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

• ClinicalTrials.gov Identifier: NCT03351829
• Recruitment Status: Unknown
• First Posted: November 24, 2017
• Last Update Posted: November 30, 2017
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: November 20, 2017
• First Posted Date: November 24, 2017
• Last Update Posted Date: November 30, 2017
• Estimated Study Start Date: December 1, 2017
• Estimated Primary Completion Date: January 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2017)

Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 6 months ]

Physiological parameter (measuring cytokine response, fever, symptoms)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2017)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Beta-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

Study Arms

Experimental: Gene-modified autologous stem cells

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

Intervention: Genetic: Gene-modified autologous stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 20, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: January 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03351829
• Other Study ID Numbers: GIMI-IRB-17008
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: November 2017