have not recovered completely (to < Grade 1) from the side\n             effects of the earlier investigational agent.\n\n          3. Patients with known brain metastases (except for patients who have previously-treated\n             CNS metastases, are asymptomatic, and have had no requirement for steroids or\n             anti-seizure medication for two months prior to first dose of study drug.)\n\n          4. Patients with a history of myocardial infarction or uncontrolled cardiac dysfunction\n             during the previous 6 months.\n\n          5. Patients with diabetes mellitus requiring insulin therapy at screening or patients\n             with clinically significant diabetic complications, such as neuropathy, retinopathy,\n             peripheral vascular disease or nephropathy.\n\n          6. Clinically significant medical condition of malabsorption, inflammatory bowel\n             disease, or chronic diarrheal condition that might affect the absorption of the\n             investigational agent.\n\n          7. Patients on chronic anticoagulation treatment. Prophylactic anticoagulation with\n             low-molecular heparin is allowed.\n\n          8. Patients with inter-current illness including, but not limited to ongoing or\n             clinically significant active infection, symptomatic congestive heart failure,\n             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social\n             situations that would limit compliance with study requirements.\n\n          9. Patients with a known history of allergic reaction to any other medication considered\n             to be clinically significant by the investigator.\n\n         10. Women who are pregnant or nursing.\n\n         11. Patients with immune deficiency and at increased risk of lethal infections, for\n             example, known h/o HIV, HBV or HCV.
Inclusion Criteria:\n\n          -  Patients having histologically and/or cytologically confirmed non-haematological\n             malignancy that is metastatic or unresectable and for which standard\n             curative/palliative treatment does not exist or is no longer effective or is not\n             tolerated by patient.\n\n          -  Patients of either sex, of all races and ethnic groups, and more than 18 years of\n             age.\n\n          -  ECOG (Eastern Cooperative Oncology Group) performance status less than 2.\n\n          -  Patients with life expectancy of at least 4 months.\n\n          -  Patients with measurable or evaluable disease per Response Evaluation Criteria In\n             Solid Tumors (RECIST) version 1.1.\n\n          -  Patients must have adequate organ and marrow function as defined below:\n\n          -  Absolute neutrophil count more than equal to 1500/cmm\n\n          -  Platelets more than equal 100,000/cmm\n\n          -  Total bilirubin within normal limits of the institution.\n\n          -  AST/ALT less than equal 2.5 X institutional upper limit of normal (ULN) or less than\n             equal 5 X institutional upper limit of normal (ULN) in the presence of liver\n             metastases\n\n          -  Creatinine less than equal 1.5 X institutional upper limit of normal (ULN)\n\n          -  Women of childbearing potential and men willing to agree to use adequate\n             contraception (hormonal or barrier method of birth control; abstinence) prior to\n             study entry, during the duration of study participation and for at least 4 weeks\n             after withdrawal from the study, unless they are surgically sterilised.\n\n          -  Ability to understand and the willingness to provide a written informed consent\n             document.\n\n        Exclusion Criteria:\n\n          1. Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted\n             anti-cancer therapy or surgery within 4 weeks (3 months for monoclonal antibodies,\n             radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before\n             study drug administration and have not recovered (to < Grade 1) from the toxic\n             effects from any prior therapy.\n\n          2. Patients having received any other investigational agents within 4 weeks prior to the\n             date of enrolment and have not recovered completely (to < Grade 1) from the side\n             effects of the earlier investigational agent.\n\n          3. Patients with known brain metastases (except for patients who have previously-treated\n             CNS metastases, are asymptomatic, and have had no requirement for steroids or\n             anti-seizure medication for two months prior to first dose of study drug.)\n\n          4. Patients with a history of myocardial infarction or uncontrolled cardiac dysfunction\n             during the previous 6 months.\n\n          5. Patients with diabetes mellitus requiring insulin therapy at screening or patients\n             with clinically significant diabetic complications, such as neuropathy, retinopathy,\n             peripheral vascular disease or nephropathy.\n\n          6. Clinically significant medical condition of malabsorption, inflammatory bowel\n             disease, or chronic diarrheal condition that might affect the absorption of the\n             investigational agent.\n\n          7. Patients on chronic anticoagulation treatment. Prophylactic anticoagulation with\n             low-molecular heparin is allowed.\n\n          8. Patients with inter-current illness including, but not limited to ongoing or\n             clinically significant active infection, symptomatic congestive heart failure,\n             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social\n             situations that would limit compliance with study requirements.\n\n          9. Patients with a known history of allergic reaction to any other medication considered\n             to be clinically significant by the investigator.\n\n         10. Women who are pregnant or nursing.\n\n         11. Patients with immune deficiency and at increased risk of lethal infections, for\n             example, known h/o HIV, HBV or HCV.
Patients must be assigned to S1400B
Patients must have progressed on Arm 2 (docetaxel) of this sub-study
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients with unknown primary melanoma (Tx) who present with cutaneous, subcutaneous, nodal and/or lung metastases that are completely surgically resected with free margins are allowed; these patients are allowed even if they don’t fit the strict staging criteria; for stage IV patients LDH within the institutional ULN must be documented within 4 weeks prior to randomization (M1c is not eligible) \r\n* NOTE: all subjects should be classified as IIIB, IIIC, M1a or M1b including subjects with disease recurrence after adequate surgical excision of the original primary melanoma; that is the treating team/physician investigator should review an overall TNM status (that includes primary tumor presentation and disease recurrence status) and provide a designation of IIIB, IIIC, M1a or M1b
Patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support; patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of interferon (IFN)-alfa or ipilimumab hazardous, should not be enrolled on this protocol; the risks and benefits of being treated with standard adjuvant IFN-alfa should be weighed very carefully in consultation with behavioral health or psychiatry
Blood transfusion will be allowed for patients with hemoglobin less than 9 g/dl and filgrastim (G-CSF) is allowed for neutropenic patients at time of enrollment; chemotherapy treatment can only be administered 48 hours post G-CSF therapy
Patients with low risk (stage IA or IIA) nodular lymphocyte predominant histology
NOTE: Patients who would be excluded from treatment on this protocol strictly for laboratory abnormalities can be included at the principal investigator’s discretion after consultation with the membership of the Texas Children's Cancer Center (TXCCC) Lymphoma Team
Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible for this study; note:\r\n* For the purpose of this study, chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural based secondary tumor nodules will be considered localized disease\r\n* Patients with regional node involvement, based on clinical suspicion confirmed by pathologic documentation are considered to be non-metastatic\r\n* Patients with discontinuous osseous lesions within the same bone are considered to be non-metastatic\r\n* Tumors arising in the bony skull (extra-dural) are considered to be extracranial
No prior chemotherapy or radiation therapy is allowed; patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if unplanned excision was attempted or accomplished as long as adequate imaging was obtained prior to surgery
Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium and spine are not eligible
Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2 are eligible
Arm 2 patients must have progressed/recurred on bevacizumab as the most recent regimen; patients on arm 2 should continue on bevacizumab as clinically necessary to control brain edema
Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of TRC102
Patients who have previously been treated with eribulin are allowed to participate in the microdialysis portion of the study only
Any contraindications to treatment with LC Bead device (e.g. patients with large diameter arteriovenous shunts or patients with a right-to-left shunt)
Patients with pheochromocytoma
Active cytomegalovirus (CMV) retinitis or other active CMV-related organ dysfunction; patients with a history of treated CMV infection are not excluded
Patients with active malignancies other than skin cancers are ineligible for this study
Patients who have adenocarcinomas of the ampulla, distal bile duct, and duodenum
Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
Pediatric patients with progressive DIPG
Patients with lymphomas are excluded
Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody
ALL PATIENTS:
Patients must be assigned to S1400D
Patients must not have had any prior exposure to any agent with FGFR inhibition as its primary pharmacology
Patients must have progressed on Arm 2 (docetaxel) of this sub-study
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients with tumors with anticipated transurethral resection time greater than 1 hour
Patients must be assigned to S1400C
Patients must have progressed on Arm 2 (docetaxel) of this sub-study
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients with any stage of pathologically confirmed cluster of differentiation (CD)3+ acute, lymphoma, chronic, or smoldering subtypes of ATLL
Patients with normal, mild or moderate hepatic dysfunction are eligible
Patients having no distinct measurable lesions outside of the field of radiation
Patients must have had verification of the malignancy at relapse, including immunophenotyping to confirm diagnosis
Patients requiring anticonvulsants known to activate the cytochrome p450 system, in particular anticonvulsants such as phenytoin, carbamazepine, and phenobarbital, are not eligible; benzodiazepines and gabapentin are acceptable
ALL patients who cannot receive any asparaginase products (E. Coli, PEG-asparaginase, or Erwinia asparaginase) on this study (eg, due to prior severe pancreatitis, stroke or other toxicity) are not eligible; patients with clinically significant prior allergies to PEG-asparaginase are eligible if Erwinia L-asparaginase can be substituted
Active cytomegalovirus (CMV) retinitis or other active CMV-related organ dysfunction; patients with a history of treated CMV infection are not excluded
Patients’ AML must carry mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2
Patients with active central nervous system leukemia as they may develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (patient can receive monthly intrathecal maintenance chemotherapy)
Patients who are found to have a cancer positive for the marker human epidermal growth factor receptor 2 (HER-2)/neu (Note: this exclusion criterion applies only to patients at the New York University [NYU] Tisch and Bellevue sites where there is currently a protocol open and available for patients who are HER-2/neu positive; this exclusion criterion does not apply to patients at the South Africa site)
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers
Patients must not be candidates for curative locoregional treatments; patients with recurrent locoregional disease following surgery and/or radiation for who a resection is unacceptably morbid and unlikely to be curative are eligible; patients must be reviewed at the Moffitt Cutaneous Tumor Board prior to enrolling on trial to verify unresectability
Patients on any anticoagulants except aspirin are not eligible
Patients that have active hemolytic anemia
PHASE II: The patient meets the criteria required for the imaging study in which the site is participating:\r\n* NOTE: Eligibility for participating in either imaging sub-study will depend on the availability of the imaging sub-study at a particular institution\r\n* For participation in the FDG-PET sub-study:\r\n** Patients must NOT have poorly controlled diabetes (defined as fasting glucose level >= 200 mg/dL) despite efforts to improve glucose control by fasting duration and adjustment of medications\r\n** Patient must NOT weigh more than the maximum weight limit for the PET table\r\n** Patients must have an evaluable lesion of > 20 mm in size on standard practice imaging study as assessed by site (either primary pancreas mass or metastasis)\r\n* For participation in the FLT-PET sub-study:\r\n** Patients must be able to lie still for a 1.5 hour PET scan.\r\n** Patient must NOT have a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-fluorothymidine\r\n** Patient must NOT weigh more than the maximum weight limit for the PET table\r\n** Patients must have an evaluable lesion in the pancreas > 20 mm in size on standard practice imaging study as assessed by site (lesion must be likely primary adenocarcinoma of the pancreas that is not primarily fibrotic or mucinous in nature)
Patients with hyponatremia (sodium < 130 mmol/L)
Patients requiring treatment with corticosteroids are eligible
Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration
Patients who are receiving drugs that prolong the QTc are not eligible
Patients who have a prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment are not eligible
Diagnosis: \r\n* Patients with refractory or recurrent solid tumors (excluding central nervous system [CNS] tumors) and patients with unresectable translocation positive renal cell carcinoma (tRCC) are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse\r\n* The diagnosis of translocation morphology or transcription factor E (TFE) renal cell carcinoma is established by having characteristic morphology AND either a) strong nuclear TFE3 or TFEb staining on immunohistochemistry OR b) cytogenetic studies of the tumor demonstrating a TFE translocation OR c) fluorescent in situ hybridization (FISH) demonstrating a TFE translocation
Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial
Patients who have received prior therapy with a temozolomide-based regimen are eligible; Note: patients who have progressed on a poly adenosine diphosphate ribose polymerase (PARP) inhibitor and temozolomide regimen are not eligible for Part A of the study
Patients on Part B of the study with known bone marrow metastatic disease will be eligible for the study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients on Part C with ALL: bilirubin (sum of conjugated + unconjugated) =< 1.5 x ULN for age
Patients on Part C with ALL: SGPT (ALT) =< 225 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
Serum total bilirubin < 2 mg/dl; patients with Gilbert’s syndrome are excluded from the requirement of a normal bilirubin and patients will not be excluded if liver enzyme elevation is due to tumor involvement; NOTE: adult values will be used for calculating hepatic toxicity and determining eligibility, as is standard on Pediatric Oncology Branch (POB) phase I trials
For patients < 18 years of age, their legal guardian must give informed consent; pediatric patients will be included in age-appropriate discussion in order to obtain verbal assent
Durable power of attorney form offered (patients >= 18 years of age only)
Patients must be candidates for SRS and planning to undergo SRS
Patients must be candidates for ipilimumab as determined by the treating physician
Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
Patients must have results from the determination of BAF250a immunohistochemistry (IHC) status and must have a BAF250a expression status that is currently open to enrollment
Patients must have progressed on, be ineligible for, or have declined participation in GOG-0254 provided that protocol is actively accruing patients
Patients who have met the pre-entry requirements
Patients whose circumstances do not permit completion of the study or the required follow-up
Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
Patients may have had prior systemic therapy without constraint on the number of prior treatment regimens except:\r\n* Patients may not have had > 450 mg/m^2 doxorubicin \r\n* Patients may not have had > 3000 centigray (cGy) to fields encompassing the entire pelvis
Patients with a history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; 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 are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease
Patients must meet pre-entry requirements as specified
Patients who have mucinous, squamous, sarcomas, or carcinosarcomas
Patients with known immunodeficiency disorder, or presumed to be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) monoclonal antibody (mAb)
Patients with non-secretory MM or known primary amyloidosis are not eligible
Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted
Patients with previous autologous or allogeneic HCT are allowed to enroll
Patients must not be eligible for full ablative regimens by the attending physician
Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis
All patients must have a psychosocial evaluation prior to transplant as per COH SOP
Patients with myeloproliferative neoplasms
Patients with relapsed or refractory AML age >= 18 years are also eligible for treatment; patients may have been treated for antecedent hematologic disorder with myeloid growth factors, recombinant erythropoietin, thalidomide, lenalidomide, 5-azacitidine or the 5 day schedule of decitabine; patients who have received the 10 day schedule of decitabine for treatment an antecedent hematologic disorder or AML are not eligible
Patients should have no evidence of immune dysfunction
Patients with pericardial masses > 1 cm or thoracic lesions larger than 2 cm will be excluded
Patients must have autologous transduced activated T-cells with >= 20% expression of GD2
Patients must be > 18 years old.
Patients undergoing a total body irradiation (TBI)-based conditioning regimen (TBI 1200 cGy)
Patients on warfarin (patients on injectable blood thinners, such as Lovenox, are able to continue those)
Patients who are taking other insulin secretagogues and/or insulin
Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites) histologically proven SCCHN with no definitive evidence of metastatic disease; in summary, those patients eligible are:\r\n* Stage IVa-b SCCHN other than OPC, or\r\n* OPC, HPV-negative, IVa-b, or\r\n* OPC, HPV positive, with greater than 10 pack-year smoking history and N2b-N3 disease
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-1
Patients with ureteral obstruction (i.e., hydronephrosis identified on CT imaging) must undergo stent or nephrostomy tube placement prior to study entry
Patients must meet the pre-entry requirements specified
Patients who have circumstances that will not permit completion of this study or the required follow-up
Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) antibody
Patients receiving nilotinib 200 mg PO BID or a lower dose are not eligible
The target population of this study are patients who have a suboptimal response to steroids as their first line of treatment for acute GVHD (ie steroid refractory); this protocol is designed to provide second line therapy, and is not for patients (pts) in whom additional, alternate immunosuppressive agents have already been added
As patients with steroid refractory acute GvHD are quite ill with multiple abnormal labs and organ dysfunction, there are no explicit laboratory values or degree of organ dysfunction that specifically preclude enrollment on this study; baseline lab studies will be obtained and followed throughout this trial as the standard of care for patients with GvHD
Patients with known antibodies to immunoglobulin (Ig)A
Cervical cancer:\r\n* Patients with the following pathology findings may be treated with pelvic radiation with or without weekly cisplatin at the treating physician’s discretion; the decision to add weekly cisplatin for these patients is at the treating physician’s discretion\r\n** Patients with intermediate-risk features including two of the following histologic findings after radical hysterectomy:\r\n*** 1/3 or more stromal invasion\r\n*** Lymph-vascular space invasion\r\n*** Large clinical tumor diameter (> 4 cm)\r\n** Patients with cervical cancer treated with a simple hysterectomy with negative margins\r\n* Patients with any of the following criteria following radical hysterectomy are eligible for this study and must receive weekly cisplatin:\r\n** Positive resected pelvic nodes and para-aortic nodes negative if removed: Note: if para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy\r\n** Microscopic parametrial invasion with negative margins
Patients who exceed the weight/size limits of the treatment table or CT scanner
Patients with positive or close (< 3 mm) resection margins
Patients residing in prison
Patients with immune deficiency are excluded
Patients must have a positive screening Epstein-Barr virus (EBV) antibody titre on screening test
Patients are allowed to have up to 3 prior treatments
Patients must have had histologic verification of malignancy at original diagnosis or relapse; all patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL) are eligible except for patients with primary or metastatic central nervous system (CNS) tumors or patients with primary cutaneous ALCL
Parts A and B: Patients who are able to swallow liquid or use a nasogastric or gastrostomy (G) tube are eligible
Patients with carcinoid tumors
Patients must have the ability and willingness to come to Clinical Center for bi-weekly follow-up appointments
Any of the following conditions: \r\n* Serious or non-healing wound, ulcer, or bone fracture\r\n* Current use of therapeutic warfarin; Note: low molecular weight heparin is allowed; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria\r\n* History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding\r\n* History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug\r\n* Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation\r\n* HIV-positive patients on combination antiretroviral therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis
Patients may be excluded at the discretion of the PI/LAI if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk
Patients must be clinical American Joint Committee on Cancer (AJCC) stage IIIA or IIIB (AJCC, 7th ed.) with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team, involving evaluation by at least 1 thoracic surgeon within 8 weeks prior to registration; Note: For patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and a medical oncologist, or pulmonologist
Patients with multiple, ipsilateral pulmonary nodules (T3 or T4) are eligible if a definitive course of daily fractionated radiation therapy (RT) is planned
Diabetic patients requiring insulin for glucose control at the time of study entry
Refractory or relapsed HL patients that are also candidates for ASCT
Patients enrolled on another therapeutic study
Patients with serum human anti-human antibody (HAHA) against daclizumab
Pathologic confirmation of DCIS of the female breast without invasive cancer, with diagnosis rendered on core biopsy only, completed within 60 days before registration; patients diagnosed with DCIS on the basis of surgical biopsy are not eligible for this study\r\n* Patients with microinvasion on diagnostic core biopsy, defined as tumor =< 1mm in greatest dimension, will be allowed to participate\r\n* All patients must have a clip placed, either at the time of the diagnostic biopsy or at the time of the baseline MRI prior to the start of treatment
Serum estradiol level assay (required for patients < 55 years of age and one year or more of amenorrhea) < 20 pg/mL
Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis
Patients of childbearing age who are unwilling to practice contraception or other means of avoiding pregnancy
History of hemoptysis within 30 days of registration; Note: patients who have minimal bleeding from the mouth, which is clearly not related to a source in the lungs, i.e., surgery such as a non-lung biopsy, are eligible only after good hemostasis has been documented
Newly diagnosed patients may need to be on steroids due to surgery or control of neurologic symptoms; patients on steroids postoperatively or for control of tumor-related edema are eligible, but attempts to keep patients on the lowest dose necessary to control symptoms should be made
All patients or their legal guardians (if the patient is < 18 years old) or durable power of attorney (DPA) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study; when appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent
Assignment of DPA to a family member or guardian should be offered to all patients 18 years of age or older
Patients with an HGG that was completely resected with good margins
Patients with a known coagulation disorder are excluded; patients with a first-degree relative with a history of venous thrombosis before age 50 years (yrs) or an arterial thrombosis before age 40 yrs must have the following testing performed prior to enrollment to exclude a heritable disorder; patients with a suspected disorder will be excluded
Patients who have had a thromboembolic event that is not line-related are excluded
Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
Patients 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 thrombophilic history
Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
Patients must have histologic proof of active AML at time of enrollment
Patients with and without FLT3 mutations will be eligible to participate
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients who have met the pre-entry requirements specified
Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration or nutrition
Patients with GOG performance status of 3 or 4
Serum magnesium within normal range (patients may receive magnesium supplementation to achieve normal levels)
* Phase 1 (Part A3) - COMPLETE: Patients with relapsed or refractory neuroblastoma, with or without bone marrow involvement, who are not eligible for Part A1 or A2 or cannot enroll on Part A1 because of stratum suspension or lack of available slots (these patients will be enrolled at one dose level below the dose level at which patients on Part A1 are actively enrolling)
* Phase 2 (Part C): Patients with ALK+ relapsed or refractory ALCL (excluding patients with primary cutaneous ALCL)
Patients who are currently receiving other anti-cancer agents, with the exception of hydroxyurea for patients with ALCL, are not eligible
Patients who are not candidates for HDR brachytherapy
Patients residing in prison
Patients with a history of an invasive malignancy within the last 3 years are not eligible for the protocol; patients who are no evidence of disease (NED) from a prior invasive malignancy for at least 3 years or longer are eligible for the trial; patients with history of benign tumors such as a pituitary macroadenomas, meningiomas, or craniopharyngiomas are eligible as long as the benign tumor is under local control regardless of the time frame; patients with concurrent adequately treated basal cell or squamous cell carcinoma of the skin are also eligible for the protocol
Patients with Aplastic anemia and Fanconi anemia
Patients with chemotherapy (chemo)-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic subclassification
Patients with histologically proven HL will be eligible for transplantation after failing prior therapy
Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will be ineligible for transplant in this trial
Patients eligible for any higher priority transplant protocols
Patients receiving Coumadin
Patients should not meet criteria for post PV or post ET-myelofibrosis (MF)
Patients should not meet criteria for post PV or post ET-myelofibrosis (MF)
Patients will not be excluded on the basis of sex, racial or ethnic background
Uncontrolled viral, bacterial, or fungal infections (currently taking medication and with progression of clinical symptoms or findings); patients with symptoms consistent with respiratory syncytial virus (RSV), influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay)
Are \BCG Unresponsive\ which refers to patients with high-grade NMIBC who are unlikely to benefit from and who will not receiving further intravesical BCG. The term \BCG unresponsive\ includes patients who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapse with high-grade CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the patients who may be included in the study:
Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, patients can enter the study)
Patients who cannot hold instillation for 1 hour
Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation
Pathology confirmation of GCT histology at Memorial Sloan-Kettering Cancer Center (MSKCC) or a collaborating treating institution; in exceptional circumstances, patients without pathological diagnosis may be included in the study following discussion with national principal investigator, Dr. Feldman, (or national Co-principal investigator [PI] or MSKCC Co-PI if the national PI is unavailable) if they meet the one of the following criteria:\r\n* Patients with testicular mass (detected clinically and/or by ultrasound), and/or mediastinal or retroperitoneal lymphadenopathy or pineal tumor AND elevated serum tumor markers (human chorionic gonadotropin [HCG] and/or alpha-fetoprotein [AFP]); patients with elevated lactate dehydrogenase (LDH) only will not be included without pathological confirmation of GCT since LDH is a nonspecific marker for GCT and could potentially be elevated in other malignancies such as lymphomas\r\n* Initial treatment without biopsy confirmation is usually recommended and tissue confirmation may be obtained after initiating therapy
Patients must be enrolled between 8 to 20 weeks post OLT
Patients must have been assigned to S1400I
Patients who can complete PRO forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I EQ-5D Questionnaire within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study
Patients must be offered the opportunity to participate in specimen banking for future use to include translational medicine studies
This eligibility criterion does not apply to patients enrolled after August 28, 2011; patients who are not candidates for surgical cytoreduction are eligible for the chemotherapy randomization; patients are not considered candidates for surgical cytoreduction if complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking
Patients must have met the pre-entry requirements as specified
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
Patients undergoing pre-treatment secondary cytoreduction will undergo therapy with bevacizumab on cycle #2
Patients undergoing pre-treatment surgery for purposes other than cytoreduction may also participate provided they meet eligibility; patients randomized to arms containing bevacizumab must wait a minimum of 28 days since that procedure to begin protocol treatment; patients who undergo an uncomplicated port placement must wait a minimum of 7 days to begin protocol treatment
Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e., >= 11 mg/dL)
Patients must not have baseline bone lesions or plasmacytomas
Patients with monoclonal gammopathy of undetermined significance are not eligible
For patients enrolling in the four expansion cohorts:
NSCLC patients must meet criteria for MET and/or Axl expression or,
HNSCC patients must meet criteria for MET and/or Axl expression or,
Patients must not have a clinically relevant hearing impairment > grade 2
Patients must agree to participate in the translational medicine studies
Patients must agree to have blood specimens submitted for pharmacokinetic analysis
Patients must be offered the opportunity to consent to the use of specimens for future research
Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
Patients who are not candidates for or have declined an allograft
Patients with acute myelofibrosis are excluded
Patients may have failed prior allograft
Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.
Patients who are on hemodialysis.
Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
Tumor Requirements: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) are eligible.
Patients undergoing renal dialysis.
Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease
Patients must meet pre-entry requirements
Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:            \r\n* Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 & node positive, IB2, IIA, IIB, IIIB, or IVA disease
Patients assessed at presentation as requiring interstitial brachytherapy treatment
Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy
Patients of all ages.
Patients unlikely to be available for evaluation at the transplant center on Day 28 and 56 of therapy.
Patients on dialysis.
Patients on mechanical ventilation.
Patients must have stage IV gastric or GEJ adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, (immunohistochemistry [IHC] 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:chromosome 17 centromere probe [CEP17] ratio >= 2.0); MSKCC confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC for purpose of analysis and will not impact the patient's eligibility
Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting.
Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with non-ulcerated T1b N1a disease are not eligible; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible
Patients with multiple regional nodal basin involvement are eligible; gross or microscopic extracapsular nodal extension is permitted
Patients must be offered the opportunity to participate in specimen banking as outlined
Patients must be willing to have blood draws for PK/ADA analysis as outlined, should the patient be randomized to the MK-3475 arm
Patients must not be registered until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 working days of receiving the e-mail notification
Patients with an active severe infection that required anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, patients with tumor fever may be enrolled)
Patients must agree to blood samples during screening and at the end of treatment for cytogenetic analysis.
SPECIMEN SUBMISSION CRITERIA: Patients must be offered optional participation in banking of specimens for future research
Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
Patients may be:
On an effective combination cART regimen, generally a 3-drug regimen based on Department of Health and Human Services (DHHS) treatment guidelines\r\n* Patients must be on cART >= 4 weeks; and\r\n* Evidence of viral suppression defined as HIV viral load < 200 copies/mL; and \r\n* No symptomatic AEs > grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) criteria probably or definitely attributed to cART; and\r\n* No laboratory AEs noted on protocol defined screening laboratories > grade 1 by CTCAE criteria probably or definitely attributed to cART, with exceptions noted below\r\n* Note: if cART is modified during the screening period, patients must be on an effective new regimen for >= 2 weeks and otherwise meet eligibility criteria\r\n* Most patients have viral loads that are suppressible to < 50 copies/mL, but about 25% of patients will occasionally have blips up to 400–500 copies/mL, which do not appear to correlate with lack of viral suppression in most studies; thus, an HIV viral load of =< 400 copies/mL for an occasional “blip” will be allowed, if there is documentation of an HIV viral load < 200 on the same regimen and no significant treatment interruption
Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician; patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol
Patients must not have received prior WBRT (previous SRS/SRT done at least 4 weeks from the planned start of WBRT is acceptable); patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Patients with known diagnoses that are associated with germline DDR defects such as Li Fraumeni syndrome and ataxia telangiectasia are excluded from the study
Patients with primary oropharynx HNSCC must be HPV (-) according to local institutional definition using either p16 immunohistochemistry or HPV testing
Patients on tacrolimus or any other immunosuppressants with significant interaction with cisplatin
Main Criteria for Inclusion:\n\n          1. Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV) who\n             progressed following ? 1 lines of prior systemic therapy, including immune checkpoint\n             inhibitor (eg, anti-PD-1), and if BRAF mutation-positive, after BRAF inhibitor\n             systemic therapy. Patients must have no other therapy options that are expected to\n             have significant benefit in the opinion of the Investigator and must have:\n\n               -  At least 1 measurable target lesion, as defined by RECIST 1.1. Lesions in\n                  previously irradiated areas should not be selected as target lesion, unless\n                  treatment was ? 3 months prior, and there has been demonstrated disease\n                  progression in the lesion\n\n               -  At least 1 resectable target lesion to generate TIL of a minimum 1.5 cm in\n                  diameter post-resection; surgical removal with minimal morbidity (defined as any\n                  procedure for which expected hospitalization is ? 3 days)\n\n          2. Patients must be ?18 years and ?70 years of age at the time of consent. Enrollment of\n             patients >70 years of age may be allowed after consultation with the Medical Monitor\n\n          3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of\n             0 or 1 and an estimated life expectancy of ? 3 months\n\n          4. In the opinion of the Investigator, patient must be able to complete all\n             study-required procedures\n\n          5. Patients of childbearing potential or their partners of childbearing potential must be\n             willing to practice an approved method of birth control during treatment and for 12\n             months after receiving last protocol-related therapy\n\n             Approved methods of birth control are as follows:\n\n               -  Combined (estrogen and progestogen containing) hormonal birth control associated\n                  with inhibition of ovulation: oral; intravaginal; transdermal\n\n               -  Progestogen-only hormonal birth control associated with inhibition of ovulation:\n                  oral; injectable; implantable\n\n               -  Intrauterine device (IUD)\n\n               -  Intrauterine hormone-releasing system (IUS)\n\n               -  Bilateral tubal occlusion\n\n               -  Vasectomized partner\n\n               -  True sexual abstinence when this is in line with the preferred and usual\n                  lifestyle of the patient. Periodic abstinence (eg, calendar ovulation,\n                  symptothermal, post-ovulation methods) is not acceptable.\n\n          6. Patients must have the following hematologic parameters:\n\n               -  Absolute neutrophil count (ANC) ? 1000/mm3\n\n               -  Hemoglobin ? 9.0 g/dL\n\n               -  Platelet count ? 100,000/mm3\n\n          7. Patients must have adequate organ function:\n\n               -  Serum alanine transaminase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) and\n                  aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT) ? 3\n                  times the upper limit of normal [ULN]), patients with liver metastasis ? 5 times\n                  ULN\n\n               -  An estimated creatinine clearance (eClCr) ? 40 mL/min using the Cockcroft Gault\n                  formula at Screening\n\n               -  Total bilirubin ? 2 mg/dL: Patients with Gilbert's syndrome must have a total\n                  bilirubin ? 3 mg/dL\n\n          8. Patients must be seronegative for the human immunodeficiency virus (HIV) antibody,\n             hepatitis B antigens, and hepatitis C antibody or antigen\n\n          9. Patients must have recovered from all prior therapy-related adverse events (AEs) to ?\n             Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03), except for\n             alopecia or vitiligo, prior to enrollment (tumor resection), with a washout period\n             from prior anticancer therapy(ies) to the start of planned NMA-LD of a minimum\n             duration detailed as follows:\n\n               -  Targeted therapy: prior targeted therapy with a MEK/BRAF or other-directed agent,\n                  is allowed provided the washout period is a ? 21 days or 5 half-lives, whichever\n                  is longer prior to the start of NMA-LD\n\n               -  Chemotherapy: adjuvant, neoadjuvant or definitive chemotherapy/ chemoradiation is\n                  allowed provided the washout period is ? 21 days or 5 half-lives, whichever is\n                  longer prior to the start of NMA-LD\n\n               -  Immunotherapy: prior checkpoint-targeted therapy with an anti-CTLA-4/anti-PD-1,\n                  other monoclonal antibody (mAb), or vaccine is allowed if disease progression is\n                  confirmed prior to or within the washout period of ? 21 days before the start of\n                  NMA-LD\n\n               -  Palliative radiation therapy is permitted between biopsy and NMA-LD if it does\n                  not involve lesions being selected as target or nontarget\n\n               -  Patients may undergo preplanned procedures if within 2 to 3 weeks prior to the\n                  start of NMA-LD\n\n         10. Patients with documented Grade 2 or higher diarrhea or colitis as a result of previous\n             treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at least\n             6 months and/or had a normal colonoscopy post immune checkpoint inhibitor treatment by\n             visual assessment, prior to start of NMA-LD\n\n         11. Patients must have the ability to understand the requirements of the study, have\n             provided written informed consent, as evidenced by signature on an informed consent\n             form (ICF) approved by an Institutional Review Board/Independent Ethics Committee\n             (IRB/IEC), and agree to abide by the study restrictions and return to the site for the\n             required assessments\n\n         12. Patients have provided written authorization for use and disclosure of protected\n             health information\n\n        Criteria for Exclusion:\n\n          1. Patients with melanoma of uveal/ocular origin\n\n          2. Patients who have received an organ allograft or prior cell transfer therapy that\n             included a nonmyeloablative or myeloablative chemotherapy regimen (not applicable for\n             patients in the retreatment Cohort 3)\n\n          3. Patients with symptomatic and/or untreated brain metastases (of any size and any\n             number)\n\n               -  Patients with definitively treated brain metastases may be considered for\n                  enrollment after discussion with the Medical Monitor, and must be stable for ? 2\n                  weeks prior to the start of NMA-LD\n\n          4. Patients who are pregnant or breastfeeding\n\n          5. Patients who are on a systemic steroid therapy at a dose of > 10 mg of prednisone or\n             equivalent per day\n\n               -  A short course of higher-dose steroid therapy is allowed in cases of exacerbation\n                  of known disease or for treatments of new acute symptoms\n\n          6. Patients who have active medical illness(es) that in the opinion of the Investigator\n             would pose increased risk for study participation that may include active systemic\n             infections, such as syphilis, or any other infections requiring antibiotics,\n             coagulation disorders, or other active major medical illnesses of the cardiovascular,\n             respiratory, or immune system\n\n          7. Patients who have any form of primary immunodeficiency (such as severe combined\n             immunodeficiency disease [SCID] or acquired immunodeficiency syndrome [AIDS])\n\n          8. Patients who have a history of hypersensitivity to any component or excipient of the\n             TIL therapy and other study drugs:\n\n               -  NMA-LD (cyclophosphamide, mesna, and fludarabine)\n\n               -  IL-2\n\n               -  Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin)\n\n               -  Any component of the TIL infusion product formulation including dimethyl\n                  sulfoxide [DMSO], human serum albumin [HSA], IL-2, and dextran-40\n\n          9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or New York Heart\n             Association (NYHA) functional classification > Class 1 at Screening. All patients must\n             have echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) at Screening. For\n             patients ? 60 years or patients who have a history of ischemic heart disease, chest\n             pain, or clinically significant atrial and/or ventricular arrhythmias, a cardiac\n             stress tests must be performed showing LVEF ?45%, and if any wall movement\n             abnormalities, they must be reversible.\n\n         10. Patients who have obstructive or restrictive pulmonary disease and have a documented\n             FEV1 (forced expiratory volume in 1 second) of ? 60%\n\n         11. Patients who have had another primary malignancy within the previous 3 years (with the\n             exception of carcinoma in situ of the breast, cervix, or bladder, localized prostate\n             cancer and nonmelanoma skin cancer that has been adequately treated)\n\n         12. Patients who have been shown to be BRAF mutation positive (V600), but have not\n             received prior systemic therapy with a BRAF-directed kinase inhibitor\n\n         13. Patients who have received a live or attenuated vaccine within 28 days of the start of\n             NMA-LD\n\n         14. Patients whose cancer requires immediate attention or who would otherwise suffer a\n             disadvantage by participating in this trial\n\n         15. Patients protected by the following constraints:\n\n               -  Hospitalized persons without consent or persons deprived of liberty because of a\n                  judiciary or administrative decision\n\n               -  Adult persons with a legal protection measure or persons who cannot express their\n                  consent\n\n               -  Patients in emergency situations who cannot consent to participate in the trial
Hematology/biochemistry (as dictated by local hospital practice) should indicate fitness for randomization options and parameters should be in line with considerations specified in the summary of product characteristics; hematological parameters should not be supported by transfusion to enable entry into the trial; liver function and renal function tests must form part of the pre-treatment assessment for patients who may be randomized to receive paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy e.g. patients with impaired renal function may not be considered for arms B and C of InPACT-neoadjuvant but may be considered for arm A
Previous treatment with investigational agents that inhibit MDM2 or MDMX activity (some MDM2-treated patients may be eligible)
Patients must have the potential for benefit from local therapy (at the discretion of the investigator)
Patients must complete all required pretreatment evaluations
Patients whose entry to the trial will cause unacceptable clinical delays in their planned management
Patients who are taking Coumadin or Coumadin derivatives.
Patients must be able to receive weekly cisplatin
Patients requiring para-aortic radiotherapy
Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months after treatment;\r\n* NOTE: patient with < 6 moths of life expectancy will be treated with palliative QUAD shot radiotherapy and those with > 6 moths of life expectancy will be treated with conventionally fractionated full dose re-irradiation approach; additional other factors determining which patients will be treated with Quad shot therapy rather than full dose are if the patients have poor performance status, bulky or diffuse disease, significant medical co-morbidities, and significant metastatic disease burden
Patients aged ?18 years at time of screening
Patients undergoing current treatments for other cancers
Patients must have a GOG performance status of 0 or 1
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients must have signed an approved informed consent and authorization permitting release of personal health information; individuals with impaired decision-making capacity are not eligible to participate on the study
The patient must be accessible for scheduled visits, treatment and follow-up. Patients registered on this trial must be treated at the participating center which could be the Principal or a Co- investigator's site.
Male patients.
Patients must have tumor tissue available for submission to assess gene expression of ERCC1 and XRCC1; patients must also be offered participation in banking for future use of specimens
Patients with artificial urinary sphincter or any penile implant
Patients in the USA: Glucagon
Patients in Canada and Europe: Buscopan (Hyoscine)
Patients must have been assigned to S1400A
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
For patients enrolled in Part 2SA who are receiving anti-PD-1 mAb therapy, marrow and hepatic function as defined in criteria 8a and 8b may be up to CTCAE Grade 2 if first reviewed, found to be within acceptable safety parameters for treatment with pembrolizumab, and approved by the Sponsor Medical Monitor.
