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 (Jun 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
Treatments studied
Chemotherapy
Other
Cancer type
Acute Lymphoblastic Leukemia
Biomarker criteria
Required: CD19 positive
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Demographics
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.
Frequently asked questions
Is NCT06481735 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior immunocellular therapy, hematopoietic stem cell transplant, anti-leukemic therapy disqualifies patients from enrollment.
Does this trial require CD19?
Yes, CD19 positive is a required biomarker for enrollment.
Is there an age limit?
Yes. Patients must be 70 years or younger and at least 16 years old.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
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