NCT06014073

TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL

A Phase 1/2 Single-center Study Evaluating the Safety and Efficacy of TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell (ATHENA) Therapy in Adults With Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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 (SPPL3) 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.

Detailed 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.

Conditions

• Non Hodgkin's Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T)	Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (1 × 10\^7 cells/kg); Phase 2 : dose of RP2D. No more than 2 × 10\^5 per kilogram of allogenic residual CD3+T cells harbouring in grafts can only be released for recipient infusion.
DRUG	Fludarabine	Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.
DRUG	Cyclophosphamide	Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.

Timeline

• Start date: 2023-09-06
• Primary completion: 2025-09-01
• Completion: 2026-09-01
• First posted: 2023-08-28
• Last updated: 2025-05-25

Locations

3 sites across 1 country: China