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

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

This is a Phase I/II clinical trial of gene transfer for treating Beta-thalassemia using a self-inactivating lentiviral vector to functionally correct the defective gene(s). The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.

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 transfer, 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 an experimental gene transfer procedure performed in a laboratory to insert the related gene into the participant's autologous 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 individuals.

Inclusion Criteria:

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

Exclusion Criteria:

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