Treatment of Relapsed or Refractory B-cell Malignancies by CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This is a single arm, open-label, phase 1/2 study to evaluate the safety and efficacy of anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
详细描述
Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CAR-T therapy showed great effect on patients with relapsed or refractory B cell malignancies. CAR consists of single chain variable fragment (scFv) and activation domain of T cell. In preclinical study, the researchers constructed a second generation CAR containing CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.
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
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;
- •B cell hematological malignancies include the following three categories:
- •B-cell acute lymphocytic leukemia (B-ALL);
- •Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
- •Aggressive B-cell lymphoma (DLBCL, BL, MCL);
- •< 70 years old;
- •Expected survival time > 6 months;
- •Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
- •Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.
排除标准
- •With a history of epilepsy or other central nervous system diseases;
- •Having graft-versus-host reaction, requires the use of immunosuppressants;
- •The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);
- •Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
- •Not curable active infection;
- •Patients with active hepatitis B or hepatitis C virus infection;
- •Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
- •Using product of gene therapy before;
- •Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);
- •Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
- •Patients with HIV-infection;
- •Any situation that may increase the risk of patients or interfere with test results.
研究组 & 干预措施
Second generation CAR-T cells
Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2 in the absence of disease progression or unacceptable toxicity.
干预措施: Second generation CAR-T cells (Genetic)
结局指标
主要结局
Number of participants with adverse events
时间窗: 5 years
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)
次要结局
- Overall survival(5 years)
- Relapse-free survival(5 years)
- Rate and quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells(5 years)
- Event-free survival(5 years)
- One-month remission rate(1 month)