Patients must be able to tolerate oral medication and not have evidence of active bowel obstruction\r\n* Note: patients can have a history of prior bowel obstruction, provided the patient is not having symptoms of bowel obstruction at the time of enrolment and the bowel obstruction is not anticipated to recur during the participation in the study
Inclusion Criteria for Phase 1b:\n\n          1. Patients must have histologically or cytologically confirmed advanced solid tumors\n             with a histology and/or molecular alteration of interest as defined in Section 4,\n             detected by a CLIA-certified or equivalently accredited diagnostic laboratory\n\n             • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E\n             mutations) patients must have archival tissue available for analysis by Ignyta; all\n             other patients must send tissue to Ignyta, if tissue is available\n\n          2. Prior Treatment:\n\n               -  Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior\n                  therapies are allowed\n\n               -  NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET\n                  inhibitor-naïve will be enrolled; (any number of other prior therapies are\n                  allowed); all other histologies with RET alterations must be RET inhibitor-naïve\n\n               -  Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or\n                  BRAF V600E mutations) may have had prior TKIs and any number of other prior\n                  therapies\n\n          3. Measurable disease according to RECIST v1.1 for all patients except patients with RET\n             altered tumors; patients with RET altered tumors must have evaluable disease, but are\n             not required to have measurable disease\n\n          4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis\n             are allowed. The use of seizure prophylaxis is allowed. Patients requiring steroids\n             must be at a stable or decreasing dose for at least 2 weeks prior to the start of\n             RXDX-105 treatment.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n          6. Able to ingest oral medication\n\n          7. Other inclusion criteria apply\n\n        Exclusion Criteria for Phase 1b:\n\n          1. Treated with systemic anticancer therapy or an investigational agent within 2 weeks or\n             5 half-lives, whichever is shorter, prior to start of study drug treatment (4 weeks\n             for antibody therapy and immunotherapy, and 2 weeks for bevacizumab in colon cancer\n             patients)\n\n          2. Major surgery 21 days or less prior to starting study drug or has not recovered from\n             adverse effects of such therapy\n\n          3. Radiotherapy within 2 weeks prior to start of study drug treatment (palliative\n             radiation or stereotactic radiosurgery within 7 days prior to start of study\n             treatment). Patients must have recovered from all radiotherapy-related toxicities\n\n          4. History of non-pharmacologically induced prolonged QTc interval (e.g., repeated\n             demonstration of a QTc interval > 500 milliseconds from ECGs performed at least 24\n             hours apart)\n\n          5. Major active infection requiring parenteral antibiotics\n\n          6. Severe or unstable medical condition, such as congestive heart failure (New York Heart\n             Association [NYHA] Class III or IV), ischemic heart disease, uncontrolled\n             hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an\n             uncontrolled cardiac arrhythmia requiring medication (? Grade 2, according to NCI\n             CTCAE v4.03), myocardial infarction within 6 months prior to starting study treatment,\n             or any other significant or unstable concurrent medical illness that in the opinion of\n             the Investigator would preclude protocol therapy\n\n          7. History of other previous cancer that would interfere with the determination of safety\n             or efficacy of RXDX-105 with respect to the qualifying solid tumor malignancy\n\n          8. Known infection with human immunodeficiency virus (HIV) and active hepatitis B or\n             hepatitis C\n\n          9. Current participation in another clinical study of an investigational agent, vaccine,\n             or device. Concomitant participation in observational studies is acceptable\n\n         10. Presence of a significant gastrointestinal disorder that, in the opinion of the\n             Investigator or Sponsor, could interfere with absorption of RXDX-105 (e.g.,\n             malabsorption syndrome, gastrointestinal surgery)\n\n         11. Known hypersensitivity to any of the components of RXDX-105
Fasting triglycerides =< 5 x time the upper limit of normal; patients above this level may be eligible with permission of the study chair; triglycerides may be \normalized\ prior to study entry with use of an antilipemic agent (atorvastatin, fenofibrate)
History of hypertriglyceridemia with triglyceride levels > 200 mg/dl; patients with triglyceride levels < 200 receiving treatment for hypertriglyceridemia or hyperlipidemia are considered eligible
Patients with high-risk uterine leiomyosarcoma (LMS), Federation of Gynecology and Obstetrics (FIGO) stage I (confined to corpus +/- cervix); patients with known uterine serosa involvement are not eligible; patients should have had, at least, a complete hysterectomy (including removal of the cervix); bilateral salpingo-oophorectomy is not required \r\n* Institutional pathology review calls the uterine leiomyosarcoma “high grade”\r\n* Additionally, if the pathology report indicates a mitotic rate, the mitotic rate should be greater than or equal to 5 mitoses/10 high-power field\r\n* All patients must be no longer than 12 weeks (3 months) from surgical resection of cancer at the time of enrollment on study; if a patient requires a second operation to complete her surgery, i.e., trachelectomy to remove the cervix and/or bilateral salpingo-oophorectomy (BSO), the 12 weeks may be counted from the time of the second operation\r\n* Patients who had a “morcellation” hysterectomy procedure that involved morcellation within the peritoneal cavity are eligible IF a second operation is performed and biopsies from the second procedure show no evidence of leiomyosarcoma
Patients who have met the pre-entry requirements specified
Patients participating through United States (U.S.) sites must sign an approved and authorization permitting release of personal health information
Patients who have had prior therapy with docetaxel, gemcitabine hydrochloride, or doxorubicin hydrochloride at any time in their history
Patients with recurrent uterine LMS
Known deleterious germline mutation of BRCA1/2 (Patients in Cohorts A and A1)
Consultation, agreement, and documentation in the patient’s chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol
Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN’s that contain some secondary (minor) foci of adenocarcinoma are also not eligible
ANC: for patients with lymphoma ?750/mm3 (?0.75 × 10^9/L), for patients with advanced solid tumors ?1,000/mm3 (?1.0 × 10^9/L),
Patients must be offered the opportunity to participate in specimen banking for future use
Patients with multiple or multifocal GBM
MF PATIENTS: Patients must have a confirmed diagnosis (by blood or bone marrow) of myelofibrosis (MF), as defined by WHO criteria\r\n* NOTE: if diagnosis was performed an outside facility, a copy of the report is sufficient for registration purposes; however, local pathology review at one of the main sites should still be obtained
MF PATIENTS: Patients must be intermediate I risk or beyond and meet the following:\r\n* In need of treatment\r\n* Intolerant or refractory to ruxolitinib (or other investigational Janus kinase [JAK]-inhibitors) OR unlikely to benefit from ruxolitinib\r\n* Ineligible or refusal to undergo stem cell transplantation
MF PATIENTS: Patients must have an ECOG status 0-2
MF PATIENTS: ALT/AST =< 2.5 x ULN
Patients who have received any investigational products, antineoplastic therapies, or radiotherapy within 14 days prior to registration are not eligible; NOTE: patients actively receiving hydroxyurea are eligible and may continue to receive hydroxyurea through cycle 1 of protocol treatment; if the platelet count remains above 1 million after cycle 1, hydroxyurea can be used at the treating physician’s discretion, if the platelets are 1000 x 10^9/L, or more, or if there are symptoms from thrombocytosis
Patients who have a requirement for constant administration of proton pump inhibitor, histamine-2 (H2) antagonist, or pancreatic enzymes are not eligible; intermittent usage of antacids or H2 antagonists are allowed
Patients BRAF mutation status must be known
Patients are excluded if they have known involvement of melanoma within the gastrointestinal tract
Patients must not be receiving erythroid stimulating agents (EPO: Procrit, Aranesp)
Serum potassium >= 3.5 mEq/L\r\n* Hypokalemia can be managed and corrected at the physician’s discretion; patients who have hypokalemia must have a repeat serum potassium level drawn within 7 days before starting study drug; patients with a supported potassium level at >= 3.5 can be considered eligible at the physician’s discretion
Patients with synchronous colon cancers are eligible and staging for stratification will be based on higher N stage of the more advanced primary tumor; however, patients with synchronous colon and rectal primary tumors are not eligible
Hepatitis B + patients may be enrolled at the discretion of the investigator
Applies only for patients without the deletion 5q 31.1; patients must have failed treatment with an erythropoietic growth factor, or have a low probability of response to rhu-erythropoietin; patients with low probability of response to rhu-erythropoietin or prior erythropoietin failures are defined as follows:\r\n* Prior erythropoietin failure-requires a minimum trial of >= 40,000 units epoetin alfa/week x 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks with failure to achieve transfusion independence in dependent patients or a failure to achieve a >= 2 g rise in hemoglobin sustained for >= 4 weeks in non-transfusion dependent patients\r\n* Low erythropoietin response profile-rhu-erythropoietin and epoetin alfa-naïve patients receiving >= 2U packed (p)RBC/month for a minimum of 8 weeks, and serum erythropoietin > 500 mU/mL in the 8 weeks prior to randomization for a hemoglobin < 9.5 g/dL
Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/mL
Patients must have completed 16 weeks of monotherapy with lenalidomide
Patients must show failure to achieve MER (major erythroid response) or have achieved MER but relapsed on Arm A
Primary refractory patients will be eligible if, on day 14 of their previous chemotherapy regimen, they have significant residual disease; patients who received only hypomethylating agent or low dose therapy for Induction are not considered primary refractory for purposes of this study and are not eligible
Patients enrolled on the expansion portion of the study will consist of two cohorts: those patients who are triple-negative, BRCA-mutant positive and those patients who have triple-negative, non-BRCA mutated breast cancer
Patients aged >= 50 and < 75 years (yrs) with CMML, or previously untreated MDS or MPD
Patients < 12 yrs of age must be discussed on a case by case basis with the primary investigator (PI) of the protocol prior to registration
MPD: Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to postpolycythemic marrow fibrosis
MPD: Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis
Paroxysmal nocturnal hemoglobinuria (PNH): Patients with the non-aplastic form of PNH (cellular bone marrow) who have had a history of life-threatening complications of their disease including thrombotic events, severe hemolysis or Budd Chiari syndrome are eligible; other patients may be considered following approval at PCC and approval by the Principal investigator
As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients receiving erythropoiesis-stimulating agents or other hematopoietic growth factors.
SUB-PROTOCOL AIM A: Patients who required therapeutic doses of anticoagulants
Patients must be suitable for and willing to undergo a radical prostatectomy at the completion of study therapy
Patients with known proliferative and/or vascular retinopathy;
Patients with adenocarcinoma of unknown primary are excluded
Patients with a diagnosis of two co-existing primary cancers are excluded
Metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are not eligible.
Patients must have:
Patients not considered in the opinion of the investigator eligible, or patients unwilling to undergo intensive salvage therapy including ASCT
Patients who have:
Patients who:
Patients with:
Patients must have a GOG performance status of 0 or 1.
Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.
Patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) are allowed to have prior mFOLFIRINOX in combination with BBI608 in the metastatic setting.
Patients enrolling onto Arm B (mFOLFIRINOX) are allowed to have prior Gemcitabine with nab-Paclitaxel in combination with BBI608 in the metastatic setting.
Patients with neuroendocrine neoplasms will be excluded.
For patients enrolling onto Arm B (mFOLFIRINOX) or Arm C (FOLFIRI)
For patients enrolling onto Arm D (MM-398 with 5-FU and leucovorin)
Patients must have progressed on abiraterone and/or enzalutamide.
Patients must have the ability to understand, and have signed an approved ICF
For inclusion in Cohort 1, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide but must not have previously received taxane-based systemic chemotherapy for mCRPC (previous treatment with six cycles of docetaxel for metastatic castration-sensitive prostate cancer (mCSPC) is permissible). NOTE: patients receiving fewer than 2 cycles of taxane based regimen due to intolerance are eligible for cohort 1.
For inclusion in Cohort 2, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide and must have progressed subsequent to receiving ? 2 cycles of a taxane-based regimen for mCRPC.
Patients who have had a local MGMT testing that is unmethylated are not allowed to participate
Inclusion Criteria: (For all patients unless otherwise specified)\n\n          -  Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to\n             definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR\n             mutant NSCLC.\n\n          -  Patients with controlled brain metastases\n\n          -  ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1\n\n          -  Presence of at least one measurable lesion according to RECIST 1.1\n\n          -  Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to\n             take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on\n             antiviral therapy for at least 4 weeks after the last dose of EGF816\n\n          -  Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but\n             undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible\n             for the study.\n\n          -  For Phase I: patients must have failed no more than 3 lines of any systemic\n             antineoplastic therapy for advanced NSCLC, including EGFR-TKI\n\n          -  For Phase II: patients must be naïve from any systemic antineoplastic therapy in the\n             advanced setting. Patients who have failed no more than 1 cycle of systemic\n             antineoplastic therapy in the advanced setting are allowed.\n\n        Exclusion criteria: (Applies to all patients unless otherwise specified)\n\n          -  Patients with a history or presence of ILD or interstitial pneumonitis, including\n             clinically significant radiation pneumonitis (i.e. affecting activities of daily\n             living or requiring therapeutic intervention)\n\n          -  Presence or history of another malignancy\n\n          -  Undergone a bone marrow or solid organ transplant\n\n          -  Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not\n             mandatory)\n\n          -  Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use\n             at the time of study entry except for control of brain metastases, topical\n             applications, inhaled sprays, eye drops or local injections\n\n          -  Patients with clinically significant, uncontrolled heart disease\n\n          -  Any prior therapies ? 4 weeks prior to the first dose of study treatment\n\n          -  Patients who are receiving treatment with medications that are known to be strong\n             inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the\n             start of EGF816 treatment and for the duration of the study.\n\n          -  Patients who have impairment of GI function or GI disease that may significantly alter\n             the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled nausea, vomiting,\n             diarrhea, or malabsorption syndrome)\n\n          -  Patients who are receiving treatment with any enzyme-inducing anticonvulsant that\n             cannot be discontinued at least 1 week before first dose of study treatment, and for\n             the duration of the study\n\n          -  Women of child-bearing potential, defined as all women physiologically capable of\n             becoming pregnant, unless they are using highly effective methods of contraception\n\n          -  Sexually active males unless they use a condom during intercourse while taking drug\n             and for 3 months after stopping treatment Other protocol-defined inclusion and\n             exclusion criteria may apply.
CD30 immunohistochemical staining using the anti-CD30 Becton Dickinson monoclonal (BerH2) antibody must be available on the most recent biopsy specimen; during dose escalation, patients can be either CD30 positive or CD30 negative; during dose expansion, 15 patients must be CD30 positive and 15 patients must be CD30 negative
EXCLUSION FOR COLLECTION OF T CELLS/PBMCS: Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation
EXCLUSION FOR TREATMENT: Patients will be excluded if they have isolated extra-medullary relapse of ALL
EXCLUSION FOR TREATMENT: Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient’s ability to endure known side effects of cytokine release syndrome or neurologic toxicity
Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; patients with known AIDS will be ineligible for this protocol; patients with clinical suspicion of AIDS and who are unwilling to have an HIV test are not eligible for this trial
Patients whose insurance will not cover proton therapy will still be eligible for the study
Patients must have:
Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans (Refer to Appendix 3)
Patients deemed to have mild hepatic impairment should not be considered for this study; patients with a direct bilirubin level greater than 2.0 mg/dL at screening should be excluded
Patients with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field; the boost volume must be limited to < 50% of the ipsilateral lung volume
Patients who have recovered from exploratory thoracotomy
Patients must have an EKG and ECHO or MUGA scan prior to entering the study.
Patients with simultaneous primaries or bilateral tumors.
Patients with non-secretory MM or known amyloidosis are not eligible
Patients must have baseline skeletal survey (whole body x-ray) to document lytic lesions, osteopenia or compression fracture
Patients must be offered participation in banking of specimens for future research; with the patient’s consent, specimens (serum and bone marrow biopsy core) must be submitted to the repository; patient consent must be obtained before specimens are submitted
Patients with AML\r\n* Patients with therapy-related myeloid neoplasms are allowed\r\n* Patients with AML that has evolved from an antecedent hematologic disorder are allowed\r\n* Patients will be eligible regardless of their ultimate plans or candidacy for allogeneic stem cell transplant
Patients must have been treated with 1-2 courses of therapy as first therapy for AML, commonly described as remission induction; examples include, but are not limited to:\r\n* Anthracycline containing regimens\r\n* Nucleoside analogs as monotherapy or in combination\r\n* Deoxyribonucleic acid (DNA) methyltransferase inhibitors
Patients in CRi must have evidence of hematologic recovery after prior therapy to at least: absolute neutrophils >= 0.8 x 10^9/L
Patients in CRi must have evidence of hematologic recovery after prior therapy to at least: platelets >= 75 x 10^9/L
Patients in CRi must have evidence of hematologic recovery after prior therapy independent of red blood cell transfusions
Patients who have met the pre-entry requirements
Patients who do not have GTN
Patients with non-gestational choriocarcinoma
Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4
Patients whose circumstances at the time of study entry do not permit completion of the study or required follow-up
Patients with a history of other malignancies treated curatively greater than one year prior to enrollment and without evidence of relapse at the time of enrollment are eligible
B-ALL patients must be enrolled on AALL08B1 or APEC14B1 (if open for the classification of newly diagnosed ALL patients) prior to treatment and enrollment on AALL0932\r\n* Note: B-LLy patients are not eligible for AALL08B1, and can enroll directly onto AALL0932
Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible\r\n* Note: for B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted
Patients with porphyria are not eligible
Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Patients with previously documented macular degeneration or diabetic retinopathy
Patients previously treated with irinotecan-containing regimen
One of the following pathologic T-classifications: pT2 or pT3\r\n* Patients with positive surgical margins are eligible
Patients must have a histologically proven diagnosis of endometrioid endometrial adenocarcinoma by endometrial curettage or biopsy within 8 weeks prior to registration; central pathology review will be required as part of the study but not for registration purposes
Patients must not be currently taking or have ever taken vorinostat (Zolinza, Merck), panobinostat (Farydak, Novartis) or romidepsin (Istodax, Gloucester Pharmaceuticals)
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Diagnostic stereotactic biopsy: Patients diagnosed with DIPG may choose to have a stereotactic biopsy prior to starting radiation therapy.
Screening for Rb applies to all patients with available tissue except for patients diagnosed with DIPG and bi-thalamic tumors.
Patients with a diagnosis of oligodendroglioma or oligoastrocytoma are not eligible.
Patients diagnosed with DIPG: any variances in the radiotherapy dose within 10% of the current standard dose (54 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment
Patients diagnosed with HGG: any variances in the radiotherapy dose within 10% of the current standard dose (59.4 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.
Patients diagnosed with primary spinal tumors any variances in the radiotherapy dose within 10% of the current standard dose (54 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.
Female patients with infants must agree not to breastfeed their infants while on this study.
Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer with documented disease progression (disease not amendable to curative therapy); histologic confirmation of the original primary tumor is required via the pathology report; NOTE: patients with mucinous histology are NOT eligible; patients with carcinosarcoma histology are NOT eligible
Patients must have:
Activated Partial Thromboplastin Time (APTT) patients beeing treated with anticoagulants are excluded if teh coagulation parameters are outside the therapeutic intervals as described in the SmPC/USPI for the administered treatment
Patients with phaeochromocytoma.
Patients who have received hematopoietic growth factor support within 14 days of day 1 of ibrutinib; patients who are Jehovah’s witnesses may be given an erythropoiesis-stimulating agent before and during the trial in lieu of red blood cell transfusions but anemia and/or red blood cell (RBC) transfusion dependence cannot be used for response assessment in these patients
Patients with the factor interacting with poly(A) polymerase alpha (PAPOLA) and cleavage and polyadenylation specific factor 1 (CPSF1) (FIP1L1)-platelet-derived growth factor receptor, alpha polypeptide (PDGFRalpha) fusion even with resistance to imatinib (such patients are no longer defined as systemic mastocytosis by the WHO)
Patients with concomitant primaries of the bladder/urethra are allowed, as long as these sites are surgically resected and non-invasive cancers (< cT1N0)
Patients with medical conditions precluding leukapheresis
Patients should not be eligible or able to receive approved therapy of confirmed clinical benefit in this patient population
T1 patients need to have evidence of muscle included in their latest biopsy; and if not a re-TURBT has to be done prior to enrollment
Eligible patients must have appropriate staging studies identifying them as specific subsets of the revised International Association for the Study of Lung Cancer (IASLC) stage IA based on the following combination of Tumor Node Metastasis (TNM) staging: T1a,N0,M0 or T1b,N0,M0
Patients with primary tumors > 3 cm
Patients must be post-menopausal women, as defined in the protocol
Patients with endometrial disorders, including evidence of endometrial hyperplasia, dysfunctional uterine bleeding or cysts
Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g., *6)
Patients with relapsed or refractory AML\r\n* Patients without a response after two cycles of a 10-day course of decitabine\r\n* Patients with primary refractory AML (persistent disease after standard induction with 7+3) or relapsed AML\r\n* Patients who have relapsed post-allogeneic transplant
Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
Patients must have pathologically confirmed GIST
Eligible patients must have histopathologically confirmed myxoid liposarcoma with confirmation of DDIT3 rearrangement
Patients who have met the pre-entry requirements specified in Section 7.0
Patients must be able to follow concomitant medication restrictions:
known or suspected past hepatitis C infection (including patients with past interferon 'curative' treatment),
body piercing or tattoos. At the discretion of the investigator, additional patients may also be tested for hepatitis C.
For patients with LM: Confirmed diagnosis of LM by positive CSF cytology.
For patients with LM and/or BM, CNS complications that require urgent neurosurgical intervention
Patients that have received prior taxane-based chemotherapy or abiraterone in any setting will not be eligible for the expansion cohort. Additional exclusion criterion for patients undergoing tumour biopsy:
Age > or equal to 60 years; patients younger than 60 who are unsuitable for or unwilling to receive standard cytotoxic chemotherapy are also eligible to be enrolled
Patient must be willing to undergo biopsies as specified by the protocol; the biopsy requirement can only be waived if deemed unsafe by the patient’s treating physician or the principal investigator (PI)
Patients with compression of the optic chiasm due to a macroadenoma or patients at high risk of compression of the optic chiasm (tumor within 2 mm of optic chiasm).
Patients who are not euthyroid as judged by the investigator.
Patients must have BRAFV600E mutation
Patients (at institutions listed) must be offered the opportunity to participate in the optional S1406 Co-Clinical PDX Model trial; participating patients must have a fresh tissue biopsy for the Co-Clinical PDX Model Trial completed within 7 days of Step 2 Randomization
Biopsy of a metastatic lesion is not required for protocol entry but all patients with reasonably accessible lesions (chest wall, breast, skin, subcutaneous, superficial lymph nodes, bones and liver metastases) must agree to biopsy (lung and brain metastasis will not be biopsied):\r\n* Biopsies may be done with local anesthesia or intravenous conscious sedation, according to standard institutional guidelines\r\n* If a biopsy requires general anesthesia, then it is only allowed if acquisition of tissue is necessary for clinical reasons (i.e. is clinically indicated), and excess tissue that would otherwise have been discarded is then used for research purposes; if a biopsy requires general anesthesia, then a biopsy of that site for research purposes only, without a coexisting clinical indication is not allowed on this protocol\r\n* Patients with reasonably accessible lesions as described above, who will not agree with the biopsy, will not be enrolled in the trial\r\n* Patients with NO reasonably accessible lesions as described above can be enrolled in the trial
Patients may receive bisphosphonates; however, if used, bone lesions may not be used for progression or response
Patients who have exhibited hypersensitivity reactions to regorafenib and/or a structural compound, biological agent, or formulation (e.g., sorafenib)
At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator’s discretion
Immunocompromised patients
Patients actively receiving insulin are excluded unless approved by the IND medical monitor, the IND sponsor, and the treating radiation oncologist
Patients who underwent an R2 resection are not eligible
Patients with wounds that have not fully healed are not eligible
No patients being decisionally impaired
Decisionally impaired patients
Patients with ASM and MCL with or without an AHNMD are required to have at least one of the eligible organ damage findings as defined by the international consensus response criteria
Patients presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (e.g. AML)
Patients with the FIP1L1-PDGFRalpha fusion even with resistance to imatinib (such patients are no longer defined as systemic mastocytosis by the WHO)
Patients must have a site of metastatic disease that can be safely resected or biopsied for tissue sufficient for TIL harvest
Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment; patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam will be eligible
Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
Patients treated with TNF antagonists.
Patients (with skin metastases only) who will be therapeutically anticoagulated with heparins or Coumadin at the time of the biopsy (they are eligible if anticoagulation can be held prior to biopsy as per investigator); patients on aspirin and other platelet agents are eligible
Patients with any of the following constitutional conditions are not eligible:\r\n* Fanconi anemia\r\n* Shwachman syndrome\r\n* Any other known bone marrow failure syndrome\r\n* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 \r\nNote: enrollment may occur pending results of clinically indicated studies to exclude these conditions
Patients must not be pregnant or lactating as chemotherapy is thought to present substantial risk to the fetus/infant
Patients with serious non-healing wounds, ulcers, or bone fractures
Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)
Patients will be staged for risk classification and treatment at diagnosis using Children's Oncology Group (COG) staging guidelines
Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
Patients with Gleason score >= 8; PSA > 20; OR clinical stage >= T3 are ineligible for this trial\r\n* Should findings of extracapsular extension or seminal vesicle invasion be noted on prostate MRI, this study, if used, will not render patients ineligible for accrual to this protocol; primary tumor staging for eligibility purposes is to be based on palpable or core biopsy evidence only with respect to extracapsular extension or seminal vesicle involvement
At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion
Patients with a known or suspected urea cycle or other metabolic disorder are not eligible
Patients with abnormality of the tibial metaphyseal plate on plain x-ray prior to study entry are not eligible
Patients must be considered unresectable or inoperable. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
Eligible patient must show evidence of wild-type (WT) p53 as assessed by central DNA sequencing conducted at Dr. Jeffrey Sklar’s laboratory at Yale University Cancer Center; note, that since patients with AML have a rapidly proliferating disease, patient can be enrolled and begin treatment prior to obtaining the results of this test; patients who are found to the TP53 mutated will be removed from study and can continue on single agent decitabine; however patients will continue to be followed for toxicity
Patients with previously untreated AML with core binding factor (CBF) chromosomal aberrations (inv[16]/t[16;16] or t[8;21]); Note that patients with relapsed or refractory AML with CBF chromosomal aberrations will be eligible
Patients with known TP53 mutations or chromosome 17 or 17p deletions
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: \r\n* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations \r\n* Rash must cover less than 10% of body surface area (BSA) \r\n* 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%, alclometasone dipropionate 0.05%) \r\n* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
Patients having out of range values for:
Treatment naive patients in first-line or pre-treated patients with no more than 2 lines of prior therapy
Dose Escalation: Patients with relapsed or refractory AML
Dose Expansion: Patients with relapsed AML or patients who refuse, or are not suitable candidates for induction therapy
Patients refractory to ublituximab + TGR-1202
Patients with any form of active primary or secondary immunodeficiency.
Patients with ocular melanoma.
Patients with adrenal insufficiency or patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Local steroid therapies (eg, otic, ophthalmic, intraarticular, or inhaled medications) are acceptable
Patients with co-morbidities that would make the use of radiation too toxic to deliver safely, such as serious local injury or collagen vascular disease
Patients whose screening renal biopsies for RAIN show dominant causes of renal damage not related to AL amyloidosis
Patients must have pathologically confirmed GIST
In the dose expansion portion of the phase I study, patients must have locally advanced, unresectable or metastatic GIST that is resistant to imatinib; this population includes patients who have not been treated with imatinib (imatinib naive) but considered to have primary resistance to imatinib, i.e. KIT/PDGFRA wild-type GIST, and patients with imatinib-refractory disease, i.e. has had prior treatment with imatinib
Patients with previous solid and hematologic tumors, that have been treated with no evidence of recurrence within the last 5 years, are permitted.
Patients with steroid myopathy.
Patients who have uterine sarcomas, carcinosarcomas, serous tumors (any component) or pure clear cell carcinomas.
Patients must have histopathological confirmation of pancreatic adenocarcinoma prior to entering this study
Presence of more than 55% pro-lymphocytes in peripheral blood; patients with Richter’s transformation are not excluded
Patients who have a known dasatinib-resistant ABL-kinase mutation such as T315I are not eligible; for confirmation, please contact PI
Able to receive ibrutinib through commercial supply, i.e., insured patients meeting Food and Drug Administration (FDA)-approved indications
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients who are undergoing concomitant radiotherapy are NOT eligible for participation
Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off such medications by the time of registration
Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator in consultation with the ophthalmologist.
Patients with any type of recurrent pancreatic adenocarcinoma
Patients with uncontrolled diarrhea or persistent nausea/vomiting requiring daily antiemetic therapy for symptom management within the past 21 days
All patients with gastroenteropancreatic NETs must have progressed on (or are intolerant of) prior somatostatin analog
Patients with pancreatic NETs must have progressed on (or are intolerant of) either everolimus or sunitinib
Institutions must offer patients the opportunity to submit tissue for future correlative studies
Patients must have at least 3 distinct metastatic sites with at least one measurable lesion which is at least 1 cm or larger in largest diameter
Patients must have negative tests (antibody and/or antigen) for hepatitis viruses B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
Patients receiving cyclosporine A, tacrolimus, or sirolimus are not eligible for this study.
Patients with 17p deletion can only be enrolled on Arm C; these patients will receive the expanded T cells without lymphodepleting chemotherapy
Any patients with infratentorial tumors
Patients will have at least one melanoma deposit that can undergo serial biopsy (at least 2 time points) during the neoadjuvant phase of the protocol; patients must be willing to provide tumor samples at the time points specified in the Study Procedure Tables
Patients must have a diagnosis of a chronic GVHD according to the National Institute of Health (NIH) Consensus Criteria
The expanded cohort will consist of predominantly (> 50%) p53 mutated HNSCC patients at the MTD
Pre-existing hearing impairment (patients who are willing to accept risk of further impairment will be considered after audiologic testing)
Patients with electronic pacemakers or defibrillators are excluded from this study, as the effect of electroporation on these devices is unknown; patients with lower extremity lesions may be discussed with the medical monitor
Patients with acute GVHD grade II-IV
Major inclusion criteria:\n\n          1. A histologically or cytologically confirmed solid tumor that is locally advanced,\n             recurrent, or metastatic; for which curative resection is not currently possible; and\n             for which systemic treatment with one of the selected anti-cancer agents is a\n             reasonable therapeutic option.\n\n          2. Must be ? 18 years of age\n\n          3. Has disease such that progression or response to therapy can be evaluated objectively\n             while on protocol.\n\n          4. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n\n          5. Male or female patients of childbearing potential must agree to use contraception or\n             avoidance of pregnancy measures during the study and for 30 days after the last dose.\n\n          6. Females of childbearing potential must have a negative serum pregnancy test.\n\n          7. Must have aspartate transaminase (AST) ? 2.5 × upper limit of normal (ULN) and alanine\n             transaminase (ALT) ? 2.5 × ULN. Patients who do not have hepatocellular carcinoma but\n             who have liver lesions or liver metastases may be eligible if AST ? 3.5 × ULN and AST\n             ? 3.5 × ULN if agreed upon by the investigator and medical monitor for the sponsor.\n\n          8. Hemoglobin (Hgb) ? 9 g/dl\n\n          9. Total bilirubin ? 1.5 × ULN. For patients with liver lesions, total bilirubin ? 2.0 ×\n             ULN may be enrolled if agreed upon by the investigator and medical monitor for the\n             sponsor\n\n         10. Creatinine ? 1.5 × ULN or creatinine clearance ? 60 mL/min/1.73 m^2 for patients with\n             creatinine levels above institutional upper limit of normal (using the Cockcroft-Gault\n             equation).\n\n         11. Absolute neutrophil count ? 1.5 × 10^9/L\n\n         12. Platelets ? 100 × 10^9/L\n\n         13. Life expectancy ? 3 months\n\n        Major exclusion criteria:\n\n          1. Received anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational\n             agents within 7 days of first dose of protocol therapy. Patients may begin protocol\n             therapy on a date determined by the investigator and medical monitor for the sponsor\n             after a minimum of 7 days since last receiving anti-cancer treatment, provided that\n             all adverse events related to that have resolved or have been deemed irreversible.\n\n          2. Major surgery within 4 weeks prior to first dose; major surgery is defined as a\n             procedure requiring any of the following: general anesthesia, intubation and\n             mechanical ventilation, or major incision (e.g., thoracotomy, laparotomy)\n\n          3. Any known, untreated, brain metastases. Patients with treated brain metastases must\n             have no clinical symptoms from the metastases, and must be either off steroids or on a\n             stable dose of steroids ? 10 mg prednisone or equivalent for at least 2 weeks prior to\n             protocol enrollment. Patients with known leptomeningeal metastases are excluded, even\n             if treated.\n\n          4. Pregnant or breastfeeding or expecting to conceive or father children within the\n             projected duration of the study.\n\n          5. Significant gastrointestinal disorder(s), in the opinion of the Principal\n             Investigator, such as active inflammatory bowel disease, extensive gastric or small\n             intestinal resection (which has resulted in short-gut syndrome or the inability to\n             take oral medications).\n\n          6. Unable or unwilling to swallow either BBI503 daily or an oral selected anti-cancer\n             therapeutics; or, unwilling to receive intravenous injection of IV anti-cancer\n             therapeutics.\n\n          7. Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface\n             Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid\n             (HCV RNA] (qualitative) is detected).\n\n          8. Uncontrolled concurrent illness including, but not limited to: ongoing or active\n             infection requiring therapy, clinically significant non-healing or healing wounds,\n             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,\n             significant pulmonary disease (shortness of breath at rest or on mild exertion),\n             uncontrolled infection or psychiatric illness/social situations that would limit\n             compliance with study requirements\n\n          9. Subjects with a history of another primary cancer with the exception of: a) curatively\n             resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;\n             c) localized prostate cancer not requiring systematic therapy; and d) other primary\n             cancer with no known active disease present, and no treatment administered in the 2\n             years prior to enrollment.\n\n         10. For patients to be treated with a regimen containing capecitabine: a) Known\n             hypersensitivity to capecitabine, b) Known dihydropyrimidine dehydrogenase (DPD)\n             deficiency, c) Significant gastrointestinal disorder(s) that would, in the opinion of\n             the Investigator, prevent absorption of an orally available agent\n\n         11. For patients to be treated with a regimen containing sunitinib: a) Uncontrolled\n             hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg\n             despite optimal medical management), b) Evidence of bleeding diathesis or a clinically\n             significant coagulopathy (? CTCAE Grade 3) within 4 weeks prior to the start of study,\n             c) Recent hypoglycemia, d) Uncontrolled thyroid dysfunction despite optimal medical\n             therapy\n\n         12. For patients to be treated with a regimen containing doxorubicin: a) Known left\n             ventricular ejection fraction < 50%, b) Hypersensitivity to doxorubicin\n\n         13. A patient to be treated with a regimen containing nivolumab or pembrolizumab will be\n             excluded if the patient: a) Has an active autoimmune disease requiring\n             immunosuppression with the exception of subjects with isolated vitiligo, resolved\n             childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism,\n             and euthyroid patients with a history of Grave's disease, b) Has had a previous\n             life-threatening (CTCAE grade 4) immune-mediated adverse reaction; or, a previous\n             severe (CTCAE grade 3) immune mediated adverse reaction that required treatment with\n             corticosteroids (more than 10 mg/day prednisone or equivalent dose) for longer than 12\n             weeks, c) Has a transplanted organ, d) Has interstitial lung disease or active,\n             non-infectious pneumonitis, e) Has received a live vaccine within 30 days prior to\n             first dose, f) Previous severe hypersensitivity reaction to another monoclonal\n             antibody (mAb), g) Has been treated with another monoclonal antibody ? 4 weeks before\n             first dose.
Patients must be at least 18 years old.
Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant, or patients who are breastfeeding are not eligible for this trial.
Patients must have relapsed or become refractory to conventional therapy, with a regimen including some combination of high dose methotrexate, doxorubicin, cisplatin, ifosfamide and etoposide; and have had histologic verification of osteosarcoma at original diagnosis or at the time of recurrence
Patients receiving bisphosphonates
Patients with chronic non-T-cell-based lymphocytic leukemia are eligible if they have isolated lymphocytosis (Rai stage O) on the condition that they do not require systemic treatment for their disease [\B\ symptoms, Richter's transformation, lymphocyte doubling time (<6 months) and they do not have lymphadenopathy of hepatosplenomegaly].
Patients on immunosuppressants, systemic corticosteroids, or any other investigational product.
Patients who have undergone a diverting tracheostomy which is either a) traversing directly through tumor, b) has been placed for true airway insufficiency; patients with a tracheostomy placed preemptively for impending airway compromise remain eligible for enrollment
Patients receiving a haploidentical / T cell-depleted transplant are eligible to follow a modified treatment plan that does not include withdrawal of immunosuppression
Patients with Fanconi anemia or other cancer-predisposition syndromes
Patients with expected survival < 12 weeks
Aged at least 18 years. Japan patients aged at least 20 years.
Patients must have central lab confirmation of tumour T790M status from a biopsy taken after disease progression on the most recent treatment regimen. Only patients with T790M+ will be included in the study
Patients for whom the delivery of APBI is not feasible or any of the dosimetric treatment criteria have not been met
Breast implants (patients who have had implants removed are eligible)
Patients who have received trabectedin (Yondelis, ET-743) or participated in the phase III clinical study of trabectedin NCT01343277 previously will not be eligible
Patients are eligible upon progression after definitive local treatment (usually concurrent chemoradiation) if they are not candidates for salvage surgery or re-irradiation; patients are also eligible after progression on first line chemotherapy for recurrent disease
Patients on anticonvulsant therapy may continue these at the discretion of their treating physician; however, it is recommended that anticonvulsant levels be checked periodically as clinically indicated if possible
Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (i.e. filgrastim, sargramostim); two weeks must have elapsed if patients received polyethylene glycol (PEG) formulations
Patients with a history of non-central line related thrombosis, more than one prior central-line related thrombosis, or known coagulopathy will not be eligible; patients with a first degree family member with a known coagulopathy will be excluded, and therefore, obtaining a family history is essential when possible; patients actively on anticoagulation therapy are not eligible
Patients who have received pomalidomide in the past are not eligible; patients who have prior treatment with other immunomodulatory drugs (IMiDs) (thalidomide, lenalidomide) ARE eligible if they meet all other eligibility criteria and did not have \significant toxicity\ associated with lenalidomide or thalidomide use; a “significant” toxicity will be defined as one that required a dose reduction or discontinuation due to toxicity; please discuss any questions with the PI
Patients that are considered candidates for ipilimumab therapy
Patients with known sensitivity to retinoic acid derivatives
Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision is not permitted as part of the protocol and any patients given this treatment would be excluded from the study.
Patients with pheochromocytoma
Patients unable to ambulate or who have amputations or paralysis of any extremity
Patients who have received TOK-001 (Galeterone®) or any other investigational product directed towards the androgen receptor or androgen biosynthesis.
Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma (NPC) that has recurred at locoregional and/or distant sites; NOTE: patients with local recurrence at the bony skull-base as the only site of index disease are excluded; patients with locoregional recurrence without distant metastases must have undergone radical radiotherapy previously
Concomitant medications:\r\n* Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)\r\n* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible\r\n* Patients who are currently receiving another investigational drug are not eligible\r\n* Patients who are currently receiving other anti-cancer agents are not eligible\r\n* Patients who are currently receiving the enzyme inducing anticonvulsants: phenytoin, phenobarbital, carbamazepine, oxcarbazepine are not eligible; patients who are currently taking rifampin, voriconazole, itraconazole, ketoconazole, aprepitant, or St. John’s Wort are not eligible\r\n* Use of warfarin is not allowed while on study; patients already on warfarin should use alternative anticoagulants while on this study; warfarin must not have been administered within 7 days of starting protocol therapy\r\n* Patients receiving medications that prolong the QTc
Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1
Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease
Patients must not be eligible for a higher priority (e.g.; phase II/III), National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, and Gynecologic Oncology Group (NRG) protocol for the same population if one exists
Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible; patients with a history of hypothyroidism are eligible provided they are currently euthyroid
Patients must not be eligible for a higher priority NRG clear cell protocol (Gynecologic Oncology Group [GOG]-0283); rare patients ineligible for GOG-0283 may be eligible for this trial without prior treatment on dasatinib therapy (e.g. they have been deemed allergic to dasatinib)
Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
Patients must be able to tolerate lumbar puncture and/or Ommaya taps
Patients who have previously been unable to tolerate ceritinib, in the opinion of the investigator. Exceptions to this exclusion include nausea, vomiting and diarrhea in patients taking ceritinib under fasted conditions.
Patients need to have biopsiable disease to enroll on cohort 1-2; patients eligible for cohort 3 with a germline BRCA alteration can be enrolled even if they do not have biopsiable disease
Patients are to be treated with hypofractionated RT
Significant dermatological disease including, but not limited to, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg, blepharitis, cheilitis, cellulitis, cyst); exception: patients with grade =< 2 cetuximab-related rash, xerosis, fissures or paronychial inflammation are eligible
Patients who are currently enrolled on another clinical trial
Patients must be ipilimumab-eligible. (This includes: 1) patients previously untreated with ipilimumab; 2) patients previously treated (more than 1 year previously) with ipilimumab using a route of administration other than intravenous infusion; and 3) patients previously treated with antitumor agents other than intravenous ipilimumab).
Patients who were previously treated with ipilimumab administered by intravenous infusion.
