Steroid treatment within seven (7) days prior to study treatment. Patients that require intermittent use of bronchodilators, topical steroids or local steroid injections will not be excluded from the study. Patients who have been stabilized to 10 mg Prednisolone PO QD (or equivalent), daily (or less) at least seven (7) days prior to study drug administration are allowed. Phase 2 Tumor-specific Eligibility Criteria Phase 2 patients must meet the cohort-specific inclusion/exclusion criteria in addition to the general inclusion/exclusion criteria for Phase 1 and Phase 2 study listed above. Cohort 1: Patient Population: Relapsed/Refractory SCLC
PHASE I INCLUSION CRITERIA
PHASE II INCLUSION CRITERIA: ECOG performance status of 0-1
PHASE II INCLUSION CRITERIA: Hemoglobin > 9 g/dL
PHASE II INCLUSION CRITERIA: Absolute neutrophil count > 1.5 x 10^9/L
PHASE II INCLUSION CRITERIA: Platelet counts > 100 x 10^9/L
PHASE II INCLUSION CRITERIA: Serum bilirubin < 2 x ULN
PHASE II INCLUSION CRITERIA: Life expectancy of at least 3 months
PHASE II INCLUSION CRITERIA: Women must not be pregnant or breastfeeding
SCREENING PHASE INCLUSION CRITERIA
DOSE EXPANSION PHASE ADDITIONAL INCLUSION CRITERIA
INDUCTION PHASE INCLUSION CRITERIA:
RESEARCH PHASE INCLUSION CRITERIA: In patients with suspected liver disease, bilirubin must be =< 2.5 mg/dL
ECOG performance status of 0-2 Inclusion Criteria for Phase 2 Sub-study Cohort:
INCLUSION CRITERIA SEARCH PHASE
INCLUSION CRITERIA FOR TRANSPLANT PHASE
SPECIFIC INCLUSION CRITERIA FOR PHASE II
INCLUSION CRITERIA FOR CONTINUING THERAPY ON THE EXTENSION PHASE:
Additional inclusion criteria for phase 2 Subjects only:
Criteria for the Phase 1b:
INCLUSION CRITERIA (EXPANSION PHASE ONLY)
Participants with measurable disease per RECIST v1.1 Additional Inclusion Criteria for Participants Who Backfill Cleared Cohorts of Phase 1a and Phase 1b:
PHASE II REGISTRATION - INCLUSION CRITERIA
PHASE I INCLUSION CRITERIA:
PHASE II INCLUSION CRITERIA:
PHASE III INCLUSION CRITERIA:
INCLUSION CRITERIA FOR FOCUS GROUPS (PHASE I)
INCLUSION CRITERIA FOR PILOT-TESTING (PHASE II)
ECOG ? 3 Phase 2 Inclusion Criteria:
PHASE II: Meet all the Phase 1 inclusion criteria
Inclusion criteria for intervention phase
Any factor included as exclusion criteria in the participating center’s treatment policy statement
EXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients receiving any other investigational agents
EXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Women who are pregnant or breastfeeding
Olaparib\r\n* No additional exclusion criteria
EXCLUSION CRITERIA FOR ENROLLMENT
EXCLUSION CRITERIA FOR T CELL TREATMENT:
PHASE I EXCLUSION CRITERIA
Patients meeting any one of these exclusion criteria will be prohibited from participating in this study.
Pregnancy or breastfeeding, or intending to become pregnant during the study Exclusion Criteria based on Organ Function or Medical History Cardiovascular Patients who meet the following cardiovascular exclusion criterion will be excluded from study entry:
TREATMENT EXCLUSION CRITERIA
The following are considered criteria for exclusion from the exploratory genetic research:
Medication-related exclusion criteria
TREATMENT EXCLUSION: Active hemorrhagic cystitis
Preoperative Exclusion Criteria
Intraoperative Exclusion Criteria
EXCLUSION CRITERIA FOR STRATA A, B, D AND E
Subjects with CNS disease are eligible, with exceptions as noted in the exclusion criteria
TREATMENT EXCLUSION CRITERIA
TREATMENT EXCLUSION
Cohort specific exclusion criteria (cohorts and groups without applicable specific exclusion criteria are not listed separately and should follow the general exclusion criteria)
DONOR: The NMDP guidelines for exclusion criteria will be used.
SCREENING PHASE EXCLUSION CRITERIA
SCREENING EXCLUSION CRITERIA
Normal MRI exclusion criteria will apply; a standard MRI safety form will be used to identify potential conditions warranting exclusion
MEDICATION-RELATED EXCLUSION CRITERIA
ATEZOLIZUMAB-SPECIFIC EXCLUSION CRITERIA
BEVACIZUMAB-SPECIFIC EXCLUSION CRITERIA
RECIPIENT EXCLUSION CRITERIA
IMMUNOTHERAPY-RELATED EXCLUSION CRITERIA
MEDICATION-RELATED EXCLUSION CRITERIA:
ADDITION EXCLUSION CRITERIA FOR GROUP A (LOW TUMOR BURDEN) ONLY
STEP 1 SCREENING EXCLUSION CRITERIA
COHORT 1 EXCLUSION CRITERIA
COHORT 2 EXCLUSION CRITERIA
COHORTS 1 AND 2 EXCLUSION CRITERIA
EXCLUSION CRITERIA FOR ALL STUDY ARMS
PART 1 EXCLUSION CRITERIA: Subjects < 0.5 M^2
DRUG-SPECIFIC EXCLUSION CRITERIA
EXCLUSION CRITERIA (ENROLLMENT)
EXCLUSION CRITERIA (TRANSPLANT)
PANOBINOSTAT MAINTENANCE EXCLUSION
EXCLUSION CRITERIA FOR SCREENING:
EXCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
EXCLUSION CRITERIA FOR PATIENTS WITH CLL, MCL, OR ALL (COHORT A)
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Platelet count < 75,000/mm^3
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Treatment with other investigational agent(s) within 30 days of planned lymphodepletion
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Serum creatinine > 2.5 mg/dL
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): SGOT > 5 x upper limit of normal
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Bilirubin > 3.0 mg/dL
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Patients who are HIV seropositive
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Women who are breastfeeding
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Patients who have contraindication to cyclophosphamide chemotherapy
EXCLUSION CRITERIA FOR TNBC: ANC < 1000/mm^3
EXCLUSION CRITERIA FOR TNBC: Platelet count < 75,000/mm^3
EXCLUSION CRITERIA FOR TNBC: Treatment with other investigational agent(s) within 30 days of planned lymphodepletion
EXCLUSION CRITERIA FOR TNBC: SGOT > 5 x upper limit of normal
EXCLUSION CRITERIA FOR TNBC: Bilirubin > 3.0 mg/dL
EXCLUSION CRITERIA FOR TNBC: Patients who are HIV seropositive
EXCLUSION CRITERIA FOR TNBC: Breast-feeding women
EXCLUSION CRITERIA FOR TNBC: Patients who have contraindication to cyclophosphamide chemotherapy
Subjects where more than 10% of the total esophagus volume receives more than 50% of the prescribed RT dose Main exclusion criteria for cPoP
Subjects enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following:
DONOR EXCLUSION CRITERIA:
EXCLUSION CRITERIA - ARM A:
EXCLUSION CRITERIA - ARM B:
EXCLUSION CRITERIA FOR ENROLLMENT: The presence of active GVHD requiring treatment
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Creatinine >= 2.5
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: HIV-1/2 or HTLV-1/2 positivity
SCREENING EXCLUSION CRITERIA
SCREENING EXCLUSION CRITERIA:
INTRA-OPERATION EXCLUSION CRITERIA (RANDOMIZATION ARMS ONLY)
Any patient ?18 and ?89 who presents for a colonoscopy and who does not have criteria for exclusion
BEVACIZUMAB-SPECIFIC EXCLUSION CRITERIA:
TREATMENT EXCLUSION CRITERIA:
CHEMOTHERAPY/CELL INFUSION EXCLUSION CRITERIA:
EXCLUSION CRITERIA FOR CONSENT B
Other exclusion criteria:
EXCLUSION CRITERIA AT TIME OF INFUSION:
INTRAOPERATIVE EXCLUSION CRITERIA:
Tumor type specific exclusion criteria
TREATMENT EXCLUSION CRITERIA:
EXCLUSION CRITERIA FOR CD34+ TOPOFF WITHOUT CONDITIONING (COHORT 2):
EXCLUSION CRITERIA (ALL COHORTS)
EXCLUSION CRITERIA (SUBJECTS STRATIFIED INTO THE THORAX HIGH VOLUME TREATMENT SITE)
Laboratory criteria for exclusion within 14 days prior to randomization.
Platelet count < 125x10^9 / L Exclusion criteria for Group 2
Pregnant or lactation. Exclusion criteria for HSV-Tk infusion:
PATIENT EXCLUSION CRITERIA:
DONOR EXCLUSION CRITERIA:
EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL
EXCLUSION CRITERIA FOR TREATMENT: Hct less than or equal to 24%
EXCLUSION CRITERIA FOR TREATMENT: ANC less than or equal to 1000
EXCLUSION CRITERIA FOR TREATMENT: Platelets less than or equal to 75,000
EXCLUSION CRITERIA FOR TREATMENT: Creatinine greater than or equal to 1.5 x ULN
EXCLUSION CRITERIA FOR TREATMENT: Bilirubin greater than or equal to 2.0 x ULN
PHASE 2 SPECIFIC EXCLUSION CRITERIA
PHASE 1 AND GENERAL EXCLUSION CRITERIA
Patients should not enter the study if any of the following exclusion criteria are fulfilled
SCREENING EXCLUSION CRITERIA:
EXCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT
EXCLUSION CRITERIA FOR MAINTENANCE THERAPY
Other Exclusion Criteria
EXCLUSION CRITERIA:
Must not meet any exclusion criteria defined in main study except for exclusion criteria \Subject must not have primary refractory disease\ which is related to prior carfilzomib
EXCLUSION CRITERIA SEARCH PHASE
EXCLUSION CRITERIA FOR TRANSPLANT PHASE: Life expectancy severely limited by concomitant illness or uncontrolled infection
Step I Exclusion Criteria:
Step II Exclusion Criteria:
TREATMENT EXCLUSION CRITERIA:
MEDICATION-RELATED EXCLUSION CRITERIA
METASTATIC SAFETY COHORT EXCLUSION CRITERIA
NEOADJUVANT EXCLUSION CRITERIA
Patients requiring treatment with strong CYP2C8 inhibitors Additional exclusion criteria for PDR001/Everolimus
EXCLUSION FOR ENROLLMENT/SCREENING (ARMS 1 AND 2)
EXCLUSION FOR TREATMENT (ARMS 1 AND 2)
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. Exclusion from the genetic research may be for any of the exclusion criteria specified in the main study or any of the following:
Exclusion Criteria – Arms B and C
EXCLUSION CRITERIA PRIOR TO TRANSPLANT:
STAGE I EXCLUSION CRITERIA:
STAGE 2 EXCLUSION CRITERIA:
Exclusion of patients with creatinine > 2.0
Exclusion of patients with bilirubin > 2.0
There will be no exclusion criteria based on organ function
There will be no exclusion criteria based on organ function.
