Multi-CAR-T Cells Targeting B Cell Lymphomas

Study Overview
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Brief Summary
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This study aims to evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting B cell surface molecules including CD19 and alternative CARTs as booster and consolidation treatment for patients with highly resistant B cell lymphomas, including primary mediastinal B cell lymphoma (PMBCL) and BCL involving central nervous system (CNS-BCL). Clinical response and development of a simplified and standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Detailed Description
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Chimeric antigen receptor (CAR) T cell therapy has proven effective in treating B cell malignancies. However, post CD19-CART relapses occur at high rate due to the CD19 antigen loss or the exhaustion of CART cells. Furthermore, the success of treating relapsed/refractory B cell lymphoma (BCL) such as primary mediastinal B-cell lymphoma (PMBCL) and CNS-involved BCL has been limited. To overcome tumor escape and prolong in vivo CART efficacy, we have developed a novel multiple CAR-T therapy regimen including booster and consolidation CART applications to to target highly-refractory cancer. Selected patients will be enrolled after target antigen confirmation including CD19, CD20, CD22, CD70, CD13, CD79b, GD2 and PSMA through immunostaining of their tumor specimens. The aim is to evaluate safety and long term efficacy of the multiple CART therapy strategy in the BCL patients.

Official Title
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Primary, Booster and Consolidation Multi-CAR-T Cell Therapy for the Treatment of Refractory B Cell Lymphomas

Conditions
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B Cell Lymphoma (BCL)

Intervention / Treatment
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* Biological: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age older than 6 months. Primary B cell lymphoma surface expression of CD19 and/or CD22/CD70/PSMA/ CD13/CD79b/GD2 molecules. The KPS score over 80 points, and survival time is more than 1 month. Greater than Hgb 80 g/L. No contraindications to blood cell collection. Exclusion Criteria: Accompanied with other active diseases, and difficult to assess response after treatment. Bacterial, fungal, or viral infection, unable to control. Living with HIV. Active HBV and HCV infection. Pregnant and nursing mothers.6. under systemic steroid treatment within a week of the treatment. 7. Prior failed CAR-T treatment.

Ages Eligible for Study
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Minimum Age: 6 Months
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: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2<br>Patients who have relapsed and refractory B cell lymphoma (BCL) after chemotherapy will be treated with a combination of 4SCAR gene-engineered T cells. | Biological: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2<br>* Patients who have relapsed and refractory B cell lymphoma (BCL) after conventional chemotherapy will be treated with multiple 4SCAR gene-engineered T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion | Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells in patients with relapsed B cell lymphoma (BCL) using CTCAE 4 standard to evaluate the level of adverse events | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti tumor activity of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion | Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMBCL, CAR-T, CD19, CD20, CD22, CD70, PSMA, CD13, CD79b, GD2, CNS-BCL