Patients who had a stereotactic needle biopsy
Patients with macular degeneration, uncontrolled glaucoma or markedly decreased visual acuity
Patients who have been resistant to previous TKI therapy are not eligible
Participants who are receiving any other investigational agents\r\n* Patients who have previously received ibrutinib will be ineligible in the Phase Ib portion of the study of the CLL arm\r\n* MCL patients who have been on ibrutinib for less than 6 months (180 days) from the time of registration are eligible in the Ib portion of the trial; no washout will be required
Patients are allowed to have received prior treatment with mFOLFOX6; if patients are currently receiving treatment with mFOLFOX6, the subject must have documented disease progression; patients must also be able to tolerate standard mFOLFOX6; reduced dosing of mFOLFOX6 at enrollment is exclusionary
History of >= grade 3 allergic reaction to mFOLFOX6 (patients successfully desensitized to oxaliplatin are eligible or those willing to undergo desensitization during the first two cycles of mFOLFOX6 per institutional guidelines)
If needed, patients should be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation
Patients with cancer are eligible provided they meet the specifications
Patients may not smoke or plan to smoke tobacco or marijuana during study therapy
History of arterial thromboembolic (arterial blood clot) or hemorrhagic event with the exception of patients with pulmonary embolism stable on an anticoagulation regimen
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) or patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual [DSM]-IV) are not eligible; Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug\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 9-item (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)
Patients who have endometrial carcinosarcoma; patients with ovarian cancer who have histology other than high-grade serous in the absence of a deleterious BRCA mutation; if the patient has a deleterious BRCA mutation, any histology will be accepted
Patients must be eligible for radical cystectomy and refuse this standard of care treatment or not be a surgical candidate for radical cystectomy based on other comorbidities
Patients with single or multiple lung metastases at diagnosis or that develop over the course of treatment
Patients requiring a field size > 40 cm as IMRT cannot be performed at extended source-to-surface distances (SSDs)
Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity based on physician’s assessment
Patients with baseline corrected QT (QTc) prolongation greater than grade 1 are excluded from this study; patients with grade 1 QTc elevation are eligible but must be monitored with electrocardiogram (ECG) (EKG) exams, for the first 3 cycles of treatment; eribulin time to maximum concentration (Cmax) after infusion is about 10 minutes, and half life is 40 minutes; ECG (EKG) should be performed between 10 to 40 minutes after eribulin administration (on day 1 and day 8 of treatment); continued ECG (EKG) monitoring beyond cycle 3 can be done at the discretion of the treating physician
Patients with intolerance to sunitinib and/or regorafenib
Patients with transfusion-dependent thrombocytopenia are not eligible
Patients who are randomized to the control arm must not receive therapy based on prior molecular profiling
Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone)
This must be the patient’s FIRST mobilization attempt
Patients with nasopharynx or salivary gland primary site will be excluded from this trial
Patients with unresectable melanoma
Patients must have received a biologic therapy (interleukin 2 or ipilimumab) and a BRAF and/or MEK inhibitor (if tumor contains the V600E or V600K mutation) for metastatic disease; if patient did not receive such agents, rationale for not treating the patients with the agent must be cleared study principal investigator (PI) (ie no V600e/k BRAF mutation or patient with autoimmunity, thus not eligible for biologic therapy)
Patients with known macular degeneration or uncontrolled glaucoma
Patients who are pomalidomide refractory, defined as patients who progress on or within 60 days of pomalidomide when given as a single agent or with dexamethasone
Unilateral or bilateral retinoblastoma (RB) patients are eligible
Patients with phaeochromocytoma
Patients with pheochromocytoma
Primary refractory patients (never responded to any therapy) are eligible
Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity
Patients receiving concurrent corticosteroids for reason(s) other than for physiologic maintenance treatment; patients should otherwise discontinue corticosteroids prior to registration to study
Patients with Trisomy 21
Patients must have confirmation of DT/DF by local pathologist prior to registration
Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
Patients must have a minimum expected duration of survival of greater than 6 weeks as determined and documented by the attending surgeon or medical oncologist
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, pregnant or lactating females
Patients with active moderate or severe major mood or psychiatric disorder as judged by the investigator, primary care physician, counselor, psychiatrist, or as a result of the patient‘s mood assessment questionnaire that may interfere with the ability to comply with the trial; in addition, given the prior mood-associated toxicities, patients with a history of psychiatric hospitalization within the past 5 years, electroconvulsive therapy (ECT) within the past 5 years, or whose psychiatric condition has been unstable within 2 months prior to study enrollment requiring addition or change of psychotropic medications are not eligible; examples include, but are not limited to:\r\n* Medically documented history of or active major depressive episode requiring inpatient or intensive outpatient therapy, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or active ideation, or homicidal ideation (immediate risk of doing harm to others); patients under the care of a primary care physician who are treated with one oral agent and who have not required dose adjustments or new medications within 2 months prior to study enrollment and who otherwise meet eligibility requirements may be enrolled\r\n* >= Common Terminology for Adverse Events (CTCAE) version 4.0 grade 3 anxiety\r\n* Patients meeting the cutoff score of >= 12 in 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 who select 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) are not eligible
No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol
Patients with more than 6 discrete extra-cranial lesions
Patients should have any of the below to be eligible\r\n* Are not candidates for intracavitary brachytherapy due to poor geometry or poor response to external beam radiation therapy (RT)\r\n* Patients with co-morbid medical conditions, bleeding disorders, poor anesthetic risk precluding brachytherapy\r\n* Patients who refuse brachytherapy or prefer external beam hypofractionated approach\r\n* Patients requiring interstitial brachytherapy\r\n* Note: patients may be discovered during standard therapy and enrolled prior to boost
Patients with a history of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued are not eligible for participation
Patients having previously undergone splenectomy.
Patients with sickle-cell anemia or thalassemia major.
Patients with hypercalcemia (blood levels greater than 11.5 mg/dL) and/or abnormally high vitamin D levels (in patients with kidney disease, blood calcium levels must be 9.5 mg/dL or lower before starting paricalcitol)
Patients who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation
Patients with known active central nervous system leukemia should be excluded from this clinical trial; patient receiving intrathecal chemotherapy prophylaxis should not receive pomalidomide for >= 3 days after administration
For patients to be treated with a regimen containing 5-fluorouracil/leucovorin:
For patients to be treated with a regimen containing capecitabine:
For patients to be treated with a regimen containing oxaliplatin:
For patients to be treated with a regimen containing irinotecan:
For patients to be treated with a regimen containing bevacizumab:
For patients to be treated with a regimen containing regorafenib:
Patients with second malignancies may be eligible at discretion of principal investigator (PI) given acute life threatening nature of untreated AML or higher risk MDS; patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible
Patients who have not previously been treated with HMA therapy will be excluded
Patients on enzyme-inducing anticonvulsive agents are excluded
Phase Ib only:\r\n* Patients with metastatic rectal cancer are allowed if their primary site meets other eligibility criteria and chemoradiotherapy is recommended as initial therapy for symptom palliation by the multidisciplinary treating team\r\n* Patients with locally advanced unresectable rectal cancer are allow provided:\r\n** There is no evidence of recto-vaginal, recto-vesicular, recto-intestinal fisutalization\r\n** Standard dose and schedule chemoradiotherapy is recommended as initial therapy by the multidisciplinary treating team
Patients ? 16 years old
Patients smoking in excess of 2 packs of cigarettes per day
Patients with uncorrectable electrolyte abnormalities.
Patients with active inflammatory processes including T max > 101 or active tissue inflammation are excluded
Patients must not be on steroids other than for physiologic replacement
Patients with resected primary must be active participants of the NSABP Patient Registry and Biospecimen Profiling Repository (MPR-1) study. Patients with intact primary and metastatic KRAS wild-type disease at presentation (treatment naive), must have signed consent for quadruple wild-type central testing for treatment-naive tumor sample submission
Patients must have an accessible metastatic lesion for pretreatment core biopsy procurement.
Patients must have CA125 level >= 10 to participate in the immunotherapy aspect of the trial and receive oregovomab; if the patient has CA125 >= 10 who is not eligible to receive oregovomab (e.g. allergic to the drug) but is eligible for the rest of treatment, this patient should be accrued to the part of protocol without oregovomab
Patients who cannot undergo staging laparoscopy; for example, this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful; the patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy
Patients with a recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficiency’s, hypogammaglobulinemia or dysgammaglobulinemia
Patients are allowed to receive, but are not required to receive, one additional prior treatment regimen (including a single chemotherapeutic, a combination of chemotherapeutics, or biologic drugs such as bevacizumab) for management of their recurrent or persistent disease
At least one site of accessible disease for pre- and post-treatment core biopsies for at least 20 patients per arm on the expansion cohorts.
Patients who are curable by conventional multidisciplinary management.
Patients with unstable angina or serious arrhythmia
Patients must agree to have a biopsy at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
Patients who have previously provided samples at any time after trastuzumab resistance will be exempt from biopsy at the start of therapy
Patients who have had a simple hysterectomy (cut through hysterectomy)
Patients who have borderline resectable disease using National Comprehensive Cancer Network (NCCN) definition
Patients in whom iodine contrast is contraindicated
Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:\r\n* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular\r\nmanifestations\r\n* Rash must cover less than 10% of body surface area (BSA)\r\n* 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%)\r\n* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
COHORT II: Patients must not have >= grade 2 hearing deficits
Patients have CTC >= 3
Patients planned invasive dental procedures
Patients must have prior treatment with >= 2 cycles of lenalidomide and >= 2 cycles of bortezomib (either in separate regimens or as part of the same regimen) (primary refractory of subjects refractory to the most recent regimen are eligible)
Patients must have a Karnofsky performance status (KPS) >= 80% and be considered candidates for general anesthesia, hepatic resection and hepatic artery pump placement
Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon
Patients with a diagnosis of chronic hepatitis B are ineligible due to the possibility of immunosuppression on study treatment
Any condition that impairs patient‘s ability to swallow whole pills; patients with feeding tubes, intractable nausea or vomiting, or a malabsorption syndrome are not eligible
Patients on bisphosphonates and/or endocrine therapy are eligible
Patients who are simultaneously enrolled in other treatment studies
Patients with neuromuscular disorders that are associated with elevated CK
Patients with known BRAF^V600X mutation: patients must have BRAF^V600X mutated, histologically confirmed cancer that is metastatic or unresectable and for which curative or standard therapies do not exist or are no longer effective\r\n* NOTE: colorectal cancers with BRAF mutations ARE NOT allowed\r\n* NOTE: any mutation at the V600 position that results in a change from V (valine) is allowed; this includes E, D, K, R or other mutations not noted here at the V600 position
Patients with active biliary obstruction; NOTE: patients for which a shunt has been in place for at least 10 days prior to the first dose of dabrafenib are allowed
Patients who are eligible for curative treatment (ablation or resection or transplantation)
Patients must not have evidence of extensive or “matted/fixed” pathologic adenopathy on preoperative imaging
Patients receiving or participating on any other experimental agents/clinical trials are not eligible for participation
Patients with previously documented macular degeneration or diabetic retinopathy are ineligible
Patients must be unresponsive to androgen-deprivation therapy (ADT), as indicated by a rising PSA level above the ADT nadir
Patients must have been surgically or medically castrated; if the patient is being treated with medical castration, he must be willing to continue this treatment for the duration of the study; ADT should not be initiated, terminated, or dose-adjusted during the study
Patients who are pregnant or breast-feeding; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant
Patients should avoid CYP3A4 inhibiting foods including grapefruit and Seville orange juice
Histologic or cytologic diagnosis of SCLC (Note: patients with mixed histology are not eligible)
Patients who have been treated with abiraterone will be excluded
Patients who are already known homozygous for the UDP glycosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele, and patients of Asian descent homozygous or heterozygous for the UGT1A1*6 allele will be excluded
Patients on other experimental protocols for prevention of acute GVHD
Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on protocol 2660 is contraindicated for that patient the patient will be excluded from the protocol; patients with Gilbert’s syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the protocol
Patients with a significant other medical conditions that would make them unsuitable for transplant
All patients must have a baseline Mini Mental Status Examination score >= 21
All patients must be eligible to have either IMRT or IMPT as determined by the study radiation oncologist
All patients must be able to adequately read, write and speak to participate in the cognitive and quality of life assessments; however mild to moderate deficits in these functions due to tumor are allowed
Patients with gliomatosis will be excluded
Patients with Gliadel bis-chloroethylnitrosourea (BCNU) implanted wafers will be excluded
Patients weighing greater than 136 kilograms will be excluded
Patients must have a normal baseline ophthalmologic examination or have only clinically-insignificant abnormalities; patients with significant visual/ocular abnormalities identified during the baseline eye exam may be eligible after discussion with the study principal investigator (PI) and it is thought that the abnormalities pose no increased risk with study therapy
Patients who have not been tested within 3 months prior to starting adjuvant therapy must be tested for hepatitis B and hepatitis C serologies during study screening\r\n* Patients with positive hepatitis B or C serologies without known active disease must meet the eligibility requirements for ALT, AST, total bilirubin, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and alkaline phosphatase on at least two consecutive occasions, separated by at least 1 week, within the 30 day screening period
Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation; for Cohorts A and D patients must have progressed on, been intolerant to, or refused prior sorafenib therapy; Cohort E patients must have received at least one line of chemotherapy for BTC
Patients with undetectable HCV RNA
Patients with any intercurrent organ damage or medical problems that would prohibit therapy are NOT eligible for participation
Patients with baseline troponin levels greater than the institutional limit of normal
Patients must have one of the following disease characteristics:\r\n* Therapy-related myeloid neoplasm (t-MN) age >= 18 years\r\n** Patients must have received cytotoxic chemotherapy, radiation, or a drug known to affect the properties of deoxyribonucleic acid (DNA) or cell growth, prior to current diagnosis of t-MN; this broad definition is meant to include any prior therapy with chemicals that affect DNA replication, DNA integrity, or DNA structure, or chemicals that alter cell growth; this includes traditional cytotoxic chemotherapy, newer immunologic agents that have been shown to have cytotoxic activities in addition to immunosuppressive functions, and other chemicals; note that patients with primary AML could be diagnosed with a t-MN if morphology/cytogenetic analysis clearly indicated that the second process is not a relapse of the original disease\r\n* AML arising from an antecedent hematological disorder age >= 18 years\r\n* De novo AML in patients age >= 60 years\r\n* Relapsed and/or refractory AML >= 18 years
Use of investigational agents/any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea (NOTE: for patients with hyperleukocytosis [white blood cell (WBC) > 20,000/uL], hydroxyurea [and leukapheresis, if clinically indicated] will be initiated and these patients will receive 5-azacytidine when the WBC count has decreased to =< 20,000/uL; hydroxyurea can be overlapped with 5-azacytidine in selected cases, after consultation with the study chair; hydroxyurea must be discontinued before the initiation of the HiDAC/mitoxantrone chemotherapy)
Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), etc.). Patients with a remote history of asthma or mild active asthma are eligible.
-  INCLUSION CRITERIA:\n\n          -  Patients must have histologically confirmed hairy cell leukemia or hairy cell leukemia\n             variant .with a need for therapy\n\n          -  Patients must be Pseudomonas-immunotoxin naive\n\n          -  Patients must have had at least 2 prior purine analogs, or at least 1 course of purine\n             analog and 1 of either rituximub or BRAF inhibitor.\n\n          -  Men or women age greater than or equal to 18 years.\n\n          -  ECOG performance status less than or equal to 2.\n\n          -  Patients must have adequate organ function\n\n        EXCLUSION CRITERIA\n\n          -  Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior\n             to entering the study.\n\n          -  Patients who are receiving any other investigational agents.\n\n          -  Patients with known brain metastases should be excluded from this clinical trial\n\n          -  Patients with clinically significant ophthalmologic findings during screening\n\n          -  Pregnant or breastfeeding females.\n\n          -  Positive for Hepatitis B core antibody surface antigen unless the patient is on\n             Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.\n\n          -  Lymph nodes greater than 4cm or prior splenectomy\n\n          -  Active second malignancy requiring treatment other than minor resection of indolent\n             cancers like basal cell and squamous skin cancers\n\n          -  HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count\n             of greater than 200.\n\n          -  History of allogeneic bone marrow transplant.\n\n          -  Patients with history of both thromboembolism and known congenital hypercoagulable\n             conditions.\n\n          -  Uncontrolled pulmonary infection, pulmonary edema.\n\n          -  Aequate oxygen saturation\n\n          -  Radioimmunotherapy within 2 years prior to enrollment in study.\n\n          -  Adequate hematologic function\n\n          -  Adequate lung function\n\n          -  Patients with history of thrombotic microangiopathy or TTP-HUS.\n\n          -  Patients with QTc interval (Federica) elevation > 500 msec based on at least 2\n             separate 12-lead ECGs\n\n          -  Patient on high dose estrogen\n\n          -  Patients with clinical evidence of disseminated intravascular coagulation
Patients may not be taking any concomitant drugs that are contraindicated based on the drug-interaction table
Patients with known deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme
Patients who are unable to return for follow-up visits as required by this study; patients with a history of second malignant tumor, other than the common skin cancers - basal and squamous carcinomas, within the past 3 years and uncertainty about the histological nature of the metastatic lesions; cases with other types of malignancies should be reviewed and decided by the principal investigator (PI) of the study
Patients must agree to research blood sampling to participate in study
Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient’s mood assessment questionnaire (treating physician to decide on whether to administer 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) or patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV) are not eligible; Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4) 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 (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)
Aged at least 18 years. Patients from Japan aged at least 20 years.
Patients who have uterine sarcomas, carcinosarcomas, any serous histology or pure clear cell carcinomas
Patients who have hypoglycemia with a value of =< 50 mg/dL
Patients must complete all screening assessments as outlined in the protocol
Patients with abnormal calcium, potassium, or magnesium levels that is or cannot be adequately corrected to =< grade 1 prior to initiation of study drugs
Patients must receive RT at the participating institution.
Patients with BRAF WT cancers
For Part 2 of the Study only, patients must have measurable disease by RECIST 1.1 and be in one of the the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have been previously treated with BRAF and/or MEK inhibitors
Group 4: Patients with NRAS mutated melanoma
Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
Concomitant medications\r\n* Patients receiving stable or decreasing corticosteroids are not eligible for other concurrent conditions (e.g. asthma, autoimmune diseases, rash, documented adrenal insufficiency) are eligible for this study\r\n* Patients who are currently receiving another investigational drug are not eligible\r\n* Patients who are currently receiving other anti-cancer agents are not eligible
Prior therapy\r\n* Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion\r\n* Patients who have undergone prior autologous or allogeneic SCT are not eligible\r\n* Patients with HL who were stage IA or IIA at initial diagnosis and treated with either radiation alone or < 4 cycles of chemotherapy are not eligible
Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim are not eligible
Patients to be enrolled in the Cetuximab or Panitumumab combination arms must have colorectal cancer which is K-Ras wild-type.
Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), etc.). Patients with a remote history of asthma or mild active asthma are eligible.
Patients having undergone splenectomy.
Patients with nervous system tumors associated with NF2 (e.g., schwannomas, meningiomas, ependymomas, or gliomas) will not be excluded from this clinical trial unless (in the opinion of the investigator) these tumors are growing and are likely to require treatment during the clinical trial
Patients with neuromuscular disorders that are associated with elevated CK.
Patients with pelvic and/or retroperitoneal nodes < 2 cm in short axis are eligible as they are not considered to have definitive metastases
Patients on hemodialysis
Expanded cohort only: Cohort 1: patients with predominant metastatic bone disease; Cohort 2: patients with primary squamous head and neck cancers; Cohort 3: patients presenting any molecular abnormality of interest, which can include an ALK translocation, ALK amplification, ALK mutation and overexpression as determined by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), array Comparative Genomic Hybridization or direct sequencing (aCGH); a c-MET abnormality, either c-MET amplification by FISH, overexpression by IHC or c-MET mutation; BRAF, DDR2 and CDKN2A mutations; and, finally, TRIM 16 expression and CCN2 expression
Psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk
Endometrial cancer patients must have underwent surgical treatment (total abdominal hysterectomy/bilateral salpingo oophorectomy [TAH/BSO]) and radiation therapy (EBRT or IVRT)
Patients who are new visits to Female Sexual Medicine Program or patients who are not consistently using any vulvovaginal health promotion strategies (e.g., pelvic floor exercises, dilator therapy, moisturizers) recommended by the Female Sexual Medicine Program
Patients who are undergoing concomitant radiotherapy are NOT eligible for participation
Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration; NOTE: Vitamin supplements are acceptable
Patients who are receiving concomitant D2-antagonists (such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide) are NOT eligible for participation; patients must be off any such medications by the time of registration
Patients whose primary therapy was changed due to suboptimal response of toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
Patients aged > 18
Patients may not have been treated with prior sipuleucel-T
Patients who have undergone splenectomy
Patients with known atypical transcript
Patients with synchronous primaries are included
Patients with recent excisional node biopsies/neck dissections are included if material is evaluable for extracapsular spread
Patients must have clear margins after wide local excision; patients with nodes that are palpable or detectable on radiologic imaging must have an adequate lymphadenectomy
Patients must be adequately recovered from surgery, radiation therapy, or any surgical complications prior to enrollment; in general, this means patients will be off antibiotics from wound infections and drains removed; however if necessary, patients can be treated with a drain in place at the discretion of the principal investigator (PI) if the 90 days window is about to expire
Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until day 5 of treatment
No minimum platelet count is required by this trial, as this is a frequent manifestation of poor-risk chronic GVHD, and such patients may benefit from this protocol therapy
Patients with irreversible damage as the only manifestation of chronic GVHD (irreversible contractures or sicca syndrome)
Patients must have either (1) refractory or relapsed high-risk NB (including n-myc proto-oncogene [MYCN]-amplified stage 2/3/4/4S of any age and MYCN-non amplified stage 4 in patients greater than 18 months of age) resistant to standard therapy, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies
Patients taking enzyme inducing anticonvulsants
Anticoagulation is permitted but patients may only be on lovenox for this purpose.
For all patients:
Patients with secondary AML should have failed no more than two (2) prior regimens
Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
Participants with gross hematuria are not eligible; patients with microscopic hematuria are eligible
ONLY APPLIES TO PATIENTS IN GROUP B (COMBINATION THERAPY)
ONLY APPLIES TO PATIENTS IN GROUP B
ONLY APPLIES TO PATIENTS IN GROUP C (CORRELATIVE COHORT)
FOR COHORT 1: (BEVACIZUMAB ELIGIBLE)
Patients must not have psoriasis or porphyria
Patients must not have known or suspected glucose-6-phosphatase (G-6P) deficiency
Patients must not be receiving treatment for rheumatoid arthritis or systemic lupus erythematosus
Patients must have pathologically confirmed recurrence at the time of catheter placement
Patients previously treated with stereotactic radiosurgery, stereotactic radiotherapy, brachytherapy, Gliadel wafers or other intratumoral chemotherapy are eligible
Patients whose tumors are located less than 2 cm from the ventricles
Patients with normal level of serum ionized calcium and phosphate.
Patients engaged in a resistance exercise training program.
Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g, *6)
Patients with a pathologically proven diagnosis of NSCLC and consented to receive CXRT at MD Anderson
Patients > or = 18 years old
Patients who are enrolled in other symptom management or symptom clinical trials
Patients who currently have bile duct obstruction or cholelithiasis
Patients with APL (FAB type M3) or CML in blast crisis.
Patients who have already undergone excisional biopsy for qualifying DCIS
Same as above and patients undergoing single fraction spinal SBRT
Patients with lesions in the upper cervical spine (C1-C5) or cervicothoracic junction (C6-T3)
Patients requiring general anesthesia for fiducial placement
Patients with primary disease arising in the posterior elements of the VB in question
Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
Previously untreated, histologically proven primary squamous cell carcinoma arising in the oral cavity, oropharynx, or supraglottic larynx, and amenable to transoral approach; NOTE: in some cases, patients with disease deemed amenable to transoral approach at the time of diagnosis may have their entire primary tumor extirpated via diagnostic biopsy; when this happens, patients will remain eligible for the protocol as long as they have evaluable disease in the neck; in this case, the choice between a transoral procedure plus dissection or neck dissection alone will be made by the surgeon as per standard of care
Adequate swallowing function or gastric-tube for drug administration; of note, lapatinib can be administered via gastrostomy (G)-tube in a slurry for patients who cannot swallow
Criteria that need to be met to participate in this study:\n\n          -  Patients must be > 12 months and < 30 years of age when registered on study.\n\n          -  Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than\n             a partial response to standard treatment or persistent neuroblastoma that had at least\n             a partial response to standard treatment. All patients must have at least ONE site of\n             evaluable disease.\n\n             o Patients who have at least a partial response to standard treatment who still have\n             neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy\n             done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or\n             refractory neuroblastoma do not need to have a biopsy done to enter on study.\n\n          -  Patients must have adequate heart, kidney, liver and bone marrow function. Patients\n             who have bone marrow disease must still have adequate bone marrow function to enter\n             the study.\n\n          -  MLN8237 must be swallowed as whole tablets. Therefore, patients must be able to\n             swallow pills to be eligible for study. One tablet is the size of small breath mint,\n             or baby aspirin. Due to the size of MLN8237 tablets, patients must have a body surface\n             area of at least 0.38 m2 to be eligible for study. A body surface area is a\n             combination of a patient's height and weight. An example of a child with a BSA of 0.45\n             is a child that is 25 inches tall and weighs 25 pounds.You can use the link below to\n             calculate your child's body surface area and determine if they are too small for this\n             trial.\n\n        Patients cannot participate in the study if:\n\n          -  Patients who have received prior MLN8237 are excluded from all phases of the study.\n             Patients previously treated with irinotecan and/or temozolomide will be eligible if\n             they have not had documented progressive disease during treatment with a regimen\n             containing these agents.\n\n          -  They have other medical problems that could get much worse if they had this treatment.\n\n          -  They are on dialysis for bad kidney function.\n\n          -  They are pregnant or breast feeding.\n\n          -  They have active infections such as hepatitis or fungal infections.\n\n          -  They have an allergy to treatment with cefixime and cefpodixime.\n\n          -  They have brain metastasis at study entry, or have received cranial spinal radiation.\n\n          -  They have had an allogeneic stem cell transplant (received stem cell from someone\n             else).\n\n          -  They can't cooperate with the special precautions that are needed for this trial.
Confirmation of BRAF mutation-positive malignancy is required for selection of patients for vemurafenib therapy
Patients who, for any reason, are not able to comply with the national legislation
Staging laparoscopy is not required at the outset of the trial, including in patients who might otherwise receive staging laparoscopy per National Comprehensive Cancer Network (NCCN) guidelines (high-risk body and tail lesions), because patients will receive systemic chemotherapy at equivalent dose to patients who have documented stage IV disease
Patients with unresectable lung metastases
[Applicable only for France] All patients included in the trial must be affiliated with a social security regime or be a beneficiary of the same in order to be included in the study.
Patients may have received any prior therapy deemed necessary for induction of remission except for patients whom have progressed while on sorafenib; patients who have responded to sorafenib previously are eligible for enrollment on the protocol
Patients must discontinue antiandrogen therapy for at least 4 weeks (e.g. flutamide, bicalutamide, nilutamide) prior to registration with no evidence of a falling PSA after washout; patients on steroids are eligible as long as they will be switched to prednisone
Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St John’s wort, etc.) must be discontinued before registration; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) are forbidden during the trial and must be stopped prior to registration; no washout period will be required for any of these agents; patients on megestrol acetate for hot flashes are allowed to continue therapy
Patients on stable doses of bisphosphonates or denosumab which have been started prior to registration may continue on this medication, patients who are not on bisphosphonates or denosumab are eligible as long as they initiate therapy prior to registration
Patients with cystoscopically detected bladder tumors requiring TURBT
Patients with bladder tumors which are endoscopically resectable by surgeon’s judgment with only one trip into the operating room
Cytologic or histologic proof of adenocarcinoma of the pancreas is required prior to treatment; patients with Islet cell tumors are not eligible
For stage I seminoma patients only, definitive surgical intervention within ten weeks prior to registration; patients undergoing scrotal violations (scrotal orchiectomy, transscrotal biopsy, testicular fine needle aspiration, scrotal exploration) will be eligible
Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed, progressed, or become refractory to conventional therapy; patients with neurofibromatosis (NF-1) are eligible
Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required
Patients with a history of thromboembolism unrelated to a central line, or patients with a known predisposition syndrome for thromboembolism are not eligible
Patients with a significant systemic illness that is not well-controlled in the opinion of the treating physician are not eligible
Serum potassium (K)+ < 3.5 mmoL/L; patients with a K+ < 3.5 mmoL/L are required to have a documented subsequent K+ > 3.5 prior to enrollment to be eligible
Patients taking drugs leading to significant QT prolongation
Patients must be previously untreated
Patients on continuous steroid therapy for at least 72 hours (hrs) (or other continuous immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression; patients must have had 6 weeks of discontinuation of any continuous steroid therapy (taken for at least 72hrs duration) prior to enrollment (except steroids used for allergic reactions or as anti-emetics for systemic chemotherapy which are permitted)
Patients who are intolerant of, or ineligible for 5-FU, oxaliplatin, and/or the combination of both
Patients with a pelvic mass of any size that is causing pain, or other subjective symptoms that are intolerable to the patient
Patients who, for any reason, are not able to comply with the national legislation.
Both KRAS wild type and KRAS mutant patients are eligible
Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled, as indicated by a baseline pattern of > 3 watery or soft stools daily in patients without a colostomy or ileostomy; patients with a colostomy or ileostomy may be entered at investigator discretion
All patients must be surgical candidates for complete hysterectomy and bilateral salpingo-oophorectomy and pelvic and aortic lymphadenectomy
Patients must have Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
Patients who have circumstances that will not permit completion of this study or the required follow-up
Patients with GOG performance grade of 3 or 4
Patients scheduled to undergo laparotomy *Both optimal and suboptimal patients will be eligible for the study (Suboptimal patients, as well as those who undergo only exploratory laparotomy, are eligible.)
Patients who provide consent for placement of the IP port system, if randomized to Regimen II (Study treatment: dd-TCip therapy)
Electrocardiogram (ECG): Patients with normal ECG, Asymptomatic patients with abnormal ECGs not requiring medical intervention
Patients for whom completion of this study and/or follow-up is deemed inappropriate for any reason
Patients with any signs/symptoms of interstitial pneumonia
Any patients already on beta-blockers or contraindicated to receive beta-blockers
Any patients planning to receive Avastin or any other anti-angiogenic drugs
Note: patients with a negative or equivocal overall result (FISH ratio of < 2.0 or =< 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment
It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with SRS or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one residual (i.e. non-SRS-treated or non-resected) lesion is measurable (>= 10 mm); the location of the measurable lesion should be documented in the patient chart and case report form
Patients who have had prior WBRT and/or SRS and then whose prior treated 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
For patients who undergo surgery, postoperative whole brain radiation therapy will not be allowed while patients are on study; patients will require discontinuation of neratinib if WBRT will be administered; however, if the treating provider feels that targeted radiosurgery (SRS, gamma knife, etc) would be of benefit postoperatively, patients may proceed with this and then begin neratinib AFTER radiation completes
Patients cannot have hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation
Patients already taking HCQ or chloroquine for other diagnosis
Patients with centrally-located pulmonary or mediastinal primary tumors or metastases adjacent to or invading large blood vessels
Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, Allan Friedman, John Sampson, or Peter Fecci, or their designate, will be excluded
Patients must not have diagnosis of agammaglobulinemia; patients with the following will be excluded:\r\n* Undetectable anti-tetanus toxoid IgG (except for retreatment)\r\n* Known history of agammaglobulinemia
Patients previously treated outside of Northwestern must have their pathology slides sent to Northwestern for review and confirmation\r\n* NOTE: a copy of the pathology report is sufficient for registration
Patients who exhibit any other serious concurrent infection or other medical illness which would jeopardize their ability to receive the therapy outlined in this protocol with reasonable safety will NOT be eligible for participation
Patients with neurofibromatosis 1
Asymptomatic patients
For patients with carcinoid tumors, patients must have progressed on, be currently receiving, or be intolerant to octreotide therapy; for patients with pancreatic neuroendocrine tumors, the prior or current use of octreotide or somatostatin analogues is permitted, but not required; if the patient is on octreotide, regardless of whether the patient has a carcinoid or pancreatic neuroendocrine tumor, the patient must be on a stable dose of somatostatin analogue for at least two months
Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
Patients with a diagnosis of intrahepatic cholangiocarcinoma
Adequate renal and hepatic function (creatinine <2mg/dL and eGFR more than 30cc/minute, bilirubin <2mg/dL). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman. Patients with Gilbert's syndrome are eligible.
Concurrent chemotherapy, radiotherapy, or immunotherapy, including other monoclonal antibodies. Localized radiotherapy to an area not compromising bone marrow function does not apply. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.
Patients must have signed an authorization for the release of their protected health information.
Patients must be >/= 18 years old.
Patients must not be pregnant or breast feeding. Patients must not be pregnant because lacosamide produced developmental toxicity in rats following administration during pregnancy. There is insufficient information to determine if lacosamide is safe during lactation.
Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism; patients with a history of psychosis/schizophrenia or cardiac disease requiring beta-blocker treatment (unable to change medication to non-beta blocker), anti-malarial drugs, or quinine or quinidine will not be eligible for enrollment to a mefloquine containing arm; patients who are on active treatment with one of the study drugs at the time of evaluation will not be eligible for enrollment to an arm containing that study drug
Patients who do not have hypo- or hyperthyroidism
Patients must fall into Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class I or II
Patients may receive a bisphosphonate.
Confirmed relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL); patients should have received at least 1 prior treatment regimen; prior treatment must have included at least one full cycle of a proteasome inhibitor (e.g., bortezomib) and at least one full cycle of an immunomodulatory (IMiD) (e.g., thalidomide, lenalidomide or pomalidomide); patients who have had prior ARRY-520 and carfilzomib will be allowed in the dose escalation phase, however prior ARRY-520 and carfilzomib will be excluded in the dose expansion cohort 1 of part A; there will be 2 cohorts in the dose expansion of part A: cohort 1 will be patients who are carfilzomib sensitive; cohort 2 will be patients who are carfilzomib refractory
Patients with pc-ALCL that has spread systemically (e.g., to lymph nodes, bone marrow, or visceral organs) may be included so long as pc-ALCL was the primary diagnosis for at least 6 months before systemic involvement was confirmed; MF patients must be stage IB or greater
pc-ALCL and MF patients must have progressed or relapsed after treatment with local radiation therapy, phototherapy, topical chemotherapy, or have failed systemic therapy of at least one single agent (e.g., methotrexate or bexarotene or other non-CD30 antibody) or one multi-agent chemotherapy (e.g. CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone); pc-ALCL classified patients are required to have one or more cutaneous tumors that by history have been present for at least 3 months
All patients must be considered an eligible candidate for systemic therapy as determined by the investigator; to be eligible, LYP patients must be in need of systemic therapy i.e., have scarring or active lesions (>= 10 per month), or any number of active lesions on face, hands, or feet
Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution
FOR FIRST COHORT ONLY, NOT REQUIRED FOR BIOMARKER COHORT: Patients will be allowed to eat pomegranates and drink pomegranate juice provided that the patient has been taking these for 4 weeks or more with evidence of progressive disease as outlined above; these patients should be instructed to continue to take pomegranates and/or pomegranate juice as per the same schedule while on study; documentation of amount and duration will be captured for those patients taking pomegranates or pomegranate juice; those patients who have not been taking pomegranates or pomegranate juice prior to study entry will not be allowed to begin these while on study
Patients with one prior relapse on a bevacizumab or an anti-VEGF(R) (i.e., VEGF-trap, vandetanib, cediranib, sunitinib, sorafenib, XL184, etc.) containing regimen are allowed to participate
Standard pediatric indications for myeloablative transplantation for patients undergoing HSCT at Children’s National Medical Center per institutional guidelines
History of prior Lupron intolerance; Note: patients ARE eligible if prior or current Lupron exposure
Hemoglobin >= 9 gm/mcl (patients may be transfused to meet this requirement)
Patients with any NIH subtype (classic or overlap) of chronic GVHD who are starting treatment with ECP
Patients must have resectable adenocarcinoma of the esophagus or GE-junction and are medically fit to undergo surgery; patients must have no evidence of distant metastasis based on imaging studies
Patients with a prior history of marked intolerance to 5-fluoropyrimidines (5-FU, floxuridine, capecitabine, 5-fluorocytosine [flucytosine]), since such patients may have deficiency of dihydropyrimidine dehydrogenase, which places them at risk for severe and life-threatening toxicity with 5-FU
No more than 4 prior chemotherapy regimens for metastatic disease for those in the dose escalation cohorts; prior trastuzumab and lapatinib are allowed for the HER2+ population; once we reach the expanded recommended phase 2 dose (RP2D) cohorts, patients enrolled must have received =< 3 prior regimens\r\n* Patients enrolled in ARM C may remain on trastuzumab without a washout period\r\n* Patients enrolled in ARM D may remain on lapatinib without a washout period
For Arms A, C or D, 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 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) or patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV); NOTE: for patients with psychotropic treatments ongoing at baseline, the dose and schedule should not be modified within the previous 6 weeks prior to D1 of treatment with BKM120\r\n* >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety \r\n* At screening, meets the cut-off score of >= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder (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 unless overruled by the psychiatric assessment\r\n* Note: The psychiatric judgment overrules the mood assessment questionnaire result/investigator's judgment
Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
Progression during or within 6 months following administration of a standard regimen for treatment of metastatic disease that included oxaliplatin with any of the following agents with or without bevacizumab:\r\n* 5-fluorouracil (5-FU) with or without leucovorin or levoleucovorin\r\n* Capecitabine\r\nNOTE: in patients receiving FOLFOX, oxaliplatin is sometimes discontinued due to toxicity or as part of maintenance therapy strategy; if such patients progress while on 5-FU alone, they are eligible for this trial; as an example, a patient who is begun on FOLFOX or CapeOx (with or without bevacizumab), whose oxaliplatin is held for neurotoxicity and who is switched to capecitabine monotherapy or capecitabine with bevacizumab, would be considered to have had ONE prior therapy OR patients who develop metastatic disease within 9 months of adjuvant FOLFOX for stage II or III colon cancer
Patients with pheochromocytoma
Patients of East Asian ancestry
East Asian patients (Chinese, Japanese, Taiwanese, and Korean ancestry) are excluded during stage I of the study (dose escalation phase)
Every effort should be made to switch patients taking drugs that are known to be sensitive substrates of these enzymes to other medications 1 week prior to starting therapy; if a patient’s medication cannot be switched, the patient’s eligibility will be determined following a review of their case by the principal investigator
Patients with a history of deep vein thrombosis must be on anti-coagulation therapy prior to enrollment; patients requiring prophylactic anti-coagulation are eligible
Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 1.5 ULN; note: optimal glycemic control should be achieved before starting trial therapy; at the principal investigator’s discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted
Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists            \r\n* In general, this would refer to any active GOG phase III or rare tumor protocol for the same patient population
Patients must have a GOG performance status of 0 or 1
Patients must meet pre-entry requirements as specified
Patients allergic to nonsteroidal antiinflammatory drug (NSAID)
Patients with known glucose-6-phosphate dehydrogenase deficiency
Patients with porphyria cutanea tarda
Patients with psoriasis
Patients with pre-existing maculopathy or retinopathy of the eye
Patients who have a pre-existing myopathy
Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
Caution should be exercised in patients who are regularly taking narcotic analgesics, particularly higher doses; the doses of narcotic analgesics may need to be reduced, patients may need to be monitored closely for drug interactions, and the risks and benefits of participation in the study should be considered; clinical judgment should be exercised to manage this potential drug interaction
Patients who require radiotherapy to distant metastases during induction systemic therapy are eligible
Patients who are currently taking vitamin supplements including lycopene and beta-carotene are eligible
Patients who are currently taking Coumadin are not eligible
Patients are offered registration to the correlative study CALGB-151105
Patients consuming >= 6 servings per day of fruits and vegetables (not including juices), as determined by the run-in dietary recalls, are not eligible
All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole and who are then randomized to ARM 2 must have sirolimus reduced according to the Standard Practice Antifungal Therapy Guidelines
Patients must have a Zubrod performance status of 0, 1, or 2 and in the registering physician’s opinion be medically suitable to undergo cystectomy
Patients must be offered the opportunity to participate in specimen banking for future use to include the translational medicine studies
Disease to be treated on protocol is less than 2 mm from the spinal cord and therefore will not meet dose constraints; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Areas to be treated on protocol do not include metastases to liver, brain or lung; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Patients had at least one prior regimen consisting of at least 1 cycle
If not previously transplanted, patient should be either ineligible for autologous stem cell transplant (ASCT), or must have declined the option of ASCT; patients who have previously had ASCT and have subsequently progressed are eligible, provided other entry criteria are met
Previously untreated patients with lymphoplasmacytic lymphoma (of any subtype: IgG, IgA, IgM) in the asymptomatic phase
Patients with positive antinuclear antibody (ANA) and/or anti-double strand (ds) DNA antibodies
CML CP patients are excluded if they are in Complete cytogenetic response (CCyR)
Patients with CML AP, CML BP, or Ph+ ALL are excluded if they are in Major Hematologic Response (MaHR).
Patients must consent to an indwelling central venous catheter
Patients must be at least 48 hours from placement of central catheter before receiving first dose of bevacizumab
LUNG (ONLY APPLIES TO PATIENTS WITH PRIMARY OR METASTATIC LUNG LESIONS NOT PREVIOUSLY TREATED WITH RT):
Patients cannot have more than 3 lung lesions\r\n* Patients with a single lung lesion other than the primary tumor and no other thoracic or extra-thoracic disease will not be eligible
Patients taking tolbutamide, warfarin, zidovudine, benzodiazepines, clonazepam, diazepam
Concurrent treatment with corticosteroids. If they are already on steroids, patients will be allowed to enroll on the study but will need to taper off as soon as possible.
Patients with MDS should have failed prior therapy with a hypomethylating agent or, if associated with a 5q- chromosomal abnormality, lenalidomide. NOTE: Patients with 5q- unable to receive or intolerant to lenalidomide are also eligible.
