Relapsed or refractory (r/r) CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL) and B-Cell Non-Hodgkin Lymphoma (B-NHL). MedDRA version: 20.0 Level: LLT Classification code 10029593 Term: Non-Hodgkin's lymphoma NOS System Organ Class: 100000004864 MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 20.0 Level: LLT Classification code 10000845 Term: Acute lymphoblas
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Phase 1b: Subject 70 mL/min/1.73 m2. Alanine aminotransferase (ALT) = 5 x upper limit of normal (ULN) and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert’s syndrome or lymphomatous infiltration of the liver). Adequate pulmonary function, defined as = Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) = 92% on room air. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) = 4
Exclusion criteria
Exclusion criteria: 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Subject has any condition that confounds the ability to interpret data from the study. 4. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment. 5. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy. 6. Prior CAR T cell or other genetically-modified T cell therapy. 7. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. 8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion. 9. Subject has presence of acute or chronic graft-versus-host disease (GVHD). 10. Subject with active autoimmune disease requiring immunosuppressive therapy. 11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months. 12. Subject with a concomitant genetic syndrome, with the exception of Down’s syndrome. 13. Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion. 14. Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis. 15. Subject is pregnant or nursing. 16. Subject has used the following: Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted. Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide = 300 mg/m2) given after leukapheresis to maintain disease control must be stopped = 7 days prior to LD chemotherapy. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week prior to leukapheresis. Oral anticancer agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis. Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis. Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R). Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion. Radiation within 6 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives Phase 1b: The primary objective of the Phase 1b is to identify the recommended Phase 2 dose (RP2D) of JCAR017 in pediatric subjects with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Phase 2: The primary objective of Phase 2 is to evaluate the efficacy of JCAR017 in the following disease cohorts: - Cohort 1 (r/r B-ALL): Overall response rate (ORR) defined as proportion of subjects with a complete response (CR) or complete response with incomplete blood count recovery (CRi) on Day 28 that must be confirmed on Day 56 - Cohort 2 (minimal residual disease [MRD]+ B-ALL): MRD- rate defined as proportion of subjects with a MRD- response on Day 28 that must be confirmed on Day 56 - Cohort 3 (r/r B-cell non-Hodgkin lymphoma [B-NHL] (diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL] or primary mediastinal large B-cell lymphoma [PMBCL])): ORR defined as proportion of subjects with a CR or partial response (PR) on Day 28.;Secondary Objective: The secondary objectives for Phase 1b and Phase 2 are: - Evaluate the feasibility of manufacturing JCAR017 measured by the percentage of product generated successfully (Phase 1b only) - Evaluate ORR in the non-selected dose from Phase 1b - Evaluate safety and tolerability assessments during 24 months after JCAR017 infusion - To further evaluate efficacy by assessing the duration of response (DOR), relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS) during 24 months after JCAR017 infusion - Evaluate the percentage of r/r B-ALL subjects who achieve CR or CRi with no MRD detected in bone marrow (BM) (<0.01% by a validated assay) assessed during 24 months after JCAR017 infusion - Assess the percentage of subjects who achieve a response after JCAR017 infusion and then proceed to hematopoietic stem cell transplant (HSCT) - Characterize the pharmacokinetic (PK) profile of JCAR017 assessed during 24 months after JCAR017 infusion;Primar | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety - Type, frequency, and severity of adverse events (AEs), including serious adverse events (SAEs) and laboratory abnormalities 2. Feasibility of manufacturing JCAR017 (Phase 1b only) - Percentage of JCAR017 product generated successfully 3. Overall response rate (ORR) in the non-selected dose from Phase 1b - Percentage of subjects achieving a confirmed CR or CRi 4. Duration of response (DOR) - Time from first response until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first 5. Relapse-free survival (RFS) - Time from first response to documentation of PD, disease relapse, or death due to any cause, whichever occurs first 6. Event-free survival (EFS) - Time from JCAR017 infusion to PD, disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first 7. Overall survival (OS) - Time from JCAR017 infusion to time of death due to any cause 8. MRD response rate (non-selected RP2D cohort in Phase 1b and Cohort 1 in Phase 2 only) - Percentage of subjects achieving a CR or CRi and a negative MRD bone marrow 9. Rate of hematopoietic stem cell transplant (HSCT) after response to JCAR017 infusion - Percentage of subjects who achieve a response after JCAR017 infusion and then proceed to HSCT 10. Pharmacokinetics (PK) - Maximum concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), including maximum expansion and duration of persistence of JCAR017;Timepoint(s) of evaluation of this end point: Timeframe for secondary endpoints: 1, 4, 5, 6, 7, 8, 9 and 10. During 2 years after JCAR017 infusion 2. During Part A (leukapheresis and JCAR017 generation) 3. On Day 28 and must be confirmed on Day 56 | — |
Countries
Belgium, France, Germany, Italy, Netherlands, Spain, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed