Trial Outcomes & Findings for Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita (NCT NCT01001598)

NCT ID: NCT01001598

Last Updated: 2019-02-19

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

5 participants

Primary outcome timeframe

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

Results posted on

2019-02-19

Participant Flow

Patients recruited from clinic and by letter to Pediatric Hematologists in USA

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.

Participant milestones

Participant milestones
Measure	Danazol 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 Study STARTED	5
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Danazol 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 Study Hematopoietic Stem Cell Transplant	1
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Danazol n=5 Participants Subjects with either Fanconi anemia or Dyskeratosis congenita danazol: Dosage is done according to weight; capsules are 50, 100, 200 mg
Age, Categorical <=18 years	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

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

Population: 4 patients with Fanconi anemia and 1 with dyskeratosis congenita

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

Outcome measures

Outcome measures
Measure	Danazol n=5 Participants 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.
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). Virilization - definitely related	2 Participants
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). Hepatic - possibly related	1 Participants

SECONDARY outcome

Timeframe: 12, 18 and 24 weeks

Population: 2 participants withdrew before HR could be assessed.

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.

Outcome measures

Outcome measures
Measure	Danazol n=3 Participants 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.
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by hemoglobin at 12 weeks	3 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by hemoglobin at 18 weeks	3 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by hemoglobin at 24 weeks	3 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by platelets at 12 weeks	0 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by platelets at 18 weeks	0 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by platelets at 24 weeks	2 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by neutrophils at 12 weeks	0 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by neutrophils at 18 weeks	0 Participants
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy HR by neutrophils at 24 weeks	2 Participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Baseline samples were too noisy to determine gene expression.

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.

Outcome measures

Outcome data not reported

Adverse Events

Single Arm Phase I/II Study

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single Arm Phase I/II Study n=5 participants at risk
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Number of events 1

Other adverse events

Other adverse events
Measure	Single Arm Phase I/II Study n=5 participants at risk
Nervous system disorders Mood changes	20.0% 1/5 • Number of events 1
Gastrointestinal disorders Constipation	20.0% 1/5 • Number of events 1
Hepatobiliary disorders Hepatomegaly	20.0% 1/5 • Number of events 1
Endocrine disorders Virilization	40.0% 2/5 • Number of events 2

Additional Information

Colin A. Sieff

Boston Children's Hospital

Phone: 617 919-4241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place