Trial Information

Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita

Eligible patients with either Fanconi anemia (FA) or Dyskeratosis congenita (DC) will
initially receive danazol at a dose of 5 mg/kg/d orally, rounded to the nearest 100 mg. For
the first 8 weeks, the patient will be evaluated at weeks 2, 5, and 8 for hematologic
response (HR). If the patient shows a hematological response (either a hemoglobin or
platelet value no longer meeting blood cell count criteria for protocol inclusion in the
absence of recent transfusions)within the first 12 weeks on the initial dose, the study drug
will be continued at this dose for the next 6 weeks. If the patient fails to show any
hematologic response within the first 12 weeks, the dose will be escalated to 10 mg/kg/day
for the next 6 weeks, and an additional monitoring visit will be required at week 14. If at
week 18, the patient fails to show any hematological response on the increased dose, the
dose will be increased to 15 mg/kg/day for another 6 weeks (not to exceed 800 mg/day), and
an additional monitoring visit will be required at week 20. At 24 weeks, if there is no
response to this dose the patient will be taken off study drug and classified as a treatment
failure, and will be monitored at weeks 38 and week 52). After week 24, if the patient
continues to show a response, however, the study drug may be continued at the discretion of
their primary care physician, with monitoring at weeks 38 and 52.

Should the patient lose the hematologic response on 5 or 10 mg/kg/day dosing at any point
within the first 18 weeks of treatment, the dose will be escalated to 10 or 15 mg/kg/day
(not to exceed 800 mg/day), respectively. The patient will continue to be evaluated at the
next visit. If after week 24 no hematologic improvement is seen, the patient is then taken
off study drug and monitored at weeks 38 and 52.