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

Early Phase 1RecruitingNCT05745532

Shenzhen Hemogen10 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

β-thalassemia

Interventions

β-globin restored autologous hematopoietic stem cellsBIOLOGICAL

β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q

Eligibility

Sex: ALLMin age: 8 YearsMax age: 16 Years

Medical Language ↔ Plain English

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.

Locations (1)

Shenzhen Children's Hospital

Shenzhen, Guangdong, China

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 0-100 days

Overall survival

Number of patients alive through the whole trial will be record

Time frame: 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

Time frame: 0-24 months

Replication competent lentivirus (RCL)

The percentage of RCL should be negative in the 24 months after transplant

Time frame: 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.

Time frame: 0-24 months

Secondary Outcomes

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

Time frame: 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

Central Contacts

Haigang Sun

CONTACT

13823168465 sunhaigang@genomics.cn

Data from ClinicalTrials.gov

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