OncoMatch/Clinical Trials/NCT06323525
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B Cell Lymphoma
Is NCT06323525 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 (ATHENA-2 CAR-T) and Fludarabine for non-hodgkin lymphoma.
Treatment: TCR reserved and Power3 (SPPL3) gene knock-out allogeneic CD19-targeting CAR-T cell (ATHENA-2 CAR-T) · Fludarabine · Cyclophosphamide — The safety and efficacy of the chimeric antigen receptor (CAR)-T, a CD19-targeting, TRAC and Power3 (SPPL3) double genes deleted allogeneic CAR-T cell product, are undergoing rigorous evaluation in non-Hodgkin's lymphoma (NHL) subjects from our 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 HLA-mismatched fratricide between host T cells and TCR-reserved Power3 (SPPL3)-deleted allogenic CAR T cells was markedly slashed, which in combination with our observed clinical safety date 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 the ATHENA-2 study, our design is to preserve the expression of the TCR on T cells from healthy donors while selectively disabling the Power3 (SPPL3) gene to prepare ATHENA-2 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 ATHENA-2 in B-cell NHL.
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Hodgkin Lymphoma
Biomarker criteria
Required: CD19 positive (detected by immunohistochemistry [IHC]) (positive)
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) (pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1)
Allowed: IGH translocation t(11;14)(q13;q32)
Mantle cell lymphoma (MCL) (pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1)
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: anthracycline-containing chemotherapy — MCL or other types
Anthracycline or bendamustine-containing chemotherapy (MCL); Anthracycline containing chemotherapy regimen (other types)
Must have received: anti-CD20 monoclonal antibody — MCL or other types
Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) (MCL and other types)
Must have received: Bruton's tyrosine kinase inhibitor — MCL
Bruton's tyrosine kinase inhibitor (BTKi) (MCL)
Cannot have received: autologous stem cell transplant
Exception: within 3 months of planned ATHENA-2 CAR-T infusion
Autologous stem cell transplant with therapeutic intent within 3 months of planned ATHENA-2 CAR-T infusion
Cannot have received: allogeneic stem cell transplantation
History of allogeneic stem cell transplantation
Cannot have received: immunocellular therapy
Exception: within 3 months before enrollment
Patients who received any immunocellular therapy within 3 months before enrollment
Cannot have received: chemotherapy
Exception: within 2 weeks prior to lymphodepletion
Received any chemotherapy drugs or small molecule targeted drugs within 2 weeks prior to lymphodepletion
Cannot have received: monoclonal antibody
Exception: within 3 weeks prior to lymphodepletion
Received any monoclonal antibodies, antibody drug conjugates (ADCs), or bispecific antibodies within 3 weeks prior to lymphodepletion
Cannot have received: radiation therapy
Exception: within 6 weeks prior to lymphodepletion; exception if disease progressed at site or positive lesions detected by PET-CT at non-radiotherapy sites
Received radiotherapy within 6 weeks prior to lymphodepletion. However, if disease progressed at the site of radiotherapy, or if there are positive lesions detected by PET-CT at non-radiotherapy sites, enrollment is allowed.
Lab requirements
Blood counts
Absolute neutrophil count (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≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
Liver function
Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN); Total bilirubin ≤ 1.5 ULN, except in subjects with Gilbert's syndrome
Cardiac function
Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
Adequate renal, hepatic, pulmonary and cardiac function defined as: Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min. Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3 upper limit of normal (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: International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times 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