Multi-CAR-T Cells Targeting B Cell Lymphomas

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04429438

Collaborator

The Seventh Affiliated Hospital of Sun Yat-sen University (Other), Shenzhen Children's Hospital (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B Cell Lymphoma (BCL)	Biological: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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

Arm

Intervention/Treatment

Experimental: 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.

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
Prior failed CAR-T treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shenzhen Children's Hospital	Shenzhen	Guangdong	China	518000
2	Shenzhen Geno-Immune Medical Institute	Shenzhen	Guangdong	China	518000
3	The Seventh Affilliated Hospital, Sun Yat-Sen University	Shenzhen	Guangdong	China	518107