FANCA Gene Transfer for Fanconi Anemia Using a High-safety, High-efficiency, Self-inactivating Lentiviral Vector
Gene Transfer for Fanconi Anemia Using a Self-inactivating Lentiviral Vector
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low. In addition, some patients have physical defects usually involving the skeleton and kidneys. Fanconi anemia is typically diagnosed in childhood, and there is a high fatality rate. Hematopoietic stem cell transplantation (HSCT) is a common treatment for Fanconi anemia. However, there are many risks associated with HSCT including rejection of the transplanted cells and graft-versus-host disease.
The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming immune abnormalities present at the time of treatment, assessment of gene correction efficiency, and finally the long-term correction of Fanconi anemia associated disease symptoms.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Guangdong
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Shenzhen, Guangdong, China, 518000
- Shenzhen Geno-immune Medical Institute
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
- No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
- Age: ≥ 4 years.
- Karnofsky: ≥ 70%.
- ANC ≥ 5×10^8/L; PLT ≥ 2×10^10/L.
- Hemoglobin ≥ 8g/dL.
Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with
- serum creatinine ≤ 1.5×ULN;
- serum bilirubin ≤ 3×ULN;
- AST/ALT ≤ 5×ULN.
- Pulmonary function is normal; DLCO > 50%.
- Written, informed consent obtained prior to any study-specific procedures.
Exclusion Criteria:
- Diagnosis of active malignant disease or myelodysplastic syndrome.
- Diagnosis of myeloid leukemia.
- Pregnant or lactating females.
- Existence of an available HLA-identical related donor.
- Subject infected with 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Gene-modified autologous stem cells
Autologous hematopoeitic stem cells and mesenchymal stem cells transduced with lentiviral vector carrying the FANCA gene ex vivo
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Infusion for 5x10^6~1x10^7 per kilogram of body weight of 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
Time Frame: 6 months
|
Physiological parameter (measuring cytokine response, fever, symptoms)
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Treatment responses
Time Frame: 1 year
|
Blood routine indexes will be obtained 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
|
|
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.
|
1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Lung-Ji Chang, Ph.D, Shenzhen Geno-immune Medical Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Congenital Bone Marrow Failure Syndromes
- Bone Marrow Failure Disorders
- Genetic Diseases, Inborn
- Metabolic Diseases
- Hematologic Diseases
- Bone Marrow Diseases
- Anemia
- DNA Repair-Deficiency Disorders
- Anemia, Hypoplastic, Congenital
- Anemia, Aplastic
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Nutritional and Metabolic Diseases
- Hemic and Lymphatic Diseases
- Fanconi Anemia
Other Study ID Numbers
- GIMI-IRB-17021
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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