Patients may be of any ethnic background
Patients with a history of central nervous system metastasis are allowed provided they have been treated (surgery, radiation, or radiosurgery) at least 4 weeks prior to initiating study drug and do not require medication(s) to control symptoms; patients with known leptomeningeal disease are not eligible
Patients must have progressed after at least one prior systemic therapy for GCT and meet one of the following criteria:\r\n* Patients with evidence of progressive or recurrent GCT after progression prior high dose chemotherapy (HDCT) treatment, defined as meeting at least one of the following criteria:\r\n** Tumor biopsy of new or growing or unresectable lesions demonstrating viable GCT; in the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for this 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 rise\r\n* Patients deemed not to be a candidate for or benefit from potentially curative HDCT or other curative treatment options defined as follows:\r\n** Patients with inadequate renal function for HDCT\r\n** Patients who have had 3 or more lines of prior chemotherapy\r\n** Patients with late relapse (relapse > 2 years after last therapy)\r\n** Patient with inadequate stem cell collection to move forward with HDCT\r\n** Patients with significant medical or psychosocial comorbidities that are felt to be a contraindication to HDCT by the treating investigator\r\n* NOTE: There is no maximum number of prior treatments allowed\r\n* NOTE: Patients with clinically growing \teratoma\ (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery; in patients with rising tumor markers as their only evidence of disease progression where AFP is < 30 or HCG is < 15, alternate causes of increased levels of these markers should be ruled out; (e.g., hypogonadism by testosterone suppression of luteinizing hormone [LH], hepatitis, use of marijuana)
Inclusion Criteria:\n\n          1. Patients or their legal representatives must be able to provide written informed\n             consent.\n\n          2. Histologically confirmed diagnosis of supratentorial GBM (Grade 4 astrocytoma).\n\n          3. Radiographic evidence of first recurrence or progression of GBM following primary\n             therapy consisting of surgery (biopsy or resection) and chemoradiation; patients may\n             have undergone a second debulking surgery following initial recurrence or progression.\n             Patients whose tumors are O6 methyl guanyl-methyl-transferase (MGMT)\n             methylated-promoter negative need not have received chemotherapy in the past to be\n             eligible.\n\n          4. Human leukocyte antigen type HLA-A*02:01, HLA-A*02:06, or HLA-A*24:02.\n\n          5. Age ?18.\n\n          6. KPS score of ?60.\n\n          7. Serum creatinine value <2X the upper limit of normal (ULN) for the reference\n             laboratory.\n\n          8. Alanine aminotransferase/aspartate aminotransferase <3X the ULN and total bilirubin\n             <2× the ULN for the reference laboratory.\n\n          9. Patients must have recovered from the effect of all prior therapy to Grade 2 or less.\n\n         10. Patients must be at least 28 days from any major surgery, and any surgery incisions or\n             wounds must be completely healed.\n\n         11. Patients must be at least 12 weeks from the completion of prior radiation therapy (RT)\n             in order to discriminate pseudo progression of disease from progression.\n\n         12. Patients must be at least 4 weeks from the completion of prior systemic or\n             intracranial chemotherapy.\n\n         13. For patients who are not receiving therapeutic anticoagulation treatment, an\n             international normalized ratio (INR) and a PTT ? 1.5 × the ULN; patients who are\n             receiving anticoagulation treatment should be on a stable dose.\n\n        Exclusion Criteria:\n\n        Patients with any of the following will be excluded from the study:\n\n          1. Prior therapy with Bev.\n\n          2. Any anti-neoplastic therapy, including RT, for first relapse or recurrence.\n\n          3. Evidence of leptomeningeal spread of tumor or any history, presence, or suspicion of\n             metastatic disease extracranially.\n\n          4. Evidence of impending herniation on imaging.\n\n          5. Patients with infections that have required treatment with systemic antibiotics within\n             7 days of first dose of protocol therapy.\n\n          6. The need for systemic glucocorticoids in doses in excess of 4 mg/day of dexamethasone\n             or in comparable doses with other glucocorticoids.\n\n          7. Treatment with any investigational agents within 5 half-lives of the agent in question\n             or, if the half life is unknown, within 28 days of enrollment.\n\n          8. Pregnant or lactating females.\n\n          9. Prior history of malignancy within 3 years of enrollment other than basal or squamous\n             cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of\n             the breast, or prostate cancer treated with surgery or RT with a prostate specific\n             antigen of <0.01 ng/mL.\n\n         10. Patients with active autoimmune diseases within 2 years of enrollment into the study\n             including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus,\n             systemic sclerosis, Sjogren's syndrome, Wegener's granulomatosis, ulcerative colitis,\n             Crohn's disease, myasthenia gravis, Graves' disease, or uveitis except for psoriasis\n             not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism; if an\n             autoimmune condition has been clinically silent for 12 months or greater, the patient\n             may be eligible for enrollment.\n\n         11. Patients on immunosuppressive therapies; the use of topical, inhalational,\n             ophthalmologic or intra articular glucocorticoids, or the use of physiologic\n             replacement doses of glucocorticoids are permitted.\n\n         12. Patients with primary immunodeficiency diseases.\n\n         13. Patients with significant bleeding in the preceding 6 months or with known\n             coagulopathies.\n\n         14. History of abdominal fistula, intestinal perforation, or intra-abdominal abscess in\n             the preceding 12 months.\n\n         15. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or\n             untreated hepatitis C; patients who have completed a course of anti-viral treatment\n             for hepatitis C are eligible.\n\n         16. Significant cardiovascular disease, including New York Hospital Association Class III\n             or IV congestive heart failure, myocardial infarction within 6 months of enrollment,\n             unstable angina, poorly controlled cardiac arrhythmias, or stroke within the preceding\n             6 months.\n\n         17. Any other uncontrolled inter current medical condition, including systemic fungal,\n             bacterial, or viral infection; uncontrolled hypertension; diabetes mellitus; or\n             chronic obstructive pulmonary disease requiring 2 or more hospitalizations in the\n             preceding 12 months.\n\n         18. Known sensitivity to Bev or any of the components of DSP-7888 Dosing Emulsion.
Patients with uncontrolled eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations (patients without ophthalmologic involvement, rash covering < 10% of the body surface area and requiring only low potency topical steroids, and without exacerbations requiring systemic therapy are eligible)
Patients with pathologically confirmed cancers of paranasal sinuses, oropharynx, oral cavity, nasopharynx, larynx, hypopharynx, and unknown primary and will receive definitive radiation therapy with or without chemotherapy
Patients who are enrolled in a national/international cooperative group trials
Patients must meet the following criteria for unresectability as determined by two hepatobiliary surgeons and one radiologist:\r\n* When a margin negative resection would require resection of all three hepatic veins, both portal veins, or the retrohepatic vena cava\r\n* Requiring a resection that leaves less than 2 hepatic segments (not including the caudate lobe) behind with adequate arterial/portal inflow, venous outflow and biliary drainage\r\n** A patient is considered resectable if the procedure includes a minor wedge or thermo-ablation encompassing 10% or less of the volume of the remaining 2 segments\r\n* Patient’s liver metastases must comprise < 70% of the liver parenchyma; all patients must be clinically fit to undergo surgery as determined by the pre-operative evaluation
Patients must have been enrolled, or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245; results must be available before starting treatment on protocol
Patients must have esophageal, gastric or gastroesophageal adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:CEP17 ratio >= 2.0); MSKCC or enrolling institution confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC or the enrolling institution for purpose of analysis and will not impact the patient's eligibility
Patients must be willing and able to check and record daily blood pressure readings
Patients who have been previously treated with an anti-VEGF agent will be excluded from Arm A and Arm B
Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery; however, if a patient has a resection or biopsy at the site of prior stereotactic radiotherapy, convection enhanced delivery, or brachytherapy and the biopsy specimen shows recurrent GBM and EGFR amplification by FISH, the patient will be eligible; patients with recurrence outside the radiosurgery field will be considered for eligibility if the recurrence is clearly documented to be outside the field and more than 3 months have lapsed since the last dose of radiosurgery
Medications and/or diet are prohibited if they affect oral absorption of PF-00299804 or if primarily metabolized by cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6); patients must have been off treatment with these drugs for 2 weeks prior to enrollment; patients who otherwise are eligible can be enrolled only if drug substitution is performed with acceptable clinical outcome prior to enrollment
Inclusion Criteria (Treatment Arm A)\n\n          1. Patients must have histologically-confirmed solid tumors that are advanced or\n             metastatic, and refractory after standard therapy, or for which there is no standard\n             therapy.\n\n          2. Patients must have measurable disease as defined by RECIST version 1.1.\n\n          3. Patients must have received prior anticancer therapy or not be eligible for any\n             established conventional therapy whether surgical or pharmacologic.\n\n          4. Patients must have recovered from all acute adverse effects (excluding alopecia) of\n             prior therapies to baseline or <=grade 1 prior to study entry.\n\n          5. Patients must have a performance status of 0, 1, or 2.\n\n          6. Patients must be men and women >=18 years of age.\n\n          7. Patients must have adequate bone marrow function, defined as an absolute neutrophil\n             count >=1.5 x 10^9/L and a platelet count >= 100 x 10^9/L.\n\n          8. Patients must have adequate renal function, defined as serum creatinine <= 1.2 mg/dL\n             (if > 1.2 mg/dL, a calculated creatinine clearance [by the Cockcroft-Gault method]\n             must be >=60 mL/min/1.73 m^2).\n\n          9. Patients must have adequate hepatic function, defined as plasma total bilirubin <=1.5\n             mg, alanine transaminase (ALT) and aspartate transaminase (AST) <=2.5 X ULN. Patients\n             with Gilbert's disease outside these limits are judged to be ineligible.\n\n         10. Female patients of childbearing potential must have a negative serum or urine\n             pregnancy test result at time of pre-treatment screening.\n\n         11. Patients with reproductive potential must agree to use at least one form of barrier\n             contraception prior to study entry and for up to 30 days beyond the last\n             administration of study drug.\n\n         12. Patients must be judged to be capable by the Investigator of providing informed\n             consent and must be willing to provide written informed consent prior to the start of\n             any study specific procedures.\n\n         13. Patients should have a life expectancy of at least 12 weeks.\n\n        Exclusion Criteria (Treatment Arm A)\n\n          1. Patients may not have had prior chemotherapy, hormonal therapy, radiation therapy, or\n             biologic therapy in the 4 weeks prior to study entry with the exception of mitomycin C\n             or nitrosoureas, for which patients must be 6 weeks from prior treatment. For patients\n             who have been treated with targeted therapy, 5 half-lives of that therapy (or 28 days,\n             whichever is shorter) must have passed prior to enrollment in the study.\n\n          2. Patients may not have any concomitant condition that could compromise the objectives\n             of this study and the patients' compliance and ability to tolerate this therapy and\n             complete at least 2 cycles of therapy, including, but not limited to the following:\n\n               -  Congestive heart failure or uncontrolled angina pectoris, previous history of\n                  myocardial infarction within 1 year from study entry, uncontrolled hypertension,\n                  or dysrhythmias.\n\n               -  Active infection.\n\n               -  Unstable diabetes mellitus\n\n               -  Psychiatric disorder that may interfere with consent and/or protocol compliance.\n\n          3. Pregnant or breastfeeding women.\n\n          4. Patients with another malignancy in the past 3 years except: curatively treated\n             non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does\n             not require further treatment.\n\n          5. Patients with known HIV, HBV, or HCV infection.\n\n          6. Patients with an underlying diagnosis or disease state associated with an increased\n             risk of bleeding.\n\n          7. Patients with central nervous system metastases. Baseline CT or MRI scan of brain is\n             required only in the case of clinical suspicion of central nervous system metastases.\n             Patients with evidence of brain involvement, leptomeningeal disease, or seizure\n             disorder are also excluded.\n\n          8. Patients may not be treated with known CYP3A4 inhibitors or inducers.\n\n        Inclusion and Exclusion Criteria for Combination CTO Plus Temodar® (Treatment Arm B):\n        Inclusion Criteria (Treatment Arm B)\n\n        In addition to the inclusion criteria for adequate organ function as defined for the\n        patients with advanced or metastatic solid tumors, patients enrolled in Arm B (Combination\n        Therapy CTO Plus Temodar-R) must meet the following inclusion criteria:\n\n          1. Patients must have histologically proven malignant glioblastoma or other recurrent\n             malignant gliomas.\n\n          2. Measurable tumor must be present on gadolinium-enhanced MRI.\n\n          3. Patients must have a life expectancy of at least 8 weeks.\n\n          4. Patients must have a Performance Status of 0, 1, or 2 (ECOG scale).\n\n          5. Patients must be men and women >=18 years of age.\n\n          6. Patients must have recovered from all acute adverse effects (excluding alopecia) of\n             prior therapies to baseline or <=grade 1 prior to study entry.\n\n          7. Patients must have shown unequivocal radiographic evidence for tumor progression by\n             MRI scan to be performed within 14 days prior to registration and must be on a steroid\n             dose that has been stable for at least 5 days. If the steroid dose is increased\n             between the date of imaging and registration, a new baseline MRI scan is required.\n\n          8. Patients who have undergone recent resection for recurrent or progressive malignant\n             tumor will be eligible as long as all of the following conditions apply:\n\n               1. They have recovered from the effects of surgery\n\n               2. The extent of residual disease is assessed post-operatively, with an MRI scan\n                  done no later than 96 hours in the immediate post-operative period or at least 4\n                  weeks post-operatively, within 14 days prior to registration. If the 96-hour scan\n                  is more than 14 days before registration, the scan needs to be repeated.\n\n          9. Patients must have had prior radiation therapy with or without chemotherapy and must\n             have progressed following radiation therapy and must have an interval of >=12 weeks\n             from the completion of radiation therapy to registration date to minimize the\n             possibility of pseudo-progression.\n\n         10. Patients under treatment with anti-epileptic drugs which are not known CYP3A4\n             inhibitors or inducers must have been receiving a stable dose for at least 2 weeks\n             with no evidence of seizures at the time of registration.\n\n        Exclusion Criteria (Treatment Arm B)\n\n          1. Patients may not have had prior chemotherapy, hormonal therapy, or biologic therapy in\n             the 4 weeks prior to study entry with the exception of mitomycin C or nitrosoureas,\n             for which patients must be 6 weeks from prior treatment. For patients who have been\n             treated with targeted therapy, 5 half-lives of that therapy (or 28 days, whichever is\n             shorter) must have passed prior to enrollment in the study. Additional exceptions: The\n             following specific drugs are permitted shorter recovery times: 14 days for\n             vincristine, 21 days for procarbazine, and 7 days for non-cytotoxic agents such as\n             interferon, tamoxifen, thalidomide, and cis-retinoic acid.\n\n          2. Patients may not have any concomitant condition that could compromise the objectives\n             of this study and the patients' compliance and ability to tolerate this therapy and\n             complete at least 2 cycles of therapy, including, but not limited to the following:\n\n               -  Congestive heart failure or uncontrolled angina pectoris, previous history of\n                  myocardial infarction within 1 year from study entry, uncontrolled hypertension,\n                  or dysrhythmias.\n\n               -  Active infection.\n\n               -  Unstable diabetes mellitus.\n\n               -  Psychiatric disorder that may interfere with consent and/or protocol compliance.\n\n          3. Pregnant or breastfeeding women.\n\n          4. Patients with another malignancy in the past 3 years except: curatively treated\n             non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does\n             not require further treatment.\n\n          5. Patients with known HIV, HBV, or HCV infection.\n\n          6. Patients with an underlying diagnosis or disease state associated with an increased\n             risk of bleeding.\n\n          7. Uncontrolled seizure activity.\n\n          8. Patients may not be treated with known CYP3A4 inhibitors or inducers.\n\n        Inclusion and Exclusion Criteria for Combination CTO and Temodar® in combination with\n        radiation therapy (Treatment Arm C):\n\n        Inclusion Criteria (Treatment Arm C)\n\n        In addition to the inclusion criteria for adequate organ function as defined for the\n        patients with advanced or metastatic solid tumors, patients enrolled in Arm C (Combination\n        Therapy CTO and Temodar® in combination with radiation therapy) must meet the following\n        inclusion criteria:\n\n          1. Patients must have histologically proven newly diagnosed glioblastoma or other\n             malignant gliomas. Note: Patients with anaplastic oligodendroglioma with 1p/19q\n             deletion or unknown 1p/19q status are not eligible\n\n          2. Patients must have a life expectancy of at least 8 weeks\n\n          3. Patients must have a Performance Status of 0, 1, or 2 (ECOG scale).\n\n          4. Patients must be men and women >=18 years of age.\n\n          5. Patients must have undergone an MRI scan performed within 14 days prior to\n             registration and must be on a steroid dose that has been stable for at least 5 days.\n             If the steroid dose is increased between the date of imaging and registration, a new\n             baseline MRI is required.\n\n          6. Patients under treatment with anti-epileptic drugs which are not known CYP3A4\n             inhibitors or inducers must have been receiving a stable dose for at least 2 weeks\n             with no evidence of seizures at the time of registration.\n\n        Exclusion Criteria (Treatment Arm C)\n\n          1. Patients may not have had any prior chemotherapy, hormonal therapy, or biologic\n             therapy for gliomas.\n\n          2. Patients may not have any concomitant condition that could compromise the objectives\n             of this study and the patients' compliance and ability to tolerate this therapy and\n             complete at least 2 cycles of therapy, including, but not limited to the following:\n\n               -  Congestive heart failure or uncontrolled angina pectoris, previous history of\n                  myocardial infarction within 1 year from study entry, uncontrolled hypertension,\n                  or dysrhythmias.\n\n               -  Active infection.\n\n               -  Unstable diabetes mellitus.\n\n               -  Psychiatric disorder that may interfere with consent and/or protocol compliance.\n\n          3. Pregnant or breastfeeding women.\n\n          4. Patients with another malignancy in the past 3 years except: curatively treated\n             non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does\n             not require further treatment.\n\n          5. Patients with known HIV, HBV, or HCV infection.\n\n          6. Patients with an underlying diagnosis or disease state associated with an increased\n             risk of bleeding.\n\n          7. Uncontrolled seizure activity.\n\n          8. Patients may not be treated with known CYP3A4 inhibitors or inducers.\n\n          9. Patients with anaplastic oligodendroglioma with 1p/19q deletion or unknown 1p/19q\n             status are excluded.
Patients with nodal involvement are eligible
Patients with T1, N0 lesions
Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.
Patients with AML at initial diagnosis or at first relapse
Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be vaccinated and will come off study
Patients with pathologically confirmed unresectable or borderline resectable squamous cell carcinoma of the larynx, hypopharynx, nasopharynx and oropharynx will be eligible for enrollment to the clinical trial; patients will be deemed unresectable if they have clinically confirmed carotid artery encasement, skull base involvement, trismus or deep neck musculature invasion at the time of diagnosis; borderline resectability will be defined as those patients in which surgery is unlikely to result in excision of all macroscopic disease or will result in a total base of tongue glossectomy, total laryngopharyngectomy, skull base resection or carotid resection
Patients on Coumadin therapy are eligible for study; there have been some reports of prolonged INR in this patient population and regular screening is recommend in this population, but this should not exclude a patient from participation
Patients with recurrent or refractory ESFT. Patients with de novo poor prognosis/high risk ESFT: (Eligible for vaccine manufacturing at diagnosis but ONLY ELIGIBLE FOR IMMUNOTHERAPY IF DEMONSTRATES PERSISTENT/RECURRENT/ REFRACTORY DISEASE)
Patients with tumors adjacent to a vertebral body are eligible, unless there is demonstrable bone invasion, as long as all gross disease can be covered to the total radiation dose while respecting spinal cord tolerance
Serious concomitant medical illnesses that would jeopardize the patient’s ability to receive the regimen with reasonable safety
Patients with diagnosis by fine needle aspiration (FNA) cytology only
For gastrointestinal stromal tumors (GIST), patients must have failed previous therapy with imatinib and sunitinib. Patients with known PDGFR mutations are excluded, but mutation testing is not required for study entry.
For anaplastic thyroid cancer (ATC), patients must have histologically or cytologically diagnosed advanced ATC.
HLA-A*0201 positive (to enable immunization with the HLA class I restricted gp100[g209-2M] peptide); stage IIB or IIC patients will be enrolled after review and approval by the principal investigator (PI); (a tool to determine the projected survival at 5 years, like, but not limited to, the nomogram at www.melanomaprognosis.org; if the projected survival is less than 50% at 5 years, then the patient is considered for enrollment; this is with the recognition that the adjuvant, if effective offers a significant impact in that group of stage II patients)
Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine)
Patients may or may not have started bisphosphonates
Patients that have active hemolytic anemia
Patients with known splenomegaly
Pediatric patients (younger than 18 years) will be excluded.
Patients that cannot tolerate being scanned for an additional 12 minutes with arms above their head will be excluded.
Hepatitis A, B and C status will be tested prior to therapy, but results will not exclude patients from participation (if positive, patients will be told they are at higher risk of adverse effects from allogeneic transplantation)
Patients with a creatinine greater than 2.5 times the upper limit of normal are eligible, but will be told that they are at greater risk for kidney damage that could possibly result in temporary or even permanent dialysis
Patients must have both a disease-specialist (rheumatologist/immunologist, or neurologist) physician and a bone marrow transplant physician evaluation at the treating center before a patient is considered eligible; both specialists must agree that the patient is a candidate for transplantation and patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS) must have failed standard therapies
Patients must satisfy the American College of Rheumatology (ACR) criteria for the diagnosis of SLE
Patients must have received a trial of IV cyclophosphamide pulse greater than 500 mg/square meter at least once within the previous 6 months, unless contraindicated because of severe cytopenias or intolerance
Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol
Patients who were receiving axitinib tablets at the time their previous trial ended
Patients eligible for a curative autologous HCT
Creatinine < 2 mg %; patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman
Bilirubin < 2 mg %; patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman
Patients must not have ocular melanoma
Each patient will have undergone definitive resection to be eligible for enrollment; this will be followed by standard of care conformal external beam RT with concurrent TMZ; patients are not permitted to have had any other conventional therapeutic intervention other than steroids, or current radiation or TMZ therapy prior to enrollment (TMZ must have been administered > 6 months before enrollment); patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded and replaced if needed; patients who received immunosuppressive therapy for an autoimmune disorder or an organ transplant and/or require prolonged steroid therapy (> 30 days) will be excluded
Patients with an active infection requiring treatment or an unexplained febrile (> 101.5 degrees Fahrenheit [F]) illness
Patients with demonstrated allergy to TMZ or who are otherwise unable to tolerate TMZ for any reason will be excluded and replaced if needed; patients who are found after enrollment to be unable to tolerate TMZ will not be a candidate for the vaccine despite being previously enrolled and will be removed from the study and replaced
Patients who have previously been administered basiliximab or who have had an allergic reaction to basiliximab or one of its components in the past will be excluded
Patients undergoing either a Type II or III radical hysterectomy (Piver Classification)
Patients unable to withstand prolonged lithotomy and steep Trendelenburg position
Medulloblastoma patients >= 3 and < 5 years old at diagnosis who have non-metastatic disease with no more than 1 cm^2 of residual tumor are also eligible; medulloblastoma patients in the >= 3 and < 5 years old age group with anaplastic or large cell histology or with v-myc avian myelocytomatosis viral oncogene homolog (MYC) or v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification are excluded; pathology from collaborating institutions must be centrally reviewed prior to enrollment for confirmation
Desmoplastic medulloblastoma patients who are >= 3 to < 5 years of age will NOT be eligible for the low risk arm of the protocol
Medulloblastoma patients who are >= 3 and < 5 years of age with no more than 1cm^2 of residual tumor and with no evidence of CNS metastasis; medulloblastoma patients in the >= 3 and < 5 years old age group with anaplastic histology, large cell histology, melanotic differentiation, or myogenic differentiation or tumors with MYC or MYCN gain or amplification are excluded; pathology from collaborating institutions’ patients must be centrally reviewed prior to enrollment for confirmation
Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed)
Patients may have had up to 2 prior relapses.
Patients who have fragmented mechanical heart valves
For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, left ventricular function < 50%
Patients must have a family member who is matched at 2, 3, or 4 HLA antigens typed as described above and willing to donate 80-100 ml or bone marrow for mesenchymal stem cell (MSC) generation or the angioblast mesenchymal precursor cells will be used for the cord blood co-cultures; patients that are high risk for relapse are eligible to use the angioblast \off-the-shelf\ mesenchymal precursor cells
Patients must have had at least one prior therapy to be eligible for either the first or second stage a) Patients are eligible with any number of prior regimens regardless of what those regimens contained (i.e. prior Bortezomib or combination gemcitabine and adriamycin is acceptable).
Patients who have a programmable shunt will not be excluded
Both pediatric and adult patients of any age are eligible
Patients with obstructive or symptomatic communicating hydrocephalus
Severe major organ toxicity; specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than or equal to grade 2; patients with stable neurological deficits (because of their brain tumor) are not excluded; patients with =< 3 hearing loss are not excluded
Patients must have no rapidly progressing or deteriorating neurologic examination
Histologic documentation of prostatic adenocarcinoma; patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible; all eligible patients must have a known Gleason sum based on biopsy or transurethral resection of the prostate (TURP) at the time of registration
Patients must have either:\r\n* A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%; please note that for the purposes of the nomogram calculation, the pre-biopsy prostate specific antigen (PSA) value must be used OR\r\n* Prostate biopsy Gleason sum >= 8 \r\n(NOTE: the Kattan nomogram probability must be calculated for all patients, including those eligible based on Gleason sum >= 8 only)
Patients who fulfil the diagnostic criteria of HLH.
MRI scan of the target plexiform neurofibroma(s), performed according to study requirements, including axial and coronal short tau inversion recovery (STIR) images within 4 weeks of enrollment on study; patients with orbital plexiform neurofibromas (PNF’s) must have a baseline ophthalmologic evaluation performed prior to study enrollment by an ophthalmologist familiar with the protocol guidelines; patients with pain associated with the target PNF must be able to fill out the Pain Medication Diary with at least one week of documentation prior to study enrollment
Patients with symptomatic uremia, uncontrolled edema or unstable serum electrolytes should not enter the trial until such time as they have been stabilized – such patients should be discussed with the principal investigator
Patients with B-Cell CLL or PLL who:\r\n* Failed to meet National Cancer Institute (NCI) Working Group criteria 2 for complete or partial response after 2 cycles of therapy with regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or with disease relapse within 12 months after completing therapy with a fludarabine (or another nucleoside analog) containing regimen\r\n* Failed FCR or pentostatin/cyclophosphamide/rituximab (PCR) combination chemotherapy at any time point\r\n* Patients with novo or acquired “17p deletion” cytogenetic abnormality; patients should have received induction treatment but could be transplanted in 1st CR
Inclusion Criteria:\n\n        All patients must meet the following inclusion criteria. All tests and eligibility criteria\n        must be completed within four weeks of completion of radiation and chemotherapy, following\n        surgery.\n\n          -  Patients must have sufficient tumor lysate protein that was generated from the\n             surgically obtained tumor material. Patients must also have sufficient DCVax-L product\n             available after manufacturing. These determinations will be made by Cognate\n             BioServices, Inc. (Cognate) and communicated to the clinical site through the Sponsor,\n             or its designee.\n\n          -  Patients with newly diagnosed, unilateral GBM (Grade IV) are eligible for this\n             protocol. An independent neuropathologist will review this diagnosis during the\n             enrollment process.\n\n          -  Subjects ?18 and ?70 years of age at surgery who are capable of informed consent.\n             Patients must be able to understand and sign the informed consent documents indicating\n             that they are aware of the investigational nature of this study.\n\n          -  Patients must have a life expectancy of >8 weeks.\n\n          -  Patients must have a KPS rating of ?70 at the baseline visit (Visit 3).\n\n          -  Primary therapy must consist of surgical resection with the intent for a gross or near\n             total resection of the contrast-enhancing tumor mass, followed by conventional\n             external beam radiation therapy and concurrent Temodar chemotherapy. Patients having a\n             biopsy only will be excluded. These primary treatments must be completed at least two\n             weeks prior to first immunization.\n\n          -  Patients may have received steroid therapy as part of their primary treatment. Steroid\n             treatment must be stopped at least 10 days prior to leukapheresis.\n\n          -  Patients must not have progressive disease at completion of radiation therapy.\n             Patients with suspected pseudoprogression will be enrolled and analyzed separately.\n\n          -  Patients must be willing to forego cytotoxic anti-tumor therapies except temozolomide\n             essentially according to the schedule of the Stupp Protocol (Stupp et al. N Engl J Med\n             352: 987-96, 2005) while being treated with DCVax-L. DCVax-L treatment must be given\n             as described and temozolomide/Temodar treatment schedules must be given essentially\n             according to the Stupp Protocol.\n\n          -  Patients must have adequate bone marrow function (e.g., hemoglobin >10 g/dl, white\n             blood count 3600-11,000mm3, absolute granulocyte count ?1,500/mm3, absolute lymphocyte\n             count ?1,000/mm3, and platelet count ?100K/mm3. Eligibility level of hemoglobin can be\n             reached by transfusion.\n\n          -  Adequate liver function (SGPT, SGOT, and alkaline phosphatase ?1.5 times upper limits\n             of normals (ULN) and total bilirubin ?1.5mg/dl), and adequate renal function (BUN or\n             creatinine ?1.5 times ULN) prior to starting therapy.
Patients with cluster of differentiation (CD)34 selected auto grafts
Patients must have a direct bilirubin < 1.5 x upper limit of normal (ULN) for age or normal; these criteria may be waived for patients with known or suspected liver involvement by leukemia following review and approval by the study chair or vice chair
Patients must have an alanine transaminase (ALT) < 5 x ULN for age; these criteria may be waived for patients with known or suspected liver involvement by leukemia following review and approval by the study chair or vice chair
Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the treating physician; patients with underlying cardiopulmonary dysfunction should be excluded from the study
Patients refractory to red blood cell or platelet transfusions
Patients who are on hemodialysis.
All patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory baseline biopsy; it is preferred that this lesion be a lesion that progressed or arose while on the prior PARP therapy
CRC: at least 2 prior systemic regimens in the metastatic setting, and as appropriate in patients whose tumors are microsatellite instability-high (MSI-H), pembrolizumab as well.
Patients will then be assigned to one of two cohorts:\r\n* Cohort 1 will include patients who have relapsed /progressed within the first 180 days post-transplant and who are still within 3 months from date of progression-relapse\r\n* Cohort 2 will include patients who have either i) relapsed/progressed beyond day 180 post-HCT, ii) those with persistent stable disease or persistent disease with regression between days 28-100 after allogeneic HCT, or iii) those who progressed or relapsed within 180 days after HCT but were not started on this protocol within 3 months from date of progression or relapse could also be enrolled under cohort 2\r\n** NOTE: the inclusion of patients with persistent stable or persistent regressing disease in this protocol is not meant to advocate treatment; however, if the attending physician is inclined to offer treatment then these patients would be eligible for this study
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Patients are allowed to receive, but not required to receive biologic (noncytotoxic) therapy as part of their treatment regimen, e.g. bevacizumab
Patients who are deemed eligible for transplant by their treating physician
Patients must have progressed on, or be intolerant to ado-trastuzumab emtansine in the LABC/MBC setting
Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab)
Patients who have previously been treated with doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone, or any other anthracycline derivative
Patients with previous exposure to brentuximab pre-transplant are eligible for the study
Transplant eligible patients are eligible
Patients must have had 2 or more prior therapeutic attempts defined as:
Patient's ALT and AST must be < 5 x institutional upper limit of norm ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible after consultation with the Study Chair or Vice Chair.
Female patients with infants must agree not to breastfeed their infants while on this study.
Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.
Female patients with infants must agree not to breastfeed their infants while on this study.
Pregnant patients may not receive this experimental therapy
Patients must meet diagnostic criteria for NF2 including presence of bilateral VS (10 patients) or idiopathic VS without evidence of genetic syndrome (10 patients)
Male and female TAM patients ? 2 years old at the time of first dose administration. Patients < 12 years old can only be included in the study after first IA has shown that it is safe and well tolerated in patients ? 12 years old (Section 3.5).
The presence of TAM as per below diagnostic criteria at baseline (or screening if baseline visit is skipped). All the criteria have to be met for the patients included in the study:
Patients with ALT > 10x ULN at screening.
Patients with proven TTP as per historical data (as defined by ADAMST13 activity test) and if already available results of ADAMST13 test done at screening.
Patients previously treated with eculizumab for TAM.
Patients with known or suspected hereditary complement pathway deficiency. This exclusion criterion is not applicable to patients with complement pathway abnormalities/upregulation known to be associated with increased risk of transplant associated microangiopathy
Patients with mixed histology SCLC and NSCLC are permitted
Uncontrolled hypercalcemia ( ?1.5 mmol/L ionized calcium or Ca > 12 mg/dL) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (patients receiving bisphosphonate therapy or denosumab to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible, though patients receiving denosumab must be willing and eligible to receive bisphosphonates instead)
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRG-analogue therapy for the duration of the trial
Patients with unresectable, malignant pleural or peritoneal mesothelioma who have progressed on first-line pemetrexed-based chemotherapy
Patients with obstructed gastrointestinal tract or uncontrolled vomiting
Patients with only one kidney that is ipsilateral to the mesothelioma
Patients with verrucous or adenocarcinoma
Patients with T1 tumors on both cords (T1b)
Patients with T2b-T4 true larynx tumors
Patients with primary supraglottic tumors that involve the true larynx
Patients with chronic diarrhea of grade 2 or greater despite maximal medical management.
Patients who cannot receive cyclophosphamide
Patients who have an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled.)
No St John's wort supplement or other herbal supplementation is allowed while on trial; patients are not to take grapefruit juice during study treatment
Patients who have persistently elevated systolic blood pressures (BPs) >= 145 or diastolic BPs >= 90 need to have their systolic or diastolic BP controlled with anti-hypertensive agents for at least 3 days prior to the initiation of cell therapy; patients already on anti-hypertensive agents will have their medicine adjusted based on the clinical judgment of the patient care team
Diagnosis of skin, gut and/or liver steroid-refractory GVHD by clinical assessment of treating physician following allogeneic HCT. Patients who fail to respond to steroids by 7 days are considered steroid-refractory
Patients with psoriasis
Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency
Patients who have previously been treated with IMGN901
Patients must be untreated or have had only one prior chemotherapy regimen for ALL or LL; previously treated patients will be analyzed separately
Patients wanting to pursue transplant
Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), etc.). Patients with a remote history of asthma or mild active asthma are eligible.
Patients who cannot lie flat for 20 minutes
Previously untreated RT patients deemed ineligible for, or that refuse, intensive chemotherapy are eligible.
Patients must have at least one additional lesion (measurable by RECIST v1.1 or non-target) identified as a control untreated lesion to be left untreated and followed for response.
Patients with electronic pacemakers or defibrillators are excluded.
Patients residing in prison
Patients with extrapleural pneumonectomy (EPP)
Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
Patients with baseline creatinine kinase (CK) > ULN
Patients are allowed to have previously received, but are not required to receive, one or two additional cytotoxic regimens for management of recurrent or metastatic disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
Patients with pheochromocytoma
Patients must be considered unresectable or medically inoperable; patients who decline surgery are also eligible
Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 and of ipilimumab (diameter >= 10mm), percutaneously
Patients with cytogenetic breakpoint cluster region (BCR)-Abl variants and additional chromosomal abnormalities (‘clonal evolution’) will be eligible; cytogenetics to be performed, but results are not required to start therapy in patients with hematologic progression
Note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
Patients must have potentially resectable non-small cell lung cancer (NSCLC) by VATS as determined by a multidisciplinary team review; this primary should not have undergone any neoadjuvant chemotherapy (chemo-) or radiation therapy; only those patients undergoing surgery by conventional VATS will be included; (robotic procedures will not be eligible for inclusion in this study)
patients requiring total parenteral nutrition
Patients who are known purified protein derivative (PPD) positive will be screened for active tuberculosis prior to starting treatment with BCG
Patients with implantable or wearable electrical devices will be excluded from this study
Patients must have histologically or cytologically confirmed SCCHN that is recurrent and/or metastatic and not amendable to curative therapy by surgery or radiation; SCCHN originating from the following sites are eligible: oral cavity, oropharynx, larynx, hypopharynx and paranasal sinus; for patients with a diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved by the principal investigator
Histologically or cytologically confirmed B-cell NHL that has relapsed from, or is refractory to, standard therapies (including autologous transplantation) known to provide clinical benefit, but have not been treated with bendamustine for their lymphoma\r\n* Patients with limited exposure to Bendamustine (less than 2 full cycles) may be included, based on Principal Investigator (PI) discretion
Inclusion Criteria:\n\n        Male or Female, age ? 18 years Patients with higher risk MDS with a blast count < 20% at\n        the time of screening IPSS Int-2 or High Risk Serum Ferritin ? 300 ng/mL at screening.\n\n        Sexually active women must use an effective method of contraception, or must have undergone\n        clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be\n        postmenopausal (defined as amenorrhea for at least 12 months)\n\n        Exclusion Criteria:\n\n        Patients currently receiving any therapy other than AZA for MDS (a ? 4 week washout period\n        for any agent (excluding AZA) used to treat MDS prior to first dose of study treatment is\n        required).\n\n        Patients who have received > 2 cycles of AZA or decitabine at the time of randomization.\n        Patients who have received iron chelation therapy within 1 month of screening.\n\n        Patients who have received growth factors within 1 month of screening. Patients who have\n        received Revlimid within 1 month of screening. Patients who have undergone hematopoietic\n        stem cell transplant. ECOG Performance Status > 2 Systemic diseases (cardiovascular, renal,\n        hepatic, etc.) which would prevent study treatment Patients with uncontrolled systemic\n        hypertension Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or\n        unstable cardiac or coronary artery disease not controlled by standard medical therapy\n        Patients with a diagnosis of or history of clinically relevant ocular toxicity related to\n        iron chelation Diagnosis of liver cirrhosis (either established diagnosis or diagnosis by\n        liver biopsy or central ultrasound reading) Clinical or laboratory evidence of active\n        Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA\n        positive and ALT above the normal range). History of HIV positive test result (ELISA or\n        Western blot) Presence of a surgical or medical condition which might significantly alter\n        the absorption, distribution, metabolism or excretion of study drug Patients with an active\n        malignancy (currently or within the past two years) with the exception of basal cell skin\n        carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in\n        situ. History of drug or alcohol abuse within the 12 months prior to enrollment. History of\n        non-compliance to medical regimens or patients who are considered potentially unreliable\n        and/or not cooperative.\n\n        Patients with a known hypersensitivity to azacitidine, mannitol, or deferasirox. Calculated\n        creatinine clearance <40mL/min Serum creatinine greater than 1.5x ULN at screening Urine\n        protein/creatinine ratio> 1 AST or ALT greater than 3x ULN at screening Direct Bilirubin\n        greater than 1.5x ULN at screening. Patients who received treatment with systemic\n        investigational drug within the past 4 weeks or topical investigational drug within the\n        past 7 days or are planning to receive other investigational drugs while participating in\n        the study Patients participating in another therapeutic clinical trial Pregnant or nursing\n        (lactating) women, where pregnancy is defined as the state of a female after conception and\n        until the termination of gestation, confirmed by a positive hCG laboratory test. Women of\n        child-bearing potential, defined as all women physiologically capable of becoming pregnant,\n        unless they are using effective methods of contraception during dosing of study treatment.\n        Sexually active males unless they use a condom during intercourse while taking drug and for\n        3 months after stopping AZA and should not father a child in this period.
Patients who require or may be expected to require urgent treatment with docetaxel during the study (e.g., patients with visceral metastases).
Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
Patients with a solitary kidney
Patients with known active brain metastases; patients with a history of treated brain metastasis are eligible if the patient is off systemic steroids and there are no clinical indications of central nervous system (CNS) progression for a least 1 month; patients with glioblastoma multiforme are eligible if the above criteria are otherwise met; note: many clinical trials do not allow enrollment of such patients; if the physician, in good conscience, feels that applicable protocols for their patient do exist, enrollment onto this trial is acceptable, assuming other eligibility criteria are met
Relapsed or refractory B-ALL due to receive salvage 1, 2, 3, 4, 5, or 6; half of the patients, i.e. 5 out of the first 10 patients, and 5 out of 10 patients thereafter, need to be in earlier line of salvage therapy, defined as 1st, 2nd, or 3rd line of salvage therapy; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor; patients in salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy; patients with ALL of T cell origin (T-ALL) can not be treated
Patients must discontinue any medication that causes a strong CYP3A4 inhibition 1 week prior to treatment initiation; patients who are not able to discontinue these drugs are considered ineligible
Participants must be on a stable antiretroviral regimen per current International Acquired Immunodeficiency Syndrome (AIDS) Society guidelines as follows, with no intention of changing the regimen within 8 weeks after ibrutinib initiation:\r\n* Choice of regimen: The specific antiretroviral agents are at physician discretion, and the use of investigational agents currently available on an expanded-access basis is allowed; use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) is prohibited\r\n* Patients with mantle cell lymphoma, CLL, or SLL must be on non-cytochrome P450, family 3, subfamily A, polypeptide 4 (CYPA3A4) modulating antiretroviral agents (Stratum C) to be eligible for this study\r\n* Patients may be switched to non-conflicting regimens in order to participate\r\n* Stability of regimen: With the exception of patients on zidovudine-based ART, any changes in antiretroviral regimen must be made at least 4 weeks prior to ibrutinib initiation; patients taking zidovudine-based ART must change to a non-zidovudine-based regimen at least 2 weeks prior to ibrutinib initiation; changes to ART therapy during the study may be made if medically necessary (e.g. toxicity, treatment failure)
Patients currently on other protease inhibitors; patients can be switched to an alternative combination antiretroviral therapy regimen, as deemed appropriate by their HIV care provider
Patients previously treated with sunitinib or crizotinib
Patients who are actively receiving other cytotoxic or antibiologic chemotherapies; for patients with Her-2/neu positive disease, trastuzumab (Herceptin) is NOT ALLOWED on this study, and should be withheld during the 8 weeks of therapy, and can be resumed no sooner than 14 days following completion of protocol therapy
Patients who are platelet or red blood cell transfusion-dependent are eligible
Patients must have relapsed or refractory MCL
Patients on systemic anticoagulants are excluded from this study
Male or female patients and no race-ethnic restrictions
Patients are unwilling, or who are determined to be medically unfit for or resistant to standard intensive induction chemotherapy; patients who are medically unfit will be determined by the treating primary hematologist and the principal investigator (including but not limited to evaluation of co-morbidities, and response and complications to previous AML treatment strategy)
Patients with sickle cell disease and sickle cell crisis
Patients who have benign or malignant soft tissue tumors of the extremities, flanks, pelvis, or shoulders that require surgical intervention
Patients on dialysis
Patients with acute medical condition (e.g. pneumonia, sepsis) that is expected to hinder them from completing this study
Patients must provide a pretreatment saliva sample for genomic analysis
Patients with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate; pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population
Patients cannot be on a transplant list
Durable power of attorney form offered (patients >= 18 years of age only)
Patients on beta blockers
Patients with known glucose-6-phosphate deficiency, psoriasis, porphyria and psychosis
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
Platelet count ? 100,000 plts/mm3 (without transfusion); ? 75,000 plts/mm3 for patients with hepatocellular carcinoma only. For hematologic malignancy patients blood counts cited above do not apply
Patients who require treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1mg allowed for port line patency permitted).
