RecruitingPhase 1Phase 2NCT06014073

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


Sponsor

Chinese PLA General Hospital

Enrollment

30 participants

Start Date

Sep 6, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing an "off-the-shelf" allogeneic (donor-derived, not the patient's own) CAR-T cell therapy targeting CD19, for people with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) who have not responded to or have relapsed after multiple prior treatments. **You may be eligible if...** - You are between 18 and 70 years old - You have confirmed relapsed or refractory B-cell NHL, including DLBCL, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, or related types - You have received prior standard therapy (including anti-CD20 antibody-based chemoimmunotherapy) that failed or caused relapse - You have at least one measurable tumor on imaging - You are in reasonably good health **You may NOT be eligible if...** - You have never received prior therapy - You have active brain (CNS) lymphoma involvement - Your organ function is significantly impaired - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALTRAC 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.

DRUGFludarabine

Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.

DRUGCyclophosphamide

Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.


Locations(3)

Biotherapeutic Department, Chinese PLA General Hospital

Beijing, China

EdiGene Inc

Beijing, China

School of Life Sciences, Peking University

Beijing, China

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NCT06014073


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