Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of patients with adverse event
研究概览
简要总结
In the conventional treatment options, B cell leukemia could be treated with chemotherapy drugs or HSCT. But chemotherapy could barely cured leukemia. And HSCT is often limited by lacking of HLA-matched donors, even if those patients who received HSCT still could be relapsed. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with relapsed or refractory B cell leukemia, including relapsed cases after HSCT. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells. At the same time, evaluating the possible and clinical responses of using donor-derived T cells engineered CAR-T cells.
Detailed Description: This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator. And optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. The source of T cells for CAR-T is from two aspects, one is autologous, the other is donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depend on the situation of individual CAR-T cells preparation.
详细描述
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The source of T cells used to prepare CAR-T could be either autologous, or donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with CD19+ B-cell leukemia as comfirmed by Flow Cytometry
- •Age: 1-70 years old
- •Expected survival > 12 weeks
- •Creatinine < 2.5 mg/dl
- •ALT/AST < 3x normal
- •Bilirubin <2.0 mg/dl
- •Sucessful test expansion of T-cells
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis
- •Voluntary informed consent is given
排除标准
- •Pregnant or lactating women
- •Uncontrolled active infection
- •Active hepatitis B or hepatitis C infection
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- •Previously treatment with any gene therapy products
- •Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
- •Active central nervous system leukemia
- •Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade Ш or Ⅳ cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases)
研究组 & 干预措施
anti-CD19-CAR-T cells
patients receive chemotherapy(CF, cyclophosphamide and Fludarabine) on day -6 to day -1, then infusied with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity.
干预措施: anti-CD19-CAR-T cells (Drug)
结局指标
主要结局
Number of patients with adverse event
时间窗: 6 weeks
asverse event is evaluated with CTCAE, version 4.0
次要结局
- Number of patients with tumor response(8 weeks)
- Detection of transferred T cells in the circulation using quantitative -PCR(6 weeks)