Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A

This is an interventional treatment trial for Fanconi Anemia Complementation Group A focused on measuring anemia, bone marrow failure, gene therapy Read More

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. Maximum age: 17 years
5. 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)

6. 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
7. Provide informed consent in accordance with current legislation
8. 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. Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
2. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those predictive of these conditions in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
3. Patients with somatic mosaicism associated with stable or improved counts in all PB cell lineages
4. Lansky performance index ≤ 60%
5. Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
6. Pre-existing sensory or motor impairment > = grade 2 according to the criteria of the National Cancer Institute (NCI)
7. Pregnant or breastfeeding women

8. Hepatic dysfunction as defined by either:

   • Bilirubin > 3 x the upper limit of normal (ULN)
   • Alanine aminotransferase (ALT ) > 5 x ULN
   • Aspartate aminotransferase (AST) > 5 x 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)
    • 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