β-thalassemia
Conditions
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.
Interventions
β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q
Sponsors
Shenzhen Hemogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 16 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall survival | 0-24 months | Number of patients alive through the whole trial will be record |
| 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 |
| Replication competent lentivirus (RCL) | 0-24 months | The percentage of RCL should be negative in the 24 months after transplant |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 |
Countries
China
Contacts
Primary ContactHaigang Sun
Outcome results
None listed