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

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT03351829

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Beta-Thalassemia	Genetic: Gene-modified autologous stem cells	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2017

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [6 months]
Physiological parameter (measuring cytokine response, fever, symptoms)

Secondary Outcome Measures

Treatment responses [1 year]
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.
Quality of life [1 year]
Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Diagnosis of active malignant disease (other than Bowen disease or cervical cancer); or has family history of cancer.
Myelopathy, tumor-related cytogenetic changes or other more severe blood diseases.
Has alcoholism experience within 6 months prior to enrollment.
History of epilepsy.
History of bone marrow transplantation.
Existence of an available HLA-identical related donor.
Pregnant or lactating females.
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.
Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong	China	518000

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

Principal Investigator: Lung-Ji Chang, PhD, Shenzhen Geno-Immune Medical Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute

ClinicalTrials.gov Identifier:

NCT03351829

Other Study ID Numbers:

GIMI-IRB-17008

First Posted:

Nov 24, 2017

Last Update Posted:

Nov 30, 2017

Last Verified:

Nov 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute

Beta Thalassemia

Lentiviral vector

Gene

Additional relevant MeSH terms:

Thalassemia

beta-Thalassemia

Study Results

No Results Posted as of Nov 30, 2017