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Trial record 3 of 14 for:    "Dyskeratosis Congenita"

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

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ClinicalTrials.gov Identifier: NCT01001598
Recruitment Status : Terminated (Study was terminated due to under enrollment)
First Posted : October 26, 2009
Results First Posted : February 19, 2019
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Colin Sieff, Boston Children’s Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Fanconi Anemia
Dyskeratosis Congenita
Intervention Drug: danazol
Enrollment 5
Recruitment Details Patients recruited from clinic and by letter to Pediatric Hematologists in USA
Pre-assignment Details
  1. Patients with documented Fanconi anemia (FA) or dyskeratosis congenita (DC)
  2. Peripheral blood cytopenias (without transfusion, and at least one result obtained in the past two months that meet criteria): ANC < 500/uL or platelets < 30,000/uL or Hb < 8.0 gm/dl
  3. . Not pregnant
  4. Not on birth control
  5. Consent
  6. 3 yrs/ > 14 kg.
Arm/Group Title Danazol
Hide Arm/Group Description Subjects with either Fanconi anemia or Dyskeratosis congenita enter a single arm 24 week danazol dose escalation study: Dosage 5mg/kg/d; if no response at 12 weeks increase to 10 mg/kg/d; if no response at 18 weeks increase to 15 mg/kg/d. If no response stop at 24 weeks. Responders continue danazol at discretion of PCP.
Period Title: Overall Study
Started [1] 5
Completed 3 [2]
Not Completed 2
Reason Not Completed
Hematopoietic Stem Cell Transplant             1
Adverse Event             1
[1]
Monitoring visits at 2, 5, 8, 12, 18, 24 wks - visits at 14 and/or 20 weeks if dose escalation
[2]
3 completed study (2 FA and 1 DC) in 2011
Arm/Group Title Danazol
Hide Arm/Group Description

Subjects with either Fanconi anemia or Dyskeratosis congenita

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

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
5
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
3
  60.0%
Male
2
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
5
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
  20.0%
White
4
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
1.Primary Outcome
Title 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).
Hide Description All toxicities were collected and adjudicated to definitely-related, possibly-related, or unrelated to the treatment.
Time Frame 48 weeks (24 weeks treatment and 24 weeks extension phase)
Hide Outcome Measure Data
Hide Analysis Population Description
4 patients with Fanconi anemia and 1 with dyskeratosis congenita
Arm/Group Title Danazol
Hide Arm/Group Description:
Subjects with either Fanconi anemia or Dyskeratosis congenita enter a single arm 24 week danazol dose escalation study: Dosage 5mg/kg/d; if no response at 12 weeks increase to 10 mg/kg/d; if no response at 18 weeks increase to 15 mg/kg/d. If no response stop at 24 weeks. Responders continue danazol at discretion of PCP.
Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
Virilization - definitely related
2
  40.0%
Hepatic - possibly related
1
  20.0%
2.Secondary Outcome
Title The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy
Hide Description

The optimal dose could not be calculated because the number of participants needed to do this were not enrolled. Hematologic response rate (HR) was calculated for each participant at Week 12, 18, and 24. HR was defined by hemoglobin (Hg), platelets or neutrophil response. Please find the evaluation criteria used below:

Hemoglobin response: Hgb≥8 g/dL if baseline Hgb≤7 g/dL, or Hgb rise ≥1 g/dL from baseline if baseline Hgb>7 g/dL. No RBC transfusion during the 8 weeks prior to response evaluation.

Platelet response: Platelet count ≥30,000/ μL if baseline platelet count ≤20,000/ μL, or platelet count rise >10,000/ μL from baseline if baseline platelet count >20,000/ μL. No platelet transfusion during the 4 weeks prior to response evaluation.

ANC response: ANC count ≥1,000/ μL if baseline ANC count ≤500/ μL, or ANC count rise >500/ μL from baseline if baseline ANC count >500/ μL.

Time Frame 12, 18 and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
2 participants withdrew before HR could be assessed.
Arm/Group Title Danazol
Hide Arm/Group Description:
Subjects with either Fanconi anemia or Dyskeratosis congenita enter a single arm 24 week danazol dose escalation study: Dosage 5mg/kg/d; if no response at 12 weeks increase to 10 mg/kg/d; if no response at 18 weeks increase to 15 mg/kg/d. If no response stop at 24 weeks. Responders continue danazol at discretion of PCP.
Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
HR by hemoglobin at 12 weeks
3
 100.0%
HR by hemoglobin at 18 weeks
3
 100.0%
HR by hemoglobin at 24 weeks
3
 100.0%
HR by platelets at 12 weeks
0
   0.0%
HR by platelets at 18 weeks
0
   0.0%
HR by platelets at 24 weeks
2
  66.7%
HR by neutrophils at 12 weeks
0
   0.0%
HR by neutrophils at 18 weeks
0
   0.0%
HR by neutrophils at 24 weeks
2
  66.7%
3.Secondary Outcome
Title 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
Hide Description The gene expression profiles were planned to be run on bone marrow samples collected from patients at baseline and 24 weeks but bone marrow was never collected at 24 weeks.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline samples were too noisy to determine gene expression.
Arm/Group Title Danazol
Hide Arm/Group Description:
Subjects with either Fanconi anemia or Dyskeratosis congenita enter a single arm 24 week danazol dose escalation study: Dosage 5mg/kg/d; if no response at 12 weeks increase to 10 mg/kg/d; if no response at 18 weeks increase to 15 mg/kg/d. If no response stop at 24 weeks. Responders continue danazol at discretion of PCP.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Single Arm Phase I/II Study
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Single Arm Phase I/II Study
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Single Arm Phase I/II Study
Affected / at Risk (%) # Events
Total   1/5 (20.00%)    
Skin and subcutaneous tissue disorders   
Rash [1]  1/5 (20.00%)  1
[1]
Danazol started at 5 mg/kg/day (200 mg/day); day 9 a rash that on her hands and spread to the rest of her body diagnosed as hives. Also on birth control (Altavera). Dermatologist at BCH recommended against re-starting the danazol.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Single Arm Phase I/II Study
Affected / at Risk (%) # Events
Total   2/5 (40.00%)    
Endocrine disorders   
Virilization  [1]  2/5 (40.00%)  2
Gastrointestinal disorders   
Constipation  1/5 (20.00%)  1
Hepatobiliary disorders   
Hepatomegaly  [2]  1/5 (20.00%)  1
Nervous system disorders   
Mood changes [3]  1/5 (20.00%)  1
Indicates events were collected by systematic assessment
[1]
Clitoral and phallic enlargement
[2]
Enlargement of the left lobe
[3]
Probably related
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Colin A. Sieff
Organization: Boston Children's Hospital
Phone: 617 919-4241
Responsible Party: Colin Sieff, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT01001598     History of Changes
Other Study ID Numbers: 09-03-0131
First Submitted: October 22, 2009
First Posted: October 26, 2009
Results First Submitted: December 20, 2018
Results First Posted: February 19, 2019
Last Update Posted: February 19, 2019