Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Adverse events that Are related to treatment
研究概览
简要总结
CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19-negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.
详细描述
B-cell acute lymphoblastic leukemia is the most common type of leukemia and the prognosis of relapsed/refractory B-ALL is poor. Chimeric Antigen Receptor-transduced T cell (CAR-T) therapy is one of revolutionary targeted immunotherapy. CD19 CAR-T is the most commonly used engineered T cell in B-ALL. The treatment effect is significant and far more than traditional therapy in relapsed/refractory B-ALL. However, the remission time after CD19 CAR-T infusion is short.CD19-positive and CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients The cause of relapse after CAR-T infusion is minimal residual disease (MRD) which will induce CD19 negative relapse. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19 negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed/Refractory B-ALL patients
- •Did not achieve complete remission after 2 times of standard plan chemotherapy
- •Relapsed after first induction chemotherapy
- •Did not response to chemotherapy before HSCT or relapsed after HSCT
- •Cannot receive allo-HSCT or refuse to receive allo-HSCT
- •Cell phenotype is CD19 and CD20/CD22/CD10/CD70 positive (single or combined)
- •Estimated survival time is more than 3 months in leukemia
- •Volunteered for this clinical trail and signed a consent form
排除标准
- •MRD was negative while the cell phenotype was CD19 expressed
- •Patients with severe insufficient cardiac, pulmonary and hepatorenal functions
- •Patients with severe mental illness, neurological disease or infectious disease
- •Patients with GVHD was taking immunosuppressants
- •Pregnant or lactating women
- •Patients have received other genetic therapy products
- •Transfection efficiency was less than 30%
- •Any situation may do harm to the subjects or interfere the results
研究组 & 干预措施
Sequential therapy with different CART
Sequential therapy With different CART including one kind of CD20/CD22/CD10-CART After CD19-CART therapy in CD19-negative relapse ALL patients, subjects will receive 1-5 x 10^6/Kg transduced CAR T cells at one time.
干预措施: Sequential Treatment With different CART (Biological)
结局指标
主要结局
Adverse events that Are related to treatment
时间窗: 2 years
Determine the toxicity profile of the CD19-targeted and CD20/CD22/CD10-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- Estimate relapse rate after infusion of CD19-CART and sequential treatment(4 years)
- Estimate 2 year progression free survival after infusion of CD19-CART and sequential treatment(2 years)
- Estimate 2 year overall survival(OS) after infusion of CD19-CART and sequential treatment(2 years)