CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Mantle Cell 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 assess the efficacy and safety of JWCAR029 in adult R/R Mantle Cell 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 relapsed and refractory (R/R) mantle cell lymphoma (MCL) in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and immune response after JWCAR029 treatment. R/R MCL patients will be enrolled in dose level of 1.0 x 10^8 CAR+ T cells. All subjects will be followed for 5 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) Mantle Cell Lymphoma

Conditions
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Mantle Cell 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: ≥ 18 years old; Sign on the informed consent; Subject must have histologically confirmed mantle cell lymphoma; Relapsed/refractory patients; 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; Expected survival is greater than 12 weeks; 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, corticosteriod, experiment agents, GVHD therapies, radiation or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis; Received allo-hematopoietic stem cell transplantation therapy previously. 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 at dose level: 1 x 10^8 CAR+T cells | Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells<br>* JWCAR029 will be administered at dose level: 1 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) | Objective response rate (ORR) in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) | Complete response rate (CRR) in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects | 3 months | 
| The best objective response rate | The best objective response rate in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects | 3 months | 
| The best complete response rate | The best complete response rate in 3 month in relapsed and refractory (R/R) mantle cell lymphoma (MCL) subjects | 3 months | 
| Number of participants with adverse events (AEs) | Number of participants with adverse events | Up to 24 months after JWCAR029 infusion | 
| Type of adverse events (AEs) | Type of adverse events | Up to 24 months after JWCAR029 infusion | 
| Severity of adverse events(AEs) | Severity of adverse events | Up to 24 months after JWCAR029 infusion | 
| Number of participants with laboratory abnormalities | Number of participants with laboratory abnormalities | Up to 24 months after JWCAR029 infusion | 
| Type of laboratory abnormalities | Type of laboratory abnormalities | Up to 24 months after JWCAR029 infusion | 
| Severity of laboratory abnormalities | 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 complete response (CR) or partial response (PR) | Up to 24 months after JWCAR029 infusion | 
| Time to complete response (TTCR) | Time from JWCAR029 infusion to first documentation of complete response (CR) | Up to 24 months after JWCAR029 infusion | 
| Cmax of JWCAR029 | Maximum observed concentration of JWCAR029 in peripheral blood | Up to 1 year after JWCAR029 infusion | 
| Tmax of JWCAR029: | Time to maximum concentration of JWCAR029 in the peripheral blood | Up to 1 year after JWCAR029 infusion | 
| AUC of JWCAR029: | Area under the concentration vs time curve of JWCAR029 in the peripheral blood | Up to 1 year after JWCAR029 infusion | 
| Progression-free survival (PFS) | Progression-free survival | Up to 2 year after JWCAR029 infusion | 
| Overall survival (OS) | Overall survival | Up to 5 year after JWCAR029 infusion | 
| Anti-therapeutic JWCAR029 antibody | Anti-therapeutic JWCAR029 antibody | Up to 2 year after JWCAR029 infusion | 
| Changes of T cell counts | Changes of T cell counts | Up to 2 year after JWCAR029 infusion | 
| Changes of Subgroups of T cell | Changes of Subgroups of T cell | Up to 2 year after JWCAR029 infusion | 
| Changes of serum cytokines | Changes of serum cytokines | Up to 2 year after JWCAR029 infusion | 
| CD19 expression in tumor biopsy samples | CD19 expression in tumor biopsy samples | Up to 2 year after JWCAR029 infusion | 
| Changes in inflammatory biomarkers such as CRP | Changes in inflammatory biomarkers such as CRP | Up to 2 year after JWCAR029 infusion | 
| Changes in inflammatory biomarkers such as ferritin | Changes in inflammatory biomarkers such as CRP | Up to 2 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, Mantle Cell Lymphoma