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

NCT01001598 | Terminated Phase 1 Results DMC

• 1 other identifier: 09-03-0131
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Fanconi Anemia; Dyskeratosis Congenita

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 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).

  All toxicities were collected and adjudicated to definitely-related, possibly-related, or unrelated to the treatment.

  48 weeks (24 weeks treatment and 24 weeks extension phase)

Secondary Outcomes (2)

• The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy

  12, 18 and 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

  Baseline and 24 weeks

Study Arms (1)

danazol

OTHER

Subjects with either Fanconi anemia or Dyskeratosis congenita

Drug: danazol

Interventions

danazol DRUG

Dosage is done according to weight; capsules are 50, 100, 200 mg

Also known as: Danocrine, Danol, Danatrol

danazol

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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
• Negative pregnancy test by hCG testing, if of child-bearing potential.
• Agreement to use a medically approved form of birth control, if of child-bearing potential.
• Signed informed consent by the patient or legally authorized representative.
• Patients must be either 3 years of age or \> 14 kg.

You may not qualify if:

• Malignancy
• Concurrent enrollment in any other study using an investigational drug.
• Concurrent use of anticoagulants.
• Use of androgen therapy within last three months.
• Patients with liver disease as defined by SGOT, SGPT or bilirubin greater than the upper limit of normal.
• Patients with renal disease as defined by serum creatinine greater than the upper limit of normal for age.
• Patients less than either 3 years of age or 14 kg.
• Patients who have HLA matched sibling donors.

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Fanconi Anemia; Dyskeratosis Congenita

Interventions

Danazol

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Skin Abnormalities; Congenital Abnormalities; Genetic Diseases, X-Linked; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Colin A. Sieff
• Organization: Boston Children's Hospital

colin.sieff@childrens.harvard.edu

617 919-4241

Study Officials

• Colin A Sieff, MB.BCh

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bone Marrow Failure Service

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 26, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2019-01

Locations

US (1)