Back to resultsSafety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
Primary Purpose
β-thalassemia
Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
β-globin restored autologous hematopoietic stem cells
Sponsored by
About this trial
This is an interventional treatment trial for β-thalassemia
Eligibility Criteria
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.
Sites / Locations
- Shenzhen Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental
Arm Description
Ten transfusion-dependent β-thalassaemia subjects aged 8-16 years will be reinfused with β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q.
Outcomes
Primary Outcome Measures
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
Overall survival
Number of patients alive through the whole trial will be record
Proportion of engraftment
Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days
Replication competent lentivirus (RCL)
The percentage of RCL should be negative in the 24 months after transplant
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.
Secondary Outcome Measures
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05745532
Brief Title
Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
Official Title
Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2020 (Actual)
Primary Completion Date
May 30, 2023 (Anticipated)
Study Completion Date
May 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shenzhen Hemogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
β-thalassemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
β-globin restored autologous hematopoietic stem cells
Intervention Description
β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q
Primary Outcome Measure Information:
Title
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
Description
The number and the percentage of adverse events related to transplantation in 100 days will be summarized according to NCI CTCAE 5.0
Time Frame
0-100 days
Title
Overall survival
Description
Number of patients alive through the whole trial will be record
Time Frame
0-24 months
Title
Proportion of engraftment
Description
Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days
Time Frame
0-24 months
Title
Replication competent lentivirus (RCL)
Description
The percentage of RCL should be negative in the 24 months after transplant
Time Frame
0-24 months
Title
Dynamics of viral integration sites (VIS)
Description
Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment . More than 1000 VIS retrieved from peripheral blood should be checked.
Time Frame
0-24 months
Secondary Outcome Measure Information:
Title
The average Insertion copy number (VCN) in peripheral blood mononuclear cells
Description
The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells
Time Frame
18-24 Months
Title
The expression level of exogenous adult hemoglobin
Description
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
Time Frame
18-24 Months
Title
Change from baseline in annualized frequency of packed RBC transfusions
Description
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
Time Frame
18-24 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haigang Sun
Phone
13823168465
Email
sunhaigang@genomics.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chao Liu, PHD
Organizational Affiliation
Shenzhen Hemogen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sixi Liu, Professor
Organizational Affiliation
Shenzhen Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shenzhen Children's Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518083
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haigang Sun
Phone
13823168465
Email
sunhaigang@genomics.cn
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Evaluation of β-globin Restored Autologous Hematopoietic Stem Cells in β-thalassemia Major Patients
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