Anti-CD19 Donor-derived CAR-T Cells for Patients With Relapsed B Cell Malignancies After Hematopoietic Stem Cell Transplantation: a Multi-center, Uncontrolled Trial.
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- the safety of anti-CD19 allo CAR-T cells
研究概览
简要总结
The patients with relapsed B cell acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplant (HSCT) have a poor prognosis, especially for these relapsed in a short time after transplantation. Nowadays there is no effective way to salvage patients in such conditions. T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability, which makes it serve well for patients with relapsed B-ALL. So we launched a multi-center clinical trial to proved the safety and efficacy of anti-CD19 CAR-T cells for relapsed B cell ALL.
详细描述
The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, for B-ALL patients suffered from relapse after allo-HSCT (hematopoietic stem cell transplant), the T cells derived from healthy donor seems like a better origin for CAR-T cells producing because T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability. So after we designed a clinical trial to manifest the safety and efficacy of anti-CD19 CAR-T cells for patients with relapsed B cell ALL.
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
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of relapsed B-cell acute lymphoblastic leukemia (B-ALL).
- •Patients have received hematologic stem cell transplantation from matching sibling donor or unrelated donor.
- •CD19-positive tumor (>20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)）
- •Hgb ≥ 7.0 (can be transfused)
- •Life expectancy greater than 12 weeks
- •Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent.
排除标准
- •Other tumors except cured non-melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with complete remission of more than 5 years)；
- •Severe mental disorders；
- •A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
- •Subjects with II-IV grade acute graft versus host disease GVHD (Glucksberg Standrad) or chronic GVHD.
- •Heart disease with grade III-IV heart failure [NYHA classification], myocardial infarction, angioplasty or stenting, unstable angina or other heart diseases with prominent clinical symptoms within one year before admission；
- •Subjects with any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, bile drainage tube or pleura/peritoneum/pericardium catheter), should be excluded. (Special central venous catheter is allowed)；
- •Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
- •Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
- •Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
- •Active infection requiring systematic treatment within 2 weeks before single collection；
- •Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
- •History of autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic lupus erythematosus) that cause end-organ damage or require systemic immunosuppressive medications or systemic disease modifying drugs in the past 2 years；
- •Presence of pulmonary fibrosis；
- •Subjects who have received other clinical trial treatment within 4 weeks before participating in this trial should be excluded. Or the signing date of informed consent is within 5 half-lives of the last application of another clinical trial (whichever is longer)；
- •Subjects with poor compliance due to physiological, family, social, geographical and other factors, or those unable to cooperate with the study plan or follow-up；
- •At the discretion of the investigator, there are complications requiring systemic corticosteroid therapy (≥ 5mg / day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive drugs within 6 months after this clinical research treatment；
- •The lactating woman who is reluctant to stop breastfeeding；
- •Any other condition considered unsuitable by the investigator.
结局指标
主要结局
the safety of anti-CD19 allo CAR-T cells
时间窗: within 4 weeks after infusion
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
the efficacy of anti-CD19 allo CAR-T cells
时间窗: 4 weeks after infusion
ratio of bone marrow blast cells
次要结局
- The long-term efficiency(up to 2 years after infusion)
研究者
Xi Zhang, MD
Chef of Hematology Department
Xinqiao Hospital of Chongqing