EXCLUSION CRITERIA - MAIN PROTOCOL
EXCLUSION CRITERIA FOR CONTINUING THERAPY ON THE EXTENSION PHASE:
Exclusion criteria will include all criteria listed for the main protocol
EXCLUSION CRITERIA PRIOR TO CELL COLLECTIONS FOR DENDRITIC CELL GENERATION:
EXCLUSION CRITERIA - RECIPIENT
IBRUTINIB-SPECIFIC EXCLUSION CRITERIA
CARDIAC EXCLUSION CRITERIA:
There is no exclusion for the presence of cytopenias
Other Exclusion Criteria
IMMUNOTHERAPY-RELATED EXCLUSION CRITERIA:
General Exclusion Criteria
EXCLUSION CRITERIA FOR SCREENING:
EXCLUSION CRITERIA FOR TREATMENT:
EXCLUSION CRITERIA - INITIAL ENROLLMENT
EXCLUSION CRITERIA FOR TRANSPLANT RECIPIENT
EXCLUSION CRITERIA RELATED TO ZIV-AFLIBERCEPT
No prior treatment with systemic chemotherapy (except as noted in exclusion criteria # 10).
Prior chemotherapy or radiation therapy for this disease (laser and cryotherapy are allowed and are not considered exclusion criteria)
They are ineligible by virtue of meeting any exclusion criteria listed above
Other Exclusion Criteria
COHORT 1 EXCLUSION CRITERIA FOR APHERESIS/TUMOR BIOPSY PORTION OF THE TRIAL (closed to enrollment as of 6/22/13):
COHORT 1 EXCLUSION CRITERIA FOR IMMUNOTHERAPY PORTION OF THE TRIAL (closed to enrollment as of 6/22/13):
COHORT 2 EXCLUSION CRITERIA:
EXCLUSION CRITERIA FOR PATIENTS
PATIENT EXCLUSION CRITERIA
EXCLUSION CRITERIA-PATIENTS
EXCLUSION CRITERIA-FCGs
EXCLUSION CRITERIA FOR PARENTS: Patient declines assent/consent (if >= 7 years)
EXCLUSION CRITERIA FOR PARENTS: Parent or child participated on prior PRISM intervention study
EXCLUSION CRITERIA FOR PATIENTS: Patient declines assent/consent (if >= 7 years)
EXCLUSION CRITERIA FOR PATIENTS: Patient participated on a prior PRISM intervention study
EXCLUSION - STUDY 1: Parkinson's disease
EXCLUSION - STUDY 1: Active foot ulcer
EXCLUSION - STUDY 2: The inclusion/exclusion criteria follows similar criteria for study #1 except only patients with confirmed peripheral neuropathy (VPT big toe greater than 25 volt) will be included; patients who have completed clinical study 1 would be eligible for study 2 if they develop CIPN as defined by VPT assessment
EXCLUSION CRITERIA FOR PATIENT PARTICIPANTS
PHASE 1: No provider exclusion criteria
PHASE 3A/3B: PATIENT EXCLUSION CRITERIA: Non-English speaker
EXCLUSION CRITERIA SPECIFIC TO SURVIVORS:
EXCLUSION CRITERIA FOR BOTH SURVIVORS AND CO-SURVIVORS:
EXERCISE EXCLUSION CRITERIA:
No allergic reactivity has been associated with olfactory training and thus there is no need for any exclusion criteria related to this
There are no other agent-specific exclusion criteria
EXCLUSION CRITERIA FOR FOCUS GROUPS (PHASE I)
PATIENT EXCLUSION CRITERIA:
PREPROCEDURAL EXCLUSION CRITERIA:
PATIENTS EXCLUSION CRITERIA:
Hepatic encephalopathy Exclusion Criteria Specific to Arm B (Gastric Cancer) (Patients who meet any of the following specific exclusion criteria will be excluded from enrollment in Arm B:)
Ongoing treatment for epilepsy Exclusion Criteria Specific to Arm C (Metastatic Pancreatic Cancer) (Patients who meet any of the following specific exclusion criteria will be excluded from enrollment in Arm C:)
PATIENT PARTICIPANT EXCLUSION CRITERIA (PHASE 1 & 2)
EXCLUSION CRITERIA FOR GROUP 2A AND 2B
No exclusion criteria relating to concomitant medications
EXCLUSION CRITERIA-PATIENTS
EXCLUSION CRITERIA-CAREGIVERS
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
READER STUDY EXCLUSION
EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Pregnant or breastfeeding
EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Karnofsky performance status < 60%
Exclusion criteria for RPFNA
Exclusion criteria for study intervention
DRIVERS EXCLUSION CRITERIA
Exclusion Criteria for 13C-MBT studies:
Exclusion Criteria for 31P-MRS studies
Eligible for donation according to the transplantation center Exclusion Criteria Donor:
A history of miscarriage in the last 6 months, in and of itself, will not be considered an exclusion
Good performance status (as defined in Exclusion Criteria)
There will be no exclusion criteria relating to concomitant medications
EXCLUSION CRITERIA FOR CALYPSO TRANSPONDERS:
EXCLUSION CRITERIA (ALL PATIENTS)
EXCLUSION CRITERIA FOR OPEN-ACCESS: More than 6 MET PET scans within the previous 12 months
EXCLUSION CRITERIA FOR ORAL LESION AND NORMAL TISSUE
EXCLUSION CRITERIA FOR DRY MOUTH STUDY
EXCLUSION CRITERIA FOR GUM STUDY
No other appropriate agent-specific exclusion criteria
CANCER-SPECIFIC EXCLUSION CRITERIA
GENERAL MEDICAL EXCLUSION CRITERIA
STEP 1: EXCLUSION CRITERIA FOR TUMOR COLLECTION
Subject Exclusion Criteria for Optional Contrast MRIs –Cohort 1 Only:
Common exclusion criterion
EXCLUSION CRITERIA - FOR MALE COHORT
EXCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: Chronic therapy with any drugs, except oral contraceptives
EXCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: Hospitalization for any reason up to 8 weeks before enrollment
EXCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: Pregnancy, labor or miscarriage within 12 weeks before admission predicted date
HEALTHY VOLUNTEER EXCLUSION CRITERIA:
SITE EXCLUSION CRITERIA:
PATIENT EXCLUSION CRITERIA:
PATIENT PARTICIPANTS EXCLUSION CRITERIA:
DRIVER EXCLUSION:
TRIAL EXCLUSION:
PATIENT EXCLUSION:
PROSPECTIVE STUDY POPULATION EXCLUSION
CHART AUDIT EXCLUSION CRITERIA:
There are no specific exclusion criteria for this study.
No exclusion criteria for this study
Other Exclusion Criteria
Subjects must be otherwise healthy except for the diagnosis of cancer, as per the exclusion criteria listed below.
Dose Expansion (Segment 2): 0 - 2
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Part I dose escalation: Participants are required to have measurable disease per RECIST 1.1 within 4 weeks of study entry
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Participants are permitted to have any number of prior therapies prior to enrollment
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Absolute neutrophil count >= 1,500 mm^3
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Hemoglobin >= 9 g/dL
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Platelets >= 100,000/mcL
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Total bilirubin =< 2 X institutional upper limit of normal (ULN)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: AST (SGOT)/ALT (SGPT) =< 5.0 X ULN if hepatic metastases are present
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Creatinine =< 1.5 X the institutional ULN OR
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: MTD expansion: Patients must be willing to undergo pre- and on-treatment tumor biopsies; patients are exempt from this requirement if, in the opinion of the investigator, the biopsy procedure would pose a significant risk or if they have only pulmonary metastatic disease
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Patients must be able to take oral medications
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Corrected QT (QTc) =< 480 msec
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Participants receiving any other study agents concurrently with the study drugs
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: MTD expansion: Patients currently taking anticoagulants and who cannot safely hold the medication to facilitate pre and on-treatment tumor biopsies are excluded from participation
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Part I dose escalation: Concurrent use of proton-pump inhibitors (PPIs) is prohibited
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of QT syndrome, Brugada syndrome, known history of QTc prolongation, or Torsades de Pointes
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of Gilbert’s syndrome
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Patients planning to embark on a new strenuous exercise regimen after the first dose of study treatment
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of a malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of retinal degenerative disease
Dose Expansion: Cholangiocarcinoma
For expansion part:
Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
For dose expansion participants who will have tumor biopsies collected:
INCLUSION CRITERIA FOR SCREENING (STEP 0 - PREREGISTRATION)
INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1)
REGISTRATION INCLUSION CRITERIA:
REGISTRATION INCLUSION CRITERIA
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Platelets >= 75,000/mm^3
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Hemoglobin >= 9.0 g/dL
INCLUSION CRITERIA FOR THIRD-LINE THERAPY: ECOG performance status 0 or 1
INCLUSION CRITERIA FOR THIRD-LINE THERAPY: Platelets >= 75,000/mm^3
INCLUSION CRITERIA FOR THIRD-LINE THERAPY: Hemoglobin >= 9.0 g/dL
Inclusion criteria associated with type and status of lymphoma
INCLUSION CRITERIA ASSOCIATED WITH HIV-1 STATUS
GENERAL INCLUSION CRITERIA (TIMELINE: 8 WEEKS PRIOR TO START OF TRIAL, UNLESS OTHERWISE SPECIFIED)
SOLID TUMOR INCLUSION CRITERIA:
INCLUSION CRITERIA FOR T CELL TREATMENT:
STEP 2 SCREENING INCLUSION CRITERIA FOR LMS PATIENTS:
TREATMENT INCLUSION CRITERIA
SPECIFIC INCLUSION CRITERIA FOR PRE-SURGICAL COHORT:
Patients with cancer of unknown primary or a rare tumor (i.e., fewer than 15 cases per 100,000 per year) with no approved therapies; (patients in this inclusion criteria must meet all other exclusion and inclusion criteria except inclusion criteria #1)
REGISTRATION/RANDOMIZATION INCLUSION CRITERIA:
Preoperative inclusion:
Intraoperative inclusion:
INCLUSION CRITERIA FOR STRATA A, B, D AND E
TREATMENT INCLUSION CRITERIA
TREATMENT INCLUSION
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: ALT (SGPT): =< 5 x ULN
INCLUSION - TREATMENT: Bilirubin ? 3x
INCLUSION CRITERIA FOR NK CELL DONOR
INCLUSION CRITERIA FOR SELECTED NK CELL DONOR
INCLUSION CRITERIA TO ENROLL AND PREPARE CELLS FOR SHIPPING TO UNIVERSITY OF MINNESOTA (UMN) FOR PROCESSING
INCLUSION CRITERIA FOR ELIGIBILITY TO RECEIVE TREATMENT
PATIENT-SPECIFIC INCLUSION CRITERIA
INCLUSION CRITERIA FOR URINARY SCREENING
INCLUSION CRITERIA FOR TREATMENT
SCREENING INCLUSION CRITERIA
RECIPIENT INCLUSION CRITERIA
OTHER INCLUSION CRITERIA:
REGISTRATION- INCLUSION CRITERIA
INCLUSION CRITERIA FOR GENETICS RESEARCH STUDY (OPTIONAL)
STEP 1 SCREENING INCLUSION CRITERIA
STEP 2 SCREENING INCLUSION CRITERIA
Within 3 weeks of any corticosteroids except per inclusion criteria above
COHORT 2 INCLUSION CRITERIA
PART 1 INCLUSION CRITERIA
PART 2 GROUP 1 INCLUSION CRITERIA: These criteria must be met by all subjects, regardless of bone marrow involvement with tumor
PART 2 GROUP 2A INCLUSION CRITERIA: These criteria must be met by all subjects, regardless of bone marrow involvement with tumor
PART 2 GROUP 3 INCLUSION CRITERIA: These criteria must be met by all subjects, regardless of bone marrow involvement with tumor
DRUG-SPECIFIC INCLUSION CRITERIA
INCLUSION CRITERIA (ENROLLMENT)
INCLUSION CRITERIA (TRANSPLANT)
PANOBINOSTAT MAINTENANCE INCLUSION
INCLUSION CRITERIA FOR SCREENING:
INCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
INCLUSION CRITERIA FOR PATIENTS WITH CLL, MCL OR ALL (COHORT A)
INCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Karnofsky performance status of >= 70%
CAPMATINIB INCLUSION CRITERIA: Life expectancy >= 12 weeks
CAPMATINIB INCLUSION CRITERIA: Platelets >= 75,000/mcL
ENTRECTINIB INCLUSION CRITERIA: ECOG performance status 0-2
ENTRECTINIB INCLUSION CRITERIA: Platelets >= 75,000/mcL
Additional inclusion/exclusion criteria per protocol.
