A Clinical Study on the Safety and Effectiveness of Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
A Clinical Study on the Safety and Effectiveness of donor derived CD19 CAR-T Cells in the treatment of R/R B-cell acute lymphoblastic leukemia
详细描述
In this study, 15 patients with relapsed refractory B-cell acute lymphoblastic leukemia were proposed to undergo CD19 CAR-T Cells therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19 CAR-T Cells therapy for relapsed refractory B-cell acute lymphoblastic leukemia; At the same time, on the basis of expanding the sample size, more safety data on CD19 CAR-T Cells treatment for relapsed refractory B-cell acute lymphoblastic leukemia were accumulated.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old, gender unlimited;
- •Abnormal B cell immunotyping was CD19 positive;
- •Patients diagnosed with B-cell acute lymphoblastic leukemia by histological or immunotyping;
- •Meets the diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and includes any of the following conditions:
- •No CR was obtained after standard chemotherapy;
- •CR was induced for the first time, but the duration of CR was less than 12 months;
- •R/R B-ALL that does not work after the first or more remedial treatments;
- •Two or more relapses;
- •The researchers believed that the patient had been adequately treated, such as auto-HSCT, auto-CART could not be prepared or preparation failed. Autologous CAR-T preparation failure was defined as including too few autologous lymphocytes (<1×109) or insufficient expansion during preparation or failure to meet the release criteria;
- •Total bilirubin ≤51 ( μmol/L), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal, creatinine ≤176.8 (μmol/L);
- •Absolute neutrophil count: ≥ 0.5×109/L; Platelet: ≥ 30×109/L; Hemoglobin ≧60g/L;
- •Echocardiography showed left ventricular ejection fraction (LVEF) ≥40%;
- •The estimated survival is more than 3 months;
- •ECOG score 0-2;
- •Women and men who are fertile must consent to the use of appropriate contraception before entering the study, during study participation, and for 6 months after transfusion (the safety of this therapy for the unborn child is not known, with unknown risks);
- •Subjects who are willing to participate in the study are able to understand and have the ability to sign informed consent.
排除标准
- •Known allergies to research preconditioning measures, etc;
- •People with a history of epilepsy or other central nervous system disorders;
- •People with a history of prolonged QT or severe heart disease;
- •Less than 100 days after receiving allogeneic hematopoietic stem cell transplantation;
- •Hiv-infected person;
- •Persons with active hepatitis B or C virus; Those who are not cured have active infections;
- •Insufficient amplification ability (< 5x) in response to CD3 / CD28 costimulatory signals;
- •Combined use of systemic steroids (e.g., prednisone ≥20mg) within 3 days prior to screening, except for ongoing or intermittent use of topical, inhaled or intranasal steroids within 2 weeks or at present; Or have systemic diseases that require long-term use of immunological agents;
- •Patients who received anti-cancer chemotherapy or other drugs within 2 weeks prior to screening;
- •Any situation that the investigator believes may increase the risk of the subjects or interfere with the study results.
研究组 & 干预措施
Administration of CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells
Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.
干预措施: CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells injection (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Up to 28 days after Treatment
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years after Treatment
Incidence of treatment-emergent adverse events \[Safety and Tolerability\]
次要结局
- Duration of remission ,DOR(Up to 1 years after CAR-T infusion)
- Overall survival, OS(Up to 2 years after Treatment)
- Event-free survival (EFS)(Up to 1 years after CAR-T infusion)
研究者
He Huang
Clinical Professor
Zhejiang University