CD20-CD19 Compound CAR (cCAR) T Cells for Patients With Relapsed /Refractory B Cell Malignancies

Study Overview
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Brief Summary
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This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD20-CD19 cCAR in patients with relapsed and/or refractory B cell malignancies.

Detailed Description
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Clinical trials with CD19-directed CARs have achieved unprecedented remission rates as high as 90%. However, recent follow-up studies have shown a substantial portion of treated patients relapsed due to antigen escape. CD20-CD19 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CD20 and CD19. CD20-CD19 cCAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape.

Official Title
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Phase I, Interventional, Single Arm, Open Label, Treatment Study to Evaluate the Safety and Tolerability of CD20-CD19 cCAR in Patients With Relapsed and/or Refractory B Cell Malignancies

Conditions
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B Cell Lymphoma, B Cell Leukemia

Intervention / Treatment
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* Biological: CD20-CD19 cCAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis based on the World Health Organization (WHO) 2008 Histologically demonstrate CD19 or CD20 expressing B cell lymphoma or B ALL Patients have exhausted standard therapeutic options Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks Female must be not pregnant during the study Exclusion Criteria: Patients declining to consent for treatment Prior solid organ transplantation Potentially curative therapy including chemotherapy or hematopoietic cell transplant Prior treatment with CD20xCD3 or CD19x3 bispecific agents
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: CD20-CD19 cCAR T cells<br>CD20-CD19 cCAR T cells transduced with a lentiviral vector to express two distinct units of anti-CD20 and CD19 CARs | Biological: CD20-CD19 cCAR T cells<br>* CD20-CD19 cCAR T cells administered to patients, will be either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |  | 28 days | 
| Type of dose-limiting toxicity (DLT) |  | 28 days | 
| Number of participants with adverse event by severity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CR1), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies | 1 year | 
| Progression-free survival (PFS) |  | 1 year | 
| Overall survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD20, CD19, cCAR, Leukemia, Lymphoma