A Phase 1/2 Study Evaluating the Safety and Efficacy of the Combination of Anti-CD19 Chimeric Antigen Receptor-Modified T Cell (CAR-T) Therapy and Hematological Stem Cell Transplantation (HSCT) for MRD+ B-cell Malignancies
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Occurrence of study related adverse events
研究概览
简要总结
For micro residual disease (MRD) positive patients who have undergone at least 2 cycles chemotherapies for their CD19+ B-cell malignancies, there would be much more risks for them to receive hematological stem cell transplantation (HSCT) than MRD- patients. In order to reduce HSCT-related adverse events for these kind of patients, investigators plan to conduct CAR-T therapies on them first to make them achieve MRD- statuses, and then transfer them to HSCT.
详细描述
In order to improve prognoses for MRD+ patients who have undergone at least 2 cycles chemotherapies, patients will receive CAR-T therapy before HSCT, once they achieve MRD- remissions, they will subsequently receive HSCT if there are no contraindications.
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;
- •The patient is MRD+ (<10%) after at least two cycles of chemotherapies.
- •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 themselves, or legally authorized representative.
排除标准
- •With a history of allo-HSCT;
- •With a history of epilepsy or other central nervous system diseases;
- •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
Combination of CAR-T therapy and HSCT
After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.
干预措施: Second generation CAR-T cells (Genetic)
Combination of CAR-T therapy and HSCT
After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.
干预措施: Hematological stem cell transplantation (Procedure)
结局指标
主要结局
Occurrence of study related adverse events
时间窗: 200 days from enrollment
defined as \>= Grade 3（NCI CTCAE version 4.03） signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment
次要结局
- Number of participants with an MRD negative complete remission after CAR-T therapy and HSCT(2 years from enrollment)