Actively Recruiting
BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed B-cell Lymphoma
Led by Chinese PLA General Hospital · Updated on 2025-06-25
30
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of a new CAR-T cell therapy called CAR19TIF cells in adults with refractory or relapsed B-cell lymphoma. This Phase 1/2, single-center study focuses on CAR-T cells modified by knocking out BCOR and ZC3H12 genes, aiming to create more functional and long-lasting immune cells. The trial addresses different types of B-cell Non-Hodgkin's lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, among others. The study has two phases. In Phase 1, between 6 and 18 patients will receive varying doses of CAR19TIF cells following chemotherapy with fludarabine and cyclophosphamide to prepare the body. Dose levels start at 5x10^5 cells/kg, with possible adjustments up or down based on safety and effectiveness, using a staggered schedule with 28 days between infusions for safety. Phase 2 will enroll 10 to 12 patients, treated at the recommended Phase 2 dose established from Phase 1 results. Participants will undergo multiple assessments including monitoring for adverse events, response to treatment, and survival over periods up to 24 months. Blood tests will track levels of CAR-T cells and related markers, while scans will assess tumor response. Safety monitoring includes checking for dose-limiting toxicities within 28 days of infusion. The study aims to gather detailed data on tolerability, pharmacokinetics, clinical responses, and long-term outcomes, with follow-up lasting up to two years after treatment.
CONDITIONS
Brief Title
BCOR and ZC3H12 Genes Knock-out 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 old, inclusive
- Histologically confirmed refractory or relapsed B-cell Non-Hodgkin's lymphomas including DLBCL NOS, PMBCL, TFL, HGBCL, FL, MCL, or MZL
- Relapsed disease defined as disease progression after remission; refractory disease defined by specific response criteria to first-line therapy
- Intolerance to standard treatment may be included based on investigator judgment
- Prior therapy requirements: for MCL, anthracycline or bendamustine, anti-CD20 antibody, and BTKi; for others, anti-CD20 antibody and anthracycline chemotherapy
- At least one measurable lesion meeting size criteria
- CD19 positive status confirmed by immunohistochemistry
- Stable and recovered toxicities from prior therapy to Grade 1 or less, except certain blood toxicities
- ECOG performance status of 2 or less
- Adequate blood counts: ANC ≥ 1 x 10^9/L, platelets ≥ 50 x 10^9/L, hemoglobin ≥ 80 g/L (except if bone marrow involvement)
- Adequate kidney, liver, lung, and heart function per specified laboratory and clinical measures
- Oxygen saturation above 91% on room air
- Willingness to practice birth control during and 6 months after chemotherapy; negative pregnancy test for females of childbearing potential
- Voluntary informed consent given
You will not qualify if you...
- Expected survival less than 3 months
- History of other malignancies unless disease-free for at least 3 years or specific exceptions
- History of allogeneic stem cell or organ transplantation
- Prior CD19 targeted therapy or CAR-T/genetically modified T-cell therapy
- Recent use of chemotherapy, targeted drugs, monoclonal antibodies, ADCs, bispecific antibodies, or radiotherapy within specified timeframes before lymphodepletion
- Presence of malignant cells in cerebrospinal fluid, brain metastases, or CNS lymphoma
- Severe hypersensitivity to study drugs or CAR19TIF components
- Uncontrolled or IV-antimicrobial requiring infections
- Active infectious diseases including HIV, hepatitis B or C, EBV, CMV
- History or presence of CNS disorders or autoimmune diseases affecting the CNS
- Cardiac lymphoma involvement or significant heart disease within 12 months
- Oncologic emergencies requiring urgent therapy within 6 weeks
- Primary immunodeficiency or recent systemic immunosuppression for autoimmune diseases
- Recent symptomatic deep vein thrombosis or pulmonary embolism
- Any condition interfering with safety or efficacy assessment
- Recent vaccination within 6 weeks prior to conditioning chemotherapy
- Unlikely to comply with study visits or procedures per investigator judgment
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.
Duration - 3 days
Participants receive conditioning chemotherapy with fludarabine and cyclophosphamide before cell infusion.
3 consecutive days of intravenous chemotherapy
Duration - Dose escalation phase: staggered infusions by 28 days; Phase 2: duration depends on treatment protocol
Participants receive CAR19TIF cell infusion with dose escalation or at the recommended phase 2 dose (RP2D) to treat refractory/relapsed B-cell lymphoma.
Infusion visits staggered by 28 days between subjects in dose escalation cohorts
Duration - Up to 24 months
Participants are monitored for safety, efficacy, and pharmacokinetics/pharmacodynamics after CAR19TIF cell infusion.
Visits for assessments up to 24 months following treatment
Trial Site Locations
Total: 1 location
1
Biotherapeutic Department of Chinsese PLA Gereral Hospital
Beijing, Beijing Municipality, China
Actively 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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