Phase I Study of JWCAR029 in Subjects With R/R CLL/SLL

Study Overview
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Brief Summary
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This is a Phase I, open-label, single-arm, single center study to assess the safety and efficacy of JWCAR029 in subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Detailed Description
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Upon the successful product generation of Relmacabtagene Autoleucel, subjects will enter the treatment phase of the study. Treatment will include lymphodepleting chemotherapy followed by Relmacabtagene Autoleucel administration. Subjects will then enter the post-treatment follow-up phase of the study and will be followed for approximately 24 months for safety, disease status, and survival. Long-term follow-up will continue under a separate long-term follow-up protocol, currently up to 15 years after the last Relmacabtagene Autoleucel administration.

Official Title
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An Open Label, Single-arm, Phase I Study of JWCAR029 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Genetic: JWCAR029 (Relmacabtagene Autoleucel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old and ≤ 75 years old; Sign on the informed consent; Diagnosis of: CLL with an indication for treatment based on iwCLL 2018 and measurable disease, or SLL (lymphadenopathy and/or splenomegaly and < 5×10^9 CD19+ CD5+ clonal B lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL); Relapsed/refractory patients, Subjects must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy; 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; 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
Maximum Age: 75 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>Dose-finding for JWCAR029 monotherapy | Genetic: JWCAR029 (Relmacabtagene Autoleucel)<br>* CD19-targeted Chimeric Antigen Receptor (CAR) T Cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related adverse events (AEs) | Type, Proportion, and Severity | 2 years | 
| Recommended dose of JWCAR029 | Recommended dose of JWCAR029 | 28 days after JWCAR029 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Objective response (BOR) rate | iwCLL2018 | 3 months | 
| Best Complete response (CR) rate | iwCLL2018 | 3 months | 
| Objective response rate (ORR) | iwCLL2018 | 3 months | 
| Complete response rate (CRR) | iwCLL2018 | 3 months | 
| MRD-negative response rate | Proportion of subjects who achieve MRD-negative OR and CR | 3 months | 
| Progression free survival (PFS) | iwCLL2018 | 2 years | 
| Overall survival (OS) | iwCLL2018 | 2 years | 
| Duration of response | iwCLL2018 | 2 years | 
| Pharmacokinetics- Maximum concentration (Cmax) | Flow cytometry and qPCR | 2 years | 
| Pharmacokinetics- Time of the maximum concentration (Tmax) | Flow cytometry and qPCR | 2 years | 
| Pharmacokinetics- area under the curve | Flow cytometry and qPCR | 2 years | 
| Serum cytokines associated with CRS | IL-6, IL-8, TGF-β1, TNF-α, etc. | 2 years |