Allogenic CD19-targeting CAR-γδT Cell Therapy in r/r NHL

Non Hodgkin's Lymphoma Clinical Trial

Official title: Allogenic CD19-targeting Chimeric Antigen Receptor γδT Cells Therapy in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Status Recruiting

Clinical Trial Summary

CD19-CAR-γδT cell therapy is a cellular immunotherapy targeting CD19 to perform CAR modification on allogeneic γδT cells. In this study, a second-generation anti-CD19 CAR prototype was constructed, bearing murine FMC63 single-chain variant fragment (scFv) together with intracellular 4-1BB co-stimulatory and CD3ζ signaling domains linked by a CD8α sequence comprising the hinge and transmembrane domains. The cells were derived from the patient's relative donors or unrelated healthy donors. Human leukocyte antigen (HLA) -mismatched or partially matched or full matched are acceptable. The upgraded version of the CAR-γδT product that has been validated for resistance to alloreactive T cell killing will be used in this study after March 20th, 2024.

This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) will be enrolled in the study and receive allogeneic CD19-CAR-γδT cell infusion. Phase 1 (n=9 to 12) is dose escalation part, and phase 2 (n=15 to 20) is expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of allogeneic CD19-CAR-γδT cell therapy in patients with r/r B-cell NHL.

Clinical Trial Description

Phase 1 (dose escalation)

In phase 1, 9-12 subjects will be enrolled. Subjects will receive 3 doses of CD19-CAR- γδ T cell therapy (2 × 10^6 cells/kg、6× 10^6 cells/kg、1.8 × 10^7 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:

1. Three patients were enrolled in the lowest dose group.

2. Subsequent patients were enrolled according to the following rules:

1. If the incidence of dose limiting toxicity (DLT) was 0/3, 3 patients were enrolled in the next high-dose group.

2. If the incidence of DLT was 1/3, 3 patients were enrolled at the same dose; If the incidence of DLT was 1/3 + 0/3, 3 patients were enrolled in the next high-dose group. If the incidence of DLT was 1/3 + 1/3, this dose was defined as maximum tolerated dose (MTD); If the incidence of DLT was 1/3 + 2/3 or 1/3 + 3/3, the previous dose was MTD.

3. If the incidence of DLT was 2/3 or 3/3, the previous dose was MTD.

To ensure the safety of the subjects, the first subject in each dose group was observed for at least 28 days after the cell infusion. If no DLT occurred, the remaining two subjects could be enrolled and treated at the same dose level. The safety data of all subjects in each dose group until day 28 should be reviewed and tolerated before proceeding to the next dose group trial. No dose escalation was allowed for the same subject during the trial. If a subject drop out during the observation period due to non-DLT reasons, new subjects should be enrolled to make up for the number of subjects who drop out.

Phase 2 (expansion cohort)

In phase 2, 15 to 20 subjects will be enrolled and receive CD19-CAR-γδ T cell infusion at dose of RP2D, which will be determined based on the MTD, occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.

Objectives

The primary objectives of the phase 1 were to evaluate the tolerability, safety, and determine recommended phase 2 dose (RP2D). The primary purpose of the phase 2 study was to evaluate the efficacy. ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin's Lymphoma

• NCT number: NCT05554939
• Study type: Interventional
• Source: Chinese PLA General Hospital
• Contact: Weidong Han, Ph.D
• Phone: +86-010-55499341
• Email: hanwdrsw@sina.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 11, 2022
• Completion date: December 31, 2026