INCLUSION CRITERIA FOR PATIENTS TO BE TREATED ON STRATA B OR C
INCLUSION CRITERIA - PART A
INCLUSION/EXCLUSION CRITERIA - PART B
INCLUSION CRITERIA - ARM A:
INCLUSION CRITERIA - ARM B:
INCLUSION CRITERIA FOR ENROLLMENT: The patient has been off all immunosuppression for at least 2 weeks at the time of PTCy-MILs collection
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: No active acute infections
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: No requirement for systemic steroids
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Platelets >= 100,00/uL (transfusions are permitted)
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: AST (aspartate aminotransferase) =< 3 x ULN
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: ALT (alanine aminotransferase) =< 3 x ULN
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Bilirubin =< 1.5 x ULN
SCREENING INCLUSION CRITERIA
SCREENING INCLUSION CRITERIA:
INCLUSION CRITERIA PATIENTS WITH SOLID TUMOR CANCERS AND MELANOMA
INCLUSION CRITERIA FOR PATIENTS WITH MALIGNANT MENINGIOMA
INCLUSION CRITERIA ALL PATIENTS
TREATMENT INCLUSION CRITERIA:
CHEMOTHERAPY/CELL INFUSION INCLUSION CRITERIA:
INCLUSION CRITERIA FOR OBSERVATION (CONSENT A)
INCLUSION CRITERIA FOR TREATMENT WITH VELIPARIB AND RADIATION (CONSENT B)
Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfils the required inclusion criteria
INCLUSION CRITERIA AT TIME OF INFUSION:
EXCLUSION CRITERIA FOR REGISTRATION: subjects receiving chemotherapy regimens not specified in the inclusion criteria
TREATMENT INCLUSION CRITERIA:
INCLUSION CRITERIA FOR CD34+ TOPOFF WITHOUT CONDITIONING (COHORT 2):
INCLUSION CRITERIA (ALL COHORTS)
INCLUSION CRITERIA (SUBJECTS STRATIFIED INTO THE THORAX HIGH VOLUME TREATMENT SITE)
Patients with tumor parameters that fall outside of the inclusion criteria above will not be eligible
INCLUSION CRITERIA FOR NB
INCLUSION CRITERIA FOR CCT: minimum life expectancy of eight weeks
LV mass on CMR > 200 grams (g) Inclusion Criteria for Group 1
PATIENT INCLUSION CRITERIA:
DONOR INCLUSION CRITERIA:
REGISTRATION – INCLUSION CRITERIA
One or more of the inclusion criteria are not met
INCLUSION CRITERIA AT TIME OF INITIAL ENROLLMENT:
OTHER INCLUSION CRITERIA:
SCREENING INCLUSION CRITERIA:
CHEMOTHERAPY/ADOPTIVE CELL TRANSFER INCLUSION CRITERIA:
INCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT
INCLUSION CRITERIA FOR MAINTENANCE THERAPY
Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria
Anastomosis or procedure (TME) was performed differently from what was defined in the inclusion criteria.
INCLUSION CRITERIA:
Known active Hepatitis B or C infections Inclusion Criteria for Part B: To qualify for enrollment, the following criteria must be met:
INCLUSION CRITERIA FOR COLLECTION AND STORAGE OF PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC)/T CELLS
INCLUSION CRITERIA FOR MODIFIED T CELL INFUSION
Participants with prior therapy, other than therapy specified in inclusion criteria
Tumor specific inclusion criteria:
Predicted life expectancy ?12 weeks. Inclusion Criteria Specific for Part A:
Step I Inclusion Criteria:
Step II Inclusion Criteria:
TREATMENT INCLUSION CRITERIA:
Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/exclusion criteria specified in the protocol appendix for each agent will take precedence for this and all inclusion criteria:
Patients must fulfill all of the general inclusion criteria
Patients must fulfill all the general inclusion criteria
Inclusion Criteria – Arms B and C
INCLUSION CRITERIA PRIOR TO TRANSPLANT:
REGISTRATION INCLUSION CRITERIA: ECOG performance status =< 1
REGISTRATION INCLUSION CRITERIA: Hemoglobin >= 10 g/dL
STAGE I INCLUSION CRITERIA:
STAGE 2 INCLUSION CRITERIA:
INCLUSION CRITERIA - MAIN PROTOCOL
UNRELATED DONOR INCLUSION CRITERIA
History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer Open-Label Treatment Period: The following inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment. Eligible patients must meet all inclusion criteria.
Patients with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol Cohort C Inclusion Criteria:
SLE INCLUSION:
SYSTEMIC SCLEROSIS (SSc) INCLUSION:
MS INCLUSION:
No prior treatment for diagnoses in inclusion criteria 1
Diagnosis of grade 1 endometrioid endometrial carcinoma without the presence of one of the 3 criteria mentioned in inclusion criteria 1
INCLUSION CRITERIA - ALL PARTICIPANTS
INCLUSION CRITERIA - RECIPIENT
History of lymphoid malignancy other than those allowed per inclusion criteria
Prior chemotherapy other than inclusion criteria
Mesothelin-positive refractory/recurrent MPM (Group 2 only) Inclusion Criteria Part B
INCLUSION CRITERIA FOR SBRT vs. RFA RANDOMIZATION
INCLUSION CRITERIA FOR NON-RANDOMIZED SBRT ARM
Criteria:
Criteria:
Criteria:
REGISTRATION #1 INCLUSION CRITERIA
Inclusion Clinical Laboratories Criteria
REGISTRATION INCLUSION CRITERIA
INCLUSION CRITERIA - HPC-A CELL DONOR: Family member (first degree relatives)
INCLUSION CRITERIA - HPC-A CELL DONOR: Not breast feeding
Tumor invasion of bone (also see inclusion criteria)
Tumors in locations other than those specified in inclusion criteria
General Inclusion Criteria
INCLUSION CRITERIA FOR SCREENING:
INCLUSION CRITERIA FOR TREATMENT:
INCLUSION CRITERIA - INITIAL ENROLLMENT
INCLUSION CRITERIA - MAINTENANCE THERAPY AFTER HSCT
In addition to the above, key inclusion and exclusion criteria are listed below.
INCLUSION CRITERIA FOR TRANSPLANT RECIPIENT
INCLUSION CRITERIA FOR HAPLOIDENTICAL DONOR
INCLUSION CRITERIA (ALL SUBJECTS)
Concurrent treatment for cancer, with specific exceptions noted in inclusion criteria
Inclusion Criteria for Part 1 and Part 2
Other Inclusion criteria for Part 1
Other Inclusion criteria for Part 2
Inclusion Criteria for Part 3
The inclusion criteria for Part 3 will be based on emerging data from Parts 1 and 2 and will be specified in an amendment.
Key Inclusion Criteria:\n\n          -  Individuals in the primary Phase 3 study (Study GS-US-312-0116) who are compliant\n\n          -  Tolerating primary study therapy\n\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Can take oral med Part 2 Inclusion Criteria:
Can take oral med Part 3 Inclusion Criteria:
Can take oral med Part 4 Inclusion Criteria:
The clinical status of the patient at inclusion is one of the following:
Inclusion Criteria:\n\n        Exclusion Criteria:
COHORT 1 INCLUSION CRITERIA FOR APHERESIS/TUMOR BIOPSY PORTION OF THE TRIAL (closed to enrollment as of 6/22/13):
COHORT 1 INCLUSION CRITERIA FOR IMMUNOTHERAPY PORTION OF THE TRIAL (closed to enrollment as of 6/22/13):
COHORT 2 INCLUSION CRITERIA:
REGISTRATION INCLUSION CRITERIA
INCLUSION CRITERIA FOR SCREENING:
INCLUSION CRITERIA FOR TREATMENT:
INCLUSION CRITERIA FOR PHYSICIANS
INCLUSION CRITERIA FOR PATIENTS
INCLUSION CRITERIA FOR CROSSOVER THERAPY
INCLUSION CRITERIA-PATIENTS
INCLUSION CRITERIA-FCGs
INCLUSION CRITERIA FOR PARENTS: Parents of children who have been diagnosed with new malignancy between 1-10 weeks prior
INCLUSION CRITERIA FOR PATIENTS: Child who have been diagnosed with a new malignancy between 1-10 weeks prior
INCLUSION - STUDY 2: The inclusion/exclusion criteria follows similar criteria for study #1 except only patients with confirmed peripheral neuropathy (vibration perception threshold [VPT] big toe greater than 25 volt) will be included; patients who have completed clinical study 1 would be eligible for study 2 if develop CIPN as defined by VPT assessment
INCLUSION CRITERIA FOR PATIENT PARTICIPANTS
EXERCISE INCLUSION CRITERIA:
CROSSOVER RE-REGISTRATION - INCLUSION CRITERIA
STRATEGISTS INCLUSION CRITERIA
PATIENT INCLUSION CRITERIA:
Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV) Inclusion Criteria Specific to Arm A (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm A:)
Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV). Inclusion Criteria Specific to Arm F (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm F:)
Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV). Inclusion Criteria Specific to Gastric Cancer (Arm B) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm B:)
Absence of HER2 expression documented as in situ hybridization (ISH) negative on previously collected and assessed tumor tissue upon initial diagnosis of disease Inclusion criteria specific to metastatic pancreatic cancer (Arm C) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm C:)
No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease Inclusion Criteria Specific to mEC (Arm E) (Patients must also meet all of the following specific inclusion criteria to be eligible for enrollment in Arm E:)
INCLUSION CRITERIA FOR GROUP 2A AND 2B
INCLUSION CRITERIA-PATIENTS
INCLUSION CRITERIA-CAREGIVERS
INCLUSION CRITERIA FOR PATIENTS: Admitted to 6E with suspected or actual new diagnosis of leukemia or lymphoma within the past 24 hours
INCLUSION CRITERIA FOR PATIENTS: Completed education to at least the 6th grade level
INCLUSION CRITERIA FOR PATIENTS: No significant auditory or visual deficits with corrective devices
INCLUSION CRITERIA FOR PATIENTS: Physiologically stable
INCLUSION CRITERIA FOR PATIENTS: Not at end of life
INCLUSION CRITERIA FOR PATIENTS: No alterations in mental status
INCLUSION CRITERIA FOR FAMILY MEMBERS: Willing to view DVD and read education booklet
INCLUSION CRITERIA FOR FAMILY MEMBERS: Selected by patient to participate
INCLUSION CRITERIA FOR FAMILY MEMBERS: No alterations in mental status
INCLUSION CRITERIA FOR FAMILY MEMBERS: Completed education to at least the 6th grade level
READER STUDY INCLUSION
REGISTRATION/RANDOMIZATION INCLUSION CRITERIA:
REGISTRATION INCLUSION CRITERIA
REGISTRATION INCLUSION CRITERIA
INCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT)
DONOR INCLUSION CRITERIA
REGISTRATION/RANDOMIZATION INCLUSION CRITERIA
Inclusion criteria for screening RPFNA
DRIVERS INCLUSION CRITERIA
Patient plans to receive concurrent chemotherapy, other than the regimens specified in the inclusion criteria
Additional Inclusion Criteria Specific for Arm A:
Additional Inclusion Criteria Specific for Arm B:
Additional Inclusion Criteria Specific for Arm C:
REGISTRATION INCLUSION CRITERIA
Inclusion Criteria:\n\n          -  referrals from the New York State Smokers' Quitline\n\n          -  at least 18 years of age
GENERAL INCLUSION CRITERIA
One of the following inclusion criteria must be true for patient to be eligible for enrollment:
INCLUSION CRITERIA (INITIAL 10 PATIENTS WITH METASTATIC PROSTATE CANCER)
INCLUSION CRITERIA: MEN WITH UNTREATED PROSTATE CANCER
INCLUSION CRITERIA: FOR MEN WITH PRESUMED PROSTATE CANCER RELAPSE
INCLUSION CRITERIA FOR OPEN-ACCESS: Female participants of childbearing age must not be lactating
INCLUSION CRITERIA FOR ORAL LESION AND NORMAL TISSUE
INCLUSION CRITERIA FOR DRY MOUTH STUDY
INCLUSION CRITERIA FOR GUM STUDY
Subject must give written informed consent. Part B, Inclusion criteria All inclusion criteria as for Part A, except for inclusion criterion 2 which is replaced by:
STEP 1: INCLUSION CRITERIA FOR TUMOR COLLECTION
Completed and documented history and physical addressing all inclusion/exclusion criteria
Common inclusion criterion
INCLUSION CRITERIA - FOR MALE COHORT
INCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: If breastfeeding, must be willing to discard breastmilk for 24 hours following zolpidem
INCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: Ability to swallow study medication
HEALTHY VOLUNTEER INCLUSION CRITERIA:
SITE INCLUSION CRITERIA:
PATIENT INCLUSION CRITERIA:
CLINICIAN PARTICIPANTS INCLUSION CRITERIA:
PATIENT PARTICIPANTS INCLUSION CRITERIA:
GARAGE INCLUSION:
DRIVER INCLUSION:
TRIAL INCLUSION:
PATIENT INCLUSION:
HEALTH CARE PROVIDER INCLUSION CRITERIA:
CHART AUDIT INCLUSION CRITERIA (BASELINE):
CHART AUDIT INCLUSION CRITERIA (POST-INTERVENTION)
Cohort 4 (severe): Bilirubin > 3 × ULN; any AST Exception to Inclusion Criterion #5 for Subjects with Normal Hepatic Function: All subjects enrolled with normal hepatic function (N=10) must meet all inclusion criteria as outlined with the exception of Inclusion Criterion #5, which should be substituted with the following criterion to be enrolled into the study:
All Cohorts
Prior anti-PD-1 treatment for combination dose expansion cohorts 3a - 3d
Prior anti-PD-1 treatment for combination dose expansion cohorts 3e - 3h
For deep tumor cohorts, patients who require uninterrupted anticoagulants of any type, on daily aspirin therapy, or NSAIAs.
