Multi-CAR-T Cells Targeting B Cell Lymphomas

Phase 1

• Conditions: B Cell Lymphoma (BCL)
• Interventions: Biological: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2

• Registration Number: NCT04429438
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

Brief Summary

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

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.

Study Timeline

• Status Verified: 2020-06
• Study Start: 2020-06-01
• Study First Submitted: 2020-06-09
• Study First Submitted QC: 2020-06-10
• Last Update Submitted: 2020-06-10
• Study First Posted: 2020-06-12
• Last Update Posted: 2020-06-12
• Primary Completion: 2023-07-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. Age older than 6 months.
2. Primary B cell lymphoma surface expression of CD19 and/or CD22/CD70/PSMA/ CD13/CD79b/GD2 molecules.
3. The KPS score over 80 points, and survival time is more than 1 month.
4. Greater than Hgb 80 g/L.
5. No contraindications to blood cell collection.

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Exclusion Criteria

1. Accompanied with other active diseases, and difficult to assess response after treatment.

2. Bacterial, fungal, or viral infection, unable to control.

3. Living with HIV.

4. Active HBV and HCV infection.

5. Pregnant and nursing mothers.6. under systemic steroid treatment within a week of the treatment.

6. Prior failed CAR-T treatment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2	4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2	Patients who have relapsed and refractory B cell lymphoma (BCL) after chemotherapy will be treated with a combination of 4SCAR gene-engineered T cells.

Primary Outcome Measures

Name	Time	Method
Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion	24 weeks	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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Shenzhen Geno-Immune Medical Institute; 🇨🇳 Shenzhen, Guangdong, China

Shenzhen Children's Hospital; 🇨🇳 Shenzhen, Guangdong, China

The Seventh Affilliated Hospital, Sun Yat-Sen University; 🇨🇳 Shenzhen, Guangdong, China