Patients for whom dexamethasone is contraindicated.
Unresectable stage IIIA or IIIB disease; patients must be surgically staged to confirm N2 or N3 disease; patients may have invasive mediastinal staging by mediastinoscopy, mediastinotomy, endobronchial ultrasound transbronchial aspiration (EBUS-TBNA), endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery (VATS)
Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3, N1-N3 disease are eligible if deemed unresectable; patients with T4, any N are eligible
Patients aged >= 80 are not excluded; however, candidates in this age group should be thoroughly evaluated before enrollment in the study, to ensure they are fit to receive chemotherapy, and to potentially undergo pancreaticoduodenectomy; in addition to meeting all of the baseline patient selection criteria, clinical judgment on their susceptibility to infection and expected stability of their performance status and suitability to receive intensive chemotherapy cycles, should be paid special attention to; patients should not be enrolled in the study should there be any hesitation on any of these considerations; baseline criteria for all patients enrolled on the study must be carefully evaluated and all criteria followed appropriately
Patients must be clinically suitable for cryoablation therapy
If an open biopsy is performed, the patient must be at least one week post biopsy; this requirement does not apply to patients who undergo stereotactic biopsies
Patients with partial or complete bowel obstruction due to abdominal carcinomatosis
Prior treatment with capecitabine and/or celecoxib is allowed; however, patients with a documented history (at the time of enrollment) of >= grade 3 toxicities with capecitabine or celecoxib are excluded
Patients with a prior serious infusion reaction to cetuximab
Patients with a history of gross hemoptysis (defined as bright red blood of ½ teaspoon or more) will be excluded from this trial
Patients must have melanoma that is documented to contain a BRAFV600E or BRAFV600K mutation by a FDA-approved test.
Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with bevacizumab, vemurafenib and cobimetinib.
Patients with a history of second malignant tumor, other than the common skin cancers - basal and squamous carcinomas, within the past 3 years and uncertainty about the histological nature of the metastatic lesions; cases with other types of malignancies should be reviewed and decided by the principal investigator (PI) of the study
Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing information must be followed and precautions have to be taken into consideration (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not receive bevacizumab).
ALL PATIENTS:
Concomitant chemotherapy and radiotherapy while on protocol is prohibited; prednisone therapy will not be permitted with the exception of brief courses (=< 14 days) used for inflammatory conditions unrelated to CLL; patients may receive intravenous immunoglobulin (IVIG) while on protocol; patients may receive erythropoietin, darbepoetin, filgrastim, peg filgrastim, or sargramostim while on protocol; patients with cellular immune cytopenias may receive cyclosporine (pure red cell aplasia, etc.) while on study but consultation with principal investigator (P.I.) (or designee) is required
SCREENING: Patients must be aware of the neoplastic nature of their illnesses, the experimental nature of the therapy, alternative treatments, potential benefits, and risks
SCREENING: Patients must be willing to sign an informed consent and undergo resection of their malignancies at the National Cancer Institute (NCI), to ensure vaccine development
-  Adult patients with histologic verification of carcinoma of the pancreas (T1-3, N0-1)\n             who have undergone surgical resection within the past 4 - 12 weeks. Patients with R1\n             resections are excluded.\n\n          -  Must meet all laboratory safety criteria and not have active or history of autoimmune\n             disease or conditions, be treated with immunosuppressive drugs, or require the use of\n             systemic steroids. Primary intraoperative chemotherapy will be allowed.\n\n          -  Pregnant or nursing women will be excluded. Subjects with active infection, HIV,\n             Hepatitis B or C will be excluded.
Patients with advanced cancer must meet one of the following criteria (does not apply to first-degree relatives or individuals with pre-invasive histology enrolling only for EGFR germline mutation testing):\r\n* Patients must have biopsiable disease and be willing to undergo biopsy for molecular profiling or\r\n* Patients must have enough and adequate archival material from a previous biopsy to perform molecular profiling analyses; the adequacy of the material provided will be determined by the principal investigator in conjunction with the laboratories performing the molecular profiling analyses or\r\n* Patients must have previously undergone a successful molecular profiling of their tumor with mutation analysis of any of the genes described or anaplastic lymphoma receptor tyrosine kinase (ALK) break apart fluorescence in situ hybridization, as part of this protocol (crossover patients) or other molecular profiling protocols such as the Lung Cancer Mutation Consortium protocol among others
SUNITINIB MALATE ARM: Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
Patients with known syndromes that alter radiosensitivity
Ongoing use of an LH-RH agonist (or antagonist); patients who agree to stop LH-RH agonist therapy will be eligible but may need to wait until their required washout period is over; patients whose washout period is greater than 6 weeks will not be eligible; duration of washout period varies with the formulation of the LH-RH agonist being used and should be 2 weeks after the next dose would be scheduled; specifically:\r\n* For patients receiving a monthly formulations of LH-RH agonist, 6 weeks must pass from the last dose before eligibility;\r\n* For patients receiving a 3-month depot formulation of LH-RH agonist, 14 weeks must pass from the last dose before eligibility;\r\n* For patients receiving a 4- month depot formulation of LH-RH agonist, 18 weeks must pass from the last dose before eligibility;\r\n* For patients receiving a 6- month depot formulation of LH-RH agonist, 26 weeks must pass from the last dose before eligibility;\r\n* For patients with an annual LH-RH implant, 2 weeks must pass after removal of the implant before eligibility
Patients with diabetic retinopathy
Patients in sinus rhythm
Patients with stable respiratory status (no respiratory distress)
Patients scheduled for extrapleural pneumonectomy
Patients with second (2nd) or third (3rd) degree atrioventricular (AV) block
Patients already taking class Ic or III antiarrhythmic drugs
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients must agree to avoid grapefruit or grapefruit juice and Seville (sour) oranges during the entire study
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients who have had > 60 Gy total radiation to the pons (e.g. patients who have received re-irradiation)
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients have significant acute deterioration in neurologic status in 72 hours prior to enrollment, in the opinion of the treating physician
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients are known to be refractory to red blood cell or platelet transfusions
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients who are receiving any other anticancer or investigational drug therapy
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients who are required to receive any medication which can prolong the QTc interval
NON-PROGRESSED DIPG (STRATUM 2): Patients must have had their last fraction of focal irradiation to the primary site > 14 days prior to enrollment; patients must not have received local palliative irradiation or craniospinal irradiation
NON-PROGRESSED DIPG (STRATUM 2): Patients must agree to avoid grapefruit or grapefruit juice and Seville (sour) oranges during the entire study
NON-PROGRESSED DIPG (STRATUM 2): Patients who have had > 60 Gy total radiation to the pons (e.g. patients who have received re-irradiation
NON-PROGRESSED DIPG (STRATUM 2): Patients have significant acute deterioration in neurologic status in 72 hours prior to enrollment, in the opinion of the treating physician
NON-PROGRESSED DIPG (STRATUM 2): Patients are known to be refractory to red blood cell or platelet transfusions
NON-PROGRESSED DIPG (STRATUM 2): Patients who are required to receive any medication which can prolong the QTc interval
Inclusion Criteria:\n\n        Patients must meet all of the following inclusion criteria to be eligible to enroll in this\n        study.\n\n          1. Written informed consent obtained prior to any screening procedures and in accordance\n             with federal, local, and institutional guidelines.\n\n          2. Age ?18 years.\n\n          3. Patients with advanced solid malignancies or NHL for which all standard therapeutic\n             options considered useful by the investigator have been exhausted.\n\n          4. Patients must have objective evidence of progressive disease on study entry:\n\n               1. Advanced solid malignancies: Measureable disease as defined by RECIST 1.11.\n\n               2. NHL: Measureable disease including target lesion(s) as defined by the Lugano\n                  Classification2 for initial evaluation and staging.\n\n          5. Patients must have a site of disease amenable to biopsy and be a candidate for biopsy\n             according to the treating institution's guidelines.\n\n          6. Eastern Cooperative Oncology Group (ECOG) performance status of ? 1.\n\n          7. Adequate hepatic function:\n\n               1. Total bilirubin < 1.5 times the upper limit of normal (ULN) (except patients with\n                  Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total\n                  bilirubin of ? 3 times ULN),\n\n               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 times\n                  ULN (except patients with known liver involvement of their advanced solid\n                  malignancy or NHL who must have their AST and ALT ? 5.0 times ULN).\n\n          8. Adequate renal function: estimated creatinine clearance of ? 60 mL/min, calculated\n             using the formula of Cockroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL);\n             multiply by 0.85 if female.\n\n          9. Female patients of child-bearing potential must agree to use dual methods of\n             contraception (including one highly effective and one effective method of\n             contraception) and have a negative serum pregnancy test at Screening, and male\n             patients must use an effective barrier method of contraception if sexually active with\n             a female of child-bearing potential. For both male and female patients, effective\n             methods of contraception must be used throughout the study and for 3 months following\n             the last dose.\n\n         10. Adequate hematopoietic function: total white blood cell (WBC) count ? 1500/mm3,\n             absolute neutrophil count (ANC) ? 1000/mm3, hemoglobin (Hb) ? 10.0 g/dL, and platelet\n             count ? 75,000/mm3.\n\n         11. Dose Escalation Phase: Patients will be enrolled according to their NAPRT1 status at a\n             ratio of 2:1 (NAPRT1 negative:NAPRT1 positive). The NAPRT1 status must be determined\n             prior to enrollment based on evaluation of a fresh tumor biopsy or archival tissue\n             taken ? 6 months of screening.\n\n         12. Dose Expansion Phase (KPT-9274 ± niacin ER cohort only): Patient tumors NAPRT1 and\n             IDH1 tumor status must be determined at the central laboratory prior to enrollment.\n\n             a. Confirmation of NAPRT1 expression and IDH1 mutation based on evaluation of a fresh\n             tumor biopsy or archival tumor biopsy taken ? 6 months of screening tests as follows:\n\n             i. NAPRT1 positive for expansion cohort I or III\n\n             ii. NAPRT1 negative for expansion cohort II or III\n\n             iii. IDH1 mutation status for expansion cohort IV\n\n         13. Life expectancy of ? 3 months.\n\n        Exclusion Criteria:\n\n        Patients meeting any of the following exclusion criteria are not eligible to enroll in this\n        study.\n\n          1. Female patients who are pregnant or lactating.\n\n          2. Time since the last prior therapy for treatment of advanced solid malignancies or\n             NHL**:\n\n               1. Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including\n                  investigational anti-cancer therapy ? 2 weeks prior to C1D1.\n\n               2. Palliative steroids for disease related symptoms < 7 days prior to C1D1.\n                  **Patients must have recovered or stabilized (Grade 1 or to their baseline for\n                  non-hematologic toxicities, ? Grade 2 or to their baseline for hematologic\n                  toxicities) from toxicities related to their previous treatment except for\n                  alopecia. In specific cases, patients with Grade 2 non-hematologic toxicities\n                  will be allowed following approval by the Karyopharm medical monitor.\n\n          3. Patients with known central nervous system (CNS) disease or leptomeningeal\n             involvement, regardless of response to prior therapy, are excluded.\n\n          4. Major surgery within four weeks before C1D1.\n\n          5. Impaired cardiac function or clinically significant cardiac diseases, including any of\n             the following:\n\n               1. Unstable angina or acute myocardial infarction ?3 months prior to C1D1;\n\n               2. Clinically significant heart disease (e.g., symptomatic congestive heart failure;\n                  uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor\n                  compliance with an antihypertensive regimen).\n\n          6. Active infection with completion of therapeutic antibiotics, antivirals, or\n             antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or\n             antifungals are permitted.\n\n          7. Patients with a known history of Human Immunodeficiency Virus (HIV); HIV testing is\n             not required as part of this study.\n\n          8. Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or\n             HBsAg (HBV surface antigen). Testing is not required.\n\n          9. Patients with significantly diseased or obstructed gastrointestinal tract or\n             uncontrolled vomiting or diarrhea that could interfere with the absorption of\n             KPT-9274.\n\n         10. Serious psychiatric or medical conditions that, in the opinion of the Investigator,\n             could interfere with treatment, compliance, or the ability to give consent.\n\n         11. Active peptic ulcer disease or other active gastrointestinal bleeds.
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Patients in which iodine contrast is contraindicated
Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)
Patients must have been enrolled, or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245
Patients with known concurrent activating retrovirus-associated DNA sequence (RAS)/v-RAF-1 murine leukemia viral oncogene homolog (RAF) mutation or loss of function mutation or deletion in neurofibromin (NF)1 of NF2 resulting in mitogen-activated protein (MAP) kinase pathway activation; patients are not required to be evaluated for these alterations if not already performed
Patients with diabetes requiring insulin or requiring more than one non-insulin hypoglycemia agents
For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19 IHC+ HCC patients will be eligible for Part 3.
Patients with pre-existing retinal disease on ophthalmologic exam will be excluded
Patients who have been previously treated with MET or vascular endothelial growth factor receptor (VEGFR) inhibitors (except for patients on renal cell cancer [RCC] cohort) are not eligible for the expansion cohorts but can enroll in the phase I portion
Patients with MPD
For Part 1 (phase 1, single agent): Patients with a known or presumed pathogenic KIT exon 13 or 14 resistance mutation.
Parts 2a and 2d: Patients with known or presumed pathogenic KIT exon 13 or 14 resistance mutations. (However, such patients are permitted on the combination arms of Parts 2b, 2c, 2e, or 2f.)
Patients with AST/ALT > ULN must have negative hepatitis studies
History of (within 24 months prior to enrollment) of kidney, ureter, or bladder stones with clinically significant sequelae (e.g. (painless gross hematuria; pain with or without infection; hydronephrosis, etc); patients with otherwise stable non-occluding kidney stones regardless of stone type incidentally found in computed tomography (CT) scans are eligible; patients with prior history of uric acid stones are eligible regardless of time of onset
Patients with brain metastases must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants (Enzyme-Inducing Anti-Epileptic Drugs). Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week.
Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
Minimal residual disease (MRD) will be defined separately for each test (fluorescence-activated cell sorting [FACS], FISH or cytogenetics) using standard accepted definitions (that may change over the course of this study and are therefore not listed); thus, patients will be considered eligible only in cases where residual leukemia (i.e., MRD) can be detected above control values; in cases where MRD testing is not conclusive or when there is no control value for the test, the attending pathologist will be engaged and patients will only be eligible in cases where there is clear evidence of MRD
Patients on digoxin will be excluded from this study
Patients who do not have pure uterine sarcomas (i.e., no mixed malignant Mullerian tumors).
Patients with single or multiple cerebellar or cerebral cortex lesions are eligible
Patients must have an expected minimum life span of 60 days
All patients are expected to be followed for at least 1 year after the initiation of therapy
Patients with baseline neurologic symptoms at National Cancer Institute (NCI) Common Toxicity Criteria (CTC) level 3 are not eligible
Patients who are immunologically compromised (excluding corticosteroids used for control of tumoral edema) are not eligible
Patients receiving concomitant radiotherapy or immunotherapy
Having chronic hepatitis B or C will not exclude patients from participating if they are otherwise eligible; however, requiring treatment with interferon is an exclusion; patients must be stable without having received interferon in at least 4 weeks
Patients with known heparin induced thrombocytopenia
Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; NOTE: patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
Patients must have known PI3K/mTOR pathway gene aberrations (from molecular profiling studies).
Patients must have HPV positive HNSCC containing activating PIK3CA mutations.
Inclusion Criteria:\n\n        Patients must have:\n\n          -  advanced solid tumors and have confirmed cMET dysregulation\n\n          -  at least one measurable lesion as defined by RECIST 1.1.\n\n          -  recovered from all toxicities related to prior anti-cancer therapies\n\n          -  adequate organ function\n\n          -  ECOG performance status (PS) of 0 or 1\n\n        Exclusion Criteria:\n\n        Patients must not have:\n\n          -  known hypersensitivity to any of the excipients of INC280\n\n          -  prior treatment with cMET or HGF-targeting inhibitor\n\n          -  known hypersensitivity to digoxin or rosuvastatin or its excipients\n\n          -  symptomatic central nervous system (CNS) metastases who are neurologically unstable\n\n          -  presence or history of carcinomatous meningitis\n\n          -  history of another primary malignancy that is currently clinically significant or\n             currently requires active intervention\n\n          -  Clinically significant, uncontrolled heart diseases, including QTcF ? 450 msec (male\n             patients), ? 460 msec (female patients) on the screening ECG\n\n          -  Thoracic radiotherapy to lung fields ? 4 weeks prior to starting INC280\n\n          -  Major surgery within 4 weeks prior to starting INC280\n\n          -  Patients receiving unstable or increasing doses of corticosteroids.\n\n          -  Impairment of GI function or GI disease that may significantly alter the absorption of\n             INC280\n\n          -  Patients who have received, or are expected to receive digoxin or rosuvastatin within\n             21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the\n             DDI phase.\n\n        Other protocol-defined inclusion/exclusion criteria may apply
Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse
Patients receiving (anti-thymocyte globulin) ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-C
Patients with rapidly increasing peripheral blood blast counts
Patients currently entered on Alopexx Oncology Protocol AO-101
Patients with myocardial ischemia or peripheral muscle ischemia
Patients with MDS with isolated del(5q)
B12 and folate deficient patients with and without clinical symptoms (patients could be rescreened after successful therapy of B12 and folate deficiency)
Immunocompromised patients
Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity.
Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
Patients must have had histologic verification of solid tumor, including lymphomas, at original diagnosis or relapse except in patients with intrinsic brain stem tumors, patients with optic pathway gliomas, and patients with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Prior treatment with sirolimus, cyclophosphamide or topotecan: patients previously treated with any of these drugs as single agents will be eligible for this study; patients previously treated with two of the three drugs will also be eligible, however patients previously treated with all three agents in combination will not be eligible; patients previously treated with sirolimus analogues (e.g. temsirolimus, everolimus, or ridaforolimus) are also eligible
Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
Patients who have an active or uncontrolled infection are not eligible; patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria
ALC ? 900/?l (Note: Patients with AML are not required to meet these hematologic criteria).
Patients who are not able to swallow the lenalidomide capsule as a whole are excluded from this study (capsule cannot be opened, chewed, or crushed)
Eligible patients are expected to have a complete resection based on preoperative imaging; any patient not found to be able to have complete resection will not be eligible for this study
Patients with:
Part 3: Patients must have target (?2 cm diameter) or non-target lesion cancer that is accessible for core biopsies before starting on study and after one cycle of treatment.
Patients with AML must have had at least 2 prior therapeutic attempts including frontline induction.
Patients with ALL must have had at least 3 prior therapeutic attempts including frontline induction.
Female patients with infants must agree not to breastfeed their infants while on this study.
Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ? 50 bpm.
Patients with intraocular retinoblastoma, unilateral or bilateral, who would be treated either by systemic chemotherapy, external beam radiation (EBR), or enucleation would be considered for this study
Patients with small, localized intraocular Rb amenable to focal therapy (laser or cryotherapy) would be excluded, as they would not need systemic chemotherapy
Patients above the age of 60 only with principal investigator (PI) approval
Prisoners or patients who are involuntarily incarcerated.
Patients must be eligible for Alliance A031201 and must agree to proceed to enroll in A031201
Patients who have had prior sipuleucel-T, docetaxel, cabazitaxel, abiraterone or enzalutamide as a single agent, or in combination therapy
Patient’s must be eligible to receive melphalan dose of 200 mg/m^2
For dose expansion cohorts: Dose expansion portion of study will include two separate cohorts\r\n* One cohort will incorporate patients with esophageal, gastroesophageal junction (GEJ) or gastric carcinomas (squamous cell carcinoma or adenocarcinoma if predominant histology); these patients must have received at least one prior systemic therapy for metastatic disease; patients who had prior neoadjuvant or adjuvant chemotherapy as part of curative intent primary therapy but recurred in less than 6 months would also be eligible; patients with HER2+ disease must have received trastuzumab with disease progression prior to enrollment; patients on this arm may have had prior treatment with drugs targeting the PD-1 pathway, but will be limited to a maximum of 5 patients\r\n* The second cohort will include patients who have progressed on prior PD-1 pathway inhibition (single agent or in combination) in solid tumor types where these drugs are standard of care; the reason for discontinuation of the prior PD-1 pathway drug must not have been for toxicity; eligible tumor types include melanoma, RCC, UC, NSCLC, and SCCHN, but subsequent tumor types wherein relevant agents become an approved standard of care would also become eligible
Patients must have a comprehensive geriatric assessment and chemotherapy toxicity assessment score between 7-17
Inclusion Criteria:\n\n        Patients must have:\n\n          -  advanced solid tumors and have confirmed cMET dysregulation\n\n          -  at least one measurable lesion as defined by RECIST 1.1.\n\n          -  recovered from all toxicities related to prior anti-cancer therapies\n\n          -  adequate organ function\n\n          -  ECOG performance status (PS) of 0 or 1\n\n        Exclusion Criteria:\n\n        Patients must not have:\n\n          -  known hypersensitivity to any of the excipients of INC280 or to benzodiazepines or\n             known intolerance and hypersensitivity to caffeine\n\n          -  symptomatic central nervous system (CNS) metastases who are neurologically unstable\n\n          -  presence or history of carcinomatous meningitis\n\n          -  history of another primary malignancy that is currently clinically significant or\n             currently requires active intervention\n\n          -  Clinically significant, uncontrolled heart diseases, including QTcF ? 450 ms (male\n             patients), ? 460 ms (female patients) on the screening ECG\n\n          -  Thoracic radiotherapy to lung fields ? 4 weeks prior to starting INC280\n\n          -  Major surgery within 4 weeks prior to starting INC280\n\n          -  Patients receiving unstable or increasing doses of corticosteroids.\n\n          -  Impairment of GI function or GI disease that may significantly alter the absorption of\n             INC280\n\n          -  Patients who have received or consumed, or are expected to receive or consume\n             midazolam or caffeine-containing products (e.g., tea, coffee, cola), within 2 days\n             prior to Day 1 and during the whole duration of the DDI phase (i.e., from Day -2 to\n             Day 12)\n\n        Other protocol-defined inclusion/exclusion criteria may apply
Inclusion Criteria:\n\n        Patients must be ?18 years of age\n\n        Patients must have documented IDH1 and/or IDH2 gene-mutated disease\n\n        Patients must have an advanced hematologic malignancy with an IDH1 and/or IDH2 mutation\n\n        Patient must be able to understand and willing to sign an informed consent\n\n        Patients must have ECOG PS of 0 to 2\n\n        Patients must have adequate hepatic function as evidenced by serum total bilirubin ?1.5\n        upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic\n        involvement\n\n        Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase\n        (ALP) ?3.0 × ULN, unless considered due to involvement by the neoplasm under consideration\n        for treatment\n\n        Patients must have adequate renal function as evidenced by a serum creatinine ?2.0 × ULN or\n        Creatinine clearance 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR)\n        estimation\n\n        Patients must be recovered from any clinically relevant toxic effects of any prior surgery,\n        radiotherapy, or other therapy intended for the treatment of cancer\n\n        Female patients with reproductive potential must have a negative serum pregnancy test\n        within 7 days prior to the start of therapy. Patients with reproductive potential are\n        defined as sexually mature women who have not undergone a hysterectomy, bilateral\n        oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who\n        have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at\n        any time in the preceding 24 consecutive months)\n\n        Exclusion Criteria:\n\n        Patients who have undergone HSCT within 60 days\n\n        Patients who received systemic anticancer therapy or radiotherapy <14 days prior to their\n        first day of study drug administration\n\n        Patients who received an investigational agent <14 days prior\n\n        Patients who are pregnant or breast feeding\n\n        Patients with an active severe infection who require anti-infective therapy or with an\n        unexplained fever >38.5°C during Screening visits or on their first day of study drug\n        administration (at the discretion of the Investigator, patients with tumor fever may be\n        enrolled)\n\n        Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or\n        LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within\n        approximately 28 days of C1D1\n\n        Patients with a history of myocardial infarction within the last 6 months\n\n        Patients with known unstable or uncontrolled angina pectoris\n\n        Patients with a known history of severe and/or uncontrolled ventricular arrhythmias\n\n        Patients with QTc interval ?450 msec or with other factors that increase the risk of QT\n        prolongation or arrhythmic events\n\n        Patients taking medications that are known to prolong the QT interval\n\n        Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B\n        or C\n\n        Patients with clinical symptoms suggesting active central nervous system (CNS) leukemia or\n        known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a\n        clinical suspicion of CNS involvement by leukemia during Screening\n\n        Patients with immediately life-threatening, severe complications of hematologic\n        malignancies such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or\n        disseminated intravascular coagulation
Any co-morbid condition that poses a greater threat to the patient’s life expectancy than the recurrent myeloma
Uncooperative patients, or patients who are incapable of following directions (for example, as a consequence of a neurological or psychiatric disorder).
Patients whose intramedullary canal at site of fracture measures smaller than the diameter of the sheath provided.
All patients must have an electrocardiogram (ECG) within 2 weeks of starting conditioning
Patients with relapsed or refractory AML; patients must have failed at least one prior induction regimen for AML; the maximum number of prior lines of induction is 3
Patient better served by concurrent chemoradiotherapy: the protocol recognizes that institutional standards regarding which patients are best served by operative and nonoperative approaches vary; therefore, consistent with the American College of Chest Physicians (ACCP) guidelines, the protocol recommends multidisciplinary discussion of each patient and enrollment only of patients felt best served by the approach described herein
Patients with relapsed/refractory ALL
Patients with MDS (IPSS score ? 1.5)
Patients eligible for participation in Study CLTR0310-301 (Phase III study of CPX-351 NCT01696084) or who have already participated in that study are not eligible for this study.
Patients in whom urgent treatment with docetaxel is indicated, per clinician discretion; this includes, but is not limited to patients with symptomatic visceral metastatic disease
The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.
Patients with 2+ proteinuria/moderate or more at baseline are ineligible
Therapeutic Options: Patients must be ineligible or inappropriate for other treatment regimens known to have curative potential.
Patients may receive hydroxyurea, low-dose cytarabine and/or glucocorticoids to control peripheral blood leukemic cell counts at study entry
Patients must have received crizotinib monotherapy at 250 mg BID on a continuous dosing schedule for at least 90 days; patients must be planning to start treatment at least three days, but no more than 30 days after discontinuing crizotinib monotherapy; patients who were not able to tolerate 250 mg BID of crizotinib are not eligible for this study
Patients must have had histologic verification of osteosarcoma at original diagnosis
Patients who are receiving drugs that prolong the QTc are not eligible
Patients who have previously received eribulin, halichondrin B, or analogues of halichondrin B
Patients with metastatic or locally advanced and unresectable BRAF wild-type melanoma who have either progressed following previous treatment of immunotherapy, or are not eligible for immunotherapy; patients are defined as \BRAF wild-type\ if they test negative for V600 mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay
Immunosuppressed patients
Patients who are taking simvastatin or lovastatin. Patients should be switched to alternative therapies a minimum of 2 weeks before starting study drug
Patients who require treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g. immunosuppression after organ transplantation)
Patients must agree to provide all imaging studies for central radiology review; this central radiology review may be performed retrospectively and will not be utilized for decision making for patients on study
Patients on therapeutic doses of Coumadin or Lovenox are ineligible to participate in study
For patients enrolling in this trial at Washington University School of Medicine (WUSM), it is required that WUSM patients must also enroll in Human Research Protection Office (HRPO)# 201111001; the genetic analyses for University of Florida (UF) patients will take place at WUSM under the auspices of this protocol
Patients must agree to forgo any other treatments, including but not limited to cytotoxic or biologic chemotherapies, that are intended to treat the recurrent GBM while receiving treatment with NovoTTF therapy
Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised; adequate wound healing is required prior to study entry; baseline skin exam is required for all patients
Patients taking drugs leading to significant QT prolongation
Patients currently receiving active therapy for other neoplastic disorders
Patients with known amyloidosis
Patients with known cirrhosis
Patients with any gastrointestinal dysfunctions that could interfere with the interpretation of the food effect data
Patients with known intolerance to low or high fat meals
Patients with chronic diarrhea or with grade 2 or greater diarrhea despite maximal medical management.
Patients with known amyloidosis
Patients with known cirrhosis
Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
Patients with a cardiac pacer whose heart rate is set at a fixed rate and patients on concomitant medication that may limit increase in heart rate in response to hypotension
Patients with transformed CTCL eligible for CHOP regimen
Part 2 only: Patients must be docetaxel-naive.
Patients must discontinue all herbal supplements at a minimum of one week prior to initiation of therapy (such information will be collected on each patient)
Evidence of HER2 oncoprotein expression at the 2+ level by central laboratory. Patients whose tumors exhibit 2+ staining by IHC are eligible for the study.
Patients whose tumors score 1+ by conventional IHC, are non-amplified by FISH testing, and whose tumors score > or = 10.5 by HERmark® testing, are eligible for the study.
For the 7-10% of patients without splenomegaly, the diagnostic entry criteria must include all other features described above and at least 2 of the following criteria: \r\n* Circulating myeloid precursors \r\n* White blood cell (WBC) > 10,000/uL\r\n* Increased fetal hemoglobin (HgbF) for age\r\n* Sargramostim (GM-CSF) hypersensitivity\r\nOR, patients must have been previously diagnosed with JMML
Patients must be previously untreated with HCT
Patients must not be receiving valproic acid
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
Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)
Patients that were unable to tolerate at least 1 cycle of an alkylating agent plus corticosteroid (e.g. melphalan + dexamethasone) or alternative prior regimen because of severe adverse events (e.g. hypersensitivity reaction) may be considered after discussion with the study PI/Medical Monitor.
Male patients must agree not to donate semen or sperm
Adult patients must be relapsed or refractory to at least 1 prior multi-agent systemic therapy. Pediatric patients must be relapsed or refractory to at least 2 prior multi-agent systemic therapies. Patients with acute lymphoblastic leukemia who are Philadelphia chromosome-positive must have failed a second generation tyrosine kinase inhibitor.
Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans.
Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window.
Patients with known osteopenia or osteoporosis.
Patients who may receive therapeutically effective doses via an external beam approach to the lesion of interest as specified by MSKCC Radiation Oncology Department dose constraint criteria
Patients with kyphoplasty cement or hardware that would preclude effective catheter placement
Patients with known immune impairment who may be unable to respond to anti-CTLA-4 antibody
Patients must allow biopsy at the time of fiducial placement
Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
Patients who are taking drugs which affect androgen metabolism (e.g. spironolactone, ketoconazole, finasteride, dutasteride) will not be eligible; patients who received any of these agents within the 6 months prior to evaluation will be reviewed for eligibility by the principal investigator on a case by case basis
Patients with carcinomatous meningitis
Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
Patients on systemic corticosteroids (except for patients on stable doses of hormone replacement therapy such as hydrocortisone), or other immunosuppressants (e.g., infliximab, mycophenolate mofetil) are excluded
Patients should receive concomitant therapy with bisphosphonates, regardless of the presence of bony lesions, although study physicians may use their discretion based on presence of renal insufficiency or other mitigating factors
Serum creatinine will not be used to exclude patients; patients on renal-replacement therapy (e.g., hemodialysis or peritoneal dialysis) will be eligible to participate
Light-chain (AL) amyloidosis; patients with secondary amyloidosis due to MM are eligible
Patients who are currently receiving lithium chloride (LiCl)
Only patients with a test result, using the 5-gene Hh signature assay, indicating Hhpathway activated MB are eligible for this study. All available tumor material obtained at any time during the course of the patient's disease should be submitted for these analyses
Patients with G6PD deficiency.
Patients with relapsed /refractory AML, ALL, or MLL with rearrangement of the MLL gene, including 11q23 or PTD, are eligible for the expanded cohort:
Patients may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
Male patients must agree not to donate semen or sperm.
Patients with non-secretory or hyposecretory MM
Patients with primary systemic amyloidosis.
Patients must be suitable for treatment or re-treatment with lenalidomide & dexamethasone; Note: patients previously treated with lenalidomide & dexamethasone are eligible to participate in the trial
DOSE EXPANSION COHORT: GIST patients must have had progression on or have been intolerant to imatinib and sunitinib
Because no dosing or adverse event data are currently available on the use of ENMD-2076 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
Patients who have received prior treatment with sorafenib are eligible, as long as the sorafenib was not given in combination with cyclosphosphamide and/or topotecan. Patients with tumor relapse/progression while on sorafinib or having dose modifications or experiencing toxicity that required sorafenib to be discontinued are also ineligible to participate in this study.
Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.
Patients who have an active or uncontrolled infection are excluded. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
Patients with prior allogeneic transplant are not eligible.Patients with a documented history of cerebrovascular accidents and/or TIA within the past 6 months are not eligible.
Patients with a history of venous or arterial thrombosis personally or in a first degree relative before the age of 40 years are not eligible unless the thrombotic event was associated with a central line.
Patients must not be candidates for curative resection
Patients who have recurrent disease after having had one or more prior resections may be eligible, provided that they are not candidates for further curative resection.
Patients who have recurrent hepatocellular carcinoma following hepatic transplantation are excluded unless the following criteria are met: i. Transplantation was performed at least 6 months prior to the relapse of HCC. ii. Patients are on stable immune suppressive therapy with no clinical evidence of rejection. iii. Are receiving ? 2.5 mg everolimus daily. d. Patients with known HIV infection are excluded. e. Patients with Hepatitis B are eligible provided there is no active viral replication. Patients with Hepatitis C who are not on interferon are eligible.
Patients who have a diagnosis of hepatocellular carcinoma made through radiologic imaging may be eligible, provided they meet the criteria according to the American Association for the Study of Liver Disease, AASLD (Bruix and Sherman, 2005; Bruix and Sherman, 2011)
Patients must be candidates for sorafenib
Patients enrolling onto Cohort 2b who have been taken off bevacizumab must have had at least a 28 day washout from any previous administration of bevacizumab. It is preferred that patients who fail bevacizumab prior to trial entry remain on bevacizumab in the trial.
Patients with pheochromocytoma
Patients will be eligible to enter the study between 60-120 days post-transplant
Patients who were treated with 5'-azacitidine without response prior to transplant would be eligible to participate on this protocol
Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy (such as bevacizumab) as part of their primary treatment regimen; patients are allowed to receive, but are not required to receive, non-cytotoxic therapy for management of recurrent or persistent disease
Cohort A: Stage IIA-IIIA (TanyN1M0 or T2b-4N0M0) (selected patients with single station N2 nodal involvement in close proximity to the primary tumor target may be considered eligible at the discretion of the principal investigator [PI] if all normal tissue guidelines can be met)
Patients must consent to an indwelling central venous catheter
Patients may have failed ablative therapy
Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of AZD1775 (MK-1775)
Planned WBRT based on number (>= 3 lesions) and/or size (>= 1 cm) of brain metastases (BMs); patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Patients with prior SRS will also be eligible, provided that there are new, non-irradiated measurable brain lesions
Continuation of trastuzumab and pertuzumab are allowed for those patients already on trastuzumab and pertuzumab therapy
Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
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
Patients > 16 years of age must have a Karnofsky performance level of >= 70%, and children =< 16 years old must have a Lansky performance of >= 70%; patients who are wheelchair bound because of paralysis secondary to a plexiform neurofibroma should be considered ambulatory when they are up in their wheelchair; similarly, patients with limited mobility secondary to need for mechanical support (such as an airway PN requiring tracheostomy or continuous positive airway pressure [CPAP]) will also be considered ambulatory for the purpose of the study
Patients treated by BCS or mastectomy and axillary dissection must have 1-3 positive axillary nodes (macrometastases, > 2 mm)\r\n* Note patients with additional nodal micrometastases (> 0.2-2 mm) or isolated tumor cells (=< 0.2 mm) are eligible; patients with nodal disease limited only to micrometastases or isolated tumor cells are not eligible
Patients treated by mastectomy and SLNB alone must have only 1 positive axillary node (macrometastases, > 2 mm)\r\n* Note patients with additional nodal micrometastases (> 0.2-2 mm) or isolated tumor cells (=< 0.2 mm) are eligible; patients with nodal disease limited only to micrometastases or isolated tumor cells are not eligible
Adult patients
Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during front-line therapy that is stable for at least 7 days (ie, no increase > 15% from nadir).
Patient is immunocompromised (patients with splenectomy are allowed).
Immunocompromised patient (Note: patients with splenectomy are allowed)
Immunocompromised patient (Note: patients with splenectomy are allowed)
Only lucid patients qualified to consent to neurosurgical procedure will be approached for participation in this study
Patients that have clinically indicated intraoperative sensorimotor, or language mapping, will also have simultaneous (or tandem) i2DOS for functional brain mapping; 10 patients from each cortical mapping area will be imaged; optical maps will be compared to electrophysiological maps
Up to 6 patients with recurrent/relapsed glioblastoma multiforme (GBM/AnaA) or with grade 3 anaplastic astrocytomas that with a history of progression or recurrence following radiotherapy and an alkylating agent (e.g. temozolomide) Patients with other disease types may be enrolled into the expansion phase upon approval of the Sponsor.
Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
Malignancies that are refractory to or intolerant of established therapy known to provide clinical benefit. Patients must not be candidates for anti-tumor regimes known to provide clinical benefit.
Part I: Patients with one of the following histologically- or cytologically-proven conditions: relapsed/refractory AML, relapsed/refractory MDS, or advanced CML in AP or BP (i.e., Acute Group patients).
Arm C: Patients with CML in CP after failure of 2 FDA-approved TKIs (i.e., Non-Acute group patients)
Patients who have demonstrated intolerance to dasatinib 100 mg daily will not be eligible for Part III/Arm B or C of the study.
Patients must have at least one prior trastuzumab-containing regimen
Cancer patients greater than 18 years of age who have completed all assessments required to meet the primary objectives of a parental phase 1, 2 or 3 clinical study of iniparib as monotherapy or in a combination regimen.
All patients must be prescribed combination antiretroviral therapy with the goal of virological suppression using an acceptable regimen that adheres to national guidelines for treatment of HIV infection; non-suppressed, treatment experienced patients, defined as patients with a viral load > 400 copies/mL who have been on antiretroviral therapy for more than 4 months can be enrolled if an alternative ART regimen is available that includes at least two ART drugs that, in the opinion of the site investigator, are expected to have activity based on genotypic testing (if available) and treatment history
Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
Patients with known amyloidosis.
Patients with known cirrhosis.
Inclusion Criteria for group A and B:\n\n          -  Weight loss < 10% in the last three months.\n\n          -  WHO-performance status ? 2\n\n          -  Medical inoperable patients or patients refusing surgery.\n\n          -  Chemotherapy is allowed in neoadjuvant and adjuvant setting, with exclusion of the\n             period 4 weeks pre-SBRT and 6 weeks post-SBRT.\n\n          -  Before patient registration, written informed consent must be given according to\n             ICH/GCP, national and local regulations.\n\n        Risk group A specification:\n\n          -  NSCLC (Cytological or histological proven) patients with peripheral tumors >5 cm with\n             tumor staging cT2bN0M0 or cT3N0M0 (chest wall infiltration is no exclusion criteria,\n             as long as the tumor diameter is > 5 cm).\n\n          -  Single peripheral lung metastasis in inoperable patients with a diameter of > 5 cm. In\n             case of first presentation of metastatic disease, cytological or histological proof is\n             obligated.\n\n          -  In patients without cytological or histological confirmation of NSCLC, a growing\n             FDG-PET positive lesion (SUV >5) is accepted if a contra-indication for invasive\n             diagnostic examination (or refusal) is present.\n\n        Risk group B specification:\n\n          -  Patients with ? 2 simultaneous peripheral lung metastases ? 5 cm of any origin at any\n             location in the lung.\n\n          -  In case of first presentation of metastatic disease, cytological or histological proof\n             is obligated. This is not necessary in case of a history of an already proven\n             disseminated disease.\n\n          -  Patients having ? 2 peripheral lung metastases without unacceptable dose overlap.\n\n        Exclusion Criteria:\n\n          -  Patients with central tumors\n\n          -  Pancoast tumors\n\n          -  Prior radiotherapy treatment to the thorax\n\n          -  Patients receiving any systemic treatment during SBRT\n\n          -  Pregnant patients\n\n          -  Patients previously treated with adriamycin agents in case of heart involvement within\n             the treatment field.
Only patients who are expected to survive at least 6 weeks will be eligible for this study
Patients for whom potentially curative antineoplastic therapy is available
Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
Patients must have adequate physiologic reserve as evidenced by:
Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
Patients with electronic pacemakers or defibrillators are excluded from this study
Cohorts 2 & 3 only: Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the Medical Monitor.
