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Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita

This study has been terminated.
(Study was terminated due to under enrollment)
Information provided by (Responsible Party):
Colin Sieff, Children's Hospital Boston Identifier:
First received: October 22, 2009
Last updated: September 12, 2014
Last verified: September 2014

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).

Condition Intervention Phase
Fanconi Anemia Dyskeratosis Congenita Drug: danazol Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita

Resource links provided by NLM:

Further study details as provided by Colin Sieff, Children's Hospital Boston:

Primary Outcome Measures:
  • 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). [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • The optimal dose and hematologic response rate in Fanconi anemia (FA) and Dyskeratosis congenita (DC) patients receiving danazol therapy [ Time Frame: 24 weeks ]
  • 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 [ Time Frame: 24 weeks ]

Enrollment: 5
Study Start Date: November 2009
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Subjects with either Fanconi anemia or Dyskeratosis congenita
Drug: danazol
Dosage is done according to weight; capsules are 50, 100, 200 mg
Other Name: Danocrine, Danol, anatrol

Detailed Description:

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.


Ages Eligible for Study:   3 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  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 potential.
  5. Signed informed consent by the patient or legally authorized representative.
  6. Patients must be either 3 years of age or > 14 kg.

Exclusion Criteria:

  1. Malignancy
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01001598

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children’s Hospital
Principal Investigator: Colin A Sieff, MB.BCh Boston Children’s Hospital
  More Information

Responsible Party: Colin Sieff, Director, Bone Marrow Failure Service, Children's Hospital Boston Identifier: NCT01001598     History of Changes
Other Study ID Numbers: 09-03-0131
Study First Received: October 22, 2009
Last Updated: September 12, 2014

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
Dyskeratosis Congenita
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Skin Abnormalities
Congenital Abnormalities
Genetic Diseases, X-Linked
Skin Diseases, Genetic
Skin Diseases
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on September 19, 2017