Actively Recruiting
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL
Led by Chinese PLA General Hospital · Updated on 2026-05-08
30
Participants Needed
6
Research Sites
156 weeks
Total Duration
On this page
Sponsors
C
Chinese PLA General Hospital
Lead Sponsor
P
Peking University
Collaborating Sponsor
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 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 (purified CAR-positive T cells \> 90%). 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).
CONDITIONS
Official Title
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 16 and 70 years inclusive
- Diagnosed with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) as per NCCN 2019 guidelines
- For bone marrow involvement, at least 5% leukemic blasts confirmed morphologically
- Relapsed disease defined as relapse after initial complete remission or after allogeneic stem cell transplant
- Refractory disease defined as failure to achieve complete remission after standard chemotherapy
- Toxicities from prior therapy must be stable and recovered to Grade 1 or less (except hematological or minor toxicities)
- ECOG performance status of 2 or less
- Adequate kidney, liver, lung, and heart function as specified
- Both genders willing to use birth control from consent through 6 months post-chemotherapy
- Females of childbearing potential must have negative pregnancy test
- Able and willing to voluntarily participate and sign 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
- Received immunocellular or stem cell transplant therapy within 3 months prior to enrollment
- Active central nervous system leukemia (CNS-3)
- Significant active central nervous system dysfunction
- History of severe neurological toxicity from prior leukemia treatment
- Recent anti-leukemic therapy within 5 drug half-lives prior to CAR-T treatment
- Recent radioimmunotherapy or radiotherapy within 8 weeks (except CNS prophylaxis)
- Severe allergy to study agents
- Uncontrolled or intravenous antimicrobial-requiring infections
- Active infections such as HIV, active hepatitis B or C, EBV, or CMV
- CNS disorders such as seizures, stroke, dementia, cerebellar disease, or autoimmune diseases affecting CNS
- Cardiac lymphoma involvement
- Significant cardiac disease or events within 12 months
- Need for urgent therapy for oncologic emergencies within 6 weeks
- Primary immunodeficiency
- Autoimmune diseases causing organ damage or requiring systemic immunosuppression within 2 years
- Recent symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation within 6 months
- Any condition interfering with safety or efficacy assessments
- Vaccination within 6 weeks prior to conditioning regimen
- Presence of donor-specific antibodies against the allogeneic CAR-T cells
- Unlikely to complete study visits or comply with study requirements
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 6 locations
1
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China, 100853
Actively Recruiting
2
Department of Hematology, Chinese PLA General Hospital
Beijing, China
Actively Recruiting
3
Department of Hematology, Peking Union Medical College Hospital
Beijing, China
Not Yet Recruiting
4
Department of Hematology, Heping Hospital Affiliated to Changzhi Medical College
Changzhi, China
Actively Recruiting
5
Department of Hematology, Tianjin First Central Hospital
Tianjin, China
Actively Recruiting
6
Immune Cell Therapy Center, Blood Disease Hospital, Chinese Academy of Medical Sciences
Tianjin, 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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