Subjects must be at least 4 weeks post last dose of temozolomide
Subjects has failed or intolerant to temozolomide therapy.
Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g. peripheral neuropathy) can be enrolled on a case-by-case basis with prior consultation and agreement with the Sponsor Study Physician.
Subjects who have received drugs that directly or indirectly inhibit calcineurin or Nuclear Factor of activated T cells (NFAT) activity .
Subjects must agree to undergo tumor biopsies until biopsies have been obtained from 20 subjects (i.e., biopsies are required in at least the first 20 enrolled subjects, or until a goal of 20 study biopsies are obtained); subjects in whom a biopsy is technically not feasible or in whom would result in unacceptable risk in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator
Have documented relapse or refractoriness after at least 1 line (MB and ARMS subjects) or 2 lines (NB and ES subjects) of standard-of-care therapy, including each of the following:
Subjects may not be on other therapies that affect hormone levels, such as estrogens, testosterones, ketoconazole during this study; however, megestrol for hot flashes is permitted
Subjects with gastric mucosa-associated lymphoid tissue (MALT) lymphoma must be Helicobacter pylori (HP)-negative
Subjects may not be receiving any chemotherapy or other agents intended for oncologic treatment
Subjects exhibiting idiosyncratic reactions to psoralen compounds.
Subjects with history of osteoporosis
All subjects must:
Female or male subjects whose advanced HER2 expressing cancer has failed standard of care treatments, or for whom such therapy is not acceptable to the subject. Subjects with advanced breast and gastric cancer who test positive for HER2 by ASCO/CAP criteria (either IHC or FISH) must have received prior treatment with a trastuzumab containing therapy. Subjects who have been previously treated with pertuzumab, TDM-1, lapatinib, or other available and accessible HER2-directed therapies or investigational therapies are eligible.
Tumor tissue local laboratory HER2 testing results (clinical pathology report) based on FDA or other regulatory agency approved, validated or commercially available IHC or ISH HER2 assay. Pre-screening for HER2 is allowed only for subjects with breast and gastric cancer, GE junction or esophageal cancer, where applicable. Subjects with other types of cancer must have previously tested for HER2 status by HER2 IHC or ISH assay.
Subjects who are able and willing to give written informed consent\n\n - Documented primary or secondary AML, as defined by the WHO criteria (2008), by\n histopathology refractory to previous induction chemotherapy and/or relapsed after\n achieving remission with a prior chemotherapy and who are not candidates for other\n available therapy likely to confer clinical benefit.\n\n - For Phase 2a only: in addition to inclusion criteria 2 above, patients must have a\n FLT3 mutation of any type\n\n - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2\n\n - In the absence of rapidly progressing disease, the interval from prior treatment to\n time of FF-10101-01 administration should be at least 14 days for cytotoxic agents\n other than hydroxyurea, at least 5 half-lives for non-cytotoxic agents, and 14 days\n for monoclonal antibody therapies. Hydroxyurea may be continued for a maximum of 14\n days from the start of FF-10101-01 dosing, through Cycle 1 Day 14, with a maximal dose\n of 5 grams/day\n\n - Persistent chronic clinically significant toxicities from prior chemotherapy or\n surgery must be ?Grade 2\n\n - If subject has had a hematopoietic stem cell transplant, subject must be ?60 days\n post-transplant with no clinically significant GVHD requiring systemic therapy\n\n - Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ?3 times the\n upper limit of normal and total bilirubin of ?1.5x the upper limit of normal. If total\n bilirubin is equal to or exceeds 1.5x the upper limit of normal, the subject can still\n be included if direct bilirubin is ?1.5x the upper limit of normal\n\n - Calculated creatinine clearance of ?60 mL/min\n\n - Female subjects of childbearing potential and sexually mature male subjects must agree\n to use a medically accepted method of contraception other than an oral contraceptive\n for the duration of the study.\n\n Exclusion Criteria:\n\n - Subjects diagnosed with acute promyelocytic leukemia\n\n - Subjects with Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)\n\n - Subjects with clinically active CNS leukemia\n\n - Subjects with major surgery within 28 days prior to the first administration of\n FF-10101-01\n\n - Subjects with radiation therapy within 28 days prior to the first administration of\n FF-10101-01\n\n - Subjects with active malignant disease requiring therapy other than AML or\n myelodysplastic syndrome with transformation into AML\n\n - Subjects with an active uncontrolled infection\n\n - Subjects with a medical condition, serious intercurrent illness, or other circumstance\n that, in the Investigator's judgment, could jeopardize the subject's safety as a study\n subject, or that could interfere with the study objectives\n\n - Subjects known to have human immunodeficiency virus infection, or who have active\n hepatitis B or C infection as determined by serological testing\n\n - Subjects with congestive heart failure, New York Heart Association (NYHA) Class 3 or\n 4, or subjects with a past history of congestive heart failure NYHA Class 3 or 4 and\n in whom echocardiogram or multiple gate acquisition (MUGA) scan performed within 3\n months prior to screening or at screening showed a LVEF <40%\n\n - Female subjects who are pregnant or breast feeding\n\n - Subjects on 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) or\n other drugs known to have muscle toxicity\n\n - Subjects taking strong inhibitors of CYP3A4 will be excluded from the study unless\n therapeutic substitution is possible\n\n - Subjects taking strong inducers of CYP3A4 will be excluded from the study unless\n therapeutic substitution is possible\n\n - Use of systemic immunosuppressive agents within 14 days prior to first dose of\n FF-10101\n\n - Subjects taking drugs known to cause Torsades de Pointes will be excluded from the\n study unless therapeutic substitution is possible\n\n - Subjects known to have long QT syndrome\n\n - Subjects with mean QTcF values following 3 ECGs conducted 5 minutes apart of >470 msec
Inclusion Criteria:\n\n Subjects are eligible to be included in the study only if they meet all of the following\n criteria:\n\n 1. Subjects who are males or females ? 18 years of age.\n\n 2. Subjects who are able to give written informed consent.\n\n 3. Subjects who have a documented diagnosis of MDS according to WHO criteria.\n\n 4. Subjects who have Revised International Prognostic Scoring System (IPSS-R) categories\n of Very Low, Low- or Intermediate-risk disease. Subjects with cytogenetic failure and\n ? 10% marrow blasts will be eligible.\n\n 5. Subjects who meet one of the following hematologic criteria within 8 weeks of\n registration (according to the IWG criteria) and as documented in prior transfusion\n logs or weekly hematology evaluations:\n\n - Symptomatic anemia untransfused with hemoglobin ? 9.0 g/dL or with RBC\n transfusion-dependence (i.e., ? 2 units/month) confirmed for a minimum of 8 weeks\n before randomization.\n\n - Platelet counts of < 100 x109/L\n\n - Absolute neutrophil count < 1500\n\n 6. Subjects with del(5q) who should have failed or not be a candidate for approved\n therapy (Lenalidomide) prior to enrolling on this study.\n\n 7. Subjects must meet accepted standard criteria for treatment and have failed or not be\n candidates for standard, accepted treatments.\n\n 8. Subjects who have sufficient hepatic function, defined as bilirubin 2 times the upper\n limit of normal (ULN) and alanine transaminase (ALT) and aspartate transaminase (AST)\n levels 2.5 times ULN.\n\n 9. Subjects who have sufficient renal function, defined as serum creatinine levels 1.5\n ULN.