Actively Recruiting
A Phase I/II Study Evaluating the Safety and Efficacy of BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia
Led by Chinese PLA General Hospital · Updated on 2025-06-25
30
Participants Needed
2
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new CAR T-cell therapy for adults with refractory or relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). This Phase 1/2 single-center, single-arm study focuses on the safety and effectiveness of CAR T cells with BCOR and ZC3H12 genes knocked out, called CAR19TIF cells, to improve treatment persistence and long-term response in patients who have limited options after prior therapies. The study aims to establish the best dose and assess treatment outcomes in this patient group. The study includes two phases. Phase 1 involves dose escalation or decline with 6 to 18 patients receiving CAR19TIF cells at varying doses starting from 5×10^5 cells/kg, using a staggered 28-day administration schedule to evaluate safety and efficacy. Phase 2 will enroll 10 to 12 patients treated at the recommended Phase 2 dose determined by Phase 1 results. Before CAR19TIF infusion, patients receive conditioning chemotherapy with fludarabine and cyclophosphamide. The study monitors dose-limiting toxicities and adjusts dosing to find the optimal balance of safety and effectiveness. Participants will undergo regular assessments including blood tests to measure CAR-positive T cells and CD19-positive cells over 12 to 24 months. The study tracks adverse events, response rates, survival, and progression-free survival up to two years after treatment. Patients are monitored closely for safety and treatment effects, with follow-up visits and evaluations scheduled throughout the study. The full duration of participation varies by individual treatment phase and follow-up timelines.
CONDITIONS
Brief Title
BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in r/r B-ALL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 70 years, any gender.
- Diagnosed with refractory or relapsed CD19-positive B-cell acute lymphoblastic leukemia as per guidelines.
- Morphologically confirmed with at least 5% leukemic blasts in bone marrow or quantifiable minimal residual disease after last induction treatment.
- Exhausted alternative treatment options.
- Relapsed disease defined as second or subsequent bone marrow relapse or relapse after allogenic stem cell transplant.
- Refractory disease defined as failure to achieve complete response after 2 chemotherapy cycles or chemorefractory after initial remission.
- Stable toxicities from prior therapy recovered to Grade 1 or less (except hematological or non-significant toxicities).
- ECOG performance status of 2 or less.
- Adequate kidney, liver, lung, and heart function within specified lab limits.
- Willing to practice birth control during study and negative pregnancy test for females of childbearing potential.
- Voluntary informed consent signed.
You will not qualify if you...
- Expected survival less than 3 months.
- Previous or concurrent cancer within 3 years except certain non-invasive cancers.
- Prior CD19 targeted therapy or CAR T-cell/genetically modified T-cell therapy.
- Active central nervous system leukemia or clinically suspected extra-medullary involvement.
- Burkitt cell or mixed lineage acute leukemia.
- Significant active central nervous system disorders or irreversible neurological toxicity.
- Recent radiotherapy or radioimmunotherapy within 8 weeks (except CNS prophylaxis).
- Use of anti-leukemic therapy within 5 half-lives prior to CAR19TIF administration.
- Severe hypersensitivity to lymphodepletion drugs or CAR19TIF components.
- Uncontrolled infections requiring intravenous antimicrobials.
- Active infectious diseases like HIV, hepatitis B or C, EBV, or CMV.
- Cardiac lymphoma involvement or significant cardiac disease within 12 months.
- Requirement for urgent therapy due to oncologic emergency.
- Primary immunodeficiency.
- Autoimmune disease causing organ injury or recent systemic immunosuppression.
- Recent symptomatic deep vein thrombosis or pulmonary embolism.
- Any condition interfering with study assessment.
- Vaccination within 6 weeks before conditioning.
- Unlikely to complete all study visits or comply with study requirements.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 3 days
Participants receive intravenous fludarabine and cyclophosphamide as a conditioning chemotherapy regimen before CAR19TIF cell infusion.
3 visits (in-person) on days -5, -4, and -3
Duration - Up to 12 months
Participants receive an infusion of CAR19TIF cells with dose escalation or decline in phase 1 and at recommended phase 2 dose in phase 2 to treat refractory/relapsed B-cell acute lymphoblastic leukemia.
1 infusion visit with staggered dosing by 28 days between subjects in phase 1 cohorts
Duration - Up to 24 months
Participants are monitored for safety, efficacy, and CAR T cell levels after treatment infusion.
Regular visits for assessments including safety and efficacy over 24 months
Trial Site Locations
Total: 2 locations
1
China
Beijing, Biotherapeutic Department of Chinese PLA General Hospital, China
Actively Recruiting
2
China
Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital, China
Not Yet Recruiting
Research Team
W
Weidong Han, Ph.D
Y
Yang Liu, M.D
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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