A Study of CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- safety as assessed by the occurence of study related adverse events
研究概览
简要总结
The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia.
详细描述
Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19 CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in vitro and then administered to subjects.
Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19 CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination, blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T.
Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening.
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
- 2 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •2 years to 70 years, expected survival > 3 months;
- •CD19 positive B-cell acute lymphoblastic leukemia;
- •The tumor load in the bone marrow is less than 60%;
- •Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; Peripheral Blood: WBC ≥ 2.0×109/L, Hb ≥80 g/L, PLT ≥ 30×109/L）;
- •No leukemia cells in the central nervous system;
- •No serious allergic constitution;
- •No other serous diseases that conflicts with the clinical program;
- •No other cancer history;
- •No serious mental disorder;
- •female participants of reproductive potential must have a negative serum pregnancy test;
- •Informed consent is signed by a subject or his lineal relation.
排除标准
- •Pregnant or lactating women;
- •Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
- •Active hepatitis B or hepatitis C infection;
- •Recent or current use of glucocorticoid or other immunosuppressor;
- •With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
- •Participate in other clinical research in the past three months; previously treatment with any gene therapy products;
研究组 & 干预措施
CD19 CAR-T
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
干预措施: Cyclophosphamide (Drug)
CD19 CAR-T
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
干预措施: Fludarabine (Drug)
CD19 CAR-T
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
干预措施: CD19 CAR-T (Biological)
结局指标
主要结局
safety as assessed by the occurence of study related adverse events
时间窗: 30 days
number of participants with adverse events
anti-tumor responses of CD19 CAR-T cells
时间窗: 1 year
次要结局
- Persistence of the CD19 CAR+ T cells(1 year)
- Number of participants who have T cells ablated with cetuximab(1 year)