A Phase II Open-Label, Single-Arm, Multicenter Study of JWCAR029, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells for Relapsed and Refractory (R/R) Non-Hodgkins Lymphoma

Shanghai Ming Ju Biotechnology Co., Ltd.10 sites in 1 country82 target enrollmentJune 11, 2019

ConditionsLymphoma, Non-Hodgkin Diffuse Large B Cell Lymphoma Follicular Lymphoma

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Lymphoma, Non-Hodgkin
Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Enrollment: 82
Locations: 10
Primary Endpoint: Objective response rate (ORR) in LBCL subjects in cohort A;
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase II, open-label, single-arm, multicenter study to asess the efficacy and safety of JWCAR029 in adult R/R Non-Hodgkins Lymphoma subjects in China.

Detailed Description

This is a phase II, open-label, single-arm, multicenter study conducted in adult subjects with R/R Non-Hodgkins Lymphoma in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect the patient reported quality of life changes and immune response after JWCAR029 treatment. There will be two cohorts of cohort A and cohort B. Large B cell lymphoma (LBCL) patients will be enrolled in cohort A and follicular lymphoma patients will be enrolled in cohort B. Two dose levels of 1.0 x 10\^8 CAR+ T cells and 1.5 x 10\^8 CAR+ T cells are adopted in this study in both cohorts, subjects will be randomly assigned into the two dose levels with a 1:1 ratio. All sujects will be followed for 2 years following JWCAR029 infusion.

Registry

clinicaltrials.gov

Start Date

June 11, 2019

End Date

September 30, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Ming Ju Biotechnology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must meet all of the following criteria to participate in the study:
•≥ 18 years old;
•Sign on the informed consent;
•Subject must have histologically confirmed large B lymphoma or follicular lymphoma;
•Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
•Adequate organ function;
•Adequate vascular access for leukapheresis procedure;
•Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still express CD19;
•Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of JWCAR029;

Exclusion Criteria

•Central nervous system (CNS) only involvement by malignancy or primary CNS lymphoma;
•History of another primary malignancy that has not been in remission for at least 2 years;
•Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
•Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
•Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
•Presence of acute or chronic graft-versus-host disease (GVHD);
•History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
•Pregnant or nursing women;
•Subjects using of any chemotherapy, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
•Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;

Outcomes

Primary Outcomes

Objective response rate (ORR) in LBCL subjects in cohort A;

Time Frame: 3 months

Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects；

Complete response rate (CRR) in FL subjects in cohort B

Time Frame: 3 months

Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects

Secondary Outcomes

Pharmacokinetic (PK)- Cmax of JWCAR029(up to 1 year after JWCAR029 infusion)
Overall survival(3 to 5 years after JWCAR029 infusion)
Time to complete response (TTCR)(up to 24 months after JWCAR029 infusion)
Pharmacokinetic (PK)- AUC of JWCAR029(up to 1 year after JWCAR029 infusion)
Quality of Life C30 questionnaire (EORTC-QLQ-C30)(up to 2 year after JWCAR029 infusion)
Complete response rate (CRR) in cohort A of LBCL subjects(3 months)
Adverse events (AEs)(up to 24 months after JWCAR029 infusion)
European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L)(up to 2 year after JWCAR029 infusion)
ICU and non-ICU hospitalization days(up to 2 year after JWCAR029 infusion)
Changes of T cell counts, subgroups and serum cytokines(up to 2 year after JWCAR029 infusion)
Objective response rate (ORR) in cohort B of FL subjects(3 months)
Duration of response (DOR)(up to 24 months after JWCAR029 infusion)
Duration of complete remission (DoCR)(up to 24 months after JWCAR029 infusion)
Duration of partial remission (DoPR)(up to 24 months after JWCAR029 infusion)
Time to response (TTR)(up to 24 months after JWCAR029 infusion)
Pharmacokinetic (PK)- Tmax of JWCAR029(up to 1 year after JWCAR029 infusion)
Progression-free survival (PFS)(3 to 5 years after JWCAR029 infusion)
ICU and non-ICU hospitalization reasons(up to 2 year after JWCAR029 infusion)
Changes of inflammation biomarkers-CRP(up to 1 year after JWCAR029 infusion)
CD19 expression in tumor biopsy samples(up to 2 year after JWCAR029 infusion)
Anti-therapeutic JWCAR029 antibody(up to 2 year after JWCAR029 infusion)
Changes of inflammation biomarkers-serum ferritin(up to 1 year after JWCAR029 infusion)