OncoMatch/Clinical Trials/NCT06481735
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL
Is NCT06481735 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including TCR reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T cell and Fludarabine for acute lymphocytic leukemia.
Treatment: TCR reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T cell · Fludarabine · Cyclophosphamide — 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. 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).
Check if I qualifyExtracted eligibility criteria
Cancer type
Acute Lymphoblastic Leukemia
Biomarker criteria
Required: CD19 positive
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: chemotherapy — induction
relapsed or refractory disease as defined by not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory) or relapse after achieving CR
Cannot have received: immunocellular therapy
Patients who received any immunocellular or HSCT therapy within 3 months before enrollment
Cannot have received: hematopoietic stem cell transplant
Patients who received any immunocellular or HSCT therapy within 3 months before enrollment
Cannot have received: anti-leukemic therapy
Use of previous anti-leukemic therapy within 5 half-lives prior to allogeneic Power3 (SPPL3) knock-out CD19 CAR-T administration
Cannot have received: radioimmunotherapy
Exception: except prophylaxis of CNS involvement
Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion
Cannot have received: radiotherapy
Exception: except prophylaxis of CNS involvement
Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion
Lab requirements
Blood counts
Coagulation: INR ≤ 1.5 ULN, APTT ≤ 1.5 ULN
Kidney function
Serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min
Liver function
ALT/AST ≤ 3 ULN; Total bilirubin ≤ 1.5 ULN, except in subjects with Gilbert's syndrome
Cardiac function
Ejection fraction ≥ 50%, no evidence of pericardial effusion by ECHO, no clinically significant ECG findings
Adequate renal, hepatic, pulmonary and cardiac function defined as: Serum creatinine ≤1.5 ULN or creatinine clearance ≥ 60 mL/min; ALT/AST ≤ 3 ULN; Total bilirubin ≤ 1.5 ULN, except in subjects with Gilbert's syndrome; Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by ECHO, and no clinically significant ECG findings; Coagulation: INR ≤ 1.5 ULN, APTT ≤ 1.5 ULN; Baseline oxygen saturation >91% on room air.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualify