A Phase 2, Open-label, Single-arm, Multicohort, Multicenter Trial to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects with Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL) (TRANSCEND FL)
A Phase 2, Open-label, Single-arm, Multicohort, Multicenter Trial to Evaluate the Efficacy and
Safety of JCAR017 in Adult Subjects with Relapsed or Refractory Indolent B-cell Non-Hodgkin
Lymphoma (JCAR017-FOL-001)
1. Relapsed or refractory follicular lymphoma (FL) (Grade 1, 2 or 3a) or marginal zone lymphoma (MZL) histologically confirmed within 6 months of screening, as assessed by local pathology
2. Patients should have received at least one prior therapy that includes anti-CD20 and alkylating agent
3. Follicular lymphoma patients: Received at least one prior line of systemic therapy. Patients that received one prior line of systemic therapy are eligible if they present with high risk features. Patients that received two or more prior lines of systemic therapy are eligible, assuming one of the prior lines includes anti-CD20 and alkylating agent (as listed in criterion 2)
4. Marginal zone lymphoma patients: Received two or more prior lines of systemic therapy, assuming one of the prior lines includes anti-CD20 and alkylating agent (as listed in criterion 2) or relapsed after hematopoietic stem cell transplant
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate organ function
7. Adequate vascular access for leukapheresis procedure
1. Evidence or history of composite Diffuse large B-cell lymphoma (DLBCL) and FL, or of transformed FL
2. WHO subclassification of duodenal-type FL
3. Central nervous system-only involvement by malignancy (subjects with secondary central nervous system (CNS) involvement are allowed on study)
4. History of another primary malignancy that has not been in remission for at least 2 years, with the exception of non-invasive malignancies
5. Prior CAR T-cell or other genetically-modified cell therapy
6. History of or active human immunodeficiency virus (HIV)
7. Active hepatitis B or active hepatitis C
8. Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment
9. Active autoimmune disease requiring immunosuppressive therapy
10. Presence of acute or chronic graft-versus-host=disease
11. History of significant cardiovascular disease
12. History or presence of clinically relevant central nervous system pathology
13. Allogenic-hematopoietic stem cell transplant (Allo-HSCT) within 90 days of leukapheresis
18age old over
No limit
Both
Relapsed/refractory follicular lymphoma and marginal
zone lymphoma
Intervention type: CAR-T
Name of intervention: JCAR017
Dose form / Japanese Medical Device Nomenclature: INJECTION
Route of administration / Site of application: INTRAVENOUS DRIP
Dose per administration: 1 x 10^8
Dosing frequency / Frequency of use: ONCE
Planned duration of intervention: follow-up assessment for 5 years
Intended dose regimen: infusion of JCAR017 2 to 7 days after completion of LD chemotherapy
detailes of teratment arms: Subjects will receive 3 days of fludarabine IV (30 mg/m^2/day) and cyclophosphamide IV (300 mg/m^2/day) for LD chemotherapy. JCAR017 will be administered 2 to 7 days after completion of LD chemotherapy at a dose of 1 x 10^8 CAR+ T cells(5 x 10^8 CD8+ CAR-T cells and 5 x 10^8 CD4+ CAR-T cells)
Comparative intervention name: N/A
Dose form / Japanese Medical Device Nomenclature: N/A
Route of administration / Site of application: N/A
Dose per administration: N/A
Dosing frequency / Frequency of use: N/A
Planned duration of intervention: N/A
Intended dose regimen: N/A
1. Overall Response Rate (ORR) as assessed but PET-CT and/or CT using "The Lugano Classification"
1. Complete response rate (CRR) as assessed but PET-CT and/or CT using "The Lugano Classification"
2. Duration of Response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification"
3. Duration of Response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification"
4. Progression-Free Survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification"
5. Overall Survival (OS)
6. Adverse Events (AEs)
7. Pharmacokinetics - Cmax
8. Pharmacokinetics - Tmax
9. Pharmacokinetics - AUC
10. European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30)
11. Functionality Assessment of Cancer Therapy Lymphoma Subscale (FACT-LymS)
Bristol-Myers Squibb K.K.
Toranomon Hospital and Toranomon Hospital Kajigaya Institutional Review Board
