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

ß-Thalassemia Major Clinical Trial

Official title:

A Single Center, Open Label Study to Evaluate the Safety and Efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-Thalassemia Major Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04592458
• Other study ID #: A-SOP-CT-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: November 1, 2020
• Est. completion date: November 30, 2024

Study information

• Verified date: September 2020
• Source: BGI-research
• Contact: Jing Li, PhD
• Phone: 13510560664
• Email: lijing4[@]genomics.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Subjects with ß-Thalassemia major will be recruited and their autologous hematopoietic stem cells will be collected and modified with LentiHBBT87Q system to restore the β-globin expression. After conditioning, the β-globin restored autologous hematopoietic stem cells will be infused back to patients, and a 2 years follow up visit will be conducted and the data will be collected. Participants in this study will be also asked to participant in a subsequent follow up study that will monitor the long-term safety and efficacy of the treatment for up to 13 years post-transplantation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 16 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• beta-Thalassemia
• ß-Thalassemia Major
• Thalassemia

Intervention

Biological:
• ß-globin restored autologous HSC
ß-globin restored autologous HSC modified with lentiviral vector LentiHBBT87Q

Locations

Country	Name	City	State
China	Beijing Genomics Institute At Shenzhen	Shenzhen	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
BGI-research	Shenzhen Children's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Overall survival	Number of patients alive through the whole trial will be record.	0-24 months
Primary	Proportion of engraftments	Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days.	0-24 months
Primary	Replication competent lentivirus (RCL)	The percentage of RCL should be negative in the 24 months after transplant.	0-24 months
Primary	Dynamics of viral integration sites (VIS)	Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment at 6, 12, 18 and 24 months after transplant. More than 1000 VIS retrieved from peripheral blood should be checked.	0-24 months
Secondary	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
Secondary	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
Secondary	Change from baseline in annualized frequency and volume of packed RBC transfusions	Compare the annualized number of pRBC transfusions before gene therapy with the Month 6 and Month 24 period after transplant, the percentage change will be recorded.	18-24 Months