TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL
NCT ID: NCT06481735
Last Updated: 2025-11-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
30 participants
INTERVENTIONAL
2025-02-15
2028-02-15
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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).
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B Cell Lymphoma
NCT06323525
Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR
NCT03676504
Anti-CD19 CAR T Infusion Combined With Allogeneic Stem Cell Transplantation for B-cell Leukemia/Lymphoma
NCT03110640
Sequential CAR-T Cells Therapy for CD5/CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD5/CD7-Specific CAR-T Cells
NCT06420076
Adult B-ALL Treated by CART Cell Bridging Allogeneic Hematopoietic Stem Cell Transplantation
NCT04626726
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In phase 1, 6-18 subjects will be enrolled. Subjects will receive 3 doses of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T cell therapy ( 1 × 10\^6 cells/kg、3 × 10\^6 cells/kg、6 × 10\^6 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:
Three (3) subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity (DLT), 3 additional subjects will be enrolled at the current dose level. For safety purposes, the administration of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T will be staggered by 28 days before enter into the next cohort.
Phase 2 (expansion cohort)
In phase 2, 10 to 12 subjects will be enrolled and receive cell infusion at dose of recommended phase 2 dose (RP2D), which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives
The primary objectives of the phase 1 were to evaluate the tolerability and safety of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T in patients with refractory/relapsed (r/r) B-ALL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of allogeneic Power3 (SPPL3) knock-out CD19 CAR-T in the above population.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Patients with refractory or relapsed B-ALL
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T.
TCR reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T cell
Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6 × 10\^6 cells/kg); Phase 2 : dose of RP2D.
Fludarabine
Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.
Cyclophosphamide
Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
TCR reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T cell
Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6 × 10\^6 cells/kg); Phase 2 : dose of RP2D.
Fludarabine
Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.
Cyclophosphamide
Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patient with r/r CD19+ B-ALL, as per guidelines (NCCN, 2019)
* For patients with bone marrow involvement, morphologically confirmed with ≥ 5% leukaemic blasts in the bonemarrow.
* Definition of relapsed disease: Bone marrow or extramedullary relapse after achieving CR with initial treatment, or any bone marrow or extramedullary relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
* Refractory disease is defined by not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory.
3. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. 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 3) 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.
6. Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
7. Voluntarily participate in this clinical trial and sign an informed consent form.
Exclusion Criteria
2. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
3. Patients who received any immunocellular or HSCT therapy within 3 months before enrollment.
4. Active central nervous system (CNS) leukaemia (CNS-3).
5. Clinically active significant CNS dysfunction.
6. Known history of irreversible severe neurological toxicity related to previous antileukaemic treatment leading to organic central nervous system lesions.
7. Use of previous anti-leukemic therapy within 5 half-lives prior to allogeneic Power3 (SPPL3) knock-out CD19 CAR-T administration; participation in non-interventional registries or epidemiological studies is allowed.
8. Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion.
9. History of severe immediate hypersensitivity reaction to any of the agents or any component used in this study.
10. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
11. Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection.
12. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
15. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome).
16. Primary immunodeficiency.
17. History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
18. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment.
19. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
20. Vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
21. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
16 Years
70 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Peking University
OTHER
Chinese PLA General Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Han weidong
Director of Biotherapeutic Department
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
Department of Hematology, Chinese PLA General Hospital
Beijing, , China
Department of Hematology, Peking Union Medical College Hospital
Beijing, , China
Department of Hematology, Tianjin First Central Hospital
Tianjin, , China
Immune Cell Therapy Center, Blood Disease Hospital, Chinese Academy of Medical Sciences
Tianjin, , China
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Yu Jing
Role: primary
Ying Wang
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CHN-PLAGH-BT-087
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.