Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Proportion of engraftment
研究概览
简要总结
This is an open label study to evaluate the safety and efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-Thalassemia Major Patients
详细描述
We will recruit ß-thalassaemia major patients and collect their autologous hematopoietic stem cells, which will be modified with the LentiHBBT87Q system to restore β-globin expression. After conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.
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
- 8 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •8-16 years old. Subject and/or subject's legal guardian fully understand and voluntarily sign informed consent;
- •Clinically diagnosed as transfusion-dependent β-thalassemia major;
- •With sufficient RBC infusion, subjects must maintain hemoglobin ≥9g/dL, serum ferritin threshold ≤ 3000 ng/mL and the liver iron overload mild or absent for at least 3 months before mobilization of hematopoietic stem cell;
- •Follow the arrangements for treatment and regular medical checks within two years post-transplantation
排除标准
- •The physical condition does not meet the requirements for hematopoietic stem cell mobilization and transplantation myeloablation;
- •Received gene therapy and allogeneic HSCT in the past.
- •Have an available HLA matched donor.
- •Enrolling in another clinical trial.
- •Other unsuitable conditions identified by doctors.
研究组 & 干预措施
Experimental
Ten transfusion-dependent β-thalassaemia subjects aged 8-16 years will be reinfused with β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q.
干预措施: β-globin restored autologous hematopoietic stem cells (Biological)
结局指标
主要结局
Proportion of engraftment
时间窗: 0-24 months
Neutrophil count \[ANC\] \>=500 /mm3 for 3 consecutive days and platelet count \[PLT\] \>20,000/mm3 for7 consecutive days
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 0-100 days
The number and the percentage of adverse events related to transplantation in 100 days will be summarized according to NCI CTCAE 5.0
Overall survival
时间窗: 0-24 months
Number of patients alive through the whole trial will be record
Replication competent lentivirus (RCL)
时间窗: 0-24 months
The percentage of RCL should be negative in the 24 months after transplant
Dynamics of viral integration sites (VIS)
时间窗: 0-24 months
Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment . More than 1000 VIS retrieved from peripheral blood should be checked.
次要结局
- Change from baseline in annualized frequency of packed RBC transfusions(18-24 Months)
- The expression level of exogenous adult hemoglobin(18-24 Months)
- The average Insertion copy number (VCN) in peripheral blood mononuclear cells(18-24 Months)