CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Non-Hodgkins Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells


Participation Criteria
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Eligibility Criteria
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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; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method 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; Received CAR T-cell or other genetically-modified T-cell therapy previously.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JWCAR029 treatment<br>JWCAR029 be administrated in two dose level | Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells<br>* JWCAR029 be administered at dose level: 1 x 10^8 CAR+T cells and 1.5 x 10^8 CAR+T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) in LBCL subjects in cohort A; | Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects； | 3 months | 
| Complete response rate (CRR) in FL subjects in cohort B | Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) in cohort A of LBCL subjects |  | 3 months | 
| Objective response rate (ORR) in cohort B of FL subjects |  | 3 months | 
| Adverse events (AEs) | Number of participants with adverse events, type of adverse events, severity of adverse events, and number of participants with laboratory abnormalities, type of laboratory abnormalities and severity of laboratory abnormalities. | up to 24 months after JWCAR029 infusion | 
| Duration of response (DOR) | Time from first response(PR or CR) to disease progression or death from any cause. | up to 24 months after JWCAR029 infusion | 
| Duration of complete remission (DoCR) | Time from complete response (CR) to disease progression or death from any cause. | up to 24 months after JWCAR029 infusion | 
| Duration of partial remission (DoPR) | Time from partial response (PR) to disease progression or death from any cause. | up to 24 months after JWCAR029 infusion | 
| Time to response (TTR) | Time from JWCAR029 infusion to first documentation of CR or PR | up to 24 months after JWCAR029 infusion | 
| Time to complete response (TTCR) | Time from JWCAR029 infusion to first documentation of CR | up to 24 months after JWCAR029 infusion | 
| Pharmacokinetic (PK)- Cmax of JWCAR029 | Maximum observed concentration of JWCAR029 in peripheral blood | up to 1 year after JWCAR029 infusion | 
| Pharmacokinetic (PK)- Tmax of JWCAR029 | Time to maximum concentration of JWCAR029 in the peripheral blood | up to 1 year after JWCAR029 infusion | 
| Pharmacokinetic (PK)- AUC of JWCAR029 | Area under the concentration vs time curve of JWCAR029 | up to 1 year after JWCAR029 infusion | 
| Progression-free survival (PFS) |  | 3 to 5 years after JWCAR029 infusion | 
| Overall survival |  | 3 to 5 years after JWCAR029 infusion | 
| Quality of Life C30 questionnaire (EORTC-QLQ-C30) | EORTC-QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale | up to 2 year after JWCAR029 infusion | 
| European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) | The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems) | up to 2 year after JWCAR029 infusion | 
| ICU and non-ICU hospitalization days |  | up to 2 year after JWCAR029 infusion | 
| ICU and non-ICU hospitalization reasons |  | up to 2 year after JWCAR029 infusion | 
| Anti-therapeutic JWCAR029 antibody |  | up to 2 year after JWCAR029 infusion | 
| Changes of T cell counts, subgroups and serum cytokines |  | up to 2 year after JWCAR029 infusion | 
| CD19 expression in tumor biopsy samples |  | up to 2 year after JWCAR029 infusion | 
| Changes of inflammation biomarkers-CRP |  | up to 1 year after JWCAR029 infusion | 
| Changes of inflammation biomarkers-serum ferritin |  | up to 1 year after JWCAR029 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JWCAR029, B-Cell Malignancies, non-Hodgkin lymphoma, CAR T cells, Chimeric antigen receptor, Relapsed/Refractory