Patients in expansion cohorts A and B must have measurable disease
EXPANSION COHORTS ONLY
For cohorts B1 and B2 only, biopsy confirmation of metastases (if safe and feasible at treating center)
DISEASE SPECIFIC EXPANSION COHORTS: Prior receipt of docetaxel is not permitted
For the expansion cohorts only: prior treatment with any MEK inhibitor is not allowed in the expansion cohorts
Have measurable disease based on:\r\n* Lugano classification (cohorts A, C)\r\n* International Workshop on CLL (cohorts B, D)
(For both cohorts A and B): Platelets >= 100 x 10^9/L
(For both cohorts A and B): Serum albumin > 2
Prior yttrium-90 therapy for patients in cohorts 1 or 2
For hypomethylating failure cohorts only, more than 4 months since last cycle of HMA
For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)
For the combination cohorts (cohorts 5 and 6 in Part 1) and Part 2, subjects with metastatic melanoma or NSCLC do not need to have received prior therapy
Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2).
Previous treatment with lenvatinib (except for participants previously enrolled into Cohorts 1 or 2B of this study).
Smokers and subjects who use smokeless tobacco products are excluded in all cohorts
Phase II cohorts only: patients must have measurable disease according to RECIST v.1.1 criteria. Patients enrolled in Ph Ib cohorts must have evaluable disease
Meets criteria for 1 of the 4 defined study cohorts
ADDITIONAL CRITERIA FOR COHORTS 1A AND 1B PARTICIPANTS ONLY: No corticosteroid dosing within 5 days of study therapy initiation
For patients enrolling in the four expansion cohorts:
For all cohorts:
For all cohorts:
For both cohorts:
For both cohorts:
Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and Expansion Cohorts A & B and optional, but encouraged in Escalation Cohorts 2 & 3 and Expansion Cohort C)
ALL COHORTS
Dose Expansion: Solid Tumors Not Otherwise Eligible for the Cholangiocarcinoma, Chondrosarcoma, or Non-enhancing Glioma Cohorts
Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
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.
Participants for Cohorts B and C:
Participants for Cohorts D and E:
Participants for Cohorts A, C, and E:
Potential Participants for Cohorts A, C or E who are to Receive Binimetinib:
Potential Participants for Cohorts A, C, D or E:
Potential Participants for Cohorts D or E:
Albumin >= 2.5 g/dL\r\n* NOTE: this applies to patient in the normal and renal dysfunction cohorts (N, R3 and R4); abnormal albumin is allowed for patients in the liver dysfunction cohorts
FURTHER ELIGIBILITY DETAILS FOR PATIENTS WITH PROGRESSIVE DISEASE (COHORTS 1 AND 3A/3B):
Any prior treatment with capecitabine for patients enrolled to cohorts 3a/3b and prior lapatinib for participants on cohort 3a
Safety and Expansion Cohorts
Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts:
MESOTHELIOMA COHORTS (COHORTS 1 AND 2 ONLY): Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Total bilirubin: see guidelines for individual cohorts
B) Dose Expansion Cohorts:
for intratumoral cohorts, injection of tumor would require violation of ventricular system
For participants in all combination arms (Cohorts A-E), use or consumption of any of the following substances:
Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance status of: 0 - 1 (dose escalation cohorts) or 0 - 2 (expansion cohorts)
Cohorts A & B:
Patients will be enrolled in one of the two cohorts based on diagnosis:
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
Dose and Disease Expansion Cohorts
Part 2: Subjects will be enrolled into 1 of 3 cohorts:
Note, the line of therapy limit does not apply to the biopsy substudy cohorts.
For participants enrolled in the expansion cohorts in which tumor biopsies are obtained:
Biological parent(s) of participant (child) enrolling on SJMB12; these parents will be assigned to cohort P; the exclusion criteria below do not apply to this cohort
Patients must have slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility and proper cohort assignment\r\n* HISTOLOGIC COHORT 1: Undifferentiated pleomorphic sarcoma (includes: malignant fibrous histiocytoma, myxofibrosarcoma, high grade sarcoma not otherwise specified [NOS])\r\n* HISTOLOGIC COHORT 2: Leiomyosarcoma (either uterine or extra-uterine)\r\n* HISTOLOGIC COHORT 3: Other (either malignant peripheral nerve sheath tumor or synovial sarcoma); during the phase II portion of the study, enrollment will be limited to maximum of 25 patients in this cohort\r\n** Note that the phase I is limited to the histologic subtypes listed above; since patients will be enrolling onto dose cohorts during the phase I, they will not enroll onto specific histologic cohorts, although the histologic subtype informed will be collected during patient enrollment
ELIGIBILITY FOR CHEMOTHERAPY COHORT:
ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:
COHORT B: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; patients in Cohort B must have measurable disease per RECIST 1.1
Cohort I, Ph-negative Patients Only
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
Phase I (\untreated\ expansion cohort only): no prior HMA and/or lenalidomide treatment Patient has the evidence of symptomatic anemia according to the following criteria:
Dose Expansion Cohort #2 - Patients will have first relapse of CD123+ AML.
Dose Expansion Cohort #3 - Patients will have relapse of CD123+ ALL.
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
COHORT I
COHORT II
Subcutaneous panniculitis-like T-cell lymphoma For enrollment into the AITL expansion cohort, subjects must have he diagnosis of AITL.
PIK3CA WILD TYPE COHORT (closed 03/17/2016): Life expectancy > 4 months
PIK3CA WILD TYPE COHORT (closed 03/17/2016): Leukocytes >= 3,000/mcL
PIK3CA WILD TYPE COHORT (closed 03/17/2016): Absolute neutrophil count >= 1,500/mcL
PIK3CA WILD TYPE COHORT (closed 03/17/2016): Platelets >= 100,000/mcL
For participants in MTD/OBD cohort expansion and Phase 2 only: participant has measurable disease.
EXPANDED ACCESS COHORT: Platelets >= 50,000/mcL
EXPANDED ACCESS COHORT: Serum creatinine =< 1.5 x institutional ULN OR
Cohort 2: Prior adverse reaction(s) to carboplatin
SPECIFIC INCLUSION CRITERIA FOR EXPANSION COHORT:
Cohort C: Patients in this cohort only will require a single tumor biopsy 48-72H after the first administration of IMGN853 and gemcitabine on day 1, cycle 1 of treatment, providing it is safe/feasible and confers non-significant risk to patient
For the dose expansion paired biopsy cohort:
The study will include three primary cohorts, with any of the following EBV+ diseases: Cohort A - DLBCL, 1) in first or subsequent relapse, not eligible for autologous transplantation following salvage therapy OR 2) relapse following autologous transplantation. Cohort B - HL, brentuximab vedotin (BV) treatment failure or unable to tolerate BV. Cohort C - PTLD, rituximab treatment failure.
AZD4635 in a different cohort in this study.
ADDITIONAL EXPANSION COHORT SUBJECT INCLUSION CRITERIA
Expansion phase: Tumor-specific cohort(s) at the RD:
Patients with congenital long QT syndrome (for cohort 2a and 2b [belinostat cohorts] only, electrocardiogram [ECG] not required for cohort 1)
Patients taking valproic acid =< 2 weeks prior to initiation of belinostat therapy (for cohort 2a and 2b [belinostat cohort] only)
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.
Patients must have histologically or cytologically confirmed any solid tumor (cohort 1) or prostate cancer (cohort 2); no prior treatment other than testosterone lowering therapy for mCRPC is required
Patients who are not hematopoietic stem cell transplant candidates are excluded for the DLBCL cohort (cohort #1)
Expansion Phase Cohort B: Require urgent disease response or stabilization
COHORT I ONLY: Patients are candidates for enrollment in cohort 1 if they have an indication for ruxolitinib based on splenomegaly or symptoms and are either on ruxolitinib already or going to start therapy with ruxolitinib
Subject provides consent for fresh paired tumor biopsy samples to be obtained at screening and after 4 weeks of treatment (not required for run-in cohort or expansion of run-in cohort).
