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

Primary Purpose

Beta-Thalassemia

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Gene-modified autologous stem cells
Sponsored by
Shenzhen Geno-Immune Medical Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Beta-Thalassemia focused on measuring Beta Thalassemia, Lentiviral vector, Gene

Eligibility Criteria

4 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Shenzhen Geno-immune Medical Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gene-modified autologous stem cells

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Quality of life
Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.

Full Information

First Posted
November 20, 2017
Last Updated
November 28, 2017
Sponsor
Shenzhen Geno-Immune Medical Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03351829
Brief Title
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Official Title
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Unknown status
Study Start Date
December 1, 2017 (Anticipated)
Primary Completion Date
January 1, 2019 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shenzhen Geno-Immune Medical Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta-Thalassemia
Keywords
Beta Thalassemia, Lentiviral vector, Gene

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Gene-modified autologous stem cells
Arm Type
Experimental
Arm Description
Autologous stem cells transduced with lentiviral vector carrying the related gene ex vivo
Intervention Type
Genetic
Intervention Name(s)
Gene-modified autologous stem cells
Intervention Description
1 infusion for 5x10^6~1x10^7 gene-modified cells; or more infusions depending on the circumstances
Primary Outcome Measure Information:
Title
Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
Description
Physiological parameter (measuring cytokine response, fever, symptoms)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Treatment responses
Description
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.
Time Frame
1 year
Title
Quality of life
Description
Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lung-Ji Chang, PhD
Phone
86-075586725195
Email
c@szgimi.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lung-Ji Chang, PhD
Organizational Affiliation
Shenzhen Geno-Immune Medical Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shenzhen Geno-immune Medical Institute
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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