Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Proportion of engraftment
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 8 Years to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: β-globin restored autologous hematopoietic stem cells (Biological)
Outcomes
Primary Outcomes
Proportion of engraftment
Time Frame: 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)
Time Frame: 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
Time Frame: 0-24 months
Number of patients alive through the whole trial will be record
Replication competent lentivirus (RCL)
Time Frame: 0-24 months
The percentage of RCL should be negative in the 24 months after transplant
Dynamics of viral integration sites (VIS)
Time Frame: 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 Outcomes
- 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)