Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients

Conditions
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β-thalassemia

Intervention / Treatment
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* Biological: β-globin restored autologous hematopoietic stem cells


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Ten transfusion-dependent β-thalassaemia subjects aged 8-16 years will be reinfused with β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q. | Biological: β-globin restored autologous hematopoietic stem cells<br>* β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) | The number and the percentage of adverse events related to transplantation in 100 days will be summarized according to NCI CTCAE 5.0 | 0-100 days | 
| Overall survival | Number of patients alive through the whole trial will be record | 0-24 months | 
| Proportion of engraftment | Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days | 0-24 months | 
| Replication competent lentivirus (RCL) | The percentage of RCL should be negative in the 24 months after transplant | 0-24 months | 
| Dynamics of viral integration sites (VIS) | Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment . More than 1000 VIS retrieved from peripheral blood should be checked. | 0-24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The average Insertion copy number (VCN) in peripheral blood mononuclear cells | The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells | 18-24 Months | 
| The expression level of exogenous adult hemoglobin | 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 | 18-24 Months | 
| Change from baseline in annualized frequency of packed RBC transfusions | 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 | 18-24 Months |