Exploratory Clinical Study of GoFast CAR T-Cell Platform Targeting CD19 CAR T-Cell Therapy for Recurrent Refractory B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
This is an investigator-initiated, prospective, open-label exploratory clinical study designed to evaluate the safety and preliminary efficacy of GoFast CD19 CAR T-cell therapy in adult patients with recurrent or refractory B-cell lymphoma. Eligible patients will undergo screening, baseline assessment, peripheral blood or leukapheresis collection, lymphodepleting chemotherapy, and intravenous infusion of GoFast CD19 CAR T cells. The study plans to enroll 9 participants using a sequential dose-escalation design. The primary outcome is objective response rate, and secondary outcomes include complete remission rate, overall survival, progression-related survival outcomes, duration of response, MRD negativity, and adverse events.
详细描述
This study will enroll adult patients with recurrent or refractory B-cell lymphoma who are CD19-positive and meet the protocol-defined eligibility criteria. After signing informed consent, participants will undergo screening assessments, including medical history, physical examination, performance status assessment, laboratory tests, infection screening, imaging evaluation, and assessment of feasibility for CAR T-cell preparation.
Eligible participants will undergo peripheral blood or leukapheresis collection for preparation of autologous GoFast CD19 CAR T cells. Before CAR T-cell infusion, participants will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 from Day -5 to Day -3. After completion of lymphodepletion, GoFast CD19 CAR T cells will be administered by intravenous infusion according to the assigned dose cohort.
The study uses a dose-escalation design with three planned dose cohorts: 0.3 × 10^6 cells/kg, 0.6 × 10^6 cells/kg, and 1.2 × 10^6 cells/kg. Each participant will receive a fixed dose according to the assigned cohort. Dose escalation will proceed only after review of safety data from the previous cohort and confirmation that no dose-limiting toxicity or other unacceptable safety signal has occurred.
Participants will be closely monitored after CAR T-cell infusion for adverse events, including cytokine release syndrome, neurotoxicity, tumor lysis syndrome, cytopenia, infection, organ dysfunction, and laboratory abnormalities. CAR T-cell expansion, lymphocyte subsets, cytokines, blood routine tests, biochemical tests, coagulation function, and organ function will be evaluated at protocol-defined time points.
Tumor response will be assessed using imaging and clinical evaluation at predefined follow-up visits, including Day 28 and Week 12 after CAR T-cell infusion. Participants with complete or partial response will continue follow-up for up to 1 year after enrollment. The primary endpoint is objective response rate. Secondary endpoints include complete remission rate, overall survival, time to progression, disease-free survival, duration of response, event-free survival, MRD negativity rate, and the incidence and severity of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •Histologically or cytologically confirmed primary refractory or relapsed/progressive large B-cell lymphoma.
- •Expected survival of more than 3 months.
- •CD19-positive B-cell lymphoma confirmed by flow cytometry or immunohistochemistry.
- •ECOG performance status of 0 to 2 or KPS score greater than
- •Adequate venous access for leukapheresis or peripheral blood collection, with no contraindication to blood cell separation.
- •White blood cell count ≥ 1 × 10^9/L and lymphocyte count ≥ 0.3 × 10^9/L.
- •INR < 1.7 or prothrombin time prolonged by less than 4 seconds above the normal value.
- •ALT and AST ≤ 2.5 × upper limit of normal.
- •Total bilirubin ≤ 2.0 mg/dL, equivalent to 34.2 μmol/L.
- •Able to understand and voluntarily sign the written informed consent form.
排除标准
- •Pregnant or breastfeeding women.
- •Active hepatitis B virus or hepatitis C virus infection.
- •HIV/AIDS infection.
- •Any uncontrolled active infection.
- •Systemic corticosteroid use within 2 weeks before signing informed consent, except inhaled corticosteroids.
- •Active cardiac disease requiring treatment or poorly controlled hypertension.
- •Unstable or active ulcer disease or gastrointestinal bleeding.
- •History of organ transplantation or currently awaiting organ transplantation.
- •Central nervous system involvement by lymphoma.
- •Current participation in another clinical trial.
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for this clinical study.
结局指标
主要结局
Objective Response Rate
时间窗: Up to 12 weeks after CAR T-cell infusion
Objective response rate is defined as the proportion of participants who achieve complete response or partial response according to the 2014 Lugano lymphoma response criteria after GoFast CD19 CAR T-cell infusion.
次要结局
- Complete Remission Rate(Up to 12 weeks after CAR T-cell infusion)
- Overall Survival(Up to 52 weeks after enrollment)
- Time to Progression(Up to 52 weeks after enrollment)
- Disease-Free Survival(Up to 52 weeks after enrollment)
- Duration of Response(Up to 52 weeks after enrollment)
- Event-Free Survival(Up to 52 weeks after enrollment)
- MRD Negativity Rate(Up to 12 weeks after CAR T-cell infusion)
- Incidence and Severity of Adverse Events Assessed by CTCAE v4.03(From informed consent to 52 weeks after enrollment)
- Incidence and Severity of Cytokine Release Syndrome Assessed by ASTCT Consensus Criteria(Up to 28 days after CAR T-cell infusion)
- Incidence and Severity of Immune Effector Cell-Associated Neurotoxicity Syndrome Assessed by ASTCT Criteria(Up to 28 days after CAR T-cell infusion)
研究者
Chunji Gao
Principal Investigator
Chinese PLA General Hospital