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

Is NCT06014073 recruiting? Yes, currently enrolling (Jun 2026). This Phase 1/2 trial studies multiple treatments including TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T) and Fludarabine for non hodgkin's lymphoma.

Phase 1/2RecruitingChinese PLA General HospitalNCT06014073Data as of Jun 2026Location: China

Treatment: TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T) · Fludarabine · CyclophosphamideATHENA 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.

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Extracted eligibility criteria

Treatments studied

Chemotherapy

FludarabineCyclophosphamide

Other

TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T)

Cancer type

Non-Hodgkin Lymphoma

Biomarker criteria

Required: CD19 positive (detected by immunohistochemistry [IHC])

CD19 positive (detected by immunohistochemistry [IHC])

Allowed: BCL2 rearrangement

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL)

Allowed: BCL6 rearrangement

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL)

Allowed: MYC rearrangement

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL)

Allowed: CCND1 overexpression

Mantle cell lymphoma (MCL) ... overexpress cyclin D1

Allowed: IGH t(11;14)(q13;q32)

Mantle cell lymphoma (MCL) ... chromosome translocation t(11;14)(q13;q32)

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Demographics

Ages ≤ 70

Prior therapy

Min 1 prior line

Must have received: anthracycline-containing chemotherapy — MCL

For MCL, prior therapy must have included: Anthracycline or bendamustine-containing chemotherapy

Must have received: bendamustine-containing chemotherapy — MCL

For MCL, prior therapy must have included: Anthracycline or bendamustine-containing chemotherapy

Must have received: anti-CD20 monoclonal antibody — MCL

For MCL, prior therapy must have included: Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative)

Must have received: Bruton's tyrosine kinase inhibitor — MCL

For MCL, prior therapy must have included: Bruton's tyrosine kinase inhibitor (BTKi)

Must have received: anti-CD20 monoclonal antibody — other types

For other types, prior therapy must have included: Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative)

Must have received: anthracycline-containing chemotherapy — other types

For other types, prior therapy must have included: Anthracycline containing chemotherapy regimen

Cannot have received: CD19 targeted therapy

Prior CD19 targeted therapy

Cannot have received: CAR-T therapy

Prior CAR-T therapy or other genetically modified T cell therapy

Cannot have received: genetically modified T cell therapy

Prior CAR-T therapy or other genetically modified T cell therapy

Cannot have received: autologous stem cell transplant

Exception: within 3 months of planned ATHENA CAR-T infusion

Autologous stem cell transplant with therapeutic intent within 3 months of planned ATHENA CAR-T infusion

Cannot have received: allogeneic stem cell transplant

History of allogeneic stem cell transplantation

Lab requirements

Blood counts

ANC ≥ 1 x 10^9/L, Platelet count ≥50 x 10^9/L, hemoglobin (Hgb) ≥ 80g/L (hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions above)

Kidney function

Serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 60 mL/min

Liver function

ALT/AST ≤ 3x ULN; Total bilirubin ≤ 1.5x 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 an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings. Coagulation Function: INR ≤ 1.5x ULN, and APTT ≤ 1.5x 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 NCT06014073 currently recruiting?

Yes, this trial is currently recruiting patients.

Are there prior therapy exclusions?

Yes. Prior CD19 targeted therapy, CAR-T therapy, genetically modified T cell 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.

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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