Ovarian Expansion Cohort: Subjects must have tumor tissue positive (IHC H-score ?150) for Nectin-4 expression
ADDITIONAL INCLUSION CRITERIA FOR DOSE EXPANSION COHORT
ADDITIONAL EXCLUSION CRITERIA FOR DOSE EXPANSION COHORT
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
SAFETY LEAD-IN COHORT
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)
PHARMACODYNAMIC EXPANSION COHORT: Prior receipt of docetaxel is not permitted
COHORT A
COHORT B
COHORT C
Only patients with R/R ALL will be eligible for cohort C
ADDITIONAL INCLUSION CRITERION FOR COHORT 4 (CUTANEOUS HNSCC):
During cohort expansion, subjects with advanced cancer that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
COHORT 2: Subjects in the post-operative setting (cohort 2) are not required to have measurable disease and response rate will not be assessed in cohort 2
EXPANSION COHORT
COHORT 1 (PATIENTS RECEIVING HEMITHORACIC RADIATION THERAPY)
DOSE EXPANSION COHORT:
Participants in cohort C must have completed systemic therapy (4-6 cycles cisplatin or carboplatin + etoposides) and NOT be a candidate for consolidation thoracic radiotherapy or prophylactic cranial irradiation (PCI); participants in cohort C must initiate therapy with pembrolizumab within 6 weeks of the last dose of chemotherapy (therapy must not start within 2 weeks from the last dose); participants in cohort C must not have had progression of disease prior to the start of therapy
Participants in cohort A may not have had prior therapy for their disease; participants in cohort B may not have had more than 1 cycle of systemic therapy (cisplatin or carboplatin + etoposide); participants in cohort C and D should not have had more than one prior regimen of chemotherapy
LEAD IN COHORT
History of radiation proctitis (for lead-in CRPC cohort only)
Patients for the expansion cohort must have a CTC (TelomeScan) drawn in the screening phase if other eligibility criteria are met, and must be CTC-positive in order to be eligible for enrollment in the expansion cohort
PK/PD/biomarker/metabolite expansion cohort(s) only: Subjects must consent to pre- and post-dose tumor biopsies and additional sample collection procedures.
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
mCRPC EXPANSION COHORT: Patients must have metastatic, progressive, castrate resistant prostate cancer (mCRPC)
mCRPC EXPANSION COHORT: ECOG performance status =< 2
mCRPC EXPANSION COHORT: Leukocytes >= 3,000/mcL
mCRPC EXPANSION COHORT: Hemoglobin >= 9 g/dL
mCRPC EXPANSION COHORT: Patients who have had prior treatment with olaparib or other camptothecin inhibitors
Prior liver-directed radiation therapy in cohort 1 (advanced cirrhosis group) or cohort 2 (low functional volume group)
Phase Ib part: treatment-naïve Stage III A/B NSCLC not eligible for surgical resection or concurrent chemoradiation (Arm A expansion cohort) or treatment-naïve SCCHN eligible for fractionated curatively intended RT with concurrent cisplatin (Arm B expansion cohort)
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 5: Treatment-naïve patients with cMET dysregulation
That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion and Cohort 6 ONLY)
Creatinine clearance above limits set in the protocol for each cohort
Have provided written consent for mandatory pre- and post-treatment biopsy (expansion cohort only)
No prior treatment for myelofibrosis (for cohort 1 only)
COHORT I:
COHORT II: Patient must be >= 60 years
COHORT II: The surgical treatment must be intended to be a lumpectomy
COHORT II:
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 in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies
Refractory to standard available therapies. Expansion Cohort 1 Specific Inclusion Criteria:
Not eligible for Expansion Cohort 3. Expansion Cohort 2 Specific Inclusion Criteria:
Not eligible for Expansion Cohort 3. Expansion Cohort 3 Specific Inclusion Criteria:
Pregnant patients (Cohort D)
In expansion cohort only: patient’s kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status must be known prior to enrollment
Absolute neutrophil count (ANC) ? 1.5x10^9/L for paclitaxel cohort, and ? 1.0x10^9/L for endocrine therapy cohort
Platelets (plt) ? 100 x 10^9/L for paclitaxel cohort, and ? 75, 000 for endocrine therapy cohort
Patients must undergo surgery and must not have further treatment. (For MTD expansion cohort only)
THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: In Cohort 2, if disease progression occurs before Part 1 data are available, then they will be transferred to Cohort 1.
For Dose Expansion Cohort: HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:\r\n* Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection\r\n* Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml\r\n* AFP > three times normal and doubling in value in the antecedent 3 months\r\n* In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
DOSE EXPANSION COHORT: Prior treatment with at least one line of systemic therapy
DOSE EXPANSION COHORT: ECOG performance status 0-2
DOSE EXPANSION COHORT: Platelets ? 100,000/mcL
DOSE EXPANSION COHORT: Hemoglobin ? 9 g/dL
DOSE EXPANSION COHORT: ALT(SPGT) ? 2.5 X ULN
DOSE EXPANSION COHORT: ALP ? 2.5 X ULN
DOSE EXPANSION COHORT: Pregnant or nursing
Participants who have received or plan to receive any additional treatment for glioblastoma aside from surgical resection and conventional radiotherapy (cohort 1), pembrolizumab (cohorts 1a and 1b) and temozolomide (cohort 1b) including but not limited to temozolomide (cohort 1 & 1a participants), stereotactic radiosurgery, placement of Gliadel (carmustine; BCNU) wafers, any other intratumoral or intracavitary treatment, brachytherapy, novo-tumor treating fields (Optune), or investigational therapeutic agents
COHORT 1A & 1B PARTICIPANTS ONLY:
pStat3+ upon central testing of archival tumor specimen\r\n* Cohort A: pStat3 score of >= 5 by central testing\r\n* Cohort B: pStat3 score of 3-4 by central testing (Note, Cohort B will only open if there are at least 2 objective responses observed in the first stage of Cohort A)
Dose expansion cohort: the inclusion and exclusion criteria for the expansion cohort are the same as above, except for the expansion cohort also required to express AR (score 1+ or more) by IHC in archival bladder cancer samples or fresh biopsy specimens (if archival tissue not available)
COHORT EXPANSION PHASE: Histological or cytopathological diagnosis of advanced/metastatic unresectable colorectal cancer with known rat sarcoma viral oncogene homolog (RAS) mutational status; patients with known B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations will not be eligible for the expansion cohort; all patients must have received and progressed or be intolerant of an oxaliplatin-containing regimen and an irinotecan-containing regimen
OTHER ELIGIBILITY CRITERIA (APPLIES TO BOTH COHORT A AND COHORT B UNLESS SPECIFIED)
Cohort 1 - ATRT
Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic disease
During cohort expansion, subjects with various solid tumors that have received at least one and no more than 5 prior treatment regimens
For Cohort Expansion:
Serum LDH > 2 x ULN (Upper limit of normal); 9. For Cohort B subject must be ? 65 years of age at the time of signing the informed consent form (ICF) and transplant non-eligible (TNE); excluding the subjects who meet the Cohort A criteria 10. For Cohort C subject must be after first autologous stem cell transplantation (ASCT) for NDMM and meet the following criteria:
For Cohort Expansion:
Subjects in Cohort A may have asymptomatic LM detected by MRI. (Subjects with symptoms or signs attributed to LM will be enrolled in Cohort B whether or not they have brain metastases)
Inclusion Criteria:\n\n        Phase 1a\n\n          -  Aged 18 years or older\n\n          -  Histologically or cytologically confirmed solid tumor or hematologic malignancy\n\n          -  Life expectancy of 12 weeks or longer\n\n          -  Must have received ? 1 prior treatment regimen\n\n          -  Must not be a candidate for potentially curative or standard of care approved therapy\n\n        Phase 1b\n\n          -  Aged 18 years or older\n\n          -  Cohort A: Histologically or cytologically confirmed pancreatic adenocarcinoma,\n             triple-negative breast cancer, urothelial cancer with at least 1 measurable or\n             evaluable target lesion\n\n          -  Cohorts B, C, D, E and G: Histologically confirmed multiple myeloma and\n             measureable/evaluable disease\n\n          -  Cohort F: Confirmed acute myeloid leukemia or myelodysplastic syndrome\n\n          -  Cohort H: Individuals diagnosed with lymphoma\n\n          -  Prior therapy:\n\n               -  Cohort A: No more than 1 prior chemotherapy regimen for advanced or metastatic\n                  disease (not including neoadjuvant and/or adjuvant therapy)\n\n               -  Cohorts B, C, D, E and G: Must have relapsed from or have been refractory to ? 2\n                  prior treatment regimens\n\n               -  Cohort F: May have received any number of prior treatment regimens or be\n                  treatment-naïve\n\n               -  Cohort H: Must have relapsed from or have been refractory to available treatments\n\n        Phase 2\n\n          -  Aged 18 years or older\n\n          -  Cohorts I and J: Confirmed acute myeloid leukemia or high risk myelodysplastic\n             syndrome\n\n          -  Prior therapy:\n\n               -  Cohorts I and J: Must have failed prior therapy with a hypomethylating agent\n                  (HMA)\n\n        Exclusion Criteria:\n\n          -  Prior receipt of a JAK1 inhibitor (Phase 1a only)\n\n          -  Known active central nervous system metastases and/or carcinomatous meningitis\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status > 2\n\n          -  Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone,\n             carfilzomib, bortezomib, lenalidomide, azacitidine, pomalidomide or PI3K? inhibitor\n             (Phase 1b and Phase 2 only, as appropriate to treatment cohort)\n\n          -  Known human immunodeficiency virus infection, or evidence of hepatitis B virus (HBV)\n             or hepatitis C virus (HCV) infection or risk of reactivation
Cohort 3: Participants must have cholangiocarcinoma.
For PCNSL cohort:
EPd Cohort:
EN Cohort:
Patients that have received prior enzalutamide in any setting will not be eligible. Exclusion criterion only for patients entering phase Ib expansion cohort:
COHORT 2 ONLY (BONE-ONLY)
COHORT 3 (RARE HISTOLOGIES)
METASTATIC SAFETY COHORT
Patients may not have been included in any prior IMCgp100 trial, regardless of treatment cohort
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
COHORT A (MEDICAL) SPECIFIC INCLUSION:
COHORT B (SURGICAL) SPECIFIC INCLUSION:
Participants for Cohort A:
Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:
Expansion cohort: a final expansion cohort for this study in a subset of interest utilizing the recommended dosing of combination; this cohort will include patients harboring characteristics that may predict response of combination or with clinical features that proved to derive most benefit of the study combination during preclinical studies; cancers with positive BRAF (V600) mutation detected by a CLIA-certified laboratory
PHASE I AND PK EXPANSION COHORT:
Patient must not have received any previous treatment with any aurora-kinase inhibitors (MTD expansion cohort only)
Patient must not have a history of gastric resection (MTD expansion cohort only)
ONLY APPLIES TO PATIENTS IN GROUP C (CORRELATIVE COHORT)
FOR ALL (COHORT 1 AND COHORT 2):
Amendment (January 2014): only subjects with the following histologies will be eligible\r\n* Cohort # 1 (pancreatic cohort): locally advanced or metastatic pancreatic adenocarcinoma\r\n* Cohort #2 (biliary tract cohort): locally advanced or metastatic cholangiocarcinoma, gall bladder adenocarcinoma, or ampullary carcinoma; patients with adenocarcinoma of unclear primary that are most likely of biliary tract origin (in the opinion of the treating physician) will also be allowed on this cohort
The use of the 5-alpha-reductase inhibitor dutasteride and systemic steroids must be discontinued within 4 weeks of degarelix injection for Cohort 1, 2, and 4, and within 4 weeks of surgery for Cohort 3
FURTHER ELIGIBILITY DETAILS FOR PATIENTS WITH OPERABLE DISEASE (COHORT 2):
EXPANSION COHORT ONLY: Karnofsky >= 70% or ECOG =< 1
EXPANSION COHORT ONLY: Platelets >= 100,000/mm^3
EXPANSION COHORT ONLY: Current treatment on another clinical trial
EXPANSION COHORT ONLY: Pregnant or breastfeeding
Efficacy Expansion Cohort (Second-Line Cervical Cancer)
Subjects enrolled in Expansion Cohort 3 must be willing to have 2 on-treatment tumor biopsies.
Inclusion Criteria:\n\n        Part 1 and Part 2 cohort 3: Patients diagnosed with AML ( bone marrow (BM) or peripheral\n        blood (PB) blast counts >/= 20%) and have received prior chemotherapy and/or standard of\n        care and have relapsed, refractory or Minimal Residual Disease (defined as patients showing\n        residual blast 10-14 days post-induction chemotherapy).\n\n        • Patients that are not candidates to receive standard of care and/or refusing the standard\n        care of therapies will also be considered.\n\n        Part 2 - Cohort 1 and 2: Newly diagnosed, previously untreated de novo or secondary AML\n        population (AML with bone marrow or peripheral blast counts 20%):\n\n          -  Cohort 1: Fit to receive intensive remission induction chemotherapy.\n\n          -  Cohort 2: Unfit to receive or not considered a candidate for intensive remission\n             induction chemotherapy.\n\n        Part 1 and 2:\n\n          -  Life expectancy at least 12 weeks.\n\n          -  Hydroxyurea is allowed on study to control total peripheral white blood cell count but\n             must be ceased 24 hours prior to first dose.\n\n          -  Off of prior therapy for 2-4 weeks prior to first dose.\n\n          -  ECOG performance status: 0 to 2.\n\n          -  Resolved acute effects of any prior therapy.\n\n          -  Adequate renal and hepatic function.\n\n        Exclusion Criteria:\n\n          -  Patients with acute promyelocytic leukemia, AML with known central nervous system\n             (CNS) involvement unless the patient has completed treatment for the CNS disease, has\n             recovered from the acute effects of therapy prior to study entry, and is\n             neurologically stable.\n\n          -  Patient is known refractory to platelet or packed red cell transfusions per\n             institutional guidelines.\n\n          -  Prior treatment with a compound targeting CXCR4.\n\n          -  Chronic systemic corticosteroid treatment.\n\n          -  Known or suspected hypersensitivity to recombinant human proteins.\n\n          -  Chronic graft versus host disease (GVHD), active GVHD with other than Grade 1 skin\n             involvement, or GVHD requiring systemic immunosuppressive treatment (Part 1 and cohort\n             3).\n\n          -  Not recovered from stem cell transplant associated toxicities (Part 1 and cohort 3).\n\n          -  Prior treatment with hypomethylating agents or chemotherapy for antecedent\n             myelodysplastic syndrome (MDS) (Part 2, cohort 2)\n\n          -  AML associated with favorable risk karyotypes, including inv(16), t(8;21), t(16;16),\n             or t(15;17) (cohort 2)\n\n          -  Candidates for allogeneic stem cell transplant (Part 2, cohort 2)\n\n          -  Known hypersensitivity to cytarabine or daunorubicin (Part 2, cohort 1) and decitabine\n             or azacitidine or mannitol (Part 2, cohort 2).
Cohort Expansion: Subjects must be determined to be HA-high based on tumor biopsy that meets the requirements noted in the previous inclusion criterion.
Cohort-specific criteria for Phase 2:
EXPANSION COHORT ONLY:
Candidate for neoadjuvant chemotherapy with a standard of care, anthracycline-based regimen (Cohort 2 preferred over Cohort 1)
Histologically confirmed, Stage IB-IVB, invasive cervical carcinoma associated with HPV 16 and/or 18 and meeting the following eligibility criteria for either Cohort 1 or Cohort 2;
Cohort 1
Cohort 2
Has >= Grade 2 persistent non-hematological toxicity related to the transplant. Donor lymphocytes infusion (DLI) is not permitted <= 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2
Prior treatment with NaPi2b- targeted therapy. Bevacizumab-Specific Exclusion Criteria (for Participants in Second Ovarian Expansion Cohort Only):
DOSE EXPANSION COHORT:
DOSE EXPANSION COHORT EXCLUSION:
DOSE EXPANSION COHORT: GIST patients must have had progression on or have been intolerant to imatinib and sunitinib
Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
Cohort A: Eligible for chemotherapy
Cohort B: T2a-4N0M0 who are not candidates for cohort A or who will not be treated with chemotherapy (due to patient preference or at the recommendation of the treating physician)
Melanoma Cohort: Participants with histologically confirmed incurable, advanced melanoma not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved) in the metastatic setting Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of Phase 1b:
For the fifth cohort during Part 2 Cohort Expansion, participants with solid tumors must have evidence of BCL-2 expression.
Expansion cohort only: Advanced lymphoma confirmed by histopathology
For Cohort Expansion Phase (Part 2) only: Patients who are positive for the D835 mutation at Screening are excluded.
Part B Expansion Cohort 1 (CRPC):
Part B Expansion Cohort 6 (LY2875358 plus trametinib in participants with uveal melanoma with liver metastasis): Contra-indications for trametinib
Dose expansion cohort (B): no prior chemotherapy is allowed
Patients with known primary or metastatic CNS disease, are eligible for participation in cohort B, but not in cohort A
COHORT B OVERVIEW: patients 60 or older with untreated classical Hodgkin lymphoma (regardless of stage) will be eligible for cohort B
Enrollment on the St. Jude Lifetime Cohort (SJLIFE) protocol
For Cohort 2, Cohort 3, and the Randomized Phase, tumor must be shown to have an FGFR3 mutation or gene fusion.
COHORT A:
COHORT B:
DEFINITION OF RISK COHORT FOR CONSIDERATION OF RPFNA
Surgical cohort (cohort A only): percutaneous or transjugular biopsy incomplete or not performed
Breast cancer patients in the expansion cohort must be hormone sensitive or have refractory disease
Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ? 50% of cells.
Cohort B only: (N = 5 evaluable patients): Planned nephrectomy within 12 weeks following protocol scan
EXPANSION COHORT: Patients with diagnosis of NB (in accordance with the International Criteria, i.e., either histopathology or bone marrow involvement)
EXPANSION COHORT: Patients must be able to undergo PET scan without sedation
EXPANSION COHORT: Patients must have MIBG-avid disease and evaluable disease on MIBG scan at the time of enrollment onto the protocol
EXPANSION COHORT: Cardiac, pulmonary, gastrointestinal and neurologic toxicity should all be =< grade 2
Meets the criteria below for the appropriate cohort:
Cohort 2 only: discontinued lenvatinib due to toxicity
Subject Exclusion Criteria for Cohort 1 and Cohort 2:
Inclusion criterion for normal cohort
Expansion cohort at the RD: All patients must have:
Cohort 3 (moderate): ? 1.6-3 × ULN; any AST
To be enrolled in the TNBC expansion cohort, participants must have:
To be enrolled in the NSCLC expansion cohort, participants must have:
To be enrolled in the HNSCC expansion cohort, participants must have:
Patients in the expansion cohort undergoing tumor biopsies may not be on anticoagulants
All Cohort A Dose Escalation Participants:\r\n* Prior hormonal therapy: Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting (including prior fulvestrant), as long as the last dose is >= 14 days prior to first dose of study treatment\r\n* Prior biologics / investigational therapy: Prior therapy with biologics and investigational drugs is allowed, as long as the last dose is >= 21 days prior to first dose of study treatment\r\n* Prior CDK4/6 inhibition is allowed; participants who have had prior ribociclib must have received treatment at full-dose without any dose reductions; the last dose is required to be >= 21 days prior to first dose of study treatment\r\n* Treatment with prior PD1/PDL1/CTLA4 inhibitors is prohibited\r\n* Prior radiotherapy: Participants may have received radiotherapy for palliative purposes but must have completed treatment ? 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities\r\n* Evaluable or measurable disease by RECIST 1.1
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer according to ASCO CAP guidelines
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Evaluable or measurable disease by RECIST 1.1
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior CDK4/6 inhibition is allowed; participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions; the last dose is required to be >= 21 days prior to first study treatment
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Treatment with prior PD1/PDL1/CTLA4 inhibitors is prohibited
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior hormonal therapy: \r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy (including prior fulvestrant) in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior chemotherapy:\r\n* Participants may have received chemotherapy for advanced breast cancer as long as the last dose is >= 21 days prior to registration
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior biologics / investigational therapy: \r\n* Prior therapy with biologics and investigational drugs is allowed, as long as the last dose is >= 21 days prior to first dose of study treatment
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior radiotherapy;\r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing > grade 1 treatment related toxicities
Cohort A Dose Expansion (Ribociclib + PDR001): Prior hormonal therapy: \r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment
Cohort A Dose Expansion (Ribociclib + PDR001): Prior biologics / investigational therapy: \r\n* Prior therapy with biologics and investigational drugs is allowed, as long as the last dose is >= 21 days prior to first dose of study treatment
Cohort A Dose Expansion (Ribociclib + PDR001): Prior radiotherapy: \r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities
Cohort A Dose Expansion (Ribociclib + PDR001): Treatment with prior CDK4/6 inhibitors is prohibited
Cohort A Dose Expansion (Ribociclib + PDR001): Treatment with prior PD1/PDL1/CTLA4 is prohibited
Cohort A Dose Expansion (Ribociclib + PDR001): Measurable disease by RECIST 1.1 is required
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer according to ASCO CAP guidelines
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior hormonal therapy:\r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment\r\n* Participants must have progressed on an aromatase inhibitor in the metastatic setting or experienced disease recurrence within 6 months of completing adjuvant therapy with an aromatase inhibitor\r\n* Treatment with prior fulvestrant is prohibited
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior chemotherapy:\r\n* Participants may have received up to one prior line of chemotherapy for advanced breast cancer as long as the last dose is >= 21 days prior to first dose of study treatment
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior biologics / investigational therapy:\r\n* Prior therapy with biologics and investigational drugs is allowed, as long as the last dose is >= 21 days prior to first dose of study treatment
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior radiotherapy:\r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Treatment with prior CDK4/6 inhibitors are prohibited
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Treatment with prior PD1/PDL1/CTLA4 inhibitors are prohibited
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Measurable disease by RECIST 1.1 is required
Has completed prior therapies according to the criteria below:\r\n* Cytotoxic chemotherapy - at least 21 days since last dose prior to first dose of ribociclib\r\n* Small molecule inhibitors - at least 14 days since last dose prior to first dose of ribociclib\r\n* Monoclonal antibodies - at least 3 half-lives since last dose prior to first dose of ribociclib; exception: denosumab for bony metastases is allowable\r\n* Immunotherapy (e.g. tumor vaccines) - at least 42 days since last dose prior to first dose of ribociclib\r\n* Radiation - at least 14 days since last dose prior to first dose of ribociclib
Phase I (dose escalation and \pre-treated\ expansion cohort only): refractory to or not amenable or eligible for established MDS therapy (HMA, lenalidomide)
Patients in dose escalation and all expansion cohorts except first relapse AML may have received up to three prior lines of therapy.
Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
To be enrolled in the dose escalation or in the MTD expansion, Subject must have a locally confirmed diagnosis of either of the following tumor types:
In the dose de-escalation cohort: subjects must have evaluable disease
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
Dose Escalation (Segment 1): 0 - 1
NOTE: the first subject in the first dose cohort must be >= 18 years of age if an adult has not been treated at that dose cohort on the companion Stanford protocol “Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults with Recurrent or Refractory B Cell Malignancies” and undergone safety evaluation at day 28 without evidence of dose limiting toxicity (DLT)
Extrahepatic spread; for the dose escalation, regional lymphadenopathy and subcentimeter pulmonary nodules are allowed.
Part D: Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion)
Phase I Dose Escalation:
Phase 1 (dose escalation) subjects must have either:
For dose escalation: Subjects with any type of solid tumor (all comer) will be eligible for dose escalation and dose expansion at MTD in Part 1; Subjects enrolled for dose expansion (MTD expansion cohort \all comer\) will be stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
Dose Expansion cohorts: Prior treatment with osimertinib (Tagrisso®). Prior treatment with osimertinib (Tagrisso®) is allowed for subjects participating in the dose escalation portion of the study
Dose Escalation Phase and Expansion Phases will exclude patients for the following:
Dose Escalation Phase and Expansion Phase Cohort A:
Dose Escalation Portion: Patients must satisfy one of the following criteria:
Bone only patients during dose escalation portion.
INCLUSION CRITERIA FOR DOSE ESCALATION COHORT
EXCLUSION CRITERIA FOR DOSE ESCALATION COHORT
Subjects must have evaluable disease for the dose escalation, and measurable disease for the dose expansion.
Dose escalation only: known grade 4 toxicity probably or definitely attributed to past irinotecan treatment
Patients in Cohort 1 (dose escalation) may have any level of expression
DOSE ESCALATION COHORT: Prior receipt of docetaxel is permitted
DOSE ESCALATION COHORT: Measurable disease is not required for enrollment
known bone marrow involvement due to underlying malignant disease, in dose-escalation phase only
Arm A dose escalation: patients with histologically or cytologically proven advanced solid tumors for which standard treatments are not available, or for whom the current dose level of cisplatin in combination with pemetrexed is appropriate; =< 2 prior cytotoxic chemotherapy regimen
Phase Ia (dose-escalation)
Paired, pre- and post-treatment, tumor biopsy is optional for subjects enrolled in the Dose Escalation and Food-effect cohorts
For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
All patients (dose escalation and dose expansion phases) must be willing to undergo pre- and post-treatment biopsies
For the dose escalation phase, the trial population will be limited to solid tumor types
Patients are not required to have HER-2 or epidermal growth factor receptor (EGFR) over-expression to be on this study at the dose escalation cohort; however, patients will be required to have HER-2 overexpression and/or EGFR overexpression for the extension and expansion cohorts\r\n* If the patient has had HER-2 expression measured prior to enrollment, the report alone will be accepted the dose escalation phase of the study\r\n* If the patient has had EGFR expression measured prior to enrollment, the report alone will be accepted on the dose escalation phase of the study.\r\n*If the patient has not had HER-2 or EGFR expression measured prior to enrollment on this study, it would be obligatory for the patient to have the tests performed to justify their status; HER-2 status can be performed by a variety of tests; either immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) assay are acceptable if breast tumor tissues (previously frozen) are available; the test can be done at Ohio State University (OSU) or elsewhere if the patient is from out of town
During the Dose Escalation Phase: only adult patients with active disease failing standard therapy
Patients with CEA plasma levels > 1000 ng/mL are excluded during dose escalation, but may be included after the MTD is determined.
For the dose escalation cohort, patients may have received any number of prior therapies
Dose Escalation cohort only: Willingness to participate in the SPECT/CT imaging as required by the protocol
DOSE ESCALATION COHORT: Prior treatment with at least one line of systemic therapy
DOSE ESCALATION COHORT: Subjects with advanced and unresectable solid tumor who progressed on at least one line of systemic therapy, and no approved therapy or standard therapy with demonstrated clinical benefit exists; and all subjects with T790M mutation positive NSCLC have progressed on osimertinib\r\n* Note: disease measurability is not required for dose escalation
DOSE ESCALATION COHORT: Leukocytes ? 3,000/mcL
DOSE ESCALATION COHORT: Platelets ? 100,000/mcL
DOSE ESCALATION COHORT: Hemoglobin ? 9 g/dL
DOSE ESCALATION COHORT: Current or anticipated use of other investigational agents while participating in this study
DOSE ESCALATION COHORT: Pregnant or nursing
Cohort 1 (dose escalation): histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes
Unlimited prior therapies are permitted for patients enrolled in the dose escalation phase of the study; patients in the expansion cohort of the study may not have any prior therapy with riluzole or sorafenib and must have biopsiable tumor
For Dose Escalation:
Escalation Phase [Inclusion]\n\n          -  Locally advanced or metastatic adult solid tumor that has progressed or was\n             nonresponsive to available therapies, are unfit for standard chemotherapy or for which\n             no standard or available curative therapy exists;\n\n          -  ECOG score of 0, 1 or 2;\n\n          -  Adequate hematologic, hepatic, and renal function;\n\n        Expansion Phase [Inclusion]\n\n          -  Escalation Phase inclusion criteria\n\n          -  Evidence of the NTRK fusion as previously determined with prior testing from a\n             Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent certified\n             laboratory.\n\n        Exclusion (for both Escalation and Expansion)\n\n        • Current treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer (EIAEDs\n        and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed)
For Dose Escalation:
For Dose Escalation (Part A): Have measurable or nonmeasurable disease.
For dose escalation part: Patients with MCL at high risk for tumor lysis syndrome
Any relapsed/refractory participants that are enrolled during the dose escalation should have received only a single previous treatment regimen Expansion Portion of the Study:
Women who are pregnant or lactating Dose-Escalation Portion of the Study:
Patients enrolled in the single agent expansion stage must have a diagnosis of EOC, while patients enrolled in the combination dose escalation or expansion stage must have a diagnosis of melanoma, NSCLC, SCLC, RCC, BLC, or TNBC.
For patients with melanoma enrolled in the combination dose escalation or expansion stage:
For patients with NSCLC enrolled in the combination dose escalation or expansion stage:
For patients with SCLC enrolled in the combination dose escalation or expansion stage:
For patients with RCC enrolled in the combination dose escalation or expansion stage:
For patients with BLC enrolled in the combination dose escalation or expansion stage:
For patients with TNBC enrolled in the combination dose escalation or expansion stage:
Consent to screening tumor biopsy (for accessible tumors when appropriate) (optional in dose escalation, mandatory in dose expansion)
For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive
Dose Escalation
Subjects must have an advanced hematologic malignancy including: Phase 1/ Dose escalation:
For subjects in the dose escalation phase and Part 1 Expansion, IDH2 mutation may be based on local evaluation. (Centralized testing will be performed retrospectively.)
Patients may have not received treatment for 28 days before the first day of the study protocol (dose escalation only)
Part B: For Part B dose-expansion: once a MTD has been established in part A, additional dose escalation will occur with subsequent dose escalation of carfilzomib; during the dose escalation of part B, patient (pt) must have at least 1 line of prior therapy and no limitations on prior therapy; patients who had prior clinical benefit/response to ARRY-520 or carfilzomib with a stable disease (SD) or better may be eligible for dose expansion of part B; dose expansion of part B will be patients who are carfilzomib sensitive
East Asian patients (Chinese, Japanese, Taiwanese, and Korean ancestry) are excluded during stage I of the study (dose escalation phase)
Dose-Escalation Stage:
Safety Cohort (Dose Escalation)
Previous treatment for MDS or MPN for dose escalation cohorts
Biopsy proven HER2 negative metastatic breast cancer (dose escalation portion and MTD expansion portion) or advanced solid tumor (dose escalation portion).
DOSE ESCALATION COHORT:
DOSE ESCALATION COHORT EXCLUSION:
DOSE ESCALATION COHORT: subjects must have histologically or cytologically confirmed sarcoma that is metastatic or unresectable
DOSE ESCALATION COHORT: patients must have had at least one prior therapy
For dose escalation monotherapy: CLL, HL, NHL, MM
For dose escalation and dose expansion in combination with BMS-936558: HL and DLBCL
Eligibility based on prior treatment with CIT depends on the mechanistic class of the drug and the cohort for which the participant is being considered, as described below. In addition, all criteria pertaining to adverse events attributed to prior cancer therapies must be met All Cohorts (Dose-Escalation in Phase 1a and Dose-Escalation, Backfill, and Expansion in Phase 1b):
Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
There is no line limit for the dose escalation cohort and the dose expansion cohort
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
Documented history of medication abuse/misuse (e.g. unsanctioned dose escalation, broken opioid agreement etc.)
Dose escalation phase prior systemic treatment requirements:
For the dose escalation cohorts, any prior number of MDS therapies, including hypomethylating agents, are permitted; for the dose expansion cohort, subjects must be azacitidine naïve, but otherwise any prior number of MDS therapies are permitted; treatment naïve patients are eligible for both the dose escalation and expansion cohorts if they are unfit for or refuse intense therapy
Participants in the dose escalation cohort must have a serum albumin of ? 3.2 g/dL at screening.
Dose Escalation Segment
Part 1, Dose Escalation: tumor tissue
Are willing to provide available pre-existing diagnostic or resected tumor samples. Providing fresh tumor biopsies are optional for all subjects in Dose Escalation cohorts. In the Dose Expansion cohort, up to 6 subjects may be requested to provide pre- and post-treatment tumor biopsies based on eligibility for the procedure. For those subjects who do not have an MMR status, inclusion in the Dose Escalation and Dose Expansion can be achieved by providing a fresh tumor biopsy for MMR testing.
Phase 1 trials in dose escalation
In the Dose Escalation Segment, patients who are refractory, relapsed, or unresponsive to standard treatment.
Patients must be considered to be suitable RIC alloHCT candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used to judge eligibility.
Eligibility criteria to participate in group 1 of the pilot study of the AYA-Hears instrument \r\nNote: participants in group 1 will not receive protocol-directed therapy
ELIGIBILITY CRITERIA - PHASE II (ARM D): Patient must not have Burkitt’s lymphoma/leukemia based on the WHO criteria
ELIGIBILITY FOR SCREENING
CRITERIA FOR DONOR ELIGIBILITY:
ELIGIBILITY CRITERIA FOR ENROLLMENT
Prior eligibility for and on study treatment from an antecedent vemurafenib protocol
Has adequate hematopoietic, coagulation, renal and hepatic function. Subject must remain eligible for continued treatment with tazemetostat according to the eligibility and treatment criteria from the antecedent study.
ELIGIBILITY CRITERIA AT TIME OF TREATMENT: EBV positive tumor
ELIGIBILITY CRITERIA AT TIME OF TREATMENT: Patients should have been off other investigational therapy for 30 days prior to infusion
MANUFACTURING SJCAR19: Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis
Eligibility for Infusion of Investigational Product:\r\n* Subjects will undergo a second evaluation of eligibility on day -2 or -1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions.\r\n** Inclusion criteria exceptions: Hematologic function parameters will not be included as a pre-infusion eligibility criterion (because lymphodepletive chemotherapy is expected to cause pancytopenia).
Eligibility for Infusion of Investigational Product:\r\n* Subjects will undergo a second evaluation of eligibility on day -2 or -1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions.\r\n* Exclusion criteria additions:\r\n** Use of corticosteroids within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).\r\n** Neurologic symptoms suggestive of an active central nervous system condition.\r\n** Signs or laboratory markers of active infection or systemic inflammatory response.
Participants must meet appropriate molecular eligibility criteria
ADDITIONAL COHORT 1 ELIGIBILITY CRITERIA
ADDITIONAL COHORT 2 ELIGIBILITY CRITERIA
ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION
ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT\r\n* Once research participants meet eligibility to proceed with Rickham placement, they will be deemed accrued on to the study
ELIGIBILITY TO PROCEED WITH CAR T CELL INFUSION
ELIGIBILITY CRITERIA FOR ENROLLMENT ON THE RE-TREATMENT STUDY
ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY AND T CELL INFUSION
History of transfusion is acceptable and transfusions may be given to meet eligibility requirements
REP ELIGIBILITY: Has not had a partial or complete response to nivolumab treatment
REP ELIGIBILITY: Serum creatinine of =< 1.5 x institutional ULN
PRE-SCREENING ELIGIBILITY
STUDY TREATMENT ELIGIBILITY
Any patient not meeting institutional standard guidelines for transplant eligibility
ELIGIBILITY CRITERIA TO BEGIN CONSOLIDATION THERAPY
CROSS-OVER ELIGIBILITY CRITERIA
Transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted
Most recent HR and HER2 receptor testing should be used to determine eligibility.
ELIGIBILITY CRITERIA FOR nEGFR TESTING
ELIGIBILITY CRITERIA FOR STUDY THERAPY
Must meet eligibility criteria for initiation of part A with the exception of being allowed to have prior nivolumab in part A of this protocol
Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nAbsolute neutrophil count >= 1,500/mcL
PHASE I STUDY ELIGIBILITY CRITERIA: \r\nWhite blood cell (WBC) >= 3,000/mcL
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPlatelets >= 100,000/mcL
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nTotal bilirubin =< 1.5 X the normal institutional limits
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients who were treated with both olaparib and cediranib, either in combination or sequentially
ELIGIBILITY CRITERIA- ENROLLMENT AND HARVEST
ELIGIBILITY CRITERIA- HARVEST
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Autologous transduced peripheral blood T-cells with >= 15% expression of 14g2a.zeta
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: ECOG performance score of 2 or less
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Absolute neutrophil count > 500 mcL
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Platelet > 20,000 mcL
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Serum AST < 5 x institutional upper limit of normal (IULN)
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Total bilirubin < 3 x IULN
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Serum creatinine < 2 x IULN
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not be currently receiving any investigational drugs
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have a tumor potentially causing airway obstruction
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not be currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporine
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have received a tumor vaccine within previous six weeks
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have a known hypersensitivity to rat monoclonal antibodies
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have a life-threatening allergy to baker’s yeast or other components of the vaccines; no history of allergic reactions to the antibiotics neomycin, streptomycin or polymyxin B
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have had a coma or long or multiple seizures within 7 days after a dose of DTP or Tdap unless a cause other than the vaccine was indicated
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Must not have evidence of previous or current infection with hepatitis B virus
DONOR ELIGIBILITY CRITERIA:
COHORT A SPECIFIC ELIGIBILITY CRITERIA:
COHORT B SPECIFIC ELIGIBILITY CRITERIA:
Hemoglobin > 8.0 g/dL; may transfuse to meet eligibility
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: Normal serum sodium levels without need for supplementation
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: ALT (SGPT): =< 5 x ULN
ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION
ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT
ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH CAR T CELL INFUSION
ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION
ELIGIBILITY TO UNDERGO LYMPHODEPLETION:
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): Research participant has completed prescribed lymphodepletion
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): Preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal range
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): Total bilirubin =< 2.0 mg/dL
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): No clinical evidence of uncontrolled active infectious process
ELIGIBILITY TO PROCEED WITH PBMC COLLECTION
ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED T CELLS:\r\n* Please note that none of these criteria are applicable of the research participant's donor is undergoing leukapheresis
ELIGIBILITY CRITERIA TO UNDERGO OPTIONAL T CELL ABLATION:\r\n* Please note that none of these criteria are applicable of the research participant's donor is undergoing leukapheresis
All subjects meeting eligibility criteria irrespective of gender, minority or other underrepresented status will be eligible for enrollment into the study
The protocol chairman will determine the eligibility of patients related to hepatic abnormalities
If total bilirubin is =< 2, fractionation is not required for eligibility determination
Eligibility criteria cannot be waived
TREATMENT ELIGIBILITY:
TREATMENT ELIGIBILITY:
Patients older than 21 will be considered for eligibility at the discretion of the principal investigator (PI)
Positive 68Ga-PSMA-R2 PET/CT scan for central eligibility assessment. Patients who receive 68Ga-PSMA-R2 as part of separate clinical protocol are eligible (must meet all study eligibility criteria)
Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was >100 days prior to study enrolment; no active infection(s); subjects meets the remainder of the eligibility criteria outlined in this protocol.
ADDITIONAL INDUCTION ELIGIBILITY CRITERIA:
PHASE 1 SPECIFIC ELIGIBILITY CRITERIA
PHASE 2 SPECIFIC ELIGIBILITY CRITERIA
GENERAL ELIGIBILITY CRITERIA
ELIGIBILITY CRITERIA TO INITIATE TREATMENT (FOR SECONDARY REGISTRATION - COHORT 1 PARTICIPANTS ONLY):
ELIGIBILITY CRITERIA: TREATMENT PROTOCOL
ELIGIBILITY CRITERIA PRIOR TO FIRST VACCINATION
SECONDARY ELIGIBILITY CRITERIA FOR GENE-MODIFIED HSPC INFUSION
ELIGIBILITY CRITERIA FOR HSPC TRANSPLANTATION
ELIGIBILITY TO RECEIVE T CELL INFUSION:
ELIGIBILITY CRITERIA FOR SECOND CELL INFUSION:
Subjects must meet all the initial eligibility criteria except for the requirement regarding previous anti-GD2-CAR therapy
Eligibility for pre-selected salvage chemotherapy, according to the Investigator's assessment.
Have had chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry; previous treatment at any time with either ruxolitinib or decitabine as single agents will not exclude eligibility; previous stem cell transplant will also not exclude eligibility as long as other inclusion/exclusion criteria have been met
Once all other eligibility criteria are confirmed, must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. Note: Apheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received.
Patients with multifocal or multicentric disease are eligible as long as at least one area meets eligibility criteria
PROSPECTIVE SCREENING ELIGIBILITY CRITERIA:
ALT <3 × ULN NOTE: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may retest the subject and the subsequent within range screening result may be used to determine the subject's eligibility.
Patient meets the eligibility criteria outlined above
CONSOLIDATION ELIGIBILITY:
Patients are eligible >= 6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met
Any individual that does not meet the eligibility criteria for transplantation or donor eligibility will not be a part of this trial
Subject is not appropriate for inclusion in the clinical trial, per the medical opinion of the Principal Investigator. Intraoperative Eligibility Criteria:
Note: Transfusions/infusions to meet eligibility criteria are not allowed but if in the opinion of the Principal Investigator, it is beneficial, the patient may be rescreened after receiving one of these procedures.
Persistence of clinically relevant therapy related toxicity from previous chemotherapy and/or radiotherapy; this does not include hemoglobin or other hematologic or laboratory criteria, as long as eligibility criteria are met as outlined above
Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria
ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS:
Exceptions to eligibility will not be granted for this study
PHASE I PORTION ELIGIBILITY CRITERIA
The patient must - at the time of re-induction - satisfy all the eligibility criteria
ELIGIBILITY TO PROCEED TO OVA:
ELIGIBILITY PRIOR TO CELL COLLECTIONS FOR DENDRITIC CELL GENERATION:
RANDOMIZATION ELIGIBILITY CRITERIA
In the event of significant BM involvement, the above hematologic criteria will not be required for enrollment eligibility
The patient currently does not meet the protocol’s eligibility/enrollment criteria for any reason
There is a high likelihood that the patient, in the opinion of the principal investigator (PI) will meet the protocol’s eligibility/enrollment criteria to proceed to transplant after standard therapy is completed
ELIGIBILITY CRITERIA FOR HISTORICAL CONTROL POPULATION
Patients with multicentric or bilateral disease are eligible if the target lesions meet the other eligibility criteria; samples from all available tumors are requested for research purposes
PRIMARY ELIGIBILITY (PRE-OPERATIVE [OP])
SECONDARY ELIGIBILITY
General Eligibility Criteria (All Parts)
Specific Eligibility Criteria, Part A
Subjects must meet general eligibility criteria.
Specific Eligibility Criteria, Part B
Subjects must meet general eligibility criteria. The specific eligibility criteria listed here will apply to subjects enrolling to different cohorts of Part B.
Specific Eligibility Criteria, Part C - Subjects must meet general eligibility criteria.
Specific Eligibility Criteria, Part D - Subjects must meet general eligibility criteria
Patients may not have clinically symptomatic hypothyroidism; testing is not required for eligibility
Patients who had prior lung resection are eligible provided they fulfill the rest of the eligibility criteria
Patients at institutions that elect to confirm eligibility locally may be pre-registered at the same time as they are randomized
Central imaging real-time review (72 hour turn around) to confirm eligibility (for institutions that opt to utilize central imaging review to confirm eligibility)
Patient eligibility criteria for entry into the project include:
FCG eligibility criteria include:
PATIENT ELIGIBILITY CRITERIA
FCG has been invited to participate in the trial with a patient who meets eligibility criteria
ELIGIBILITY CRITERIA FOR BOTH SURVIVORS AND CO-SURVIVORS:
NON-RANDOMIZED OBSERVATIONAL COMPONENT ELIGIBILITY:\r\nEnglish-speaking
Patients must meet eligibility criteria for induction of myelosuppressive chemotherapy as defined by clinical standards
Eligibility criteria same as stage I
The patient is enrolled on a COG trial that uses criteria for unrelated donor HSCT, which conflict with our eligibility criteria
PATIENTS ELIGIBILITY CRITERIA
FOCUS GROUP (PHASE 1) ELIGIBILITY CRITERIA:
USER/USABILITY TESTING (PHASE 2) ELIGIBILITY CRITERIA:
RANDOMIZED CONTROL TRIAL (RCT) (PHASE 3) ELIGIBILITY CRITERIA:
PATIENTS ELIGIBILITY CRITERIA:
CAREGIVERS ELIGIBILITY CRITERIA:
PATIENT PARTICIPANT ELIGIBILITY CRITERIA (PHASE 1 & 2)
CLINICIAN PARTICIPANT ELIGIBILITY CRITERIA
STAKEHOLDER PARTICIPANT ELIGIBILITY CRITERIA
PATIENT ELIGIBILITY REQUIREMENTS:
ONCOLOGIST ELIGIBILITY REQUIREMENTS:
Patients may undergo electrolyte repletion therapy to meet eligibility requirements
Eligibility will not be restricted by race or sex
Participants must have already met one or more eligibility criteria and have a reasonable expectation of meeting any remaining eligibility criteria for the therapeutic clinical trial
PATIENT ELIGIBILITY (AS PER SELF-REPORT)
ELIGIBILITY FOR THE OPTIONAL SUB-STUDY
ELIGIBILITY FOR THE 2-YEAR EXTENSION
GENERAL ELIGIBILITY (ALL PATIENTS):
ELIGIBILITY FOR REDUCED INTENSITY CONDITIONING:
Completed all eligibility questions
ELIGIBILITY CRITERIA FOR HIGH RISK PATIENTS FOR THE CLINICAL TRIAL
Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was > 100 days prior to study enrolment, no active infection; subject meets the remainder of the eligibility criteria outlined in the study protocol.
ELIGIBILITY CRITERIA FOR NORMAL-WEIGHT WOMEN IN PILOT STUDY
A pregnancy test will be used to determine eligibility in appropriate patients
For patients enrolled on the fluorouracil, leucovorin calcium, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) trial (HRPO# 201201124), their eligibility would include eligibility from that trial as well as the inclusion criteria outlined above
Subjects must satisfy one of the following conditions pertaining to their eligibility to undergo orthotopic liver transplantation (OLT):\r\n* HCC that is within Milan Criteria, i.e., TACE is indicated as a “bridge” to OLT (Group I); or\r\n* HCC that is outside Milan Criteria, i.e., TACE is indicated as a means of “down-staging” into transplant eligibility (Group II)
Required patient clinical data is not available for evaluation of eligibility criteria
PRIMARY ELIGIBILITY (PRE-OPERATIVE [OP])
SECONDARY ELIGIBILITY
PART A ELIGIBILITY CRITERIA
PART B ELIGIBILITY CRITERIA
Will include all prospective trial participants in this study that come from Twitter in response of our SM recruitment interventions, provided they meet the specific trial's eligibility criteria