Gene Therapy for Fanconi Anemia, Complementation Group A

Inclusion Criteria:

   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
   the trial

Exclusion Criteria:

   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
   NCI.

   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
      infection or

      - 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.