Actively Recruiting
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B Cell Lymphoma
Led by Chinese PLA General Hospital · Updated on 2025-05-25
30
Participants Needed
3
Research Sites
157 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B Cell Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 70 years inclusive.
- Histologically confirmed refractory or relapsed B-cell non-Hodgkin lymphoma including DLBCL-NOS, PMBCL, TFL, HGBCL, FL, MCL, or MZL.
- Relapsed disease defined as progression after remission with latest standard treatment.
- Refractory disease defined as no complete remission to first-line therapy with specific criteria.
- Intolerance to standard treatment as judged by investigator.
- Prior therapy for MCL must include anthracycline or bendamustine chemotherapy, anti-CD20 antibody unless tumor is CD20-negative, and BTK inhibitor.
- Prior therapy for other types must include anti-CD20 antibody unless tumor is CD20-negative and anthracycline chemotherapy.
- Transformed follicular lymphoma must have relapsed or refractory disease after transformation.
- At least one measurable lesion per Lugano 2014 criteria.
- CD19 positive by immunohistochemistry.
- Stable and recovered toxicities from prior therapy to grade 1 or less (except hematologic and non-significant toxicities).
- ECOG performance status 0 to 2.
- Adequate blood counts: neutrophils ≥1 x 10^9/L, platelets ≥50 x 10^9/L, hemoglobin ≥80 g/L.
- Adequate organ function including renal, hepatic, pulmonary, cardiac, coagulation, and oxygen saturation >91% on room air.
- Willingness to practice birth control during and 6 months after chemotherapy; negative pregnancy test for women of childbearing potential.
- Voluntary participation with signed informed consent.
You will not qualify if you...
- Expected survival less than 3 months.
- History of other malignancies unless disease-free for at least 3 years.
- Autologous stem cell transplant within 3 months prior to CAR-T infusion.
- History of allogeneic stem cell transplantation.
- Immunocellular therapy within 3 months before enrollment.
- Recent chemotherapy within 2 weeks, monoclonal antibodies or related therapies within 3 weeks, or radiotherapy within 6 weeks prior to lymphodepletion (with exceptions).
- Presence of malignant cells in cerebrospinal fluid, brain metastases, or history of CNS lymphoma.
- Presence of donor-specific anti-HLA antibodies against the CAR-T product.
- History of severe allergy to lymphodepletion drugs or CAR-T components.
- Uncontrolled infections requiring IV antimicrobials.
- Active infections including HIV, hepatitis B or C, EBV, or CMV.
- History or presence of CNS disorders such as seizures, stroke, dementia, cerebellar disease, or autoimmune CNS disease.
- Cardiac lymphoma involvement.
- Significant cardiac disease within 12 months prior to enrollment.
- Urgent need for therapy due to oncologic emergencies.
- Primary immunodeficiency.
- Autoimmune disease causing organ injury or requiring immunosuppression within 2 years.
- Recent symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation.
- Any condition interfering with study safety or efficacy assessment.
- Severe allergy history to study agents.
- Vaccination within 6 weeks before conditioning regimen.
- Unlikely to comply with study visits or procedures as judged by investigator.
AI-Screening
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Trial Site Locations
Total: 3 locations
1
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China, 100853
Actively Recruiting
2
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, China
Actively Recruiting
3
School of Life Sciences, Peking University
Beijing, China
Actively Recruiting
Research Team
W
Weidong Han, Ph.D
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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