Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector

Important Regulatory Notice:

This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.

ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.

Thalassemia is considered the most common genetic disorder worldwide. Beta-thalassemia is caused by mutations in the beta-globin gene which encodes the beta-globin protein, leading to the ineffective erythropoiesis, hemolysis and anemia. Currently, the only cure for thalassemia is bone marrow transplantation from a related, compatible donor, which has, however, the significant risk of transplant related mortality, graft versus host disease and limited source. Therefore, gene therapy, achieved by transplantation of the patient's own stem cells that have been genetically-modified with the corrected gene, could potentially cure thalassemia.

This study will use a gene transfer procedure performed to insert the beta-globin gene into the participant's autologous stem cells (hematopoeitic stem cells) using a self-inactivating lentiviral vector. The purpose of this study is to evaluate the safety and effectiveness of the gene transfer procedure and to determine the ability of the gene-corrected cells at generating new, healthy blood cells in patients.

Inclusion criteria

• Diagnosis of Beta Thalathemia.
• Age: ≥ 4 years.
• Karnofsky: ≥ 80%.
• Left ventricular ejection fraction (LVEF): > 50%; no obvious heart disease and pulmonary hypertension.
• Pulmonary function is normal; forced expiratory volumein one second (FEV1) and vital capacity greater than 60% and DLCO > 50%.
• Serum creatinine ≤ 2 × upper limit of normal range.
• MRI showed no super-iron load in the heart and liver, and no severe cirrhosis.
• Normal Coagulation.
• Written, informed consent obtained prior to any study-specific procedures.

Exclusion criteria

• Diagnosis of active malignant disease (other than Bowen disease or cervical cancer); or has family history of cancer.
• Myelopathy, tumor-related cytogenetic changes or other more severe blood diseases.
• Has alcoholism experience within 6 months prior to enrollment.
• History of epilepsy.
• History of bone marrow transplantation.
• Existence of an available HLA-identical related donor.
• Pregnant or lactating females.
• Subject infected with HIV (HIV antibody positive), Treponema pallidum antibody positive or TB culture positive.
• Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.