A Phase I Clinical Study of Dual Specificity CD19 and CD22 Chimeric Antigen Receptor T Cell Therapy in Relapsed or Refractory Acute B Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Occurrence of treatment related adverse events
研究概览
简要总结
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of dual specificity CD19 and CD22 CAR-T cells in patients with relapsed and refractory acute B lymphoblastic leukemia.
详细描述
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory acute B lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual specificity CAR enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.
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
- 14 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent could be acquired;
- •Diagnosed with relapse/refractory acute lymphoblastic leukemia;
- •Relapse was defined as recurrence of blast cell(more than 5%) in peripheral blood or in bone marrow or extramedullary involvement;
- •Refractory was defined as failed to achieve complete remission after two courses of induction therapy;
- •CD19/CD22 postive leukemia cell was confirmed by flow cytometry or immunohistochemistry within 90 days since enrollment in this trial;
- •Karnofsky score ≥70;
- •Results of pregnant test should be negative, and agree to conception control during treatment and 6 months after CAR-T infusion.
- •Adequate organ function: EF≥50%; normal ECG; CCR ≥ 50ml/min or Cr < 2.0mg/dL or < 2 times upper limitation of normal; ALT and AST<5 times upper limitation of normal; Serum bilirubin ≤ 3.0mg/dL; DLCO or FEV1 > 45% of predict value;
- •At least 2 weeks intervals since the last chemotherapy;
- •At least 2 weeks intervals since the last anti-GVHD therapy if patients have ever ;
排除标准
- •Patients diagnosed with acute promyelocytic leukemia:t(15;17)(q22;q12);
- •Women in pregnancy and lactation;
- •Uncontrolled infection, Active HBV or HCV infection, HIV positive or any other deadly bacterial/virual diseases;
- •Long term use of systemic corticosteroids(5mg per day for 2 weeks);
- •Any other uncontrolled life-threaten diseases;
- •Patients with history of anaphylaxis to any drugs;
- •With central nervous system (CNS) involvement;
- •Patients with GVHD after allo-HSCT who needed immunosuppressive agents ;
- •Patients with acute autoimmune diseases such as psoriasis or rheumatoid arthritis;
- •Other conditions that principle investigator considered may increase the risk of the patients or interference the results.
研究组 & 干预措施
BLLCAR-L10D treatment group
In BLLCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10^6, 1.5×10^6, 2.0×10^6 CAR-T cells/kg.
干预措施: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy (Drug)
结局指标
主要结局
Occurrence of treatment related adverse events
时间窗: Day 1-100 days after injection
Assessed by CTCAE v4.0
次要结局
- Objective response rate(Day 1-5 years after injection)
- Overall survival(Day 1-5 years after injection)
- Progression free survival(Day 1-5 years after injection)