Primary refractory patients
Patients with primary mediastinal DLBCL
Patients with a history of clinically significant venous thromboembolism will be excluded on cohort 2; patients with tumor associated thrombus in the renal vein will not be excluded
Patients must have a cytological or histological diagnosis of adenocarcinoma arising in the pancreas; adenosquamous cancers will be acceptable
Patients on corticosteroids for any reason
Patients must not have had disease progression while receiving siltuximab. For those patients originally assigned to placebo in the CNTO328MCD2001 study, patients who have received less than 4 months of siltuximab following crossover will also be eligible
Patients with FLT3 ITD positive AML or AML patients with other cytogenetic abnormalities who are eligible for trials of other targeted investigational agents from which the investigator feels there is greater benefit.
Patients cannot have had a second line salvage treatment (chemotherapy, biologic agents, investigational drugs, or radiation) or have had an autologous or allogeneic hematopoietic stem cell transplantation; patients can have had mixed frontline therapy such as 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) followed by 2-4 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as long as the induction chemotherapy is not more than 8 cycles in total length
Inclusion Criteria include:\n\n          -  Male and female patients, 7 to 16 years of age, inclusive, with malignant and/or\n             nonmalignant moderate to severe pain requiring or anticipated to require continuous,\n             around-the-clock, opioid treatment for at least 2 weeks (based on the investigator's\n             judgment);\n\n          -  Patients must have written informed consent provided by the parent or legal guardian\n             and assent provided by the patient, when appropriate;\n\n          -  Patients on incoming opioids must be taking ? 80 mg/day morphine or equivalent if aged\n             12 to 16 years or ? 40 mg/day morphine or equivalent if aged 7 to 11 years prior to\n             the screening visit;\n\n          -  Patients and patient's parent/caregiver must be compliant with the protocol, ie, must\n             be able to perform study assessments and understand and complete the age-appropriate\n             scale to rate pain intensity. Patients must not have a cognitive developmental delay\n             or any other condition that would preclude them from completing the age-appropriate\n             pain scale.\n\n        Exclusion Criteria include:\n\n          -  Patients who are allergic to buprenorphine or have a history of allergies to other\n             opioids (this criterion does not include patients who have experienced common opioid\n             side effects [eg, nausea, constipation]) or who have allergies or other\n             contraindications to transdermal delivery systems or patch adhesives;\n\n          -  Patients with a dermatological disorder, including burn and skin graft sites, at any\n             relevant patch application site that would preclude proper placement and/or rotation\n             of BTDS patches;\n\n          -  Patients with evidence of impaired renal function;\n\n          -  Patients with hepatic impairment;\n\n          -  Patients with history of seizures;\n\n          -  Patients with intracranial pressure;\n\n          -  Patients who have a history of sleep apnea within the past year;\n\n          -  Patients who require mechanical ventilation during study treatment period, are\n             cyanotic, or who have unstable respiratory disease;\n\n          -  Patients with clinically significant structural heart disease or a pacemaker;\n\n          -  Patients with clinically unstable cardiac disease;\n\n          -  Patients who receive or anticipate to receive investigational medication/therapy\n             during study drug treatment period.\n\n        Other protocol-specific inclusion/exclusion criteria may apply.
Patients with active infection defined as:\r\n* Positive blood culture within 48 hours of study registration\r\n* Need for supplemental oxygen or vasopressors within 48 hours of study entry
Patients with previous exposure to trabectedin
Patients unwilling to have a central catheter
Patients with a fasting plasma glucose > 1.5 ULN; Note: at the principle investigator’s discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted
Patients with symptomatic cholelithiasis
Patients with cancer potentially curable by surgical excision alone or patients who have not received therapy that might be considered standard and potentially curable
Patients who have mixed tumors with small-cell elements are ineligible
Inclusion Criteria:\n\n          1. Pathologically documented Stage IV malignant melanoma or unresectable Stage III\n             melanoma for which no standard effective therapy exists or for which an appropriate\n             window exists between alternative therapeutic options. Patients for whom early\n             treatment with vemurafenib is indicated e.g. rapidly progressing or symptomatic\n             disease, are excluded from this trial.\n\n          2. Previous surgery (other than resection of skin metastases), radiotherapy,\n             chemotherapy, immunotherapy or experimental therapy completed >4 weeks before and all\n             adverse events resolved to ? grade 1. In cases where localised radiotherapy has been\n             applied, treatment with IMCgp100 can be commenced after a two week period.\n\n          3. HLA A2 positive.\n\n          4. ? 18 years old.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status ?1.\n\n          6. Measurable disease according to RECIST 1.1 criteria. Patients participating in the\n             dose escalation part of Arm 2 only require assessable disease.\n\n          7. Life expectancy >3 months.\n\n          8. Blood tests within the following parameters:\n\n               1. Platelet count ?100 x10?/L\n\n               2. Haemoglobin ?9g/dL (blood transfusion to achieve this level is permitted)\n\n               3. Calculated creatinine clearance ?50 mL/min using the modified Cockroft-Gault\n                  equation\n\n               4. Neutrophil count ?1x10?/L\n\n               5. Lymphocyte count ?0.5x10?/L\n\n          9. Female patients of childbearing potential must use maximally effective birth control\n             during the period of therapy, must be willing to use contraception for 6 months\n             following the last study drug infusion and must have a negative urine or serum\n             pregnancy test upon entry into this study. Otherwise, female patients must be\n             postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.\n\n         10. Male patients must be surgically sterile or willing to use a double barrier\n             contraception method upon enrolment, during the course of the study, and for 6 months\n             following the last study drug infusion.\n\n         11. Patients with a history of adrenal insufficiency, maintained on stable replacement\n             dose corticosteroid (<10 mg/d prednisone or the equivalent) are eligible for treatment\n             with IMCgp100, unless there is a past history of adrenal crisis. Eligible patients\n             with a history of adrenal insufficiency receiving replacement dose corticosteroid must\n             receive prophylactic stress dose corticosteroid prior to dosing during the first four\n             doses of IMCgp100 treatment, regardless of weekly or daily dosing regimen.\n\n         12. Able to give informed consent.\n\n        Exclusion Criteria:\n\n        Patients meeting any of the following criteria will be excluded from the study:\n\n          1. Symptomatic brain metastases that are unstable, require steroids, or that have\n             required radiation within the last 28 days.\n\n          2. Other active malignancy in the past 5 years except carcinoma in situ, completely\n             excised nonmelanomatous skin cancer or any other malignancy that in the opinion of the\n             investigator is considered to be cured.\n\n          3. Comorbid medical condition that would increase the risk of toxicity in the opinion of\n             the investigator or sponsor. Symptomatic on-going infection must be resolved before\n             the patient can be treated in the study.\n\n          4. Uveitis\n\n          5. Had myocardial infarction within 1 year before enrolment, symptomatic congestive heart\n             failure (New York Heart Association >Class II), unstable angina or unstable cardiac\n             arrhythmia requiring medication.\n\n          6. Has an ejection fraction <50%.\n\n          7. Clinically significant electrocardiogram (ECG) changes that obscure the ability to\n             assess the RR, PR and QT intervals. Patients with QTc calculated by Bazetts or locally\n             preferred formula which is greater than 500ms.\n\n          8. Has hepatic function as follows:\n\n               1. Aspartate aminotransferase >2.5 x upper limit of normal (ULN)\n\n               2. Alanine aminotransferase >2.5 x ULN\n\n               3. Bilirubin >2.0 x ULN\n\n               4. Prothrombin time or partial thromboplastin time >1.5 x ULN\n\n          9. Bleeding diathesis.\n\n         10. Immunosuppressive condition or treatment including previous transplantation,\n             splenectomy or known HIV infection.\n\n         11. Has a history of adult seizures.\n\n         12. Patients with evidence of a raised intracranial pressure in Arm 2 of the study who\n             will have a CSF sample taken.\n\n         13. Patients receiving chronic corticosteroid treatment (longer than 8 weeks duration) for\n             management of pre-existing adverse events at any dose, or patients with a history of\n             chronic corticosteroid treatment longer than 8 weeks duration for adverse events\n             within 6 months.
Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:\r\n* Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: \r\n** v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of 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 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown\r\n* Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:\r\n** MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features\r\n** Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status\r\n* Patients with newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features\r\n* Patients >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S
Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible
Patients must have a Gynecological Oncology Group (GOG) performance status of 0, 1 or 2
Patients must have met all pre-entry requirements
Patients may receive estrogen +/- progestin replacement
Patients with a CA125: carcinoembryonic antigen (CEA) ratio of < 25
Patients with evidence of abdominal free air not explained by paracentesis
Patients with signs or symptoms of gastrointestinal obstruction including those receiving total parenteral nutrition (TPN), intravenous hydration or tube feeds
Patients with hypertensive crises or hypertensive encephalopathy
Patients with a GOG performance status of grade 3 or 4 are not eligible
Patients with hematologic malignancies completing a prior idelalisib study with a clinical benefit are eligible
For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ? 750 mg/dL (0.75 g/dL)
patients receiving hydroxyurea or corticosteroids that has not been discontinued at least 1 week after initiation of nilotinib
All patients must have histological evidence of a solid malignant tumor (hematological malignancies are excluded) with convincing clinical, radiographic or isotopic evidence of cancer, for which no effective proven treatment exists. CNS associated tumors are preferred, but not required. Patients must sign an informed consent that complies with the investigator/DEKK-TEC policies and approved by a Human Investigation Review Committee.
Patients with cognitive impairment or likely to develop cognitive impairment while on study
Patients with myelofibrosis (Lille > 0, transfusion dependency, progression to blast phase; however, in remission from AML) or chronic myelomonocytic leukemia (CMML); these patients will be treated with the reduced-intensity conditioning regimen #2 and will be subject to the same stopping rule as the group >= 55 years or with comorbidities
Patients must meet criteria for acute lung injury
Patients moribund or with other organ failure at possible randomization:
The subject is not a candidate for neoadjuvant chemoradiation therapy (i.e., patients with borderline resectable pancreatic ductal adenocarcinoma who are known to benefit from neoadjuvant treatment regimens)
Patients must have been =< 35 years at the time of initial diagnosis
Patients who are receiving other biologic therapies including cytokines or growth factors not specified by the protocol; herbal supplements will not result in exclusion but should be noted and reviewed with the Principal Investigator (PI)
Patients with current diagnosis of primary cutaneous ALCL (patients who have transformed to systemic ALCL are eligible).
Patients must sign an authorization for the release of their protected health information
Patients must be registered in the University of California at San Francisco (UCSF) Neuro-Oncology database prior to treatment with study drug
Patients with documented or suspected Candida meningitis.
Patients that undergo bronchoscopy and are found to have endobronchial lung cancer that is obstructive or hemorrhagic as evident by inspection or CT scan are eligible
Patients must be willing to comply with the photosensitivity guidelines for a minimum of six weeks to be in the PDT treatment group (Group 1)
Patients that have endobronchial lung cancer that is obstructive or hemorrhagic, but do not wish to undergo PDT therapy will be eligible to participate in the non-treatment group
At the time of the second bronchoscopy (if clinically necessary), all patients will undergo routine laboratory tests including a CBC, chemistry 7 panel and coagulation profile
Patients taking antioxidant therapy will be excluded from enrollment due to potential interaction with the potential oxidative mechanism of action of Photofrin®, including:\r\n* Beta-carotene\r\n* Lutein\r\n* Lycopene\r\n* Selenium\r\n* Vitamin A\r\n* Vitamin C\r\n* Vitamin E
Patients that are not willing to adhere to the photosensitivity guidelines will not be eligible
Male Patients:
All patients must:
Agree not to share study medication with another person. All FCBP and male patients must be counseled about pregnancy precautions and risks of fetal exposure.
Patients who have completed preceding gefitinib therapy from either the 1839IL/0709 (250mg dosing) study or 1839IL/0710 (250mg dosing) study and in the opinion of the investigator may benefit from further gefitinib treatment.
Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total colectomy with ileo-anal pull through (reservoir), and patients with intact colons with 5 or more adenomas in the rectum-sigmoid or reservoir
All patients must have CTCL diagnosed by morphologic, histochemical or cell surface marker criteria with stage never exceeding IB / IIB disease and mSWAT < 50%. CTCL patients with stage IA disease are not eligible for enrollment. CTCL patients with stage IB disease are eligible provided that they have failed a systemic treatment (this includes radiation). CTCL patients with bone marrow involvement but without lymph node involvement are eligible. Patients with a diagnosis of angioimmunoblastic T cell lymphoma are eligible, even with lymph node involvement. Age ? 18 years. Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale (see Appendix). Patients must have fully recovered from toxicity of prior chemotherapy or radiation therapy.
Progression of solid tumors/lymphomas: Patients demonstrating clear tumor progression 4 weeks after receiving DLI will not be eligible to receive additional DLI
Patients with a calcium level greater than 13mg/dL.
At the discretion of the principal investigator if he/she feels that the patient is unable to safely complete the study; specifically, patients must be considered medically eligible to undergo high dose chemotherapy and autologous stem cell transplantation
Patients < 65 years of age with histologically confirmed refractory or relapsed Hodgkin’s disease (including patients who fail or relapse after autologous stem cell transplant [SCT]); this upper age limit will apply to transplants from both matched related and unrelated donors
Patients up to 65 years of age at time of registration with a diagnosis of SAA; SAA is defined as follows:
Diagnosis of Fanconi anemia must be excluded in patients younger than 18 years of age by diepoxybutane testing on peripheral blood or comparable testing on marrow.
Patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than ten (10) calendar days after the date of study enrollment; patients should be enrolled preferably between day 56 and day 85 after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for tandem transplant); patients must be enrolled no later than day 200 after PBSC infusion; enrollment must occur after completion of radiotherapy, and after completion of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained within 3 weeks pre-ASCT up to the time of registration
Patients with relapsed/refractory ALL
Patients with MDS (IPSS score ? 1.5)
Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term nonchemotherapy treatment, e.g., hormonal therapy, are eligible.
All patients will have a tuberculin (purified protein derivative [PPD]) skin test or interferon-gamma release assay (IGRA) done locally prior to the inclusion into the study. Patients with active tuberculosis (TB) will be excluded from the study.
Patients are scheduled to undergo RARC at our institution
Patients with presence of multiple bladder lesions
Patients must have 1-2 intrahepatic foci of HCC and may not be candidates for refuse hepatic resection; patients who are on the organ wait list for orthotopic liver transplantation (OLT) will be considered for this trial as a “bridge” to transplant
Patients must have a minimum of two metastases per hemithorax
Patients must be aware of the neoplastic nature of their illnesses, the experimental nature of the therapy, alternative treatments, potential benefits, and risks
Patients with a positive fecal occult blood test excluding hemorrhoids
Patients must have progressed on octreotide therapy and/or radioactive isotopes linked to octreotide or its congeners if they had a positive octreotide scan; patients who have negative or mildly positive octreotide scans are exempt from this requirement
Somatostatin analogs can be continued at their tolerated dose in patients with functional symptoms related to underlying disease such as in functional islet cell, insulinomas, glucagonomas etc
Patients with prior exposure to agents targeting interleukin 6 (IL -6) or the IL-6 receptor are not eligible
Patients who are on any prohibited medication; they have to be have a wash-out period of at least 2 weeks prior to registration, in order to be eligible for the study
Female patients who are pregnant or breast-feeding are not eligible; NOTE: A woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study agent should likewise not be considered for this study
Patients residing in prison
Patients currently enrolled in another study; concurrent enrollment in another study is prohibited expect for the control arm which can be used for other protocols with HRQOL endpoints with similar instruments
Three biopsies, one pretreatment, one after BMN673 alone and one after one of the combinations of BMN673/AT13387 will be voluntary in the expansion and dose escalation cohorts; however, biopsies will be required in at least 8 patients of the 20 patients to be enrolled in the expansion cohort
Patients genotyped for UGT1A1*28 polymorphism with *1/*1 or *1/*28 genotype
Patients with both variant alleles (*28/*28)
Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g, *6)
Patients with MF who are eligible for enrollment in the pacritinib “PERSIST-2” study at Washington University School of Medicine (WUSM) (NCT02055781) Human Research Protection Office (HRPO) 201406075
Patients with markedly decreased visual acuity
The target population for this study is patients who have participated in any REGN2810\n        clinical study.\n\n        Inclusion Criteria for Patients Receiving Re-treatment:\n\n          1. Tolerated prior treatment with REGN2810 with no unacceptable toxicity (except select\n             reversible irAEs) requiring discontinuation of REGN2810\n\n          2. Developed documented progressive disease after first demonstrating clinical benefit\n             from their initial treatment\n\n          3. Eastern Cooperative Oncology Group (ECOG) performance status ? 1\n\n          4. ?18 years old\n\n          5. Hepatic function:\n\n               -  Total bilirubin ? 1.5 x upper limit of normal (ULN; if liver metastases ? 3 x\n                  ULN)\n\n               -  Transaminases ? 3 x ULN (or ? 5.0 x ULN, if liver metastases)\n\n               -  Alkaline phosphatase (ALP) ? 2.5 x ULN (or ? 5.0 x ULN, if liver metastases)\n\n               -  For patients with hepatic metastases or hepatic malignancies, exclude patients\n                  with concomitant 3 x ULN ? aspartate aminotransferase (AST) and/or alanine\n                  aminotransferase (ALT) ? 5 x ULN and 1.5 x ULN ? total bilirubin ? 3 x ULN\n\n          6. Renal function: Serum creatinine ? 1.5 x ULN\n\n          7. Bone marrow function:\n\n               -  Hemoglobin ? 9.0 g/dL\n\n               -  Absolute neutrophil count (ANC) ? 1.5 x 10^9/L\n\n               -  Platelet count ? 75 x 10^9/L\n\n        Inclusion Criteria for Patients who Will not Receive Re-treatment:\n\n        Patients must have completed participation in any REGN2810 clinical study.\n\n        Exclusion Criteria:\n\n        A patient who meets any of the following criteria will be excluded from receiving\n        re-treatment with REGN2810:\n\n          1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that\n             required treatment with systemic immunosuppressive treatments, which may suggest risk\n             for irAEs.\n\n          2. Patients who experienced an irAE in while participating in another REGN2810 protocol\n             who were unable to have their corticosteroid dose reduced to <10 mg per day prednisone\n             equivalent within 12 weeks of toxicity.\n\n          3. Patients who developed ? Grade 2 uveitis in a prior REGN2810 protocol\n\n          4. Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within\n             4 weeks prior to the first dose of REGN2810\n\n          5. Active infection requiring therapy, including known infection with human\n             immunodeficiency virus, or active infection with hepatitis B or hepatitis C virus.\n\n          6. History of pneumonitis within the last 5 years.\n\n          7. Any investigational or antitumor treatment within 30 days prior to the initial\n             administration of REGN2810.\n\n          8. History of documented allergic reactions or acute hypersensitivity reaction attributed\n             of Grade ? 3 severity during or directly following an REGN2810 infusion\n\n          9. Known allergy to doxycycline or tetracycline. (precaution due to presence of trace\n             components in REGN2810)\n\n         10. Breast-feeding\n\n         11. Positive serum pregnancy test\n\n         12. History within the last 5 years of an invasive malignancy other than the one treated\n             in this study, with the exception of resected/ablated basal or squamous-cell carcinoma\n             of the skin or carcinoma in situ of the cervix, or other local tumors considered cured\n             by local treatment.\n\n         13. Acute or chronic psychiatric problems that, under the evaluation of the investigator,\n             make the patient ineligible for participation\n\n         14. Unwilling to practice adequate contraception during the study until 6 months after the\n             last dose of study drug
Patients may not be receiving any other drugs for the treatment of GvHD or investigational agents, except for a maximum of 48 hours of prior GC therapy, as above (obviously, this requirement is waived for SA – acute GvHD patients; in this case, no requirements are mandated)
Patients with relapsed or persistent malignancy requiring immunosuppressive withdrawal or modulation (an example of this may be a patient who relapsed and was being treatment with DLI and then developed GvHD)
Patients with Richter’s transformation are not allowed in the study
Patients must meet pre-entry requirements
Patients with phaeochromocytoma
Patients with central tumors within the proximal tree or touching the mediastinal pleura
Patients with clinical symptoms consistent with active gastritis
Patients requiring iron supplementation will be excluded
NY-ESO-1 expression in tumor by immunohistochemistry (IHC) is not required prior to screening consent; however, patients must have NY-ESO-1 expression to proceed with the leukapheresis; additionally patients must also meet the following criteria to proceed with leukapheresis (any exceptions to this will require prior approval by the Apheresis director and Principal Investigator):
All patients must have an electrocardiogram (ECG) within 2 weeks of starting conditioning
Patients for whom we are unable to generate NY-ESO-1 specific cells
Patients who consume more than 3 alcoholic beverages per day
For patients with lymphomas that are considered potentially curable, all curative attempts should be exhausted before the patient is considered eligible for this study
Patients with active bipolar disorder
Patients with impaired decision making as determined by the treating physician
Patients must be pre-menopausal patients within the reproductive age range
Patients must have the cognitive ability to participate in the study
Patients who previously participated in or are currently participating in another intervention clinical trial designed to improve adherence
Patients who have met the pre-entry requirements
Patients with depth of invasion > 10 mm on first cone biopsy (or LEEP)
Patients must not be dialysis dependent
Patients must be willing to submit blood specimens
Patients must not be registered to step 2 until receiving confirmation from the ECHO Core Lab that the patient’s LVEF by echocardiogram was >= 50% by central review; patients must be registered within 5 calendar days of receiving the e-mail notification
Patients with an estimated survival of less than one year are not eligible
Patients with a motor, visual, or auditory handicap that prevents computer use (e.g., unresolved posterior fossa syndrome) are not eligible to participate in this trial
Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR existing diagnosis of/educational classification as a student with an intellectual disability are not eligible
Patients with infra-tentorial tumors are not eligible
Patients on fibrinolysis, full-dose therapeutic anticoagulation, or high dose antiplatelet therapy
Usability Test interview participants must meet criteria above and may also include patients who have undergone one or more cycles of treatment
Patients having any immediate reconstructive procedure
Patients are having bilateral mastectomy
Patients who report a baseline pain score > 3, unrelated to a breast procedure
Patients will be excluded if they are having their mastectomy performed with tumescence
Patients taking lithium
Patients with pain or dysesthesia
Patients able to complete pain assessment and quality of life surveys
Patients with a radiographic or pathologic fracture to the treatment site
Patients with painful metastases to hands and feet that need to be radiated on protocol
Patients previously treated with radioactive isotope (e.g. strontium [Sr]89) within 30 days of randomization
Must be starting a new chemotherapy regimen (patients whose treatment regimen includes an immunomodulatory agent such as lenalidomide or small molecule targeted agents such as ibrutinib or idelalisib will be included in the study; patients being treated with a single agent monoclonal antibody will not be included)
Patients undergoing RC and IC formation in an elective setting for non-metastatic cancer
Adult patients who are capable of giving consent
Patients who are not eligible for standard anesthetic induction, e.g., those needing rapid sequence induction or awake fiberoptic bronchial intubation
Patients identified by treating physician as being unsuitable for contact
Patients can be Karnofsky performance status (KPS) >= 60, as long as primary provider feels that patient is candidate for combined modality chemoradiotherapy
Patients with a feeding tube previously placed
Patients already receiving palliative care
Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated.
Patients who either
Patients on dialysis
Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study.
Patients on anti-arrhythmic drugs
Patients with persistent undistinguishable pain (pain source unidentifiable of the targeted lesion)
Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up; patients must be willing to complete neurocognitive assessments at pre-specified time points outlined in the protocol
Patients must have subjective complaints of cognitive deficits
Patients who, based on the physician’s opinion, are unable to participate in neurocognitive testing and/or neurocognitive rehab secondary to significant neurologic deficit
Patients for whom complete cavity shaving is planned (sites where this is the routine practice of the investigator will also be excluded from participation in the study)
Patients already meeting the criteria for metabolic syndrome as defined by the Adult Treatment Panel III criteria which requires 3/5 parameters encompassing glucose control, blood pressure, lipids and waist circumference; patients with 2 of the parameters at baseline will be allowed enrollment provided that one of those risk factors is hypertension (>= 130/>= 85 mm Hg)
Patients with poor cardiac function as defined by an ejection fraction < 40% are excluded (only for patients enrolled on second phase of protocol for leukapheresis)
Patients enrolled in other CGA studies will not be excluded
Patients stable enough to undergo chemotherapy as determined by the patient’s oncologist
Acute thrombocytopenia in patients with hematological malignancies who are in remission and are receiving myelosuppressive consolidation chemotherapy that is expected to induce marrow aplasia for at least 2 weeks or;
Expected chronic thrombocytopenia in patients with relapsed or refractory hematological malignancies or;
Patients with known lupus anticoagulant or positive antiphospholipid antibody
Patients must not be on enzyme-inducing antiepileptic drugs (EIAEDs)
Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until day 5 of treatment
Patients on immunosuppression are also eligible
Patients treated at collaborating sites and current St. Jude patients who are on therapy or within 3 years of completion of therapy must be =< 24 years old; all other St. Jude patients must be =< 21 years old
Patients with prior treatment with IFN-gamma will be eligible, if they previously tolerated IFN-gamma, however patients must be off of IFN-gamma for at least three weeks before initiation of therapy on this trial
Cohort B: Patients must not have any visceral lesions
Patients must, in the opinion of the treating physician, be candidates for intralesional administration into cutaneous, subcutaneous, or nodal lesions; patients must have at least 2 injectable lesions
Patients must have lactate dehydrogenase (LDH) obtained prior to registration
Patients must not require use of systemic corticosteroid within 14 days prior to registration or during protocol treatment; patients with preexisting severe autoimmune disease requiring systemic corticosteroids or ongoing immunosuppression are not eligible
Patients must be willing to submit blood and tissue specimens for translational medicine
Patients must be offered the opportunity to participate in specimen banking for future research
Tumors that are Her2 positive are eligible
Patients must have surgically resectable disease treatable by esophagectomy, as assessed by a thoracic surgeon
Female patients may not be breastfeeding at the first dose of talazoparib and must not breastfeed during study participation through 45 days after the last dose of talazoparib.
Patients with up to two recurrences are allowed.
Patients with prior allogenic transplants.
Patients intolerant to prior immunotherapy (unable to continue/receive due to immune-related AE).
Infection requiring receipt of therapeutic oral or IV anti-microbials within 2 weeks of first study treatment; patients receiving routine anti-microbial prophylaxis (for dental extractions/procedures) are eligible
Patients whose participation in this trial would require exclusion from participation in another clinical research trial related to the patient's malignant diagnosis
Patients with partial or complete limb amputations
Patients with implantable drug delivery systems, e.g. Medtronic Synchromed
Patients not receiving care at Massachusetts General Hospital (MGH)
Patients receiving supportive care alone
Patients already receiving palliative care
Adult caregivers (> 18 years) of patients who have agreed to participate in the study
Patients with a history of any musculoskeletal, cardiorespiratory or neurological diseases that preclude the participation in exercise must be evaluated by their physician to assess if they are suitable to proceed on study
Patients with galactosemia
Patients currently taking anabolic steroids will be excluded; patients taking corticosteroids are allowed on study
Excluded patients will be allowed to participate in the trial on an observational basis only
Currently receiving hospice care (patients who enroll in hospice during the trial will have the option of continuing trial participation)
Patients with currently uncontrolled cardiac arrhythmias (non-sinus rhythm) will be excluded; patients with history of arrhythmias under pharmacological/pacemaker control will be allowed, except if receiving antiarrhythmic medication listed in “contra-indicated medications” below
Patients with cognitive deficits
Patients with a clinical diagnosis of cancer that are within +/- 3 days of initiating treatment with sorafenib, sunitinib, or regorafenib.\r\n* Note: patients treated with a combination regimen that includes sorafenib, regorafenib, or sunitinib are eligible.
Patients with a prior diagnosis of hand-foot skin reaction are not eligible.
Patients taking nitrates (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate) and/or alpha blockers (e.g., tamsulosin, prazosin, afluzosin, silodosin) are not eligible.
Patients who are unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function are not eligible.
Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude epidural placement
Patients having robotic prostatectomy.
Patients must be willing to spend time for the study.
Patients who are able to follow-up in person during the trial
Patients who are willing and able to maintain a daily pain diary
Patients with high disposition of laryngospasm or apnea
Patients with lesions to the nasal mucosa
PATIENTS: Diagnosed with a primary HNC and going to receive at least 4 weeks of RT with at least 20 fractions.
PATIENTS: Having an informal family caregiver (spouse, romantic partner, adult child, or sibling) who is willing to participate. If patients do not have one consistent primary caregiver for the duration of the study, they may be accompanied to the yoga sessions by an alternate caregiver who meets eligibility criteria.
PATIENTS: Regularly (self-defined) participated in a yoga practice in the year prior to diagnosis.
PATIENTS: Cognitive deficits that would impede the completion of self-report instruments as deemed by the clinical team.
Patients must have previously undergone or plan to undergo thyroidectomy; for those patients who have previously undergone surgery, pre-operative labs, including complete blood cell count with differential must be available
Patients with myocardial ischemia or peripheral muscle ischemia
Conditioning Regimen: Patients expecting to receive any type of myeloablative HSCT conditioning regimen are eligible
PATIENTS
Patients 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
Patients with untreated clinically relevant hypothyroidism
Patients currently on investigational therapies will be evaluated by the PI on a case by case basis and study participation approval will be obtained from the treating oncologist
Patients who do not have a smart phone onto which the Under Armour application can be downloaded
Patients who are unwilling to wear the Under Armour (UA) health band
Patients unwilling to come to the Johns Hopkins campus to have the required testing performed
Patients will be ineligible if they are participating in an investigational drug treatment trial that requires structured symptom or toxicity reporting at the time of enrollment
Patients with severe cognitively impairments or who appear too weak, emotionally distraught, agitated or ill to participate, as judged by either the research study staff or an oncology provider, will be excluded
Patients who are currently actively tracking their steps using wearable technology or smartphone apps will also be excluded
PATIENTS: Admitted to the acute palliative care unit
PATIENTS: Delirium as per Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-V) criteria
PATIENTS: Hyperactive or mixed delirium with RASS >= 1 in the past 24 hours (h)
FAMILY CAREGIVERS: At the patient’s bedside at least 4 h/day
PATIENTS: On scheduled chlorpromazine within the past 48 h
Patient’s oncologist advises against the trial – in which case they can choose to receive stimulation with letrozole + gonadotropin
PATIENTS: Patients with hematologic cancer receiving care at a participating clinic.
PATIENTS: Planning to receive ongoing care from a participating oncologist.
PATIENTS: Willing to be seen at least monthly.
PATIENTS: Lacks decision-making capacity, as determined by the patient's oncologist.
PATIENTS: Unable to complete baseline interview.
Patients with a known intolerance to lactose or other constituents of Activia
Patients taking antibiotics or who plan to begin taking antibiotics
Patients seen by palliative care, thoracic oncology, pulmonary medicine, or emergency care at MD Anderson Cancer Center
HSCT DYADS: Patients or CGs who are participating in this study as individuals
Patients not available for follow-up testing
Will also include, as a control, sickle cell patients being admitted for an elective procedure and post-operative surgery patients admitted after elective procedures
Patients in the intensive care units will not be eligible
Patients already seeing pharmacy as a part of their care
Will allow participation of patients at any time since diagnosis
Patients undergoing reconstruction after mastectomy (either implant or tissue based)
Patients having no reconstruction are eligible for the study
No patients will be enrolled from vulnerable populations, including neonates, children, prisoners, or institutionalized individuals
Cognitive impairment evident patients will be evaluated with Folstein Mini-Mental Status Examination and excluded with a score less than 25
INCLUSION - STUDY 1: Cancer adult patients undergoing neurotoxic chemotherapy (agents including platinums, vinca alkaloids, taxanes, proteasome inhibitors and interferons) will be eligible to participate
Patients with chronic pain syndromes
Patients with hypersensitivity to ropivacaine/amide-type anesthetics
The patient sample is limited to patients with advanced cancer and/or patients receiving ongoing care from a medical oncologist
Patients with Mini-Mental State Examination (MMSE) < 24 will be ineligible for participation in the therapeutic trial
PATIENTS AND PARTNERS: Not oriented to time, place, or person as deemed by the clinical team
PATIENTS AND PARTNERS: Regular (self-defined) participation in psychotherapy or a formal cancer support group
Patients scheduling to undergo robot-assisted radical prostatectomy
Patients willing and able to complete the EPIC questionnaire in its entirety
Patients with significant cognitive impairment or documented psychologic impairment
Cirrhotic patients; when incidentally discovered intra-operatively, patients will be excluded from the study and replaced, but will be followed for primary and secondary endpoints
Patients with poor performance status preoperatively such that they are unable to walk up two flights of stairs
Patients scheduled for paravertebral block
TECHNOLOGY REQUIREMENT: Patients will need to own a smart phone that can interface with the Jawbone Up 24
TECHNOLOGY REQUIREMENT: Patients will need a home computer or adaptor with universal serial bus (USB) port to charge the Jawbone Up 24
Patients with islet cell/neuroendocrine or papillary cystic neoplasm
Patients must have the ability to understand visual and verbal pain scales
Patients must be eligible for epidural placement
Patients with a planned exploration with biopsies (no organs removed) will be excluded from the study
Caregivers with children (patients) who are younger than 10 years of age may be eligible to participate even though their children are too young to assent or participate themselves
Patients who have been readmitted to Pediatric BMT unit after initial transplant (not already in the study)
All patients must be able to lie supine
All patients must have a single fraction spine radiosurgery at the designated site of interest to at least a dose of 18 Gray (Gy)
All patients must have a vertebral body site to be treated located from T1 to L5
Patients who have had prior radiotherapy at the spine site and level to be treated
Patients who have > 50% vertebral body collapse
Patients deemed not be a candidate for cement augmentation for any reason
Patients who have frank mechanical pain
Patients with both pedicles involved with gross disease at the level of potential cement augmentation
Patients whose physician-approved radiation treatment plan indicates a maximum prescription dose of less than 45 Gy
Patients with scleroderma or discoid lupus
Patients who are currently taking melatonin must discontinue melatonin for 5 days before enrolling in the study
Post-menopausal women defined as either \r\n* At least 2 years without menstrual period or \r\n* Patients at least 50 years or older with serological evidence of post-menopausal status or \r\n* Hysterectomized patients of any age with follicle stimulating hormone (FSH) confirmation of post-menopausal status
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency
Patients must be able to walk unassisted without oxygen
Patients must complete the Physical Activity Readiness Questionnaire with “No” answers to all questions; if patient responds with any YES answers, OR IS OVER AGE 69, approval must be obtained from the patient’s primary care provider (PCP) or treating medical oncologist to participate in the study
Admitted to Burke Services (WBG 5th floor) with plans for inpatient myelosuppressive chemotherapy (with standard of care or protocol regimens) (this will include induction for patients with low risk APL)
Patients will not be excluded on the basis of sex, racial or ethnic background
Patients who have any major psychiatric diagnoses or thought disorder (e.g. schizophrenia, bi-polar disorder, dementia)
Patients with communication barriers (e.g., hard of hearing)
Patients with extreme mobility issues (e.g. unable to get in and out of a chair unassisted)
Patients requiring more than one platelet transfusion per day
Patients undergoing any resection requiring an anastomosis to the esophagus for palliative intent
Patients receiving preoperative enteral nutrition
Patients with allergies to any of the ingredients in the nutritional supplement
Patients of east Asian ancestry (Chinese, Japanese, or Korean origin)
Written clearance for the procedure from the patient’s oncologist
Patients who are moribund
Pediatric oncology patients undergoing a lumbar puncture in the Pediatric Sedation Suite; patients may or may not be receiving intrathecal chemotherapy
Patients who are allergic to or not tolerant of EMLA cream, propofol, or fentanyl will be excluded
Patients having their LPs done by students will be excluded
Patients with implantable drug delivery systems, e.g. Medtronic Synchromed
Patients who are not fed orally (gastrostomy [G]-tube dependent, total parenteral nutrition [TPN]-dependent)
Patients who refuse to participate
PATIENTS ONLY: Having an informal caregiver (spouse, romantic partner, adult child, sibling, or friend) who is willing to participate; if patients do not have one consistent primary caregiver for the duration of the study, they may be accompanied to the yoga sessions by an alternate caregiver who meets eligibility criteria
PATIENTS ONLY: Regularly (self-defined) participated in a yoga practice in the year prior to diagnosis
PATIENTS ONLY: Cognitive deficits that would impede the completion of self-report instruments as deemed by the clinical team
Patients with glaucoma
Evidence of disseminated intravascular anticoagulation (DIC) as determined by the patient’s primary provider
Patients who are classified as being opioid tolerant by receiving a baseline MEDD of >= 60 mg
Patients who are local and able to follow-up in the SCC within 30 days if necessary
Patients receiving scheduled benzodiazepines due to the risk of excessive sedation
Patients with opioid induced neurotoxicity (OIN) as the primary reason for OR as they may manifest symptoms of cognitive impairment
Among patients treated in the urban centers, we will specifically target patients who live more than 40 miles away from the clinic as they are more likely to experience problems with access to care.
Patients with cognitive dysfunction
Patients who are admitted for observation for < 48 hours will be excluded from the study, as one day would be difficult to provide the necessary information
Patients who are delirious
Patients admitted to the intensive care unit
Patients with ESAS > 4/10 on dyspnea
Patients who are current meditation practitioners
Patients receiving myeloablation (MA) or reduced intensity conditioning (RIC) are allowed
Patients considered by PIs/protocol team to have a complicated prior therapy or HCT regimen, or who have a low survival probability (e.g., refractory leukemia and/or undergoing 2nd HCT)
Treatable causes of fatigue have not been ruled out, at least by history and exam criteria, by the treating provider, such as uncontrolled pain, hypothyroidism, or insomnia; NOTE: if these are considered to be the primary cause for the patient’s fatigue then the patient is not eligible for this trial
Patients with pain requiring opioid pain medication; NOTE: over the counter analgesics such as Tylenol or ibuprofen are allowed
Patients scoring greater than 4 on a 0 to 10 scale with regard to sleep troubles or pain
Patients who need intraoperative evoked potential monitoring which precludes the scalp block
Patients with known cranial defects
Age >= 40 (to reduce the likelihood of enrolling patients with obstruction due to primary sclerosing cholangitis).
Patients undergoing diagnostic laparoscopy
Patients planning to undergo hand-assisted laparoscopy
PATIENTS: Previously screened and with greater than 0 level of psychological distress
PATIENTS: Willingness to participate in all study activities including data collection
PATIENTS: Willing to identify a FCG (immediate or extended family member) to participate
PATIENTS: Find conversations around religion or spirituality emotionally upsetting
PATIENTS: In hospice care
Patients with paranasal sinus or nasopharyngeal carcinoma who are about to undergo radiation therapy; patients with paranasal sinus or nasopharyngeal carcinoma who have completed radiation therapy 3-6 months prior to enrollment who then show olfactory loss on a screening test (University of Pennsylvania Smell Identification Test [UPSIT] – score of 34 or 33 or lower out of 40, depending on female/male); both those patients undergoing chemotherapy and those who did not will be eligible, and this factor will be assessed as a possible confounder/contributor in a multi-regression analysis
Only requirement for organ function is for patients to have competency to consent and participate in the study; in the arm of the study which requires patients to have olfactory dysfunction before enrollment, an UPSIT score will be used to identify these patients
Patients not available for follow-up tests
Patients with pre-existing medical conditions that would be a barrier to exercise
Patients with a GOG Performance Status of 0, 1, or 2
Patients who are able to complete the assessments
Patients must have met pre-entry requirements
Patients who are known to be hypersensitive to aprepitant, granisetron or any of the components of the patch or to dexamethasone
Patients with a paraspinal mass =< 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible
Non-ambulatory patients
Patients with rapid neurologic decline
Patients who are diabetic
If patients have a caregiver, patients should agree to bring a caregiver to one of their hospital visits or have the caregiver schedule a separate study visit
Lactating patients must agree not to nurse a child while on this trial
Patients 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; qualitative interviews will be conducted in patients with their assent/consent
Patients discharged to another inpatient facility (hospice, skilled nursing facility, long term acute care hospital [LTACH], or acute rehab) or patients discharged home with hospice will be excluded
Any patients that are transferred to another unit prior to discharge will be excluded
Any patients prescribed medications for chronic pain and/or neuropathy will be excluded, including patients under treatment of a pain specialist or substance-abuse programs
Patients on dialysis or with transplanted organs
Patients already enrolled on other studies of systemic pain control agents
Patients’ proposed post-operative treatment plan must include standard focal brain irradiation and temozolomide
Patients must not be on treatment with class Ia or class III antiarrhythmic drugs
Patients who have not completed their initial steroids
Patients must have a firm diagnosis of cGvHD, in accordance with National Institutes of Health (NIH) guidelines; patients with “overlap syndrome” are also eligible, but patients with recurrent, late onset and/or persistent acute GvHD (alone) are not eligible
Preferentially, patients should have active refractory-cGvHD; any degree of severity (as per NIH criteria) and/or pattern of organ involvement may be considered; (that said, patients with more severe and/or extensive chronic GvHD are expected to be the usual candidates for LD-TLI protocol therapy)
Cancer patients with pain that is not curable and who have not responded to opioids at reasonable doses
Patients will be excluded if they are hospitalized
Patients with only totally implanted CVCs or ports are ineligible
Patients currently enrolled on Children's Oncology Group (COG) study ACCL0934 are not eligible until they have completed the infection observation period of that study
Patients scheduled to receive broad-spectrum prophylactic antibacterial therapy are ineligible; patients only receiving prophylaxis for Pneumocystis pneumonia (PCP) (trimethoprim [TMP]/sulfamethoxazole [SMX]) or encapsulated organisms (penicillin) are eligible
Patients receiving sorafenib at the time of enrollment and those who are scheduled to receive sorafenib as part of a treatment plan are ineligible
Patients previously enrolled on this trial are ineligible
Patients may have started consolidative chest irradiation by the time of study entry
Patients may not take memantine
Within 90 days of enrollment:\r\n* Patients with a proven or probable invasive mold infection are not eligible\r\n* Patients with an incompletely treated invasive yeast infection are not eligible\r\n* Patients with an elevated galactomannan level (>= 0.5 index) within 30 days prior to time of enrollment (if performed) must have a full evaluation for invasive aspergillosis (including a negative chest computed tomography [CT] scan) during that time period to be eligible for enrollment
Patients previously enrolled on the trial are not eligible; therefore, patients with AL who were on study during intensive chemotherapy are not eligible to be enrolled during the HSCT
Patients with chronic active arthritis
Patients currently enrolled on the ACCL1034 study are not eligible until they have completed the 90 day observation period of that study
Patients may be on steroids at study entry
Patients scheduled for pancreaticoduodenectomy, central pancreatectomy or distal pancreatectomy
Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility\r\n* Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi anemia, Dyskeratosis Congenita, Shwachman-Diamond syndrome and Down syndrome will be excluded\r\n* Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded\r\n* Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers will not be excluded
Patients undergoing anterior abdominal wall hernia repairs
Patients who undergo an open, elective radical cystectomy
Patients must have completed the S1202 Brief Pain Inventory-Short Form (BPI-SF) within 7 days prior to registration; patients must have an “average pain” of at least 4 on the BPI-SF
Patients must not require selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants during study participation; patients must have been able to taper and discontinue treatment with these medications at least 7 days prior to registration (28 days for fluoxetine), and must not be experiencing antidepressant withdrawal symptoms (e.g., dizziness, nausea, sleep disturbance, or other sensory disturbances); patients must not have previously taken the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine or milnacipran; prior venlafaxine is allowed as long as it was not taken concurrently with AI therapy and was not taken for treatment of pain (e.g., prior treatment for hot flashes is permitted)\r\n* NOTE: Patients requiring antidepressants for management of depression are not appropriate candidates for this placebo-controlled study, but those who are on antidepressants for other indications, such as hot flash management, may be able to tolerate a time off of antidepressant therapy
Patients must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis (rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, polymyalgia rheumatica), or cancer involving the bone; patients with\r\nosteoarthritis are eligible
Patients who are at elevated risk for CRC, defined as having ever been diagnosed with CRC, a precancerous (adenomatous) polyp, or inflammatory bowel disease
PATIENTS WITH CIN:
PATIENTS WITHOUT CIN:
Patients without CIN will be matched on cancer diagnosis and CTX agents administered (i.e., only a platinum compound, only a taxane, or both) to the patients with CIN but will not have any of the changes in sensation or pain listed above for patients with CIN
Patients cannot be homeless or have substance dependence
Patients with known cognitive impairments
Patients may have been previously treated or previously untreated
Symptomatic patients with a BFI symptom scale of 2 points or greater
Patients with implantable drug delivery systems, e.g. Medtronic SynchroMed
Patients will receive repeated cycles of identical chemotherapy that will likely result in grades III-IV hematological toxicity; patients will be treated outside of Children’s Oncology Group (COG) protocols with specific requirements for schedule of G-CSF administration; the following categories of patients treated at Children’s Hospital of Michigan are eligible for this study:\r\n* Patients with brain tumors treated according to modified Head Start II protocol with vincristine, etoposide, cyclophosphamide, and cisplatin (OPEC) chemotherapy;\r\n* Patients with recurrent Hodgkin lymphoma treated with ICE (ifosfamide, carboplatin, etoposide) chemotherapy;\r\n* Patients with recurrent solid tumors including sarcomas, Wilms’ tumor, neuroblastomas, or brain tumors treated with high dose ICE or ICT (ifosfamide, carboplatin, topotecan) chemotherapy
Patients with vaginal stenosis
Patients who have any major psychiatric diagnoses (e.g., schizophrenia, bipolar disorder)
Patients with extreme mobility issues (e.g., unable to get in and out of a chair unassisted)
For patients aged 13-17 years, have one caregiver willing and able to participate in the study
AYA PATIENTS ONLY: Patients that are not able to participate in the study due to their medical condition and/or treatment regimen will be excluded; such exclusion will be determined by the patients' treating oncologist in conjunction with patients' family members
Patients with myocardial ischemia or peripheral muscle ischemia
Patients currently using a wearable activity tracker
Caregivers of patients undergoing HCT at Massachusetts General Hospital (MGH)
Patients treated as outpatients by the supportive and palliative care team.
Patients should describe fatigue as being present for a minimum of 2 weeks
Patients with phaeochromocytoma
Patients who are blind are excluded
Patients must have a mobile phone that can send and receive SMS/MMS messages and is internet-enabled
Patients with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs)
Patients who present to the urology clinic for non-muscle-invasive bladder cancer will be screened for participation in this pilot study (goal of 5 patients); patients who have completed transurethral resection of bladder tumor (TURBT) and are candidates for intravesical therapy are eligible for inclusion
Patients are eligible to enroll on this study with or without the enrollment of their caregiver
Patients with normal saliva production (no salivary gland changes; no xerostomia)
Patients who are on pilocarpine for ophthalmic or non-ophthalmic indications
Patients who report persistent or intermittent pain, including aching, tenderness, soreness
Patients who do not report any pain, including aching, tenderness, and soreness
Evaluation of Web-based Program: HNSCC patients who are currently undergoing or have recently completed radiation treatment (< 2 years)
Patients with known difficult airways
Patients where other lung isolation devices may be warranted (tracheostomy, nasal intubation)
Patients requiring a right sided VDLT or DLT
Patients must have no clinical evidence of cognitive impairment as determined by the palliative care physician (Memorial Delirium Assessment Score >= 7)
Patients with complete or partial bowel obstruction as determined by the palliative care physician
Patients with a bowel ostomy
Patients of Dr. Gonzalez
Patients requiring treatment in supine position
Patients who have seen an oncologist after undergoing first line treatment imaging
ONCOLOGIST: Have a patient panel that will allow for >= 6 eligible patients to be enrolled in the study
Patients who are currently receiving acupuncture for any condition or if they have ever had acupuncture before
Adult patients with hematologic malignancy admitted to Massachusetts General Hospital (MGH) HSCT are eligible for the study
Patients undergoing HSCT for a benign hematologic condition (myelodysplastic syndrome [MDS] is not considered a benign hematologic condition and patients with MDS are eligible for the study)
Patients enrolled on other supportive care intervention trials
Adult caregivers (> 18 years) of patients undergoing HSCT at MGH who agreed to participate in study
Patients having previously undergone large surgical resections of the larynx or hypopharynx will be excluded
Patients in whom the transnasal endoscope is poorly tolerated or patients in whom transnasal endoscopic laryngoscopy is contraindicated will be excluded
Patients and caregivers who are not oriented to time, place, and person
Patients who have regularly practiced yoga in the year prior to recruitment
Patients undergoing concomitant colectomy
Patients with external biliary drains
Patients with history of liver transplantation may be eligible for the dose expansion cohorts (parts 2A and 2B) of this study provided all eligibility criteria are met and provided the subject has not had any episodes of acute rejection or serious opportunistic infection within 3 months from enrollment\r\n* Certain immunosuppressive agents such as tacrolimus and sirolimus are prohibited thus liver transplant patients who require these medications for immunosuppression are not eligible\r\n* Patients receiving everolimus at immunosuppressive dosages are eligible
For patients who will receive enzalutamide monotherapy, failure or intolerance of prior sorafenib is required for enrollment; for patients who will receive combination therapy, prior sorafenib is excluded
No specific hematologic parameters for study entry are required; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm^3
Patients who require frequent (several times a day) monitoring of their blood glucose or patients who have recently been hospitalized for glucose control
Group 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFR?.
Groups 1, 2 and 3: At least 1 measurable lesion defined by mRECIST 1.1 for patients with GIST.
Group 3: Patients known to be KIT wild type.
Patients with connective tissue disorders specifically systemic lupus erythematosus, scleroderma, or dermatomyositis
Patients with fasting serum triglycerides > 300 and/or with hypertriglyceridemia requiring medication (but not patients with hypercholesterolemia: patients with hypercholesterolemia with or without medication are eligible).
Patients with an identified familial hyperlipidemia disorder.
Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients must be refractory to, and intolerant of, established therapy known to provide clinical benefit for their condition; patients in Arm L (pembrolizumab) and Arm M (nivolumab) can be treatment naïve and do not have to fail first line nivolumab or pembrolizumab if they have disease where pembrolizumab or nivolumab are Food and Drug Administration (FDA) approved for the first-line setting
If in Arm D (doxorubicin and cyclophosphamide), patients with prior cumulative doxorubicin dose of >= 260 mg/m^2
Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
Patients must be able to tolerate lumbar puncture and/or Ommaya taps
Arm C1 and C2: SCNSL patients do not require one prior CNS directed treatment; newly diagnosed SCNSL patients are eligible as long as their systemic disease has been treated and does not require any active treatment
Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded
Patients with uncontrolled major psychiatric disorders, such as major depression or psychosis, will not be eligible for this trial; patients with a history of depression or anxiety who are stable on or off psychiatric medications will be eligible
No exclusion criteria for pregnant or nursing patients from participating in this study (of note, pregnant patients will not be treated with vaginal brachytherapy, a requirement for enrolling on this study)
Patients who are enrolled in another symptom management trial or receiving active treatment under another clinical trial
Patients with bile duct obstruction
Patients: Receiving an allogeneic HSCT
Caregivers: The person in the patient’s life who is primarily responsible for care decisions, emotionally invested in the patient’s care, provides instrumental care such as transportation, and available if randomized to the fPER group to participate in the majority of intervention sessions
Patients on warfarin (patients on injectable blood thinners, such as Lovenox, are able to continue those)
Patient’s caregiver is ineligible for the study or declines study participation
Note: Patients who enroll in hospice during the trial will have the option of continuing trial participation
Patients with medical restrictions that may interfere with or prevent them from taking part in the yoga interventions per their physician’s decision
Patients currently receiving therapy for mucositis
PATIENTS:
Patient’s spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
At the patient’s bedside at least 4 hours each day during patient delirium episode
PATIENTS
Patients must have normal baseline self-reported taste perception prior to the development of cancer
Patients with a pathologically proven diagnosis of CRC seen either at MD Anderson or Lyndon B Johnson General Hospital (LBJ)
Patients continuously taking any minocycline within the last 15 days; patients who have conditions that potentially preclude use of minocycline as determined by the treating physician
Ongoing parenteral nutrition (receiving intravenous nutrition support at the time of enrollment); note: patients may be receiving maintenance intravenous (IV) fluids
Two discretionary enrollment criteria include:\r\n* Patients with ductal breast carcinoma in situ (DCIS) may be enrolled into the study if they are eligible for and considering either mastectomy or BCS with radiation\r\n* Patients taking neoadjuvant chemotherapy may be enrolled into the study if they are eligible for and considering either mastectomy or BCS
Patients will be recruited through 28-30 surgeons located in 12 surgical practice sites within Michigan, Georgia, California, and Tennessee; patients will also be recruited at the University of Michigan (UM) Comprehensive Cancer Center
Patients who are taking minocycline for other conditions, as determined by the treating physician
Patients who are enrolled in other clinical trials that have symptom management as primary outcome
Patients must have the ability to use audio media in their home and read and understand study manual provided
Patients must have a phone
Patients unable to use audio media due to auditory dysfunction
Patients who are prisoners or incarcerated
Patients with aplastic anemia or primary myelofibrosis; patients with marrow fibrosis secondary to myelodysplastic syndrome (MDS), AML or a myeloproliferative disorder other than primary myelofibrosis are eligible
Patients who are not expected to be available for follow-up in our institution for at least 180 days after the transplant
Patients who are enrolled in other symptom management clinical trials
Minocycline trial only: patients who currently have bile duct obstruction or cholelithiasis
Patients who, in the judgment of the investigator, may be unable to participate in the required study procedures
Patients with a diagnosis of polysomnographically confirmed obstructive sleep apnea or narcolepsy
Patients with > 2 hours of direct exposure to outdoor natural light per day by interview with the Study Coordinator
Patients who have taken melatonin within the past two weeks
There are no restrictions on the amount or types of prior therapy; eligible patients must be receiving ongoing chemotherapy with an oxaliplatin containing-regimen which is planned to continue for at least one month following enrollment in this trial; any dose or schedule of oxaliplatin administration is allowed as long as patients have self-reported taste disturbance that has either: 1) developed since the initiation of oxaliplatin-based therapy, or 2) a pre-existing, treatment-induced taste disturbance has subjectively worsened since initiating oxaliplatin-based therapy
Patients must have normal baseline self-reported taste perception prior to the development of colorectal or pancreatic carcinoma
Patients with the entity of acute/chronic GVHD overlap syndromes
Patients must have completed the S1200 Brief Pain Inventory-Short Form (BPI-SF) within 14 days prior to registration; patients must have a worst pain score of at least 3 on the Brief Pain Inventory (item #2) that has started or increased since starting AI therapy
Patients must have had two or fewer acupuncture treatments within the past 12 months for any reason except for joint symptoms; patients must not have had prior acupuncture treatment for joint symptoms at any time
HSCT patients with either moderate or severe immunodeficiency based on immunodeficiency scoring system would be eligible for entry on study if a nasopharyngeal wash or throat swab specimen is positive by rapid RSV antigen testing and/or on culture within 72 hours (therapeutic arms)
HSCT patients with mild immunodeficiency based on immunodeficiency scoring system would be eligible for entry on study if a nasopharyngeal wash or throat swab specimen is positive by rapid RSV antigen testing and/or on culture within 72 hours but will not be randomized to therapeutic arms and will be followed as per standard of care (control arm)
Patients may receive up to 2 doses of aerosolized ribavirin (modified regimen) before enrollment into the study
Women who are pregnant or plan a pregnancy within 8 weeks after completion of treatment (only for patients who are going to be randomized to either therapeutic arms)
Patients who are considered to be moderately or severely anemic as per the National Cancer Institute (NCI) classification will not be included in the study, i.e. patients with hemoglobin level less than 8 g/dl
Male partners of women who are pregnant (only for patients who are going to be randomized to either therapeutic arms)
Patients with palpable splenomegaly >= 16 cm below coastal margin (only applicable to patients with CML)
Patients who were already seeing PC, or whose oncologists thought they needed to see PC or enroll in hospice
Patients with airway stents undergoing bronchoscopy
Patients previously enrolled, but excluded as no stent lumen obstruction from mucus retention identified at earlier enrollment (hence excluded at that enrollment)
Patients with no stent lumen occlusion from mucus impaction as determined at the time of the initial visual bronchoscopic assessment
Previously enrolled patients who completed this protocol
Patients are not required to be registered on a COG therapeutic trial
Patient’s current chemotherapy treatment plan must include at least 1 course of:\r\n* Cisplatin at ? 50 mg/m²/dose\r\n* Ifosfamide plus etoposide or doxorubicin or\r\n* Cyclophosphamide plus an anthracycline
The patient’s current treatment plan must include an anti-emetic regimen with either ondansetron or granisetron on a scheduled basis; patients may also receive dexamethasone for antiemetic prophylaxis during the acute phase at the discretion of the treating physician; patients ? 12 years old may also receive aprepitant in conjunction with dexamethasone for antiemetic prophylaxis at the discretion of the treating physician
Patients who are currently receiving acupuncture for any condition or if they have ever had acupuncture before
If an open biopsy is performed, the patient must be at least one week post biopsy; this requirement does not apply to patients who undergo stereotactic biopsies
Patients who are not eligible to receive SCT with cyclophosphamide and total body irradiation (TBI) conditioning because they do not meet transplant criteria are also not eligible for this phenylephrine study
General exclusion criteria for transplant include:\r\n* Patients who have angina and/or congestive heart failure requiring treatment, or who have had a myocardial infarction within the past year\r\n* Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse\r\n* Patients who have any active infection; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date\r\n* Patients with diabetes who are not controlled by medical management will be ineligible\r\n* Psychiatric illness requiring psychiatric counseling or medical intervention other than antidepressant medications may make an individual ineligible and will be considered on a case-by-case basis\r\n* Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated; these decisions will be based upon estimated adequacy of patient support systems and prediction of patient’s compliance with medications, required diagnostic procedures, and/or follow-up care\r\n* Patients who have an ECOG performance status of greater than 2\r\n* Patients who have decreased pulmonary function due to any disorder as demonstrated by a diffusion capacity of less than 50% of predicted, a FEV1 of less than 60% of predicted, or a PO2 of less than 80mmHg on pulmonary function testing\r\n* Patients who have a resting ejection fraction of less than 50%\r\n* Patients who have renal disease as demonstrated by a serum creatinine clearance of greater than 2.0 mg/dL and/or a creatinine clearance of less than 50 mL/min\r\n* Patients who are pregnant or breast feeding at the time of admission for conditioning
This study is open to patients of all races and ethnicities
Patients with steroid (or immunosuppressive therapy [IST]) refractory acute GVHD (aGVHD) or chronic GVHD (cGVHD)
Patients must be scheduled for tapering doses of (or no longer treated with):\r\n* Cyclosporine;\r\n* Tacrolimus;\r\n* Sirolimus;\r\n* Steroids (patients may be on physiologic doses of steroids)
All patients undergoing planned open pancreaticoduodenectomy (PD) at Johns Hopkins Hospital (except pregnant women, adults lacking capacity to consent, non-English-speakers, and prisoners), irrespective of diagnosis, comorbidities, or administration of neoadjuvant therapy are eligible for this study
Patients undergoing pleurodesis for benign disease (e.g., spontaneous pneumothorax)
Patients are permitted to participate in other clinical trials while participating in this trial
Patients who are enrolled in another symptom management trial
Patients with nerve pathology or clinically identified neuropathy
Participation in the study must be approved by the physician directly responsible for the patient’s care while at University of North Carolina (UNC)-Hospitals
Acute or chronic respiratory disease that would compromise the patient’s ability to participate in the exercise rehabilitation program
Acute or chronic bone, joint, or muscular abnormalities that would compromise the patient’s ability to participate in the exercise rehabilitation program
No patients being decisionally impaired
Decisionally impaired patients
At the time of the wire stimulating procedure, patients will be excluded if the surgeon is unable to place the temporary stimulating lead
Patients taking concomitant alpha-adrenergic blocking agents
Patients with retinitis pigmentosa
Patients with active peptic ulceration
Patients who have previously experienced non-arteritic ischemic optic neuropathy (NAION)
Patients taking Coumadin, Pradaxa or other blood thinner drugs
Patients with bilateral upper extremity edema
Patients on diuretics solely for treatment of lymphedema are excluded
Patients with active thrombophlebitis
Patients with malignant lymphedema
Patients currently taking valproic acid
The patient’s previous chemotherapy treatment must have included a taxane (paclitaxel, nab-paclitaxel, or docetaxel) and considered the primary cause of the neuropathy by the medical team
Local infection at or near the acupuncture site; (although acupuncture is a minimally invasive procedure, patients will be excluded if there is an indication of infection)
Patients must either have grade 4 thrombocytopenia (platelet counts < 25 x 10^9/L) due to chemotherapy unless transfusion within 24-72 hours
Patients with known thrombophilic risk factors; exception: patients for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
Patients of East Asian ancestry (i.e., Chinese, Japanese, Taiwanese, or Korean)
Patients must be without evidence of M0
Patients with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field; the boost volume must be limited to < 50% of the ipsilateral lung volume
Patients can take sleep aids (e.g., hypnotics and sedatives) for insomnia if they use sleep aids as needed; patients taking sleep aids every night are excluded; use of melatonin every night is permitted and these patients are not excluded
Patients with known fructose intolerance
Patients who have dementia or a legal guardian
Caregivers will be eligible for enrollment if they identify as the person in the patient’s life who is primarily responsible for care decisions
Caregivers will be eligible for enrollment if they identify as the person emotionally invested in the patient’s care
Patients have a current diagnosis of major Axis I psychiatric disorders, neurological impairments, or muscular dystrophies
Patients must have working telephone, mobile or land line
Patients currently participating in a meditation practice for more than 1 hour per week prior to preoperative visit
An effort will always be made to recruit patient and caregiver pairs, but unpaired patients are also eligible
CAREGIVER: Unpaired caregivers, including former caregivers of patients who are now deceased, are eligible for the focus group only
Patients with a DT level > 7 will be considered on a case-by-case basis
Patients must regularly consume a diet with a glycemic load > 150 as estimated through the 3 day food recall
Patients with a new suspected or confirmed gynecologic malignancies
Patients with a suspected benign gynecologic process
Patients who are prisoners or incarcerated
Patients with baseline (at start leukemia treatment) infection, defined as patients with fever and known positive cultures at the time of registration; or chest or sinus computed tomography with findings suggestive of pneumonia or sinusitis; or one positive galactomannan test >= 1 or two positive galactomannan test >= 0.5 to 1
Participation of patients on other clinical trial protocols permitted, if not prohibited by trial guidelines
Patients unable to use audio or video media due to auditory or ocular dysfunction
Patients who are prisoners or incarcerated
Patients requiring a chest wall boost
Excluded patients will be allowed to participate in the trial on an observational basis only
Prophylaxis for patients at risk of CMV, adenovirus, EBV, BK virus, or HHV6 infection
Treatment of reactivation or infection which is defined for each virus as below:\r\n* CMV: CMV antigenemia is monitored at least weekly post transplant; reactivation is defined at CMV antigenemia with < 10 leucocytes positive or elevated polymerase chain reaction (PCR); if any patient develops CMV antigenemia with > 10 leukocytes positive or clinical evidence of CMV infection (defined as the demonstration of CMV by biopsy specimen from visceral sites [by culture or histology]) either pre or after CTL infusions, standard treatment with ganciclovir, and/or foscarnet and immunoglobulins will be initiated; patients may receive CTLs alone for antigenemia or elevated PCR without visceral infection\r\n* Adenovirus: Adenovirus infection will be 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; adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from more than two sites such as stool or blood or urine or nasopharynx; in patients who meet the criteria for disease cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity; patients may receive CTLs alone for elevated PCR in blood or stool\r\n* EBV: EBV-lymphoproliferative disease (LPD) is defined according to recent guidelines as proven EBV-LPD defined by biopsy or probable EBV-LPD defined as an elevated EBV deoxyribonucleic acid (DNA) level associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation; patients with EBV DNA reactivation only may receive CTLs on study; patients with proven or probable EBV-LPD should also receive Rituxan\r\n* BK virus: Patients post transplant may develop asymptomatic BK virus (BKV) viruria or viremia; BK reactivation will be defined as detection of elevated BK levels by PCR in blood or urine while disease will be defined as detection in multiple sites or in one site with symptoms; cidofovir has been administered intravenously in a low dose (i.e. up to 1 mg/kg 3 times weekly, without probenecid) or a high dose (ie, 5 mg/kg per week with probenecid) to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy; in patients who meet the criteria for disease cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity\r\n* HHV6: HHV6 reactivation will be defined as detection of elevated HHV6 levels by PCR in blood while disease will be defined as detection in multiple sites or in one site with symptoms; ganciclovir, cidofovir, and foscarnet have variable in vitro activity against HHV-6, and may have a role in treating HHV-6-associated disease – hence one or more of these agents will be added in patients with disease
Patients receiving anti-thymocyte globulin (ATG), or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment
Patients transplanted with hematopoietic stem cells from any source
Patients with manifestations of classic chronic GVHD
Patients who require any type of pancreas resection other than a distal pancreatectomy
Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude epidural placement
Patients undergoing immediate tissue expander reconstruction following mastectomy by any of the surgeon co-investigators are eligible for the study
Patients undergoing skin-sparing mastectomy utilizing bioprosthetic mesh are eligible for the study
Patients who are current smokers
May include patients undergoing ileostomy or colostomy reversal
Patients who may have insufficient renal capacity for clearance of Progel® polyethylene glycol load
The patient’s previous chemotherapy treatment must have included a taxane (paclitaxel, nab-paclitaxel, or docetaxel) or platinum (cisplatin, oxaliplatin, or carboplatin) and considered the primary cause of the neuropathy by the medical team
Local infection at or near the acupuncture site (although acupuncture is a minimally invasive procedure, patients will be excluded if there is an indication of infection)
PATIENTS WITH BRONJ:
All cancer patients > 18 years of any ethnicity who have been treated with intravenous zoledronate (zoledronic acid) for >=1 year duration
PATIENTS WITHOUT BRONJ:
Patients undergoing active antibiotic therapy
Patients who actively decline participation or who are judged to be in distress before the interview
Patients who have had local genotyping are eligible, regardless of the local result
ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors (including non-Hodgkin lymphomas, histiocytoses [e.g. Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), histiocytic sarcoma], and central nervous system [CNS] tumors) are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-HCG
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Patients must be scheduled for, or have intent to schedule, a screening mammogram
Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol
Patients who are undergoing colonoscopy for screening or surveillance purposes
Patients unable to undergo routine endoscopy with biopsy
Patients with suspected but no biopsy confirmed BE
Patients < 65 years without underlying renal insufficiency do not require an GFR calculation.
Pediatric patients, as pediatric cirrhosis is uncommon
Patients with underlying dementia (or on medications to treat Alzheimer’s disease such as donepezil, rivastigmine, galantamine, tacrine, or memantine), encephalopathy, or other neurological disorder known to adversely affect cognition (such as epilepsy or prior stroke) are excluded; (patients with depression or anxiety are not excluded)
Patients who had esophageal therapy with Halo radiofrequency ablation in the past, or esophagectomy
Patients with active esophagitis
Patients who previously participated in this study and are returning to the Women’s Imaging Center for follow-up diagnostic tests
Patients with any clinical breast symptoms (palpable mass, nipple discharge, etc)
One of the following high-risk groups\r\n* Patients will be eligible if they have 2 or more relatives with pancreatic cancer and have a first degree relationship with at least one of the relatives with pancreatic cancer\r\n** If only 2 family members are affected then both must have had pancreatic cancer and a first-degree relationship with individual screened\r\n** If there are more than 2 affected individuals on the same side of the family at least one of the individuals must have a first-degree relationship with the member being screened\r\n** Patients at least 40 years (yrs) old or 10 yrs younger than the youngest affected individual\r\n* Peutz-Jeghers syndrome (PJS) patients age > 30\r\n* Hereditary pancreatitis patients\r\n* Patients with familial atypical multiple mole melanoma syndrome (FAMMM)\r\n* Patients with BRCA2 mutation and at least one first or second degree relative with documented pancreatic cancer
Patient’s breast density must be known; patients must have mammographically dense breasts, American College of Radiology (ACR) Breast Imaging (BI)- Reporting and Data System Atlas (RADS) lexicon categories c or d (heterogeneous or extreme fibroglandular tissue) on their most-recent prior screening
Male patients
Patients with any clinical symptoms (palpable mass, nipple discharge, etc)
Health care centers serving low-income, Medicaid, and uninsured patients in Missouri and Illinois
Patients
Patients seen at the health care center (HC) in the preceding 2 years
Patients who have a recent telephone number in their HC records
Patients with any co-morbidities that should exclude sampling
Patients are undergoing clinically indicated EGD
Patients are not smokers
Patients are not undergoing clinically indicated EGD
Patients are smokers
Patients should, in the estimate of the treating physicians, be anticipated to have a median survival of > 1 year
Patients aged 50-74 with no evidence of a colonoscopy within 9 years or fecal testing within 11 months, and no history of colorectal disease will be eligible to receive a mailed FIT.
Patients must have a pure tone audiometry evaluation to document air conduction within 30 days prior to registration; patients with hearing loss > 40 dB in any of the five tested frequencies (250 Hertz [Hz], 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz) are not eligible; patients with active ear infections should be tested only after the acute phase of infection has resolved; for optimal results, it is recommended that testing be conducted by an audiologist, in a hearing test room, with insert earphones; Note: sites should not order audiometry evaluation until the potential participant has met all other eligibility criteria required for this study
Patients must not have documented history of gastric/duodenal ulcer within the last 12 months; participant must not currently be on treatment for gastric/duodenal ulcer or be experiencing symptoms at study entry; patients with gastroesophageal reflux disease (GERD) are eligible, however, and these patients may receive over-the-counter histamine-2 (H2) antagonists; proton-pump inhibitors, or other prescription-based treatment for GERD
Patients must be offered the option to participate in submission of specimens for banking for future translational medicine studies
Patients participating through PK sites, must be offered the option to submit blood specimens for population pharmacokinetic analysis
Patients must be offered the option to participate in the Diet and Lifestyle Substudy
Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2
Patients must complete all pre-entry assessments
Patients with GOG performance grade of 3 or 4
Patients seropositive for Human T-Lymphotrophic Virus (HTLV)-I or -II
Patients with active Hepatitis B or C viral replication by polymerase chain reaction (PCR)
All ambulatory patients taken care of by the participating pediatric hematology/oncology clinics will be eligible
Patients who have undergone a prior tubal ligation will be eligible
Patients must understand that they will be permanently sterilized
Presence of gallstones and hypertriglyceridemia (level greater than 800 mg/dl) that requires medical or surgical intervention; note: we will include patients who had an independent episode of pancreatitis after a cholecystectomy, but exclude patients who are candidates for cholecystectomy
Patients must have a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
Patients whom have failed prior attempts at allogeneic HSCT
Patients with Acute GVHD Grade III-IV
Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to ? Grade 1 within screening timeframe)
Patients already on AED(s)
Patient suffering from ongoing vomiting from any organic etiology (including patients with history of gastric outlet obstruction or intestinal obstruction due to adhesions or volvulus, patients with a symptomatic central nervous system(CNS) tumor causing nausea and/or vomiting) or patient with hydrocephalus.
Patients may have untreated OPLs (i.e., hyperplasia, dysplasia, carcinoma in situ) at the time of study entry, provided the index OPL or HNSCC was definitively treated
Individuals enrolled in or who plan to enroll in a clinical intervention trial; there must be a 30-day period between completing a previous study and enrolling in this study; the principal investigator will have the option to consider an exception for patients on drugs of interest for the purpose of this study
Patients with Fitzpatrick’s scale skin type IV-VI
All patients who are have known allergies or are sensitive to silver and acrylic adhesives
Patients may enroll simultaneously on this study and other studies, including but not limited to NSABP B52
Patients with esophageal dysmotility
Patients who are being screened for the therapeutic clinical trial will also be approached for participation into the optional sub-study evaluating sociobiological response to stress; refusal to participate in the sub-study will not impact the patient’s eligibility to participate in the therapeutic intervention\r\n* Should a patient consent to the optional sub-study, the patient may proceed with the optional baseline interventions for the optional sub-study as outlined within the protocol’s study calendar
Patients actively enrolled on any other GVHD prevention trial
Women with an intact cervix (patients who have undergone previous loop electrosurgical excision procedure [LEEP], cone and/or cryotherapy are eligible)
Patients must also receive a full myeloablative preparative regimen (patients treated with either total body irradiation (TBI)-based or high-dose chemotherapy only regimens are eligible other than high-dose busulfan containing regimens or regimens that include anti-thymocyte globulin or other T cell depleting antibodies)
Patients with hypertriglyceridemia with serum triglyceride level >= 500 mg/d (lipid lowering drugs may be used to control level)
Patients with symptomatic cholelithiasis
Patients who are taking any pills containing herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration
Patients without cGVHD are defined as having no signs or symptoms of GVHD with chronic features diagnosed at any time prior to enrollment
Patients must be active smokers (defined as smoking any cigarette, cigar or pipe in the last 30 days)
Patients who receive RT or CRT with palliative intent
Patients who chew tobacco and patients who are not smoking but are exposed to second hand smoking are excluded from this study
Patients with diagnosis of major depression or any other psychiatric disorders
Pregnant women are excluded from this study; patients enrolled in the study must be able to undergo intensive RT plus or minus chemotherapy
Patients with a prior thoracotomy within 1 week of study registration
Undecided parents (18 years and older) whose children are 11-17 year old patients who have not begun the HPV vaccine series.
Patient’s deemed otherwise clinically unfit for clinical trial per investigator’s discretion
Patients with major psychiatric illnesses who may not be able to fully participate in the brief telephone counseling (i.e. participants with schizophrenia)
Patients who refuse to be treated on a conventional autologous or allogeneic HCT protocol
Patients eligible for and willing to receive potentially curative high-dose chemotherapy and autologous HCT
Patients with renal failure are eligible; however, patients with pre-existing renal insufficiency will likely have further compromise in renal function and may require dialysis
Patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy, biopsy, and review of the biopsy pathology slides by two pathologists
Patients who are immunocompetent
Patients who are in close social contact with children under 5 years old
Patients who are in close social/domestic contact with a pregnant woman
Patients who have been previously vaccinated with vaccinia
Patients who do not undergo radical cystectomy will be withdrawn from the study
All TP53 germline mutation positive adult patients will be eligible for this study; all patients must have a documented TP53 germline mutation
Patients with congestive heart failure requiring pharmacological management
General anesthesia, if indicated, is acceptable in patients whose lesions would require general anesthesia for laryngoscopy and biopsy according to routine standard of care
Patients with a colostomy
Patients undergoing other interventions to prevent CLABSI (e.g. Children's Oncology Group [COG] ACCL1034 with chromogranin [CHG], antimicrobial lock therapy, etc.) are ineligible
Patients who only have a port are ineligible
Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternate and food supplements (i.e. PC-Spes, saw palmetto, St John wort, etc.) must be discontinued before treatment start; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery for their prostate cancer, or radiation therapy during protocol treatment
Patients on stable doses of bisphosphonates or the receptor activator of RANK-L inhibitor, denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/denosumab therapy during the study
Phase 2 Part: Patients with confirmed diagnosis of MF who meet all of the following criteria: (a) DIPSS of intermediate-1 or higher, (b) Platelet count: ? 75 (monotherapy arm) or ? 100 (combination arm), (c) ANC ? 1.0, (d) Palpable spleen ? 5cm, (e) Peripheral blood blast count <10%, (f) At least 2 symptoms measurable using the MFSAF v4.0, (g) Monotherapy Arm patients: Previously treated with a JAK inhibitor and be intolerant, resistant, refractory or lost response to the JAK inhibitor, (h) Combination Arm patients: Be on a stable dose of Ruxolitinib
Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of MLN0128 (TAK-228)
For weekly MLN0128 (TAK-228) dose cohorts, patients taking proton pump inhibitors (PPIs) are ineligible unless these patients are able to switch to a histamine (H2) blocker and/or antacid
No prior systemic therapy EXCEPT patients may be consented and enrolled if they have already started mFOLFIRINOX for up to four cycles
Patients must have histologically confirmed, newly diagnosed or recurrent from a previously treated early stage lung cancers that are locally confined, non-small cell lung cancers that are considered unresectable and for which chemoradiation will be considered definitive therapy; patients with recurrent cancer that is amendable for chemoradiation can be eligible only if patients with prior lobectomy for stage I cancer had not had adjuvant chemotherapy, and more than 8 weeks have elapsed from surgery to allow for wound healing; patients who recur from prior X-ray therapy (XRT) or stereotactic body radiation therapy (SBRT) will not be eligible
Patients who do not consent for PK studies to be performed (alternatively: patients who initially consent to be on study but withdraws consent for PK study will be taken off study and replaced)
Patients with lesions of Gleason 7 or greater outside the planned treatment area.
Breast implants at time of diagnosis; Note: patients who have had implants previously removed prior to diagnosis are eligible
Patients with known breast cancer (BRCA) mutations; patients who are not tested or whose testing result is not returned at the time of registration are not excluded from registering to this study
Patients enrolling in the BRCA-deficient cohorts must have a documented BRCA1 or BRCA2 germline mutation; alternatively, patients with tumors harboring somatic BRCA mutations may also enroll after discussion with the principal investigator
Patients with other medical conditions judged by the investigator to be clinically relevant in the setting of this study, which may include active infectious processes, intractable emesis, or chronic diarrheal disease
For medulloblastoma patients only, positive CSF cytology
Pregnant women are excluded from this research; the male partner should use a condom; Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator’s discretion after approval by the Center for Cell and Gene Therapy (CCGT) Protocol Review Committee and the Food and Drug Administration (FDA) reviewer
Patients will have to undergo mutational testing for Isocitrate dehydrogenase 1 (IDH1) on a tumor specimen before entering study. Patients are eligible for Arm C regardless of their IDH1 mutational status.
Patients must be willing to complete a bilateral mammogram at baseline with repeat exam after 12 cycles of protocol therapy; patients who have had a mammogram within 1 month prior to registration to protocol therapy will not need to repeat the exam
Inclusion Criteria:\n\n        Patients must be treated by nephrectomy and patients must meet all of the following\n        inclusion criteria to be eligible for enrollment into the trial:\n\n          1. Patients must have no evidence of macroscopic residual disease or metastatic disease.\n\n          2. Male or female, age >=18 years (age >=20 years in Japan, Korea and Taiwan).\n\n          3. Patients must be diagnosed with one of the following based on American Joint Committee\n             on Cancer (AJCC) TNM staging version 2010, Eastern Collaborative Oncology Group (ECOG)\n             performance status (PS):\n\n               -  pT2, pN0 or pNx, M0 and ECOG PS 0-1\n\n               -  pT3, pN0 or pNx, M0 and ECOG PS 0-1\n\n               -  pT4, pN0 or pNx, M0 and ECOG PS 0-1\n\n               -  Any pT, pN1, M0 and ECOG PS 0-1\n\n          4. Patients must have histologically confirmed preponderant, defined as >50%, clear cell\n             RCC.\n\n          5. Patients must not have received any previous systemic (includes chemotherapeutic,\n             hormonal, or immunotherapeutic) treatment for RCC.\n\n          6. Patients must not have received any previous anti angiogenic treatment.\n\n          7. Patients must have adequate organ function.\n\n        Exclusion Criteria\n\n          1. Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma,\n             lymphoma, or patients with any metastatic renal sites.\n\n          2. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)\n             Grade 3 hemorrhage <4 weeks of date of randomization.\n\n          3. Diagnosis of any non-RCC malignancy within the 5 years from date of randomization,\n             except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the\n             cervix uteri that has been adequately treated with no evidence of recurrent disease\n             for 12 months.\n\n          4. Any of the following within the 12 months prior to study drug administration:\n             myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,\n             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic\n             attack and 6 months for deep vein thrombosis or pulmonary embolism.\n\n          5. Gastrointestinal abnormalities
Patients with lung lesions undergoing anatomic resection (lobectomy/segmentectomy/bilobectomy/pulmonary sleeve resection/pneumonectomy) OR
Patients undergoing esophageal resection
Patients with a preexisting tracheostomy
Patients who are willing and capable to follow the instructions required to complete the study
Patients who are not awake, not alert, or who cannot express pain or discomfort related to the catheter locks
Patients who are on disulfiram, metronidazole or are dependent on alcohol
Patients who have a minocycline-rifampin coated CVC
Patients must be either post-menopausal or surgically post-menopausal
Patients receiving calcium-lowering therapy or drugs that may affect calcium levels (e.g., calcitonin, mithramycin, phosphate, denosumab) within 4 weeks of initiation of topical calcitriol. Patients who have been managed with bisphosphonates or calcium-lowering therapy for 3 months or greater prior to the start of the trial and have demonstrated evidence for stability of calcium metabolism would be considered eligible for participation in the trial.
