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

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ClinicalTrials.gov Identifier: NCT04592458
Recruitment Status : Not yet recruiting
First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Shenzhen Children's Hospital
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
β-Thalassemia Major Biological: β-globin restored autologous HSC Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arm Intervention/treatment
Experimental: Experimental
10 transfusion dependent β-thalassemia major subjects who are 8-16 years older will be transplanted with β-globin restored autologous hematopoietic stem cells that are modified with lentiviral vector LentiHBBT87Q encoding the human β-globin gene.
Biological: β-globin restored autologous HSC
β-globin restored autologous HSC modified with lentiviral vector LentiHBBT87Q

Primary Outcome Measures :
  1. 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.

  2. Overall survival [ Time Frame: 0-24 months ]
    Number of patients alive through the whole trial will be record.

  3. Proportion of engraftments [ Time Frame: 0-24 months ]
    Neutrophil count [ANC] >=500 /mm3 for 3 consecutive days and platelet count [PLT] >20,000/mm3 for7 consecutive days.

  4. Replication competent lentivirus (RCL) [ Time Frame: 0-24 months ]
    The percentage of RCL should be negative in the 24 months after transplant.

  5. Dynamics of viral integration sites (VIS) [ Time Frame: 0-24 months ]
    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.

Secondary Outcome Measures :
  1. The average Insertion copy number (VCN) in peripheral blood mononuclear cells [ Time Frame: 18-24 Months ]
    The average insertion copy number (VCN) should be ≥0.1 in peripheral blood mononuclear cells.

  2. The expression level of exogenous adult hemoglobin [ Time Frame: 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.

  3. Change from baseline in annualized frequency and volume of packed RBC transfusions [ Time Frame: 18-24 Months ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 16 Years   (Child)
Sexes Eligible for Study:   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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04592458

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Contact: Jing Li, PhD 13510560664 lijing4@genomics.cn

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China, Guangdong
Beijing Genomics Institute At Shenzhen
Shenzhen, Guangdong, China, 518083
Contact: Jing Li, PhD    +8613510560664    lijing4@genomics.cn   
Principal Investigator: Chao Liu, PhD         
Principal Investigator: Sixi Liu, Professor         
Sponsors and Collaborators
Shenzhen Children's Hospital
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Principal Investigator: Chao Liu, PhD BGI-research
Principal Investigator: Sixi Liu, Professor Shenzhen Children's Hospital
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Responsible Party: BGI-research
ClinicalTrials.gov Identifier: NCT04592458    
Other Study ID Numbers: A-SOP-CT-001
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BGI-research:
β-thalassemia major
β-globin restoration
autologous HSCT
Additional relevant MeSH terms:
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Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn