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: Unknown
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Genetic: Gene-modified autologous stem cells

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.

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

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Geno-Immune Medical Institute

Participation Criteria

Eligibility Criteria

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

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 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.

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 stem cells; Autologous stem cells transduced with lentiviral vector carrying the related gene ex vivo	Genetic: Gene-modified autologous stem cells; 1 infusion for 5x10^6~1x10^7 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): December 31, 2020

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): November 30, 2017
• Last Update Submitted That Met QC Criteria: November 28, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Beta Thalassemia; Gene; Lentiviral vector
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; 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