\n\n 10. Subjects who have a performance status of 2 on the Eastern Cooperative Oncology Group\n (ECOG) scale (refer to Appendix 2).\n\n 11. Subjects who have discontinued all previous therapies for MDS or other investigational\n therapy for at least 28 days prior to study enrollment and recovered to less than\n grade 2 toxicity from prior therapy.\n\n 12. Subjects who are able to swallow tablets.\n\n 13. Subject who are willing and able to comply with scheduled visits, treatment plans,\n laboratory tests and procedures.\n\n 14. Female subjects of childbearing potential must have a negative serum pregnancy test\n within 7 days of the first administration of study drug. For the purpose of this\n study, female subjects of childbearing potential are defined as all female subjects\n after puberty unless they are postmenopausal for at least 1 year, or are surgically\n sterile (hysterectomy or bilateral oophorectomy or tubal ligation).\n\n 15. Female subjects of child bearing potential who are willing to avoid the pregnancy\n during the duration of the study and for 30 days following the last dose of study\n drug. The effects of TEW-7197 on the developing human fetus are unknown. For this\n reason, women of child-bearing potential and men must agree to use adequate\n contraception (hormonal or barrier method of birth control; abstinence) prior to study\n entry and for the duration of study participation. Should a woman become pregnant or\n suspect she is pregnant while participating in this study, she should inform her\n treating physician immediately.\n\n 16. Subjects with QTc interval calculated according to Fridericia's formula (QTcF =\n QT/RR0.33; RR = RR interval) of ? 470 ms for males and 450 ms for females on screening\n electrocardiogram (ECG).\n\n 17. Subjects must have ejection fraction more than 50% and no clinically significant\n valvular dysfunction.\n\n 18. Subjects must have discontinued radiotherapy at least 14 days with resolution of any\n toxicity to Grade 1 or better prior to the start of treatment.\n\n Exclusion Criteria:\n\n Subjects will be excluded from the study if they meet any of the following criteria:\n\n 1. Subjects who have received treatment within the last 28 days with a drug that has not\n received regulatory approval for any indication at the time of study entry.\n\n 2. Subjects who have moderate or severe cardiac disease:\n\n 3. Subjects who have the presence of cardiac disease, including a myocardial infarction\n within 6 months prior to study entry, unstable angina pectoris, New York Heart\n Association (NYHA) Class III/IV congestive heart failure, or uncontrolled\n hypertension.\n\n 4. Subjects who have documented major electrocardiogram (ECG) abnormalities at the\n investigator's discretion (for example, symptomatic or sustained atrial or ventricular\n arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks,\n ventricular hypertrophy, or recent myocardial infarction).\n\n 5. Subjects who have major abnormalities documented by echocardiography with Doppler (for\n example, moderate or severe heart valve function defect and/or left ventricular\n ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of\n normal).\n\n 6. Subjects who have predisposing conditions that are consistent with development of\n aneurysms of the ascending aorta or aortic stress (for example, family history of\n aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large\n vessels of the heart documented by CT scan with contrast).\n\n 7. Subjects who have documented iron, B12, folate deficiency as determined by the\n investigator.\n\n 8. Female subjects who are breastfeeding, or intend to breastfeed during the duration of\n the study and for 30 days following the last dose of study drug.\n\n 9. Subjects with any other serious medical condition which in the Investigator's opinion\n would preclude safe participation in the study.\n\n 10. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the\n study.\n\n 11. Subjects with elevated Troponin 1 levels at screening or known to have persistently\n elevated brain natriuretic peptide (BNP).\n\n 12. Subjects with serious pre-existing medical conditions as follows:\n\n - History of cardiac or aortic surgery,\n\n - Hypertension that is not controlled by standard medication (to 150/90 mmHg or\n below),\n\n - Cirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,\n\n - Severe diabetes that is not currently controlled,\n\n - Current or history of interstitial pneumonitis,\n\n - Presence of aneurisms of the ascending aorta or aortic stress.\n\n 13. Subjects with known history of difficulty swallowing, malabsorption or other\n conditions that may reduce absorption of the product.\n\n 14. Subjects with major abnormalities identified by ECG or echocardiogram (ECHO), at the\n Investigator's discretion.\n\n 15. Subjects with active infection with human immunodeficiency virus, hepatitis B virus or\n hepatitis C virus.\n\n 16. Subjects with active infection requiring systemic antibiotic therapy.\n\n 17. Subjects who are currently using or planning to use:\n\n Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4
For French subjects only: Is either affiliated with or a beneficiary of a social security category.
Subjects with known HIV, active hepatitis B, or active hepatitis C (detectable RNA); HIV positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with durvalumab and/or tremelimumab; in addition, these subjects are at increased risk of lethal infections when treated with immunosuppressive therapy
Subjects who consume more than 3 alcoholic beverages per day
Subjects who have taken 5a-reductase inhibitors (finasteride or dutasteride), saw palmetto, or PC-SPES within the last 6 weeks are ineligible; subjects will be eligible for the study after the wash out period of 6 weeks
Subject’s close household contacts include children less than the age of three
Subjects less than 18 years old are being excluded in this study as melanoma is extremely uncommon in this age group and insufficient data are available in adults using dendritic cell therapy to assess potential risk in subjects less than 18 years old. Participation of women and minorities is encouraged, although it is recognized that melanoma is much more common in the Caucasian population
Study subjects with known chronic infection with HIV, hepatitis B or C, since these infections may interfere with the evaluation of vaccine-induced immune responses. Infectious disease testing will be performed whenever a study subject exhibits clinical signs of infection or to confirm a history of infection. Testing will also be performed for all study subjects undergoing leukapheresis, as required by the blood bank for autologous blood products (standard donor transmissible disease testing)
PHASE II: For those subjects with marrow involvement, the first 15 subjects enrolled after the 03.28.2017 amendment must have detectable disease at the time of enrollment
In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, are eligible if they • have relapsed and/or refractory disease, OR are>=65 years of age and not candidates for or have refused standard chemotherapy. Subjects with multiple myeloma are eligible if they have progressed despite therapy with an alkylating agent, proteasome inhibitor, and immunomodulatory agent, either as individual regimens or in combination. Subjects with NHL are eligible if they have received at least two prior lines of systemic therapy, including at least one line of immunochemotherapy with an anti-CD20 antibody (if their tumor expresses CD20). In Part 2, the NHL cohort will separately enrol subjects with double- and triple hit lymphoma, so that a minimum of 10 subjects with this subset of disease will be enrolled. To be eligible for this sub-cohort, tumor sample from the subject must demonstrate rearrangement and/or overexpression of MYC and either BCL2 and/or BCL6 genes. Evaluation of double- or triple-hit status may be performed via appropriate local testing, and the determination of double- or triple-hit diagnosis will be at the discretion of the investigator and GSK Medical Monitor.
Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of AZD1775 will be determined following review by the principal investigator
Subjects with neurofibromatosis type 1 (NF1) are also eligible
Patients with evidence of intra-tumoral hemorrhage > 5 mm maximal diameter. These subjects should be discussed with the study chair.
Subjects must be co-enrolled on protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).
Subjects with delayed healing of wounds, ulcers, and/or bone fractures
Subjects 40 years of age and older must also have a negative stress cardiac test (i.e. EKG stress test, stress thallium, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia). Stress test may be required of subjects less than 40 years of age if warranted by family history or risk factors by the treating investigator.
Subjects must refuse or be deemed ineligible for cisplatin-based chemotherapy.
Subjects must have histologically confirmed solid tumor malignancy that is metastatic or treatment refractory cancers which are not curable or do not have known palliative measures or treatments that are associated with a survival advantage (as defined by the subject or the physician investigator); enrollment of subjects with tumors that can be safely biopsied is encouraged
Subjects must be willing to refrain from sunbathing for the duration of the study.
Dose Escalation, Renal insufficiency, NSCLC and CPI-Treated Expansion Cohorts: For subjects with urothelial cancer and NSCLC: Subjects must submit a tumor tissue for Nectin-4 expression. Enrollment for these subjects is not dependent on the immunohistochemistry using the H-Score (IHC H-Score).
Subjects with central nervous system (CNS) involvement are eligible provided that they are asymptomatic and in the opinion of the study principal investigator (PI) have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion; subjects that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization
Subjects must be followed at the Cleveland clinic for AS
Subjects must be willing to adhere to the dietary modification outlined in the protocol.
Subjects not followed by the Cleveland clinic.
Subjects unable to adhere to the dietary modification outlined in the protocol.
Quantitative serum IgG levels for subjects with IgG MM must not exceed the institutional upper limit of normal (ULN)
Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis
Subjects with central nervous system (CNS) involvement are eligible provided that they are asymptomatic and in the opinion of the study principal investigator (PI) have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion; subjects that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization
Subjects not below specific total neutrophil count.
Patients with histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required (presence of arterial hypervascularity with venous washout). For subjects without cirrhosis, histological confirmation is mandatory. The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient
Subjects with prior anti-PD-1, anti-PD-L1 treatment. For Arms A and D, subjects may not have had prior 4-1BB treatment. For Arms B and E, subjects may not have had prior OX40 treatment. For Arms C and F, subjects may not have had prior 4-1BB or OX40 treatment.
For a clinical diagnosis of NF1 patients must have at least two of the diagnostic criteria for NF1 listed below:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* A neurofibroma or plexiform neurofibroma\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Known HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
Patients with evidence of intra-tumoral hemorrhage > 5 maximal diameter; these subjects should be discussed with the study chair
Only for subjects enrolled in Arm 1 - Neratinib and everolimus: subjects requiring therapy with immunosuppressive agents such as anti-tumor necrosis factor alpha (TNFa) agents (etanercept, adalimumab), azathioprine, methotrexate, cyclosporine, etc. for active autoimmune disorder.
Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
Subjects for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk
Subjects who have unknown transfusion history
All subjects must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the National Institutes of Health (NIH) consensus conference criteria; in addition to a plexiform neurofibroma, one or more of the following diagnostic criteria for NF1 must be present:\r\n* Six or more Cafe Au Lait spots (>= 0.5 centimeter [cm] in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the spheroid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this includes, but is not restricted to, subjects with any of the following:
Non-clear subjects must be ENPP3 positive, defined as IHC H-score ?15
Subjects receiving consolidative chest radiation
CELL PROCUREMENT: Subjects with relapsed fulminant CD19+ ALL that is rapidly progressing who cannot safely delay definitive treatment for their ALL by at least 4 weeks in the opinion of the investigator
Subjects must be considered appropriate candidates for high dose (HD) IL-2 by one of the treating investigators listed on the protocol; HD IL-2 candidacy evaluation is per institutional guidelines at each site and should include a dobutamine stress echocardiogram or equivalent; subjects with a positive stress test for cardiac ischemia would be excluded from this trial
Subjects with ALT > 5 x ULN at day 1 are not eligible for enrollment
Has had encephalopathy in the last 6 months; subjects on rifaximin or lactulose to control their encephalopathy are not allowed
Subjects should be in otherwise satisfactory health in the opinion of the Investigator;
Subjects that have received experimental vaccines or other immune therapies should be discussed with the principal investigator to confirm eligibility
Subjects must not be receiving any chemotherapy agents (except hydroxyurea)\r\n* Intrathecal methotrexate and cytarabine are permissible
Subjects who have undergone any recent major surgery must have done so at least 4 weeks prior to starting therapy with DS3032b, with the following exceptions: vertebroplasty and/or kyphoplasty, which must have been performed at least 1 week prior to starting DS3032b; planned elective surgery unrelated to the subject’s diagnosis of multiple myeloma, such as hernia repair, may be allowed, at the discretion of the principle investigator, as long as it was performed at least 2 weeks prior to starting DS3032b, and subjects have recovered fully from this procedure
Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects)
Subjects who have required plasmapheresis and exchange less than 2 weeks prior to initiation of therapy with DS3032b
Subjects with conditions that carry high anesthetic risk in the opinion of the treating anesthesiologist are not eligible (i.e. subjects with significant airway compression by tumor or craniofacial abnormalities).
Subjects in whom treatment planning constraints cannot be met
Subjects in whom treatment planning constraints cannot be met
Subjects who screen fails can be re-enrolled if the causation of the screen fail has been corrected
Subjects with delayed healing of wounds, ulcers, and/or bone fractures
Males and females 65 years of age and older; subjects < 65 years of age that meet any of the following criteria: \r\n* Subjects that refuse to be treated with chemotherapy based agents (this should be documented in the consent form)\r\n* Subjects that are not candidates for treatment with chemotherapy agents based on any of the following:\r\n** ECOG performance status >= 2\r\n** Cumulative illness rating scale (CIRS score) >= 6\r\n** Creatinine clearance < 70 mL/min using the Cockcroft-Gault equation
Subjects with active herpes simplex or herpes zoster; subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded; subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study
Subjects on any immunomodulatory drug
Subjects on systemic medications known to affect the Hedgehog pathway
Subjects with a history of keloids or excessive scarring
Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjects who are therapeutically anticoagulated for medical conditions unrelated to HCC such as atrial fibrillation. Subjects may be re-screened after condition is treated or anticoagulant is withheld.
