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

NCT ID: NCT03351829

Last Updated: 2017-11-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2020-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Beta-Thalassemia

Keywords

Beta Thalassemia; Lentiviral vector; Gene

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gene-modified autologous stem cells

Autologous stem cells transduced with lentiviral vector carrying the related gene ex vivo

Group Type: EXPERIMENTAL

Gene-modified autologous stem cells

Intervention Type: GENETIC

1 infusion for 5x10\^6\~1x10\^7 gene-modified cells; or more infusions depending on the circumstances

Interventions

Gene-modified autologous stem cells

1 infusion for 5x10\^6\~1x10\^7 gene-modified cells; or more infusions depending on the circumstances

Intervention Type: GENETIC

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Lung-Ji Chang

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Locations

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

Phone: 86-075586725195

Email: c@szgimi.org

Other Identifiers

GIMI-IRB-17008

Identifier Type: -

Identifier Source: org_study_id