TRAC and Power3 Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL

Non Hodgkin's Lymphoma Clinical Trial

Official title: A Phase 1/2 Single-center Study Evaluating the Safety and Efficacy of TRAC and Power3 Genes Knock-out Allogeneic CD19-targeting CAR-T Cell (ATHENA) Therapy in Adults With Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

Status Recruiting

Clinical Trial Summary

ATHENA chimeric antigen receptor (CAR)-T, a CD19-directed CAR-T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). The cells are from healthy adult volunteer donors that are knocked out of TRAC and Power3 genes ex vivo using CRISPR-Cas9 gene editing components. In this study, a second-generation anti-CD19 CAR prototype was constructed, bearing murine FMC63 single-chain variant fragment (scFv) together with intracellular CD28 co-stimulatory and CD3ζ signaling domains linked by a CD28 sequence comprising the hinge and transmembrane domains.

This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with r/r B-cell NHL will be enrolled in the study and receive allogeneic CD19-CAR-T cell infusion. Phase 1 (n=6 to 18) is a dose escalation part, and phase 2 (n=10 to 12) is a expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of ATHENA CAR-T cell therapy in patients with r/r B-cell NHL.

Clinical Trial Description

Phase 1 (dose escalation)

In phase 1, 6-18 subjects will be enrolled. Subjects will receive 3 doses of ATHENA CAR-T cell therapy ( 1× 10^6 cells/kg、3× 10^6 cells/kg、1 × 10^7 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:

Three (3) subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity (DLT), 3 additional subjects will be enrolled at the current dose level. For safety purposes, the administration of ATHENA CAR T will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of ATHENA CAR-T will be staggered by 28 days before enter into the next cohort.

Phase 2 (expansion cohort)

In phase 2, 10 to 12 subjects will be enrolled and receive ATHENA CAR-T cell infusion at dose of recommended phase 2 dose (RP2D), which will be determined based on the maximum tolerated dose (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 and safety of ATHENA CAR-T in patients with r/r B-cell NHL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of ATHENA CAR-T in the above population. ;

Related Conditions & MeSH terms

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

• NCT number: NCT06014073
• 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: September 6, 2023
• Completion date: September 1, 2026