Clinical trial NCT03351868: FANCA Gene Transfer for Fanconi Anemia Using a High-safety, High-efficiency, Self-inactivating Lentiviral Vector
Official title: Gene Transfer for Fanconi Anemia Using a Self-inactivating Lentiviral Vector
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Fanconi Anemia
Keywords: Fanconi anemia
Lentiviral vector
FANCA
Gene
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-11-24
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I/II clinical trial of gene therapy for treating Fanconi anemia using a self-inactivating lentiviral vector to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.

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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
2. No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
3. Age: ≥ 4 years.
4. Karnofsky: ≥ 70%.
5. ANC ≥ 5×10\^8/L; PLT ≥ 2×10\^10/L.
6. Hemoglobin ≥ 8g/dL.
7. 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.
8. Pulmonary function is normal; DLCO \> 50%.
9. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

1. Diagnosis of active malignant disease or myelodysplastic syndrome.
2. Diagnosis of myeloid leukemia.
3. Pregnant or lactating females.
4. Existence of an available HLA-identical related donor.
5. Subject infected with HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
6. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Primary outcomes:
measure: Safety in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Treatment responses
timeFrame: 1 year
measure: Quality of life
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Institute of Pediatrics affiliated Children's hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Children's Hospital
state: Beijing
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Capital Institute of Pediatrics affiliated Children's hospital
name: Xiao-Dong Shi, M.D./Ph. D
role: STUDY_DIRECTOR
affiliation: Beijing Children's Hospital
name: Jie Zheng, M.D./Ph. D
role: STUDY_DIRECTOR
References: