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TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL

NCT06481735 · Status: RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 30

Last updated 2026-05-08

No results posted yet for this study

Summary

The safety and efficacy of the chimeric antigen receptor (CAR)-T, a CD19-targeting, TRAC and Power3 (SPPL3) double gene deleted allogeneic CAR-T cell product, are undergoing rigorous evaluation in non-Hodgkin's lymphoma (NHL) subjects from the ATHENA trial (NCT06014073). Unexpectedly, expansion of the initial residual CD3-positive CAR T from products were measured in patients' peripheral blood (PB) without exception. Accompanying with host immune reconstitution and appearance of the detectable B cells, the CD3-positive allogenic CAR T cells exhibited a compelling amplification advantage over CD3-negative CAR T cells. The amplification of CD3-positive CAR T cell population dynamically suppressed host B cell recovery, and presumably surveilled the recurrence or progression of tumors, but did not induce typical Graft-versus-host-disease (GvHD). Additionally, a series of in vitro experiments illustrated that the human leukocyte antigen (HLA)-mismatched fratricide between host T cells and TCR-reserved Power3 (SPPL3)-deleted allogenic CAR T cells was markedly slashed, which in combination with investigators' observed clinical safety data supported the notion that only genomic deletion of Power3 (SPPL3) gene in allo-CAR T cells is sufficient to overcome GvHD and host T cell-mediated rejection response.

In this study, investigators will disable the Power3 (SPPL3) gene of T cells from healthy donors to prepare CAR T cells (purified CAR-positive T cells \> 90%). This approach harnesses the tonic signaling of CAR T cells, resulting in enhanced persistence and improved response to treatment. The purpose of this study is to evaluate the safety and efficacy of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T in B-cell acute lymphoblastic leukaemia (B-ALL).

Conditions

  • Acute Lymphocytic Leukemia

Interventions

BIOLOGICAL

TCR reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T cell

Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6 × 10\^6 cells/kg); Phase 2 : dose of RP2D.

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.

Sponsors & Collaborators

  • Peking University

    collaborator OTHER

  • Chinese PLA General Hospital

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
16 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-02-15
Primary Completion
2027-02-15
Completion
2028-02-15

Countries

  • China

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06481735 on ClinicalTrials.gov