A Phase 1/2 interventional study of danazol in Fanconi Anemia and Dyskeratosis Congenita, sponsored by Boston Children's Hospital. Terminated at 1 site in United States. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2019-02-19.
Sponsored by Boston Children's Hospital · Phase 1/2, Interventional, and Treatment
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:
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).
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.
72 studies on the registry are indexed under Fanconi Syndrome; 11 are open to participants now.
This study's enrollment of 5 is below the median of 12 across 44 interventional studies indexed under Fanconi Syndrome.
Browse Fanconi Syndrome studies →Boston Children's Hospital is the lead sponsor of 598 studies on the registry; 151 are open to participants now.
Of its 31 completed or terminated interventional studies of FDA-regulated products, 18 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects with either Fanconi anemia or Dyskeratosis congenita
Drug: danazol
Dosage is done according to weight; capsules are 50, 100, 200 mg
Also known as: Danocrine, Danol, Danatrol
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.
Time frame: 48 weeks (24 weeks treatment and 24 weeks extension phase)
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy
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
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
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
Patients recruited from clinic and by letter to Pediatric Hematologists in USA
| Milestone | Danazol |
|---|---|
| Started | 5 |
| Completed | 3 |
| Not completed | 2 |
| Withdrew: Hematopoietic stem cell transplant | 1 |
| Withdrew: Adverse event | 1 |
All toxicities were collected and adjudicated to definitely-related, possibly-related, or unrelated to the treatment.
| Participants | Danazol |
|---|---|
| Virilization - definitely related | 2 |
| Hepatic - possibly related | 1 |
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.
| Participants | Danazol |
|---|---|
| HR by hemoglobin at 12 weeks | 3 |
| HR by hemoglobin at 18 weeks | 3 |
| HR by hemoglobin at 24 weeks | 3 |
| HR by platelets at 12 weeks | 0 |
| HR by platelets at 18 weeks | 0 |
| HR by platelets at 24 weeks | 2 |
| HR by neutrophils at 12 weeks | 0 |
| HR by neutrophils at 18 weeks | 0 |
| HR by neutrophils at 24 weeks | 2 |
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.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Arm Phase I/II Study | — | 1/5 (20%) | 2/5 (40%) |
| Event | Single Arm Phase I/II Study |
|---|---|
| RashSkin and subcutaneous tissue disorders | 1/5 |
| Event | Single Arm Phase I/II Study |
|---|---|
| VirilizationEndocrine disorders | 2/5 |
| Mood changesNervous system disorders | 1/5 |
| ConstipationGastrointestinal disorders | 1/5 |
| HepatomegalyHepatobiliary disorders | 1/5 |
| Age, Categorical(Participants) | Danazol |
|---|---|
| <=18 years | 5 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Danazol |
|---|---|
| Female | 3 |
| Male | 2 |
| Ethnicity (NIH/OMB)(Participants) | Danazol |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 5 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Danazol |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 4 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Danazol |
|---|---|
| United States | 5 |
This study is terminated, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
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