Patients with hypercalcemia or kidney stones
Patients with a history of renal lithiasis within the last 5 years or patients with evidence of kidney stones on entry evaluation
Patients with hypercalcemia (using ionized calcium)
Patients taking phenobarbital, digitalis, thiazides or ketoconazole
Patients taking digoxin or patients who are susceptible to calcium-related dysrhythmias
Patients taking bile acid binding drugs (such as cholestyramine and colestipol)
Patients taking danazol
Patients taking aluminum-based antacids
Osteoporosis: patients with a history of fragility fracture, or a hip or spine T score of < -2.5 (these patients will be treated with zoledronic acid and followed, but excluded from randomization)
Patients must have an imaging abnormality that necessitated a core needle biopsy
Patients will be enrolled in one of the two cohorts based on diagnosis:
Patients who have declined further anticancer therapy will be excluded
Patients must have previously untreated AML and be candidates for intensive induction chemotherapy; patients are allowed to have had prior hydroxyurea
Patients with focal liver observations less than 5 mm or greater than 5 cm in size
Patients with contraindications to CEUS
Patients who are medically unstable, terminally ill, or whose clinical course is unpredictable
Patients who have received an investigational drug in the 30 days before CEUS, or will receive one within 72 hour after their CEUS exam
Patients undergoing cervicography OR colposcopy OR visual inspection with acetic acid (VIA) OR patients undergoing loop electrosurgical excision procedure (LEEP) for the treatment of cervical cancer
Patients of all ethnicities will be included
Patients in which gadolinium contrast is contra-indicated
Patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Patients should be capable of achieving imaging without the need for sedation or anesthesia
Patients must have a plan to receive a CD34-selected peripheral blood stem cell graft
For cohort A, only patients with metastatic cancer to the brain for whom their treating physician has planned to give immunotherapy as monotherapy are eligible for this study; this can be in the setting of a clinical trial or not
For cohort B, only patients with GBM for whom their treating physician has planned to give immunotherapy are eligible for this study; this can be in the setting of a clinical trial or not
The patient’s 4DCT-ventilation image meets the heterogeneity criteria
Patients receiving active therapy on an investigational trial at the time of enrollment should consult with the study chair regarding potential interactions with other study agents; patients who are enrolled in a clinical trial but are off-therapy and in follow up are eligible
Patients who are not planning to adhere to the required follow up schedule as outlined in this protocol
Patients who are medically unstable, terminally ill, or whose clinical course is unpredictable
NSCLC patients of all histologies may enroll to cohorts 1 and 2; only patients of non-squamous histologies may enroll to cohort 3; if enrollment to a cohort is completed, enrollment may continue to other open cohorts
Availability of the patient’s medical information
For cohort A, only patients for whom their neuro-oncologist has planned to give bevacizumab with lomustine are eligible for this study
For cohort B, only patients for whom their neuro-oncologist has planned to give bevacizumab monotherapy are eligible for this study
Patients with intracerebral hemorrhage deemed significant by treating physician are excluded
Patients undergoing a reduction mammoplasty OR
Patients considered in “vulnerable” populations
Hemosiderosis/hemochromatosis (patients can still be included in the 2nd branch without receiving ferumoxytol)
Recurrent tumors: patients with recurrent grade IV gliomas who have failed cranial radiation therapy
Healthy volunteers and normal patients not undergoing endoscopy
Patients with positive findings on prior imaging within the past 4 weeks are eligible
Patients under the care of a St. Jude Children's Research Hospital (SJCRH) physician
Patients of both genders, and all ethnic groups, under the care of a SJCRH physician
Patients less than 3 years of age who require a total length of anesthesia time greater than 3 hours (for the 18F-fluorodopamine [FLO]PET scan in conjunction with another clinical procedure requiring sedation) will be excluded from the study
Patients who refuse to participate
Patients with excessively high anesthesia risks who cannot tolerate the extra time under general anesthesia needed to perform this study; the surgeon and anesthesiologist will determine this pre-operatively
Patients with a limited (1-5) number of metastatic foci outside of the thorax who are candidates for consolidative treatment with SBRT
Patients who are claustrophobic
Patients selecting treatment outside of Memorial Sloan Kettering (MSK)
Patient agrees to participate in the clinical study and to complete all required visits and evaluations. The pediatric population has a different disease profile from the glioma patients we hope to recruit. To reduce heterogeneity in the patient population we will not consider patients younger than 18 for this study.
Patients getting a planned wedge resection as the only thoracic resectional procedure
Must be patients undergoing standard of care EGD for the confirmation of dysplasia in Barrett's esophagus (BE) or endoscopic eradication therapy (EET) for dysplasia in BE
Participants will be drawn from the pool of patients who have suspicious lesions identified on CT and who are already scheduled for a lung biopsy procedure with Dr. Hennemeyer or one of his colleagues
Patients will be asked to consent to 2 to 3 extra biopsy samples to be used for this research project
Patients not capable of getting PET study due to weight, claustrophobia, or inability to lay still for the duration of the exam
For patients highly suspected to have aGVHD and requiring systemic therapy only: Taking steroid treatment for suspected aGVHD for 3 days or less.
Patients should not have any type of curative or palliative therapy for pancreatic adenocarcinoma before enrolling in the study
Patients who are clinically unstable, patients who are seriously or terminally ill with a life expectancy of less than 1 month, and patients whose clinical course are unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (e.g., crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)\r\n* Patients with recent cerebral hemorrhage\r\n* Patients who have undergone surgery within 24 hours prior to the study sonographic examination
Patients with congenital heart defects
Patients with thrombosis within the splenic vein
Patients with known or suspected pancreatic or ovarian carcinoma who will be undergoing clinically appropriate laparoscopic evaluation or treatment; patients will not undergo laparoscopy solely for the purpose of participation in this trial
Patients who are pregnant or lactating or who suspect they might be pregnant; serum pregnancy tests will be obtained prior to each set of multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile
Adult patients who require monitored anesthesia for PET scanning
Patients who are too claustrophobic to undergo PET scanning
Patients must lack bleeding disorders, and be able to provide informed consent; the latter two criteria will be assessed from the patient’s history and the consenting interview
SUB-STUDY I: Patients considered as candidates for and medically fit to undergo prostatectomy
Patients requiring conscious sedation for imaging
Patients unable to lie prone for 30 minutes for imaging
Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone)
Patients must be willing to undergo mandatory research biopsy
Patients who are unable to lie supine for a biopsy
Patients must be willing to undergo mandatory research biopsy
Patients with histopathologic diagnosis of a solid tumor. All solid tumors will be considered, but patients with breast, pancreas, and colorectal masses will be prioritized.
Patients with a histologic diagnosis of adenocarcinoma of the esophagus located distal to the carina
Patients will be treated with neoadjuvant chemoradiotherapy for this condition
Patients with primary tumors located above the carina
For patients with reproductive potential must undergo counseling to understand unknown risks to resultant progeny.
Inclusion Criteria:\n\n          1. Patients with selected solid malignancies (NSCLC, SCLC, SqCCHN, melanoma, merkel cell\n             tumor, renal, bladder, hepatocellular, triple negative breast, or gastroesophageal\n             cancer) or Hodgkin's lymphoma\n\n          2. At least 1 measurable lesion documented on CT/MRI (RECIST criteria 1.1)\n\n          3. Eastern Cooperative Oncology Group (ECOG) performance status ? 2 (Appendix B: ECOG\n             Scoring)\n\n          4. Age ? 18 years\n\n          5. Ability to understand the purposes and risks of the trial and has signed a\n             IRB-approved informed consent form\n\n          6. Willingness and ability to comply with all protocol required procedures\n\n          7. For men and women of child-bearing potential, use of effective contraceptive methods\n             during the study\n\n        Exclusion Criteria:\n\n        Patients meeting any of the following criteria will not be eligible for study entry:\n\n          1. Known infection with human immunodeficiency virus (HIV)\n\n          2. Serious nonmalignant disease or conditions that in the opinion of the investigator\n             and/or ImaginAb could compromise protocol objectives\n\n          3. Patients who have had splenectomy.\n\n          4. Patients who have any splenic disorders that in the opinion of the investigator and/or\n             ImaginAb could compromise protocol objectives.\n\n          5. Patients who are currently receiving any other investigational agent\n\n          6. Pregnant women or nursing mothers\n\n          7. Hepatic laboratory values:\n\n               1. Bilirubin > 1.5 x ULN (institutional upper limits of normal)\n\n               2. Albumin < 2 g/dL\n\n               3. Other local safety laboratory test results (clinical chemistry and hematology)\n                  are determined to be exclusionary by the Investigator.\n\n          8. Known sensitivity to glutamic acid or glutamate.
All patients with existing plasma cell disorders and no history of psychiatric disorders and can receive conscious sedation are eligible to participate in the trial
Patients with human epidermal growth factor-2 positive (HER2+) metastatic tumors are NOT eligible.
Spanish-speaking patients will be eligible
Patients undergoing guided-bronchoscopy for diagnosis of peripheral lung lesion/s > 1 and < 3 cm in diameter located in the outer 2/3 of the lung fields
Patients who have undergone coronary artery bypass grafting (CABG) or coronary stenting in the past 3 years
Patient’s that have complex DCIS as indicated on radiology, which would require excising a large tissue volume
Patients not capable of getting PET study due to weight, claustrophobia, or inability to lay still for the duration of the exam
Patients who are eligible to receive combined dual immune-checkpoint blockade therapy with ipilimumab and nivolumab, per referring oncologist
Pre-operative adult (> 19 years of age) patients with biopsy proven (as opposed to being status post definitive surgical therapy) or highly suspected glioblastoma of the brain
Patients presenting with a pituitary nodule presumed to be resectable on pre-operative assessment
Patients with significant neurological motor deficits of the upper extremities, which would preclude them from performing the while awake intra-operative tasks
Patients taking any tetracycline class of drug (i.e. minocycline, etc)
Patients selected for Ra-223 dichloride therapy for treatment of bone metastasis by their treating physician
Vulnerable patient populations:\r\n* Patients unable to participate in the consent process (children and neonates)
Patients not capable of getting PET study due to weight, claustrophobia, or inability to lay still for the duration of the exam
PATIENT: Patients with a prior axillary procedure on the side scheduled for SLN evaluation
PATIENT: Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable; for example:\r\n* Patients on life support or in a critical care unit\r\n* Patients with unstable occlusive disease (e.g., crescendo angina)\r\n* Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia\r\n* Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)\r\n* Patients with recent cerebral hemorrhage\r\n* Patients who have undergone surgery within 24 hours prior to the study sonographic examination
PATIENT: Patients with congenital heart defects
Patients who cannot tolerate or have contra-indications to endorectal coil insertion; for example, patients with a prior abdominoperineal resection of the rectum or latex allergy
Patients with contra-indications to injection of gadolinium contrast; for example patients with prior documented allergy or those with inadequate renal function
Patients must be eligible for and must be planning to undergo radical prostatectomy
Patients with history of histologically-confirmed malignant solid tumor (histology confirmed by Memorial Sloan-Kettering Cancer Center [MSKCC] Department of Pathology); NOTE: an exception will be made for patients with brain lesions; patients identified by a radiologist to have a brain lesion with high suspicion for neoplasm given MRI features will be enrolled, prior to histological confirmation
Patients considered as candidates for and medically fit to undergo radiation and ADT
CHILD: Pediatrics patients aged 2-17 years undergoing myelosuppressive therapies for acute leukemias and other childhood cancers
Patients who are unable to tolerate general anesthesia
Patients who are felt to be a “difficult airway” for induction of general endotracheal anesthesia
Patients with excessive dental restorations and amalgam
Patients with contraindications to MR
Patients who are already eligible for and are to be treated with hypofractionated or single dose radiation for their spinal lesions\r\n* Note: The patients must have their treatments at Memorial Sloan-Kettering Cancer Center (MSKCC)
Patients with biopsy-proven extra-abdominal desmoid tumors
Patients who do not wish to participate
PHASE I: Eligible patients include patients with histologically proven neuroendocrine tumors (paraganglioma, PHEO [pheochromocytoma], or well differentiated neuroendocrine tumor [NET] of the lung or gastrointestinal [GI] system) or neuroblastoma (NB); patients, who have NB, the diagnosis must be in accordance with the International Criteria, i.e., either histopathology or bone marrow involvement; patients must be able to undergo PET scan without sedation
Patients requiring anesthesia
Adult patients who require monitored anesthesia for PET scanning
Patients must have tumors that produce CEA as documented by a current or past history of an elevated serum CEA above the institutional limit of normal, or by immunohistochemical methods; NOTE: Patients with colorectal cancer are exempt from this requirement since > 95% are CEA positive
Patients must qualify for thyroid ablation with I-131
Patients on hemodialysis
Patients with acute serious illnesses at the discretion of the primary investigator
Patients must agree to fill out the longitudinal psychosocial questionnaires assessing health related quality of life
Patients undergoing MRD allogeneic HCT
Patients receiving T cell depletion or thymoglobulin as part of their transplant
Patients have a documented ovarian abnormality on ultrasound
Patients having undergone prior hysterectomy will be eligible provided that they meet the other requirements for entry into this study
Patients who are not enrolled in the OCSP
Patients who cannot tolerate the vaginal ultrasound procedure
FLT PET: will only be performed in patients >= 10 years old
Research biopsies in consenting patients with MPNST: will only be performed in patients >= 18 years old
INCLUSION CRITERIA (NEXT 60 PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER): 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
Cancer patients who are scheduled for (perfusion) nuclear stress testing using regadenoson as stress agent
Patients consented for the trial that on the baseline 2-dimensional (2D) study have poor acoustic echo windows (i.e. a reader is unable to see in definition 2 or more segments from the apical views) will not be eligible to continue in the trial and peak hyperemia images will not be obtained
Patients must be willing and able to adhere to a special low-carb diet 24-48 hours prior to and fast 8-12 hours prior to every 18F-FDG PET scan
Patients with renal dysfunction (GFR <60) or patients on dialysis
Pregnancy; regular clinical practice already excludes pregnant patients from gadolinium contrast; the current clinical practice will be applied - patients will be verbally screened and asked if they think they could be pregnant; if the answer is yes, then the patient will be excluded from the study; if the patient is uncertain about the pregnancy status, she will be given an option to undergo a pregnancy test or not participate in the study altogether; patients who self-report that they are not pregnant will be allowed to participate in the study; this procedure is based on current department policy guidelines
Patients who have received trastuzumab must have at least a washout period for trastuzumab of 14 days, this will not apply to 89Zr-DFO-trastuzumab repeat, post treatment assessment where patients may be receiving trastuzumab
Patients who are unable to lie flat on the imaging systems long enough to permit imaging protocols to be performed
Patients who are to be treated with clinically approved or experimental regimens where ER has an important role
250 consecutive consenting patients presenting to The Ohio State University College of Dentistry for routing dental care will be recruited; adult patients presenting to the screening clinic for initial oral evaluation will be eligible to participate
Patients with a lesion < 2 mm
Patients cannot be pregnant and prisoners will not be considered for the study
Patients who cannot undergo MRIs
Patients who require general anesthesia for MIBG imaging studies
INR > 1.5 that cannot be corrected with fresh frozen plasma \r\n* For patients on Coumadin general clinical guidelines for IR ablation will be followed
Patients must document their willingness to be followed until death or time of progression; time on study for purposes of adverse event reporting however will be from the time of injection of FMISO to 24 hours after the FMISO injection (completion of drawing of second set of laboratory studies in initial 10 patients); by signing informed consent, the patients are documenting their agreement to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database
Patients who are pregnant or lactating or who suspect they might be pregnant are not eligible; a serum pregnancy tests will be obtained 24-48 hours prior to the initial PET scan in female patients who are not postmenopausal or surgically sterile
Patients with sickle cell anemia and other hemolytic anemia
Patients must be able to lie still for the tests; their girth and weight must be suitable to enter the gantry, which varies per tomograph
Patients who are pregnant or lactating or who suspect they might be pregnant; serum pregnancy tests will be obtained prior to each set of multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile
Adult patients who require monitored anesthesia for PET scanning
Patients who require sedation with general anesthesia for imaging studies are not eligible for the study
Patients who have been or are anticipated to be treated with radiosurgery
Patients suffering from active acute or chronic prostatitis
Patients must be willing to undergo serial imaging procedures
Adult patients who require monitored anesthesia for PET scanning
Patients with injection of other radioactive material within 90 days
Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable.
Patients with congenital heart defects.
Patients with tumors < 1 cm
Patients with allergies to iodinated contrast not amenable to pre-medication
Patients who are not able to lie supine with arms raised, and cooperate with breathholding instructions
Patients must be undergoing ovarian resection
Patients who are acutely ill who are deemed by their treating physician as not suitable candidates for this study
Patients undergoing neoadjuvant endocrine therapy
Patients must document their willingness to be followed for a period of time; for the purposes of imaging data analysis this will ideally be for at least 12 months after completing the investigational or recently approved therapy, however this may not always be possible; by signing informed consent, the patients are documenting their agreement to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database
Patients who are pregnant or lactating or who suspect they might be pregnant; serum pregnancy tests will be obtained prior to the baseline and subsequent multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile
Adult patients who require monitored anesthesia for PET scanning
Patients will be referred by the Urology or Medical Oncology Departments for participation in the study
Patients who are excluded from 7T MR imaging because of titanium implants that are not yet established to be safe at 7T remain eligible for the imaging at 3T
Patients under the age of 18 may not participate in 7T imaging
Minors, pregnant patients, incarcerated individuals, and individuals unable to give informed consent will be excluded from the study
Male patients
Patients with a solid lung lesion 1.5-5cm identified on chest computed tomography (CT) (obtained within previous 3 months) with the intention to undergo bronchoscopic evaluation; if the lesion is partially solid (i.e. there is a ground glass component) then the solid portion must make up > 75% of the lesion and measure at 1.5-5cm; the decision to pursue biopsy will be made by the treating physician and agreed upon by the patient; this will include patients determined to have an intermediate risk of malignancy (5-65%) and those non-surgical candidate with higher risk lesions in need of diagnosis for alternative treatment; OR
Patients whose targeted lung lesion is visualized with fluoroscopy
Patients with a pure ground-glass opacity identified on chest CT
Patients who refuse to participate
Patients preparing to receive therapy for pancreas cancer, including patients enrolled in HRPO# 201201124 or other clinical trials, are eligible
Patients must have planned treatment with doxorubicin:\r\n* Patients with sarcoma must have an initial planned regimen including 75 mg/m^2 doxorubicin for at least 4 cycles; NOTE: patients can be on additional chemotherapeutic agents \r\n* Patients with lymphoma must have an initial planned regimen including 50 mg/m^2of doxorubicin for at least 6 cycles; NOTE: patients can be on additional chemotherapeutic agents\r\n* Patients with breast cancer must have an initial planned regimen including 60 mg/m^2 of doxorubicin for at least 4 cycles; breast cancer patient enrollment will stop once 60 breast cancer patients have been enrolled; NOTE: patients can be on additional chemotherapeutic agents
Patients must have their echocardiograms performed such that strain may be calculated using either GE or Tomtec software
Patients must be eligible for breast-conserving therapy (BCT) based on clinical examination and mammography; if ultrasound is performed, findings must also be consistent with eligibility for BCT
Patient's most recent surgery was wide local excision with or without re-excision and for which there was obtained clear (>= 2 mm) margins at breast conserving surgery, and the pathology reveals pure DCIS; patients with invasive cancer or DCIS with microinvasion will not be registered on step 3, but will be followed for clinical outcomes\r\n* NOTE: if resection is documented to have reached pectoral fascia and deep margin is free but less than 2 mm, the patient is eligible\r\n* NOTE: if no residual DCIS is found on wide local excision as it was fully removed in core biopsy, the patient is eligible\r\n* NOTE: patients with lobular carcinoma in situ (LCIS) as well as DCIS are eligible
Thyroidectomy or lobectomy planned as definitive treatment for thyroid cancer or patients on active surveillance management approach
Patients who are claustrophobic
Patients who undergo intra-arterial hepatic 99mTc MAA evaluation in anticipation of 90Y microsphere radioembolization
Patients must be clinical candidates for radioembolization with either SIR-spheres or TheraSphere due to metastatic or primary malignancies of the liver
Hypertensive patients are eligible provided the hypertension is well controlled (95th percentile for age and height if patient =< 17 years) on stable doses of medication
Patients who have a serious reaction with the test/loading cetuximab dose for which they were not able to receive the full dose
Patients are deemed suitable for therapy with ADT and EBRT
Patients who because of age, general medical or psychiatric condition, or physiologic status unrelated to the presence of prostate cancer are unlikely to be candidates for repeat MRIs, or cannot give valid informed consent
Enrollment will not be restrictive and will encompass patients who are women, minorities and other underrepresented populations
Normal subjects could be recruited from the population of patients routinely undergoing PET CT for assessment of a pulmonary nodule (presumed unlikely to have marrow disease); alternatively, normal subjects could be recruited from the cohort of myeloma patients termed “asymptomatic” who are assumed not to have marrow involvement
UNC patients must co-enroll into LCCC9819 for collection of tissue samples
Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be on a stable regimen at registration; symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization; patients should be recovered from the effects of radiation; there is no required minimum recovery period; asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization
Patients with advanced AML that harbors IDH1 mutation
Patients with known active advanced malignant solid tumors are excluded (except for basal or squamous skin cancers, or carcinomas in situ); patients with additional hematologic malignancies that require treatment are excluded
-  Patient must have a histologically confirmed (biopsy-proven) diagnosis of follicular\n             B-cell non-Hodgkin lymphoma (WHO classification: follicular center grades 1, 2, and 3a\n             [3b patients are not eligible]), with no evidence of transformation to large cell\n             histology.\n\n          -  Patient must meet criteria for High Tumor Burden (higher risk) as defined by either\n             the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria [at least one\n             criterion] OR the follicular lymphoma international prognostic index (FLIPI) [score of\n             3, 4, or 5].\n\n          -  Patient must have Stage II, III or IV disease.\n\n          -  Baseline measurements and evaluations (PET/ CT) must be obtained within 10 weeks of\n             randomization to the study. Patient must have at least one objective measurable\n             disease parameter.\n\n          -  Age ? 18 years.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n\n          -  Ability to understand and willingness to sign Institutional Review Board\n             (IRB)-approved informed consent.\n\n          -  Willing to provide mandatory tissue samples (if sufficient tissue available) for\n             research purposes.\n\n          -  Adequate organ function as measured by the following criteria:\n\n               -  Absolute Neutrophil Count (ANC) ? 1000/mm³\n\n               -  Hemoglobin ? 8 g/dL\n\n               -  Platelets ?75,000/mm³\n\n               -  Creatinine clearance ? 50 mL/min, calculated with the use of 24-hour creatinine\n                  clearance or by Cockcroft-Gault formula\n\n               -  Total Bilirubin ? 1.5x Upper Limit of Normal (ULN) or ? 3x ULN for patients with\n                  documented Gilbert's syndrome\n\n               -  Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ? 2.5x ULN\n\n               -  Alkaline Phosphatase <5x ULN\n\n          -  All females of childbearing potential (not surgically sterilized and between menarche\n             and 1 year post menopause) must have a blood or urine test to rule out pregnancy\n             within 2 weeks prior to registration.\n\n          -  Women must not be pregnant or breastfeeding.\n\n          -  Patient must have had no prior chemotherapy, radiotherapy or immunotherapy for\n             lymphoma. For purposes of this trial, prednisone or other corticosteroids used for\n             non-lymphomatous conditions will not be considered as prior chemotherapy. In addition,\n             a prior/recent short course (<2 weeks) of steroids for symptom relief of\n             lymphoma-related symptoms will not make a patient ineligible.\n\n          -  Patient must have no recent history of malignancy except for adequately treated basal\n             cell or squamous cell skin cancer, Stage I melanoma of the skin, or in situ cervical\n             cancer. Individuals in documented remission without treatment for ? 2 years prior to\n             enrollment may be included at the discretion of the investigator.\n\n          -  Patient must have no active, uncontrolled infections.\n\n          -  Patients must be tested for hepatitis B virus (HBV), hepatitis B surface antigen\n             (HBsAg+) and hepatitis C (HCV) antibody within 6 weeks of registration. Patients who\n             are chronic carriers of HBV with positive HBsAg+ and positive HCV serology are\n             excluded, as chemotherapy and B-cell depleting therapy have been associated with virus\n             reactivation and fulminant hepatitis. NOTE: Patients with a past or resolved HBV\n             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence\n             of HBsAg) may be included if HBV DNA is undetectable. If enrolled, patients must be\n             willing to undergo monthly HBV DNA testing. Patients with positive HCV antibody must\n             be negative for HCV by polymerase chain reaction (PCR) to be eligible for study\n             participation.\n\n          -  HIV positive patients are not excluded, but to enroll, must meet all of the below\n             criteria:\n\n               -  HIV is sensitive to antiretroviral therapy.\n\n               -  Must be willing to take effective antiretroviral therapy if indicated.\n\n               -  No history of CD4 prior to or at the time of lymphoma diagnosis <300 cells/mm³.\n\n               -  No history of AIDS-defining conditions.\n\n               -  If on antiretroviral therapy, must not be taking zidovudine or stavudine.\n\n               -  Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia during\n                  therapy and until at least 2 months following the completion of therapy or until\n                  the CD4 cells recover to over 250 cells/mm³, whichever occurs later.\n\n          -  Evidence of significant, uncontrolled concomitant diseases that could affect\n             compliance with the protocol or interpretation of results or that could increase risk\n             to the patient.\n\n          -  No major surgery within 2 weeks prior to cycle 1, other than for diagnosis.\n\n          -  A condition that precludes oral route of administration (venetoclax).\n\n          -  No known allergies to both xanthine oxidase inhibitors and rasburicase.\n\n          -  Patient must not require the use of warfarin (because of potential drug-drug\n             interactions that may potentially increase the exposure of warfarin). Blood thinners\n             of other classes are permitted.\n\n          -  Patient may not receive the following agents within 7 days prior to the first dose of\n             venetoclax:\n\n               -  Strong and moderate CYP3A inhibitors\n\n               -  Strong and moderate CYP3A inducers\n\n               -  Consumed grapefruit, grapefruit products, Seville oranges (including marmalade\n                  containing Seville oranges), or star fruit within 3 days prior to the first dose\n                  of venetoclax.\n\n          -  Patient must not have serious medical or psychiatric illness likely to interfere with\n             participation in this clinical study.
Patients must have AML at initial diagnosis or at first relapse
Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be eligible for randomization
Patients must have histologic verification of osteosarcoma at initial diagnosis or relapse
Patients must have had evidence of having relapsed, progressed or become refractory to conventional therapy
Proteinuria > 1+ on dipstick urinalysis; patients with > 1+ proteinuria on dipstick urinalysis will undergo 24-hour urine collection for quantitative assessment; NOTE: patients with > 1 g/24 hours will be ineligible
Patients who are medically unstable
Patients with unstable cardiopulmonary conditions
Patients meeting the criteria for enrollment on research protocol 11-016 to receive DSTP3086S antibody drug conjugate (ADC) (the therapeutic ADC based on MSTP2109A) will be preferred patients for this study; patients that are to receive DSTP3086S will not be injected with DSTP2086S until imaging with 89Zr-DFO-MSTP2109A is finished, approximately 1 week
All patients who have gynecologic malignancies involving the middle third and the distal third of the vagina who will be receiving radiation therapy
Patients who have gynecologic malignancies involving the upper, middle and/or lower third of the vagina or are undergoing pelvic exenteration
Patients will be screened with a questionnaire to be sure they have no medical devices that could make the procedure unsafe
Patients whose breast lesion is unequivocally a cyst by unenhanced US
Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable
Patients on life support or in a critical care unit
Patients with congenital heart defects
Patients who have had excisional biopsy/lumpectomy of the current area of interest within the past 6 weeks
Patients scheduled for an EUS-FNA procedure of a pancreatic cyst
Contraindication for undergoing EUS/FNA procedure (such as unwilling or medically unstable patients, patients with severe coagulopathy, patients with poor visualization on EUS for various reasons, etc)
Patients must have previously responded to a molecularly-targeted therapy and subsequently developed resistance, or have an analogous clinical situation in which determining their molecular genotype is of interest clinically and/or scientifically
Patients who will undergo IVU using digital tomosynthesis and staging abdomino-pelvic CT as part of their routine care, will be invited to participate in this study
Patients who have been referred for CTU will also be invited to participate in the study
Patients who have upper tract TCC
GROUP 1: Non-oncologic patients from Veteran Affairs Medical Center (VAMC) in Houston:
Subtotal, gross total or biopsy patients will be eligible
Patients incapable of giving informed written consent, due to mental disability, altered mental status,\r\nconfusion, cognitive impairment, or psychiatric disorders\r\n* Patients scoring 14.5 or lower on the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) questionnaire will not be allowed on study
Patients must document their willingness to be followed for up to 24 months following enrollment in this imaging trial; by signing informed consent, the patients will document their agreement to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database
Patients who are pregnant or lactating or who suspect they might be pregnant; serum pregnancy tests will be obtained prior to the baseline and subsequent multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile
Adult patients who require monitored anesthesia for PET scanning
Subjects must be scheduled to begin treatment through the Vanderbilt-Ingram Cancer Center (VICC) Melanoma Program; this will include patients receiving standard-of-care chemotherapy, targeted therapy, and/or immunotherapy, as well as patients accrued to VICC clinical trials for the study of investigational agents
Patients with cT2N1-3M0 or cT2-4NxM0 will be considered eligible for participation
Patients who have had an adverse reaction to oxytocin
Patients who have any type of ferromagnetic bioimplant that could potentially be displaced
Patients with thoracic disease to be treated using radiotherapy will be eligible for this study
Note that patients will need to be sufficiently healthy to undergo audiovisual (AV) biofeedback
ARM III ONLY: Patients must have identifiable metastatic disease on at least 1 clinically indicated imaging modality; if only soft tissue metastasis, one lesion must measure at least 6 mm or greater; patients must have confirmation of prostate cancer prior to 18F-DCFBC imaging\r\n* Note: a patient who is eligible for one arm, subsequently may cross-over into a different arm
Patients are not required to have measurable disease; post-operative patients (patients who have had surgical resection of the lung) are eligible
Patients who are not planning to adhere to the required follow up schedule as outlined in this protocol
Patients undergoing an upper endoscopy for BE surveillance with prior biopsy-confirmed BE with dysplasia (at least LGD).
Patients without visible BE at time of study EGD.
Patients who require anticoagulation for whom biopsy would be contraindicated.
Patients must be assessed by surgeons and are considered surgically resectable
Patients of any ethnic background
Patients with T2b tumors or T3 tumors > 5 cm or patients with tumors involving the central chest/structures of the mediastinum
Patients who refuse to participate
Patients with congenital heart defects
Patients with renal insufficiency such that they cannot get intravenous contrast as part of screening or follow-up
Patients presenting with brain tumors will be eligible for this study
For salvage setting patients, lack of documented treatment or management recommendation on file
Inclusion Criteria\n\n        Each patient must meet all of the following inclusion criteria to be enrolled in the study:\n\n          -  Male or female patients 18 years or older.\n\n          -  Must be diagnosed with colorectal cancer (CRC) with liver metastasis and eligible and\n             scheduled for resection of liver metastases as part of their standard of care\n             treatment plan. The planned surgery must occur greater than 14 days after the day of\n             imaging.\n\n          -  Patients must consent to provide the sponsor with tumor tissue samples from their\n             resected liver metastases.\n\n          -  Easter Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n\n          -  Female patients who are post menopausal, surgically sterile, or agree to practice\n             effective methods of contraception from the time of signing the informed consent form\n             through 60 days after the dose of [68Ga]MLN6907 or agree to practice true abstinence.\n\n          -  Male patients who agree to practice effective barrier contraception during the entire\n             study treatment period and through 4 months after the dose of [68Ga]MLN6907 or agree\n             to practice true abstinence.\n\n          -  Voluntary written consent must be given before performance of any study-related\n             procedure not part of standard medical care, with the understanding that consent may\n             be withdrawn by the patient at any time without prejudice to future medical care.\n\n          -  Suitable venous access for the study-required, blood sampling (ie, including PK\n             sampling)\n\n          -  Adequate hepatic function as defined in the protocol.\n\n          -  Adequate renal function as defined in the protocol.\n\n          -  Hemoglobin ? 9 g/dL.\n\n          -  Recovery from all adverse effects from prior antitumor therapy to at least Common\n             Terminology Criteria for Adverse Events (CTCAE) (V4.03) Grade 1.\n\n        Exclusion Criteria\n\n        Patients meeting any of the following exclusion criteria are not to be enrolled in the\n        study.\n\n          -  Female patients who are lactating and breastfeeding or have a positive serum pregnancy\n             test during the screening period or a positive urine pregnancy test on Day 1 before\n             the first dose of [68Ga]MLN6907.\n\n          -  Any serious medical or psychiatric illness, condition, or personal circumstance,\n             including severe claustrophobia, severe dyspnea, severe back pain, etc., that, in the\n             judgment of the investigator or project clinician, might potentially interfere with\n             the procedures required in this study.\n\n          -  Involvement in an investigative radioactive or other research procedure within 4 weeks\n             prior to administration of [68Ga]MLN6907.\n\n          -  Major surgery within 14 days prior to administration of [68Ga]MLN6907 5. Serious\n             infection (viral, bacterial, or fungal) within 14 days before administration of\n             [68Ga]MLN6907 or evidence of active infection during screening.\n\n          -  Life-threatening illness unrelated to cancer.\n\n          -  Clinically significant central nervous system (CNS) metastases.\n\n          -  Known inflammatory bowel disease.\n\n          -  Known hepatitis B surface antigen-positive or known or suspected active hepatitis C\n             infection (testing not required).\n\n          -  History of any hypersensitivity to any component of [68Ga]MLN6907.\n\n          -  Symptomatic cardiac disease, including ventricular dysfunction, coronary artery\n             disease, or arrhythmias, if this would, in the opinion of the investigator or project\n             clinician, interfere with assessment of efficacy or safety of [68Ga]MLN6907.\n\n          -  Admission or evidence of addictive disorders (eg, illicit drug use, drug abuse, or\n             alcohol abuse) that would limit compliance with study requirements.\n\n          -  Inability to lie flat for the duration of image acquisition.
Patients unwilling to undergo serial non-invasive imaging
Patients must be able to perform ABC procedures
Patients with hypermetabolic activity and uptake in the neck, axilla, breast and inguinal region on scan, defined visually as significant lesion suspicious for malignancy by a nuclear medicine physician or trainee; (we will include a subset of patients with normal lymph nodes during screening; this subset of patients will be imaged as a negative control for this study)
Patients imaged for Cerenkov luminescence are going to be required to be in a darkened enclosure for at least 10 minutes and sit still during image acquisition, potentially covered by a dark cloth in case that the ambient light level remains too high for the ultra-sensitive camera; any conditions that would prevent this will exclude the patients
Patients with brain metastases are eligible provided they meet all other eligibility criteria and do not require corticosteroids or enzyme-inducing anticonvulsants and provided it is felt clinically that they will not require radiotherapy in the three (3) weeks subsequent to their participation in the study
Patients malignancy consistent with well differentiated (carcinoid) neuroendocrine histology
ADULT PATIENTS:
PEDIATRIC PATIENTS:
Patients must have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC); pathologic confirmation is mandated before initiation of any protocol specified imaging studies or drug administrations; it is recognized that for some patients, histologic or cytologic confirmation of cancer may be obtained following study enrollment; patient volunteers to the DW- and DCE-MRI sequence parameter optimization imaging portion of the study are eligible if they have any pancreatic lesion, histologic or cytologic confirmation of pathology is not required for this patient volunteer group
Patients must be eligible for and must be planning to undergo androgen deprivation therapy
Patients must be in adequate general medical health to safely tolerate a craniotomy
Patients unwilling to undergo craniotomy
Patients who are candidates for thyroidectomy based on fine needle aspiration biopsy results of dominant (> 1.5 cm) thyroid nodules will be considered for study enrollment.
Patients with indications that limit or extend initial surgery, including need for lymphadenopathy, recurrent laryngeal nerve (RLN) dysfunction, and concurrent primary hyperparathyroidism will be excluded.
Cannot eat normal table food by mouth; NOTE: patients with any form of feeding tube or a swallowing disorder are not eligible
Have taken fish oil, another dedicated n-3 supplement, or SH seed from another source within the last 28 days; patients on multivitamins that contain n-3 are eligible
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients who have too much esterase as determined by a pre-screen dose, with a conversion rate yielding concentration of CPT > 100 ng/ml in vitro.
Patients with lesions safely accessible for protocol driven biopsy
All patients with transdermal patches (e.g.; fentanyl, Lidoderm, scopolamine, etc)
Patients should not have either CT scanning or B-WARM if they have a fever at the time\r\n* Fever should be worked up and treated as appropriate\r\n* Patients should be afebrile for 24 hours prior to scanning or B-WARM therapy
Patients’ availability to check their weight twice per week, during the study duration
Patients with plasma alanine aminotransferase greater than 40 IU/dL
Patients with plasma aspartate aminotransferase greater than 45 IU/dL
Patients with myocardial ischemia or peripheral muscle ischemia
Patients with history of known defects in fat metabolism (ie pyruvate carboxylase deficiency, prophyria, fatty acid oxidation defects, primary carnitine deficiencies, organic acidurias, hypoglicemia) will be excluded
Patients deemed inoperable (no scheduled surgery) are eligible for this trial, as they could be surgical candidates after treatment with vemurafenib; inoperable patients must be naive to therapies targeting the MAPK pathway
Histological diagnosis other than PTC; patients with anaplastic tumors are not eligible; however, patients whose tumors contain areas of un-differentiated or dedifferentiated histology may enroll provided the original diagnosis was clearly PTC, and the tumor histology remains predominantly papillary at enrollment
Patients who have taken ASA or nonsteroidal anti-inflammatory drugs (NSAIDs) in the last two weeks or have an allergy to ASA will not be eligible for enrollment
Patients with neck dissection connected to upper aerodigestive tract
Patients found to require sternocleidomastoid muscle or internal jugular vein excision
Patients with a diagnosis that qualifies them for UCBT
Untreated esophageal varices observed on EGD or imaging study; however, patients with known portal hypertension and evidence of varices on EGD or imaging study who have undergone appropriate therapy as indicated within the last 6 months (if applicable) are eligible for enrollment.
Episodes of hepatic encephalopathy within the last 4 weeks. Patients with prior episodes of hepatic encephalopathy who are clinically stable on lactulose, neomycin, and/or xifaxan therapy are allowed.
Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
Patients self-identify as Black, African American, or White and non-Hispanic
Patients will be excluded if physicians/staff determine they will not be eligible for a trial during the study period (e.g., entering hospice; moving away)
PATIENT: MSK patients
All male patients (all ages) scheduled for standard prostate needle biopsy (first, repeat or active surveillance biopsy) under local anesthesia will be eligible for the study.
Patients that primary care providers exclude
Patients presenting as follow-ups only at the outpatient Supportive Care Center
Patients with hearing and/or visual impairments
Patients must be willing to be audio recorded during the sessions
PATIENTS: Already enrolled on hospice, or enrolling on hospice upon discharge from the hospital admission
PATIENTS: Admitted to the Intensive Care Unit (ICU) during their hospitalization
CAREGIVERS: Adult caregivers (> 18 years) of patients who have agreed to participate in study
Patients scheduled to receive first allogeneic BMT
Patients receiving care from these oncologists who are willing to complete an anonymous survey
Patients receiving care from these oncologists who are willing to be audio recorded
All participants will be recruited from patients receiving care at the HFHS
Decisionally impaired patients
Patients not residing in Pennsylvania or New Jersey
Patients who do not verbally, written, or electronically consent to participate (usability test and RCT)
OR Patients with impaired hearing or speech;
Nurses covering patients on Seidman 6 under the care of the Gynecologic Oncology service
Patients referred for consultation to the Supportive Care team
Patients have never done the ESAS before
Patients who have clinical evidence of cognitive impairment as determined by the research staff
Patients who have already done the ESAS in the past
Patients who refuse to participate in the study
Patients whose size and weight would not allow CT scanning
Follow up patients seen in the outpatient Supportive Care Center
Patients who do not undergo routine oncologic care at the chosen Partners site or Fox Chase Cancer Center
Consent both to provide data themselves and to assist in identifying eligible patients for recruitment to the trial
PATIENTS:
While we are focusing on recruitment of clinicians who treat breast, prostate, or colorectal cancers, any eligible patients of the clinicians (e.g., a testicular cancer patient) will be approached for potential participation in the study
Patients who are unable to successfully respond to the PMSA alarm and properly enter their data
Patients who are unable to validate their understanding of the pain scale
Patients younger than 18 years
Expansion cohort at the RD: All patients must have:
Patients who have previously discontinued gemcitabine-containing regimens due to gemcitabine-related toxicity.
Patients eligible for this companion sample collection protocol sample collection protocol must meet all inclusion in CLEE011A2404.
Additional Criteria for Patients Eligible to Restart Dasatinib
Patients with poorly differentiated pancreatic neuroendocrine tumors (according to WHO 2000 classification).
Inclusion Criteria:\n\n        Ostomy patients who:\n\n          -  Have healthy peristomal skin\n\n          -  Are within 12 weeks post op\n\n        Exclusion Criteria:\n\n        Ostomy patients who:\n\n          -  Have a fistula, wound, lesion or suspected infection in the peristomal area\n\n          -  Are in-patient in healthcare facility
Patients who are progressing on current fulvestrant therapy (patients who have had\n             fulvestrant therapy in the past and were subsequently treated with other therapies or\n             those who are starting fulvestrant as their next line of ET are eligible for the\n             study).
Patients who are able to tolerate flexible bronchoscopy.
Patients with bronchiectasis in the lobe of the intended implantation sites.
Patients enrolled in any other clinical studies the investigator believes to be in conflict with this investigation.
Patients must have interest in a legal consultation as specified by the I-Help model to receive free legal consultation.
Subjects with psychiatric disorders that affect their ability to consent for themselves will be excluded and not the entire population of patients with psychiatric disorders
Patients who are not candidates for RT/CRT treatment
Patients who were treated with blinatumomab in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells and did not experience unacceptable toxicities with prior blinatumomab administration; patients who were treated with chimeric antigen receptor (CAR)-modified T cells targeting CD19 in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells
Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible.
Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have interstitial lung disease/pneumonitis, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. Patients with controlled hepatitis C, in the investigator's opinion, are allowed. Patients with known hepatitis B must be HBeAg and HB viral DNA negative for enrollment. Note that, because of the high prevalence, all patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be tested and, if HBsAg positive, must be HBeAg and HB viral DNA negative for enrollment.
Patients who are receiving any other investigational agents; a minimum of 4 weeks wash-out period is required for eligibility; please contact principal investigator, Dr. Swati Kulkarni for further clarification
Patients with recurrent ipsilateral DCIS
Patients with glioblastoma multiforme