Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
Information source: Children's Hospital Boston
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fanconi Anemia; Dyskeratosis Congenita
Intervention: danazol (Drug)
Phase: Phase 1/Phase 2
Sponsored by: Children's Hospital Boston
Official(s) and/or principal investigator(s):
Colin A Sieff, MB.BCh, Principal Investigator, Affiliation: Children's Hospital Boston
Fanconi anemia (FA) and Dyskeratosis congenita (DC) are inherited bone marrow failure
syndromes. The current androgen treatments (e. g., oxymetholone) used to treat FA and DC can
cause unwanted masculinizing side effects, indicating a need for a different medication.
Danazol is a less potent androgen,and may therefore have fewer masculinizing side effects.
Danazol is currently approved by the Food and Drug Administration (FDA) for the treatment of
other diseases, but it has never been studied in patients with FA and DC.
The main purpose of this study is to see if danazol is a safe treatment for FA and DC.
Specifically,we would like to determine:
- the best dose of danazol;
- how fast hemoglobin (a protein that carries oxygen in the blood) levels rise in FA and
DC patients receiving danazol therapy; and
- the genetic pattern (known as expression profile) of certain cells in response to
danazol, which can predict how well people respond to the medication.
Subjects who enroll in the study will be treated with danazol for up to 24 weeks (about 6
months), and will have up to 11 study visits, including followup visits at 38 weeks (9
months) and 52 weeks (one year).
Official title: Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Toxicity associated with danazol therapy: virilization, and/or new or progressive evidence of either hepatic or renal toxicity at a Grade II level using National Cancer Institute Common Toxicity Criteria (NCI-CTC).
The optimal dose and hematologic response rate in Fanconi anemia (FA) and Dyskeratosis congenita (DC) patients receiving danazol therapy
The gene expression profile of progenitor cells in response to danazol, both to predict responsiveness and to screen for small molecules that show a profile similar to that of responsive patients
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.
Minimum age: 3 Years.
Maximum age: N/A.
1. Patients must be diagnosed with FA that is documented by a positive test for
increased chromosomal breakage with mitomycin C or diepoxybutane. DC patients must
have clinical features consistent with the diagnosis, abnormally short lymphocyte
telomeres < 1st centile by flow-FISH evaluation, or mutation in one of the known DC
genes (DKC1, TERT, TERC, TINF2, NOP10, NHP2).
2. At least the following peripheral blood cytopenias: (without transfusion) Absolute
neutrophil count < 500/uL or Platelet count < 30,000/uL or Hemoglobin < 8. 0 gm/dl
3. Negative pregnancy test by hCG testing, if of child-bearing potential.
4. Agreement to use a medically approved form of birth control, if of child-bearing
5. Signed informed consent by the patient or legally authorized representative.
6. Patients must be either 3 years of age or > 14 kg.
2. Concurrent enrollment in any other study using an investigational drug.
3. Concurrent use of anticoagulants.
4. Use of androgen therapy within last three months.
5. Patients with liver disease as defined by SGOT, SGPT or bilirubin greater than the
upper limit of normal.
6. Patients with renal disease as defined by serum creatinine greater than the upper
limit of normal for age.
7. Patients less than either 3 years of age or 14 kg.
8. Patients who have HLA matched sibling donors.
Locations and Contacts
Children's Hospital Boston, Boston, Massachusetts 02115, United States
Starting date: November 2009
Last updated: September 12, 2014