Fanconi AnemiaPhase 1/2NCT01001598
Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
A Phase 1/2 study testing danazol in people with Fanconi Anemia and Dyskeratosis Congenita, run by Boston Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Fanconi Anemia, Dyskeratosis Congenita
- What is being tested?
- danazol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to May 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
Official title: Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
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:
Read more
- 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).
Read the 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.
- Conditions
- Fanconi Anemia, Dyskeratosis Congenita
- Being tested
- danazol
- Medical subject headings
- Fanconi Anemia, Dyskeratosis Congenita
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
danazolDrug
Also called Danocrine, Danol, Danatrol
Dosage is done according to weight; capsules are 50, 100, 200 mg
| Study group | Role | What they receive |
|---|---|---|
| danazol | Other | Subjects with either Fanconi anemia or Dyskeratosis congenita Receives: Drug: danazol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2009 (estimated)
- Study startNov 2009
- Primary completionMay 2014
- Study completionMay 2014
Why it stopped: Study was terminated due to under enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colin Sieff, Boston Children's Hospital
- Investigators
- Colin A Sieff, MB.BCh, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01001598
- Sponsor's protocol ID
- 09-03-0131
- Status last verified
- Jan 2019
- First submitted
- 22 Oct 2009
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
- ClinicalTrials.gov ID
- NCT01001598
- Acronym / sponsor ID
- 09-03-0131
- Conditions
- Fanconi Anemia, Dyskeratosis Congenita
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to under enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 26 Oct 2009 (estimated)
- Results
- Posted 19 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| danazol | Other | Drug: danazolSubjects with either Fanconi anemia or Dyskeratosis congenita |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| danazolAlso: Danocrine, Danol, DanatrolDosage is done according to weight; capsules are 50, 100, 200 mg | Drug | danazol |
Primary outcome
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).
Time frame: 48 weeks (24 weeks treatment and 24 weeks extension phase)
All toxicities were collected and adjudicated to definitely-related, possibly-related, or unrelated to the treatment.
2 secondary outcomes
The Optimal Dose and Number of Participants With Hematologic Response Rate in Fanconi Anemia (FA) and Dyskeratosis Congenita (DC) Patients Receiving Danazol Therapy
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
Time frame: Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colin A Sieff, MB.BCh principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing danazol in people with Fanconi Anemia and Dyskeratosis Congenita, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: 48 weeks (24 weeks treatment and 24 weeks extension phase)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.