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

Beta-Thalassemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03351829
• Other study ID #: GIMI-IRB-17008
• Status: Not yet recruiting
• Phase: N/A
• First received: November 20, 2017
• Last updated: November 28, 2017
• Start date: December 1, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: November 2017
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, PhD
• Phone: 86-075586725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 31, 2020
• Est. primary completion date: January 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia

Intervention

Genetic:
• Gene-modified autologous stem cells
1 infusion for 5x10^6~1x10^7 gene-modified cells; or more infusions depending on the circumstances

Locations

Country	Name	City	State
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Treatment responses	Blood routine indexes will be got before and after treatment. Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year
Secondary	Quality of life	Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.	1 year