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Gene Therapy for Fanconi Anemia, Complementation Group A
Trial ID: NCT04248439
The objective of this study is to assess the therapeutic efficacy of a hematopoietic cell-based gene therapy for patients with Fanconi anemia, subtype A (FA-A). Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.
A Phase 2 Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
1. Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in
the presence of DEB or a similar DNA-crosslinking agent
2. Patients of the complementation group FA-A
3. Minimum age: 1 year and a minimum weight of 8 kg
4. At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3
months prior to CD34+ cell collection OR (see subsequent criterion)
5. If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB)
parameters should meet two of the three following criteria:
- Hemoglobin: ≥11g/dL
- Neutrophils: ≥900 cells/μL
- Platelets: ≥60,000 cells/μL
6. Provide informed consent in accordance with current legislation
7. Women of childbearing age must have a negative urine pregnancy test at the baseline
visit, and accept the use of an effective contraception method during participation in
1. Subjects with an available and medically eligible HLA-identical sibling donor.
2. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other
than those reported as variant(s) of normal in BM aspirate analysis. This assessment
should be made by valid studies conducted within the 3 months before the subject
commences the stem cell mobilization/collection procedures of the clinical trial.
3. Subjects with somatic mosaicism associated with stable or improved counts in all PB
cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential
mosaicism, a medically significant decrease (≥1 NCI CTCAE grade) in at least one blood
lineage over time must be documented to enable eligibility, as should <5% resistance
of bone marrow colony forming cells (CFCs) to 10nM MMC; whenever possible potential
mosaicism should also be evaluated by gene sequencing of MMC-resistant CFCs).
4. Lansky performance status ≤60%.
5. Any concomitant disease or condition that, in the opinion of the Principal
Investigator, renders the subject unfit to participate in the study.
6. Pre-existing sensory or motor impairment ≥grade 2 according to the criteria of the
7. Pregnant or breastfeeding women.
8. Hepatic dysfunction as defined by either:
- Bilirubin >3.0 × the upper limit of normal (ULN) or
- Alanine aminotransferase (ALT) > 5.0 × ULN or
- Aspartate aminotransferase (AST) > 5.0 × ULN
For subjects with bilirubin, ALT or AST above ULN, a workup to identify the etiology
of liver abnormality should be conducted prior to confirmation of eligibility as
stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron
overload, drug injury or other causes.
9. Renal dysfunction requiring either hemodialysis or peritoneal dialysis.
10. Pulmonary dysfunction as defined by either:
- Need for supplemental oxygen during the prior 2 weeks in absence of acute
- Oxygen saturation by pulse oximetry <90%.
11. Evidence of active metastatic or locoregionally advanced malignancy for which survival
is anticipated to be less than 3 years.
12. Subject is receiving androgens (i.e. danazol, oxymetholone).
13. Subject is receiving other investigational therapy for treatment/prevention of
FA-associated bone marrow failure.
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