Successful T cell test expansion (first 10 subjects)
Subjects for whom there is concern about compliance with the protocol procedures
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Subjects who provide direct healthcare or reside in healthcare facilities or in non-hospital settings such as clinics, assisted living facilities, homeless shelters, jails and prisons as well as subjects with frequent exposure to laboratory animals
Subjects who are deemed to be poor surgical risks by the treating neurosurgeon because of medical comorbidities
Subjects on medications that may not be safely stopped during the fasting portion of the study, or which may not be safely consumed without food
Subjects who have other conditions which in the opinion of the investigator contraindicate the receipt of HSV1716 or indicate subject’s inability to follow protocol requirements
PART II; Subjects must have been enrolled in Part 1 of this study and have received 1 dose of HSV1716 and have completed at a minimum the day 28 follow-up; subjects must have been categorized at a minimum as having stable disease thought to be attributable to the virus; subjects who were minimally characterized as having stable disease are also eligible if their lesion re-occurs or re-grows; the same criteria will be applied to determine eligibility for a third dose, and again for a fourth dose
Subjects must have an indication for treatment as defined by the NCI Working Group Guidelines
Subjects with active hemorrhagic diathesis
Subjects with a history of hepatitis of any etiology or hepatic insufficiency
Urine dipstick positive (>1+) for blood during screening with investigation indicating glomerular haematuria. If other causes are identified, subjects may be enrolled on resolution of the abnormality
Large subjects not fitting comfortably into the MRI scanner
History of pathologically confirmed CIN1 by colposcopically-directed punch biopsy, within 12 weeks prior to administration of first study vaccination (CIN 2/3 subjects will not be eligible);
Subjects who refuse to have their catheter removed or subjects for whom, in the Investigator's opinion, catheter retention for the duration of the study is reasonable or required;
Subjects with septic shock that requires inotropic support or is unresponsive to fluid resuscitation;
Subjects with short-term CVCs indwelling less than 5 days;
Additional Exclusion Criteria for subjects Assigned to Treatment A: Subjects unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
Subjects with uncontrolled, systematic infection should be excluded
Subjects with carcinosarcoma
Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia).
Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
Subjects must have either:
Subjects with FAB M3 (t(15;17)(q22;q21)[PML-RARalpha]) are not eligible
Subjects must not be receiving any chemotherapy agents (except hydroxyurea); intrathecal methotrexate and cytarabine are permissible
Subjects for whom a potential 29-day delay in treatment will interfere with the subject’s potential therapeutic options
Subjects with aphakia
Subjects using certain medications
Subjects must not have had prior pazopanib therapy
Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of BMN 673 will be determined following review by the principal investigator
Subjects with an indication for AHCT for the treatment of PCM as determined by the principal investigator (PI) or lead associate investigator (LAI)\r\n* Subjects following induction treatment for PCM\r\n* Subjects with recurrent or persistent evaluable disease who have not undergone AHCT for the treatment of the PCM
Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years) and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval.
Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.
The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment.
Subjects with classical carcinoid
Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study
Subjects with HNSCC:
Subjects with vitiligo or alopecia;
For treatment-naïve subjects only:
Part 2, Cohort 1: For subjects with only PAM pathway alterations, subjects must have only PAM alterations, excluding Akt2 activating mutations or amplifications, and no other genomic alterations.
Subjects with vitiligo or alopecia;
Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population.
Subjects unwilling to use acceptable methods of contraception. -Female subjects should refrain from breastfeeding throughout this period.
Subjects must fall into one of the two populations below:
Subjects who have voluntarily signed a written informed consent in accordance with institutional policies after its contents have been fully explained to them
Absence of active GVHD and off immunosuppression; subjects on tapering prednisone will be eligible if their dose is 0.25 mg/kg or less and being actively tapered; we suggest a 28 day waiting period off of immunosuppression but some subjects with rapidly progressive disease may need to be treated before 30 days and will still be eligible
Subjects who have voluntarily signed a written informed consent in accordance with institutional policies after its contents have been fully explained to them
Subjects who desire to enroll in this study and for whom anti-HER-2 therapy is not available or contraindicated, may be eligible to enroll in this trial.
Subjects actively receiving duvelisib are to be excluded from this study if they have any ongoing ? Grade 3 AE considered related to duvelisib treatment at screening
Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (for nonsquamous NSCLC) or mRECIST (for epithelial pleural mesothelioma). Subjects with resected primary tumors who have documented metastases are eligible.
Negative hepatitis B serologic tests; if positive results are not indicative of active or chronic infection, the subjects can enter the study at the investigator’s discretion
Subjects unwilling to use acceptable methods of contraception. -Female subjects should refrain from breastfeeding throughout this period.
Subjects with evidence of extraprostatic extension (T3a) or seminal vesicle involvement (T3b) on clinical evaluation
OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 loose stools daily in subjects without a colostomy or ileostomy; subjects with a colostomy or ileostomy may be entered at investigator discretion
Previously untreated subjects that meet ANY of the following criteria:\r\n* Subjects that refuse to be treated with chemotherapy based agents (this should be documented in the consent form)\r\n* Subjects that are not candidates for treatment with chemotherapy agents based on ANY of the following:\r\n** ECOG performance status >= 2\r\n** Advance age (>= 65 years)\r\n** Cumulative Illness Rating Scale (CIRS score) >= 6\r\n** Cytopenias\r\n*** Hemoglobin (Hb) =< 100 g/L (10 g/dL)\r\n*** Platelet count =< 100 x 10^9/L (100,000/uL)\r\n*** Absolute neutrophil count (ANC) =< 1.5 x 10^9/L (1,500/uL)
Subjects must have received at least one prior treatment regimen\r\n* Subjects that have received a prior Bruton’s agammaglobulinemia tyrosine kinase (BTK) inhibitor or cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition are ineligible\r\n* Subjects that have undergone prior allogeneic stem cell transplantation will only be eligible if the transplant occurred at least 1 year prior to study entry, the patient is no longer taking any immunosuppressive therapy, and there are no significant ongoing transplant-related adverse effects\r\n* Subjects must not have received chemotherapy =< 21 days prior to first administration of study treatment, monoclonal antibody =< 6 weeks prior to first administration of study treatment, and/or radiotherapy or other investigational agents =< 4 weeks prior to first administration study treatment unless the subjects’ tumor has progressed on the previous therapy and the investigator believes that the patient should not postpone further therapy and, all treatment-related toxicities have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 =< grade 1; subjects may be receiving equivalent to prednisone at a maximum dose of 20 mg/day orally
Subjects must be entered no more than 12 weeks postoperatively
Subjects with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 2 months of first dose. Subjects with glioma who are on a stable, steroid dosing regimen 5 days prior to the screening MRI may be permitted to enroll with Medical Monitor approval.
Subjects in whom everolimus is contraindicated.
Subjects of all genders and races are eligible
Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
Subjects with any prior exposure to a thrombopoietin-receptor agonist
For subjects who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the study.
Subjects must be able to discontinue any drug treatment aimed at lowering disease burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs that have more long-lasting effects on the marrow, such as thalidomide and its analogs, and interferon, subjects should discontinue these no later than day -28
Subjects should not have severe peritoneal metastases. The following criteria were applied:
Subjects in second or later relapse;
Subjects with any prior exposure to a thrombopoietin-receptor agonist
Subjects who have been diagnosed with indolent NHL that has progressed.
Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon
Inclusion Criteria:\n\n Subjects eligible for enrollment in the study must meet all the following criteria:\n\n 1. Male or female ?18 years of age\n\n 2. Able to provide written informed consent prior to any study procedures being\n performed; eligible subjects must be able to understand the informed consent form\n prior to inclusion into the study.\n\n 3. Confirmed diagnosis of newly diagnosed, persistent or recurrent CD if subjects are not\n candidates for surgery or radiotherapy CD is defined according to the criteria in the\n Endocrine Society Clinical Practice Guideline for diagnosis of CD (Nieman 2008).\n Previous medical records will be collected and used to support the diagnosis of CD.\n\n Specifically, CD is defined as\n\n - Mean 24-hour UFC level of ?1.5X ULN on repeated determination\n\n - Morning plasma corticotropin (ACTH) level of 5 ng/L (1.1 nmol /L) or more\n\n - Either MRI confirmation of pituitary macroadenoma, or inferior petrosal sinus\n gradient >3 after corticotropin-releasing hormone (CRH) stimulation for those\n patients with a microadenoma, or for subjects who have had prior pituitary\n surgery, histopathology confirming and ACTH-staining adenoma. If inferior\n petrosal sampling had been performed without CRH, then a central to peripheral\n pre-stimulation gradient >2 is required\n\n 4. Confirmed diagnosis of newly diagnosed, persistent or recurrent endogenous CS of other\n etiology if subjects are not candidates for surgery or radiotherapy. CS will be\n defined according to the criteria in the Endocrine Society Clinical Practice Guideline\n for diagnosis of CS (Nieman 2008). Previous medical records will be collected and used\n to support the diagnosis, and the differentiation of the cause of CS, specifically\n\n - Mean 24-hour UFC level of ?1.5X ULN on repeated determination\n\n - Ectopic ACTH secretion, not of pituitary origin\n\n - Ectopic CRH secretion\n\n - Adrenal-dependent CS (adrenal adenoma, adrenal autonomy)\n\n - Etiology unknown\n\n 5. Subjects MUST have elevated mean 24-hour UFC levels ?1.5X ULN of assay based on a\n minimum of four measurements from adequately collected urine. Urine may be collected\n on sequential days.\n\n 6. In addition to elevated mean UFC, presence of abnormal values from one of the\n following tests:\n\n - Abnormal DST: Elevated 8 AM serum cortisol ?1.8 ug/dL (50 nmol/L) after 1 mg\n dexamethasone orally at 11 PM the evening prior (if not conducted already in the\n diagnostic workup of the subject within the previous 2 months before start of\n Screening Phase; in that case previous test results and details of conduct will\n need to be available by the Baseline visit)\n\n - Elevated late night salivary cortisol concentrations (at least two measurements)\n >ULN NOTE: For subjects with estimated glomerular filtration rate (eGFR as\n determined by Modified Diet in Renal Disease MDRD equation) >40 and <60\n mL/min/1.73 m2 in addition to meeting the UFC criteria, late night salivary\n cortisol test results (?2 measurements) MUST also demonstrate evidence of CS.\n\n 7. Previously irradiated subjects with CD or CS of other etiology will be allowed as long\n as the radiation treatment occurred > 4 years ago and subjects have not exhibited\n evidence for improvement in their underlying Cushing's disease for 6 months. The total\n number of previously irradiated subjects enrolled in this study will not exceed 10.\n\n 8. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse\n surgery, or in whom surgery will be delayed for >6 months. Subjects may be allowed to\n participate in the trial while awaiting surgery, but must agree to complete this study\n prior to surgery. For subjects who have already undergone surgery, a minimum of 3\n months should have elapsed before the subject can be deemed a surgical failure.\n\n 9. Subjects on treatment for CD or endogenous CS of other etiology for whom treatment has\n been inadequate or not well tolerated must agree to the following minimum washout\n periods prior to the Baseline Visit:\n\n - Inhibitors of steroidogenesis (including ketoconazole): 2 weeks\n\n - Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks)\n\n - Octreotide acetate LAR and lanreotide Autogel®: 12 weeks\n\n - Lanreotide SR/long-acting pasireotide: 8 weeks\n\n - Octreotide acetate (immediate release formulation) or short-acting pasireotide: 1\n week\n\n - Mifepristone (RU 486): 4 weeks\n\n 10. Subjects on megesterol acetate (medroxyprogesterone acetate) must agree to a washout\n period of at least 6 weeks prior to the Baseline Visit\n\n 11. A female is eligible to enter and participate in the study if she is of:\n\n Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,\n including any female who is post-menopausal or surgically sterile). Surgically sterile\n females are defined as those with a documented hysterectomy and/or bilateral\n oophorectomy or tubal ligation.\n\n Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with\n an appropriate clinical profile, e.g. age > 45 years, in the absence of hormone\n replacement therapy. However in questionable cases, a blood sample with FSH > 40MIU/ml\n and estradiol < 40pg/ml (<140 pmol/L) is confirmatory.\n\n OR Child bearing potential and agrees to use highly effective methods of birth control\n while participating in the study and for 2 weeks after the study is completed.\n\n 12. Fertile men must also agree to use a medically acceptable form of birth control while\n on study drug and up to 2 weeks after the study is completed.\n\n 13. Able to comprehend and comply with procedures.\n\n Exclusion Criteria\n\n Subjects will be excluded from the study if any of the following criteria are met:\n\n 1. Subjects with Pseudo-Cushing's syndrome based on assessment of the investigator.\n\n 2. Subjects with cyclic Cushing's syndrome based on assessment of the investigator\n\n 3. Subjects with a non-endogenous source of hypercortisolism such as exogenous source of\n glucocorticoids or therapeutic use of ACTH.\n\n 4. Known inherited syndrome as the cause of hypercortisolism, including but not limited\n to multiple endocrine neoplasia Type 1, McCune Albright Syndrome and Carney Complex\n\n 5. Subjects with adrenal carcinoma\n\n 6. History of malignancy, other than thyroid, early stage prostate, squamous cell and\n basal cell carcinoma, within 3 years prior to the Screening Phase. Subjects with\n history of such allowed carcinoma must have a life expectancy of >1 year and must be\n on stable doses of their specific therapies. Subjects with early stage prostate cancer\n undergoing no treatment due to low grade potential may be enrolled.\n\n 7. Clinical or radiological signs of compression of the optic chiasm.\n\n 8. Major surgery within 1 month prior to enrollment (ICF signing)\n\n 9. Subjects with clinically significant abnormality in 12-lead ECGs during the Screening\n Phase needing medical intervention.\n\n 10. Subjects with QTc interval of >470 msec during the Screening Phase.\n\n 11. Subjects with a history of Torsades des Pointes, or ventricular tachycardia, or\n ventricular fibrillation, or history of prolonged QT syndrome (including family\n history), or use of medications resulting in QT/QTc prolongation, or hypokalemia <3.0\n meq/L.\n\n 12. Preexisting hepatic disease; subjects with mild to moderate hepatic steatosis\n consistent with fatty infiltration (non-alcoholic fatty liver disease [NAFLD] are\n allowed).\n\n 13. Positive for hepatitis B surface antigen (HbsAg) or positive hepatitis C test.\n\n 14. History or symptoms of recurrent symptomatic cholelithiasis or pancreatitis.\n\n 15. Liver function tests (LFT) must not be above the following cut-offs during the\n Screening Phase:\n\n - ALT and/or AST >3 X ULN\n\n - Total bilirubin >2 X ULN If all LFTs are within normal limits (WNL) and total\n bilirubin (TBN) is elevated, examination of direct and indirect bilirubin may be\n conducted. Subjects with isolated indirect TBN up to 3X ULN are presumed to have\n Gilbert's syndrome and may be enrolled if all other LFTs are within normal\n levels.\n\n 16. History of documented or suspected drug-induced liver injury requiring drug\n discontinuation of ketoconazole or any azole antifungals.\n\n 17. Pregnant or lactating women\n\n 18. HIV-positive.\n\n 19. History of persistent uncontrolled hypertension (>180/120 mmHg) despite medical\n intervention.\n\n 20. Subjects with hypercholesterolemia who are currently treated with atorvastatin,\n lovastatin or simvastatin and not willing or unable to change to alternative therapies\n with pravastatin, fluvastatin, and rosuvastatin within 2 weeks of start of the\n Screening Phase.\n\n 21. Body habitus preventing repeated venipuncture as required by protocol.\n\n 22. Subject is currently in another study or has received any investigational treatment\n (drug, biological agent or device) within 30 days or 5 half-lives of treatment,\n whichever is longer.\n\n 23. Repeated hospitalization for hyperglycemia or any complication of hyperglycemia and\n diabetes during the last 12 months\n\n 24. Subjects with decreased renal function as defined by eGFR <40 mL/min/1.73 m2, using\n MDRD equation for estimating renal function (eGFR).\n\n 25. Any other clinically significant medical condition, as determined by the Investigator\n that precludes enrollment and participation in the study through completion, including\n conditions that would preclude the subject from being able to follow instructions or\n to perform the necessary procedures (for example, psychiatric instability or severe\n disability).\n\n 26. Abnormal free T4. Subjects with TSH <LLN and normal free T4 are permitted to\n participate in the study.\n\n 27. Subjects who have a history of alcohol or drug abuse in the 6 month period prior to\n enrollment.\n\n 28. Subjects who have been treated with mitotane within 6 months of the Screening Phase.\n\n 29. Subjects who are currently taking any H2 receptor antagonists, proton-pump inhibitors,\n or sucralfate (all of which inhibit absorption of COR-003). A list of orally\n acceptable antacids (for example, Mylanta and Maalox) will be provided, and can only\n be taken a minimum of 2 hours after dosing of COR-003.\n\n 30. Subjects who receive any prohibited concomitant medication:\n\n - Weight loss medications (prescription or over the counter)\n\n - Acetaminophen >3 g total daily dose (due to increased hepatotoxicity)\n\n - Co-administration of strong inducers or inhibitors of CYP3A4 enzyme system that\n may interfere with the metabolism of COR-003 and cannot be discontinued prior to\n first dose\n\n - The following herbal medicines are prohibited: St John's Wort, echinacea, gingko,\n goldenseal, yohimbe, red rice yeast, danshen, silybum marianum, Asian ginseng,\n schissandra sphenanther, shankhapushi, and Asian herb mixture (Xiao chai hu tang\n and Salboku-to).\n\n - Topical or inhaled steroids\n\n - Carbamazipine, fenofibrate, carbenoxolone.\n\n - Ingestion of genuine licorice.
Subjects must not have received any chemotherapeutic agents for the AML (except hydroxyurea); intrathecal cytarabine (ARA-C) and intrathecal methotrexate are permissible
Subjects who failed at least one prior therapy (BT062/Len/dex)
Subjects who failed at least two prior therapy (BT062/Pom/dex)
Subjects with acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk
Consult with a physician experience in care and management of subjects with hepatitis B to manage/treat subjects who are anti-hepatitis B core antibody (HBc) positive
Subjects with DCIS with microinvasion
Subjects with a cluster of microcalcifications whose diameter is larger than 10 mm.
Subjects with extensive intraductal component and other characteristics not well visualized by imaging studies
Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib will be determined following review of their cases by the Principal Investigator
Subjects must have active disease appropriate for therapy
Subjects, who participated in previous ARQ 197 studies that have reached their designated end-dates, who did not meet discontinuation criteria in their original study, and who may, in the opinion of the Investigator and the Sponsor, benefit from treatment
Subjects who screen fails can be re?enrolled if the causation of the screen fail has been corrected
All subjects are required to submit a list of medications consumed within 14 days prior to receiving the first dose of AMG232 and during the protocol AMG232 treatment (weeks 1-5)
Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).
All subjects must:
CRITERIA FOR ALL SUBJECTS:
Subjects must have histological or serological proof of metastatic germ cell neoplasm (gonadal or extragonadal primary) with disease not amenable to cure with either surgery or chemotherapy; subjects with seminoma and non-seminoma are eligible, as are women with ovarian GCTs
Subjects who test positive for Clostridium difficile (C. difficile) at Screening.
All subjects must:
Subjects with known 11q23 MLL rearrangement are excluded.
Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
Eligible subjects are required to have > or = to 1 line of multi-agent chemotherapy either neoadjuvantly or adjuvantly. Subjects may have had 0-2 lines of therapy for metastatic disease.
Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to ? 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows: a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions: i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria;
All subjects must:
Subjects must have received treatment for CLL with chemotherapy agents or antibodies OR if subjects are previously untreated they must state in the consent form that they are refusing to be treated with chemotherapy or antibodies
NHL SUBJECTS:
ALL SUBJECTS:
Subjects with osteonecrosis of the jaw
Female subjects must have a negative serum human chorionic gonadotropic (hCG) test (pregnancy test not required for subjects with bilateral oophorectomy and/or hysterectomy or for those subjects who are >1 year post-menopausal); and
Subjects with uterine carcinosarcoma
Subjects with known photosensitivity diseases
Subjects with breast cancer must have been treated with at least two FDA-approved anti-HER2 directed therapies (more than two is also permissible), and subjects with gastric and gastroesophageal junction cancers must have been treated with at least one FDA-approved anti-HER2 directed therapy (more than one is also permissible); and all subjects must have refractory or relapsed/progressive disease during or following their last prior anti-HER2 directed therapy.
Subjects with negative metastatic involvement (M0).
Subjects to be treated with other than SOC
Subjects considered eligible for intensive chemotherapy
For subjects with gastric cancer:
Subjects with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including to control symptoms, within 2 months of first dose. Subjects with glioma who are on a stable, steroid-dosing regimen prior to screening MRI may be permitted to enroll with Medical Monitor approval
Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
Subjects with COPD or subjects with increased risk of respiratory depression
Subjects with narrow angle glaucoma
Subjects must have received an alkylating agent unless contraindicated; subjects may have received these agents alone or in combination with other myeloma treatments
Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study
In the opinion of the Investigator, subjects with a low chance of survival during the first 5 days of treatment.
Subjects with a history of RSV or MPV
Subjects with a history of documented Pseudomonas aeruginosa pneumonia confirmed radiographically and by culture from BAL.
Subjects with calculated BSA < 0.40 m2 are not eligible for study participation as Sorafenib dosing for this study cannot accommodate subjects of this size utilizing commercially available drug formulation.
Measurable or evaluable tumors. Subjects with neuroblastoma that is only detectable by Meta-iodobenzylguanidine (MIBG) scan are eligible. Subjects with neuroblastoma that is only detected by bone marrow aspirate/biopsy or elevated homovanillic acid / vanillylmandelic acid (HVA/VMA) are not eligible.
Subjects with abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (NOTE: subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).
Subjects with moderate valvular thickening.
Subjects with stage IIc-IV epithelial ovarian, fallopian tube and peritoneal cancer who have completed adjuvant treatment consisting of up to 8 cycles of paclitaxel and carboplatin chemotherapy or other acceptable chemotherapy after initial debulking surgery with evidence of a complete or partial response by radiological imaging. These subjects may remain on hormonal therapy during the trial if such treatment has been prescribed by their treating physician. These subjects may have been in a clinical trial for an investigational carboplatin based adjuvant therapy.
Subjects with recurrent ovarian, fallopian tube or peritoneal cancer who have clinical or radiologic evidence of a complete or partial response or stable disease after completion of first-line chemotherapy for their recurrent disease and are not suitable for additional cytotoxic therapy are eligible. These subjects may have previously received a course of adjuvant chemotherapy earlier in their disease management as described in point one above. These subjects are eligible regardless of their CA-125 results. These subjects may have been in a clinical trial of an investigational therapy.
Subjects may be on a biphosphonate provided it had not been initiated within 14 days prior to receiving the first injection of DPX-Survivac
Subjects with recent history of thyroiditis
For subjects assigned to take vorinostat, inability to take oral medications; vorinostat capsules must be administered whole; note: this criterion does NOT apply to subjects treated on the Expansion Cohort (accruals post February 1, 2013)
Respiration rate >24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived.
Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy in the period from onset of symptoms and prior to enrolment.
Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline.
Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline
Subjects who are part of the staff personnel directly involved with this study
Subjects who are family members of the investigational study staff
Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered on study with approval from the medical monitor.
Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study.
Subjects with ulcerative chest wall disease defined as non-healing wounds consistent with cancer are eligible.
Subjects with surgically unsalvageable disease (eg, sacral, spinal GCTB, or multiple lesions including pulmonary metastases) OR subjects whose planned surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity
Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
Subjects receiving procoagulant agent including desmopressin acetate (DDAVP), recombinant human antihemophilic factor (FVII) or prothrombin complex concentrate within 24 hours of enrollment
Subjects currently admitted to an inpatient unit at Michigan Medicine
Subjects will be excluded if they do not attend pre-operative clinic dedicated to RC subjects.
Subjects who are actively suicidal or homicidal
Subjects who have massages on a regular basis; regular massage usage will be operationally defined as receiving 4 or more massages/year for the last 5 years
All subjects who receive a radial forearm free flaps in the included time period, including subjects with head and neck cancer, traumatic defects, chronic wounds, or any other problems that require a radical forearm free flap for reconstruction
Subjects who have had an osteocutaneous or musculocutaneous flap
Subjects who have a radial forearm flap with a proximal skin flap or subjects that receive a “reverse” radial forearm flap
Subjects who exhibit signs of infection or a significant change from baseline test measurements via safety labs will be informed
Subjects must have a phone
Diagnosis of NF1 through germline mutation OR clinical diagnosis; for the clinical diagnosis of NF1 all study subjects must have two or more diagnostic criteria for NF1 listed below (National Institutes of Health [NIH] Consensus Conference):\r\n* Six or more cafe-au-lait spots (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in postpubertal subjects)\r\n* >= 2 neurofibromas or 1 plexiform neurofibroma\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Subjects currently using N-acetylcysteine, alpha-lipoic acid supplements, or dry whey protein supplements
Subjects are experiencing bothersome hot flashes per the study questionnaires.
Subjects already receiving other treatment for hot flashes.
Subjects who have lichen planus or lupus
Surgeon’s opinion at the time of dissection that the subject’s well-being (e.g. bleeding or other independent acute health problems) would be compromised
Subjects have to be willing to attend weekly voice therapy sessions
Subjects must have or have had at initial diagnosis, histologic proof of their malignancy; additionally they must have radiographic, nuclear image, or biopsy proof that they have had a recurrence of their disease within four weeks prior to study entry; subjects must have failed or relapsed from standard first-line chemotherapy for their tumor; young children with primary embryonal brain tumor treated according to Head Start protocol are eligible as well; subjects with bone marrow involvement are NOT eligible for study
Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
Subjects must have HL, NHL, or MM requiring PBSCT
Subjects must have a psychological and emotional state that, in the view of the investigators, allows adherence to the protocol
Female subjects capable of reproduction, and male subjects who have partners capable of reproduction, must agree to the following:
Female subjects who are surgically sterilized or who have not experienced menses for at least two years are not required to have a pregnancy test
Subjects who are actively suicidal or homicidal
Subjects who have massages on a regular basis; regular massage usage will be operationally defined as receiving 4 or more massages/year for the last 5 years
Subjects who will be receiving dasatinib
All consecutive subjects undergoing routine (standard of care) Lugol’s chromoendoscopic evaluation for suspected or known squamous cell neoplasia will be enrolled as well as any outgoing subjects referred to the clinic with any prior history of squamous cell dysplasia and/or neoplasia will also be considered eligible as they will serve as study population for the surveillance group
Inclusion Criteria:\n\n A. Subjects whose most recent (within 18 months) prior mammogram interpreted as\n heterogeneously dense (ACR BI-RADS Breast Density C) or extremely dense (ACR BI-RADS Breast\n Density D) breast tissue.\n\n AND\n\n B. Subjects who are asymptomatic and scheduled to undergo routine screening mammography.\n\n OR\n\n C. Subjects scheduled for image-guided needle biopsy as a result of findings obtained\n during standard of care imaging modalities (mammography, ultrasound and/or MRI) performed\n at the clinical site that participates in the study.\n\n Exclusion Criteria:\n\n 1. Male by birth.\n\n 2. Individual is less than 40 and greater than 70 years old.\n\n 3. Contraindication to bilateral mammography or MRI.\n\n 4. Subjects who are unable to read, understand and execute the informed consent\n procedure.\n\n 5. Subjects who have had mammography, ultrasound or MRI examination performed on the day\n of the study prior to RI8 scan.\n\n 6. Subjects who are pre-menopausal and are between the 14th and 28th day after the start\n of the menstrual cycle\n\n 7. Subjects who have significant existing breast trauma.\n\n 8. Subjects who have undergone lumpectomy/mastectomy.\n\n 9. Subjects who have undergone breast reduction or breast augmentation.\n\n 10. Subjects who have undergone any other type of breast surgery, including surgical\n biopsy.\n\n 11. Subjects who have large breast scar / breast deformation\n\n 12. Subjects who have undergone a breast needle biopsy within the 6-week period prior to\n their intended enrollment into the study.\n\n 13. Subjects who have a temperature > 100° F (37.8C) degrees on the day of the RI8\n imaging.\n\n 14. Subjects who are pregnant or lactating.\n\n 15. Subjects with known Raynaud's Disease.\n\n 16. Subjects with known Mastitis.\n\n 17. Subjects diagnosed with epileptic seizures.\n\n 18. Subjects with weight > 135kg (~300 Lbs.).\n\n 19. Subjects who are claustrophobic or have physical limitations that do not allow them to\n sit in the system chair for the required imaging session.\n\n 20. Subjects with implanted pacemaker/defibrillator, implanted venous access device\n (portacath) or other implanted devices.\n\n 21. Subject with kidney failure\n\n 22. Subject with known allergy to gadolinium\n\n 23. Subject with a history of multiple contrast MRI scans (more than 4 MRI scans over the\n past two year)\n\n 24. Inmates (45 CFR 46.306) or mentally disabled individuals.\n\n 25. Subjects with a BI-RADS category 6 (e.g. for which mammogram was performed for the\n purpose of planning cancer therapy).\n\n 26. Subjects currently participating in another investigational clinical study.\n\n 27. Subject scheduled for a biopsy due to suspicious symptomatic lump\n\n 28. Subjects who participated in the Validation Phase will not be able to participate in\n the Testing Phase
Patients determined to be at risk for esophageal cancer:\r\n* Subjects with a history of Barrett’s esophagus\r\n* Subjects with a history of low or high grade dysplasia\r\n* Subjects with a history of gastroesophageal reflux disease (GERD)\r\n* Subjects with a history of esophagitis\r\n* Subjects with symptoms of esophageal cancer (EC) referred for endoscopy (new onset dysphagia, weight loss, etc)
Subjects with severe, symptomatic dysphagia (unable to pass solids)
FOR THE 31 SUBJECTS ENROLLED IN YEAR 1: Receipt of IVIG < 27 days prior to calendar day of vaccination
Subjects deemed potentially eligible by their treating physicians will be screened for enrollment after d+60 from transplantation
Subjects considered by the investigator as unsuitable for the study for reasons not otherwise stated.
If subjects are randomized to the control group they agree to not consume fish oil capsules during the 1-year study
Subjects demonstrating markedly inappropriate affect or behavior will be excluded from the study
For the LBGT cohort study, subjects will be excluded for unwillingness to provide contact information or if they do not self-identify as LGBT in the screener
Known diagnosis of short-segment or long-segment Barrett’s esophagus as previously made by upper endoscopy showing salmon-colored distal esophageal mucosa and biopsies revealing intestinal metaplasia with goblet cells; potential study subjects may be contacted by mailings or phone calls or may be approached in clinic; additionally, potential study subjects may be approached using a web-based recruitment tool; informed consent will be obtained by a research coordinator or study investigator
Subjects who have voluntarily signed a written informed consent in accordance with institutional policies after its contents have been fully explained to them
Subjects who work night shifts are not eligible
Subjects with vitiligo or alopecia;
Subjects with diabetes on active treatment (for subjects treated on CC-223 containing arms only)
Patients receiving thiazides or furosemide diuretics, with the exception of subjects who have stable doses and have been on therapy for over six months
Subjects taking calcium supplements; if subjects are willing to discontinue these supplements, there must be a 2-month wash out period before enrollment
Subjects with suspected brain tumors undergoing surgical removal as their standard of care will be eligible; these may include subjects' status post chemotherapy and/or radiation or subjects who have undergone diagnostic biopsy for their original diagnosis and are felt to be candidates for resection
Subjects for whom exposure to a strong magnetic field would be a health risk (e.g., subjects with cardiac pacemakers or non-MR compatible metallic implants)
Subjects with risk factors for esophageal malignancy including Barrett’s esophagus and gastroesophageal reflux disease (GERD)
Subjects who have difficulty lying flat on their back for extended periods of time
Subjects must have an International Prostate Symptom Score of =< 15
For the clinical diagnosis of NF1 all study subjects must have at least two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):\r\n* Six or more cafe-au-lait spots (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in postpubertal subjects)\r\n* >= 2 neurofibromas or 1 plexiform neurofibroma\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Eastern Cooperative Oncology Group (ECOG) =< 3; subjects who are wheelchair bound because of paralysis will be considered “ambulatory” when they are up in their wheelchair; subjects have to be able to travel to the NIH for evaluations
Subjects with any type of ferromagnetic bioimplant that could potentially be displaced or damaged
Subjects with permanent tattoo eye liner (may contain metallic coloring)
The medical monitor, Dr. Lois Ayash, at minimum, may discuss the research protocol with the investigators, interview human subjects, and consult with others outside of the study about the research, shall have authority to stop a research protocol in progress, remove individual human subjects from a research protocol, and take whatever steps are necessary to protect the safety and well-being of human subjects until the Institutional Review Board (IRB) can assess the monitor’s report; shall have the responsibility to promptly report their observations and findings to the IRB or other designate official and the Human Research Protection Office at the Department of Defense; the monitor may also observe recruitment and enrollment procedures and the consent process for individuals, groups or units overseeing study interventions and interactions, reviewing monitoring plans and reports; overseeing data matching, data collection and analysis
Subjects must have had no prior therapy for cancer of the rectum
Subjects must have had no prior therapy for cancer of the esophagus
Subjects found to have any constitutionally present non-MR compatible ferromagnetic materials will be excluded from this study
Subjects who are pregnant or lactating; subjects will be co-enrolled in this study and UPCC 13413 and therefore must comply with the UPCC 13413 requirements pertaining to pregnancy, lactation, conception and contraception use throughout their participation in both studies
Subjects who have difficulty lying flat on their back for extended periods of time
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
Subjects may be excluded at the discretion of the principal investigator or study team members
Subjects with suspected brain tumors undergoing surgical removal as their standard of care will be eligible; these may include subjects status post chemotherapy and/or radiation or subjects who have undergone diagnostic biopsy for their original diagnosis and are felt to be candidates for resection
Subjects who exhibit noticeable anxiety, claustrophobia, or vertigo when moved into the scanner
Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced
Subjects who will have a delay in clinically indicated radiation therapy due to the interval between Eovist MRI imaging and biopsy
Subjects with brain metastasis are acceptable if the clinical condition has been stable for at least one month; subjects who are on stable doses (as determined by the principal investigator) of steroids may enroll in the study
Subjects with congenital long QT syndrome or subjects taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. subjects with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events
Subjects participating in another clinical investigation at the time of signature of the informed consent.
