Multi-CAR-T Cells Targeting B Cell Lymphomas

B Cell Lymphoma (BCL) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04429438
• Other study ID #: GIMI-IRB-20006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2020
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, Ph.D
• Phone: +86-0755 8672-5195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: December 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 75 Years

Eligibility

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.

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.

7. Prior failed CAR-T treatment.

Related Conditions & MeSH terms

• B Cell Lymphoma (BCL)
• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2
Patients who have relapsed and refractory B cell lymphoma (BCL) after conventional chemotherapy will be treated with multiple 4SCAR gene-engineered T cells

Locations

Country	Name	City	State
China	Shenzhen Children's Hospital	Shenzhen	Guangdong
China	Shenzhen Geno-Immune Medical Institute	Shenzhen	Guangdong
China	The Seventh Affilliated Hospital, Sun Yat-Sen University	Shenzhen	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute	Shenzhen Children's Hospital, The Seventh Affilliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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