Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
- Conditions
- β-thalassemia
- Interventions
- Biological: β-globin restored autologous hematopoietic stem cells
- Registration Number
- NCT05745532
- Lead Sponsor
- Shenzhen Hemogen
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental β-globin restored autologous hematopoietic stem cells Ten transfusion-dependent β-thalassaemia subjects aged 8-16 years will be reinfused with β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q.
- Primary Outcome Measures
Name Time Method Proportion of engraftment 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) 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 0-24 months Number of patients alive through the whole trial will be record
Replication competent lentivirus (RCL) 0-24 months The percentage of RCL should be negative in the 24 months after transplant
Dynamics of viral integration sites (VIS) 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.
- Secondary Outcome Measures
Name Time Method The average Insertion copy number (VCN) in peripheral blood mononuclear cells 18-24 Months The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells
Change from baseline in annualized frequency of packed RBC transfusions 18-24 Months Compare the annualized number of pRBC transfusions before gene therapy with the Month 18 and Month 24 period after transplant, the percentage change will be recorded
The expression level of exogenous adult hemoglobin 18-24 Months Exogenous adult hemoglobin will be evaluated by globin chains and hemoglobin synthesis on peripheral blood by HPLC and the exogenous adult hemoglobin level is ≥2.0g/dL
Trial Locations
- Locations (1)
Shenzhen Children's Hospital
🇨🇳Shenzhen, Guangdong, China