CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma

Study Overview
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Brief Summary
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This is a phase I, open-label, single-arm, multicenter study to assess the safety and efficacy of JWCAR029 in adult primary refractory DLBCL subjects in China

Detailed Description
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This is a phase I, open-label, single-arm, multicenter study conducted in adult subjects with primary refractory DLBCL in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect immune response after JWCAR029 treatment. One dose level of 1.0 x 10^8 CAR+ T cells is adopted in this study. All sujects will be followed for 2 years after JWCAR029 infusion.

Official Title
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CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma, Phase Ⅰ,Open-label,Single-arm,Muticenter Study

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Biological: JWCAR029 (CD19-targeted Chimeric Antigen Receptor 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 diffuse large B lymphoma and primary refractory with first-line therapy; 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: Subjects who have received second-line treatment or above CD19 negative 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<br>The safety and efficacy of JWCAR029 will be evaluated in 1 x 10^8 CAR+T cells dose level | Biological: JWCAR029 (CD19-targeted Chimeric Antigen Receptor Cells)<br>* Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWCAR029. During JWCAR029 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive 1 x 10^8 CAR+T cells (JWCAR029) treatment by intravenous (IV) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Types, frequency, and severity of adverse events and laboratory anomalies | Physiological parameter | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) in primary refractory DLBCL subjects | Investigator evaluated CRR in 1 month | 1 month | 
| Objective response rate (ORR) in primary refractory DLBCL subjects | Investigator evaluated ORR in 1 month | 1 month | 
| Best objective response rate (BORR) | The best response from the onset of treatment to the onset of disease progression/recurrence or to the onset of another anticancer treatment | 2 years | 
| Investigator evaluated CRR | Complete response rate (CRR) | 3 months | 
| Investigator evaluated ORR (ORR=CR+PR) | Complete response (CR) + partial response（PR） | 3 months | 
| 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 | 
| 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) | Progression-free survival | up to 2 year after JWCAR029 infusion | 
| Overall survival (OS) | Overall survival | up to 2 year after JWCAR029 infusion | 
| Changes of CRP and serum ferritin | Changes of inflammation biomarkers-CRP and serum ferritin | 1 year after JWCAR029 infusion | 
| Anti-therapeutic JWCAR029 antibody | The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion | up to 2 year after JWCAR029 infusion | 
| The concentration of Car-T cell | The concentration of Car-T cells | up to 2 year after JWCAR029 infusion | 
| The proportion of Car-T cell subgroups | The proportion of Car-T cell subgroups after infusion | up to 2 year after JWCAR029 infusion | 
| The concentration of CD19 in tumor biopsy samples | The concentration of CD19 in tumor biopsy samples | up to 2 year after JWCAR029 infusion | 
| The change of serum cytokines concentration | The change of serum cytokines concentration after JWCAR029 infusion | 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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Primary refractory