Study Evaluating the Safety and Efficacy of JWCAR029 in Adult Subjects With Relapsed and Refractory B-cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of autologous CD19-targeted chimeric antigen receptor (CD19 CAR) T cells in adult patients with relapsed and refractory B-cell Non-Hodgkin lymphoma.

Official Title
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A Phase 1, Open-Label Study of JWCAR029, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Adult Subjects With Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Biological: JWCAR029


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled in this study: Age ≥ 18 years at the time of consent Signed written informed consent obtained prior to any study procedures Relapsed or refractory B-cell NHL. PET-positive disease BY Lugano classification Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function Adequate vascular access for leukapheresis procedure Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy Subjects must agree to use appropriate contraception. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in this study: Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study) History of another primary malignancy that has not been in remission for at least 2 years. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of screening Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or JWCAR029 administration Presence of acute or chronic graft-versus-host disease (GVHD) History of cardiovascular disease History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis Pregnant or nursing women. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JWCAR029 treatment in this protocol for subjects receiving retreatment

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 a standard 3+3 dose escalation approach. 4 CAR T dosage will be tested in this study: 1×10^7, 2.5×10^7, 5×10^7, 1×10^8 CAR+ T cells. | Biological: JWCAR029<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 one dose treatment with JWCAR029 by intravenous (IV) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related adverse events (AEs) | Physiological parameter | 2 years | 
| Dose-limiting toxicities of JWCAR029 | Physiological parameter | 28 days after JWCAR029 infusion | 
| Objective response rate (ORR) | Lugano criteria | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of JWCAR029 in the peripheral blood and bone marrow | Flow cytometry and qPCR | 1 year after JWCAR029 infusion | 
| Time to maximum concentration (Tmax) of JWCAR029 in the peripheral blood and bone marrow | Flow cytometry and qPCR | 1 year after JWCAR029 infusion | 
| Area-under the concentration-vs-time-curve (AUC) of JWCAR029 in the peripheral blood and bone marrow | Flow cytometry and qPCR | 1 year after JWCAR029 infusion | 
| Complete response (CR) rate | Lugano criteria | 2 years | 
| Duration of response | Lugano criteria | 2 years | 
| Progression-free survival (PFS) and PFS ratio | Lugano criteria | 2 years | 
| Overall survival | Physiological parameter | 2 years | 
| Health-related quality of life (HRQoL) | Questionnaire | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Hodgkin Lymphoma, CD19-targeted chimeric antigen receptor, JWCAR029