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.

Study Overview

• Status: Not yet recruiting
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Genetic: Gene-modified autologous hematopoeitic stem cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, PhD; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Geno-immune Medical Institute
      • Contact: Lung-Ji Chang, PhD; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 HIV (HIV 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gene-modified autologous hematopoeitic stem cells; Gene-modified autologous hematopoeitic stem cells transduced with lentiviral vector carrying the beta-globin gene ex vivo	Genetic: Gene-modified autologous hematopoeitic stem cells; 1 infusion of 5x10^6~1x10^7 per kilogram body weight gene-modified cells; or more infusions depending on the circumstances

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response, fever, symptoms)	6 months
Tolerability of transplanted cells that are transduced ex vivo & transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen.	Monitoring the following: The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts & leukocyte clonality using PCR and sequencing analysis, and qPCR for vector copy number.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment responses	Blood routine indexes will be recorded before and after treatment. Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed.	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Principal Investigator: Lung-Ji Chang, PhD, Shenzhen Geno-immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Beta Thalassemia; Gene; Lentiviral vector
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; beta-Thalassemia
• Other Study ID Numbers: GIMI-IRB-17008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No