Know Cancer

or
forgot password

Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita


Phase 1/Phase 2
3 Years
N/A
Open (Enrolling)
Both
Fanconi Anemia, Dyskeratosis Congenita

Thank you

Trial Information

Phase I/II Dose Escalation Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita


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.


Inclusion Criteria:



1. 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).

2. 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

3. Negative pregnancy test by hCG testing, if of child-bearing potential.

4. Agreement to use a medically approved form of birth control, if of child-bearing
potential.

5. Signed informed consent by the patient or legally authorized representative.

6. Patients must be either 3 years of age or > 14 kg.

Exclusion Criteria:

1. Malignancy

2. Concurrent enrollment in any other study using an investigational drug.

3. Concurrent use of anticoagulants.

4. Use of androgen therapy within last three months.

5. Patients with liver disease as defined by SGOT, SGPT or bilirubin greater than the
upper limit of normal.

6. Patients with renal disease as defined by serum creatinine greater than the upper
limit of normal for age.

7. Patients less than either 3 years of age or 14 kg.

8. Patients who have HLA matched sibling donors.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Time Frame:

24 weeks

Safety Issue:

Yes

Principal Investigator

Colin A Sieff, MB.BCh

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital Boston

Authority:

United States: Food and Drug Administration

Study ID:

09-03-0131

NCT ID:

NCT01001598

Start Date:

November 2009

Completion Date:

March 2014

Related Keywords:

  • Fanconi Anemia
  • Dyskeratosis Congenita
  • Anemia
  • Fanconi Anemia
  • Fanconi Syndrome
  • Dyskeratosis Congenita

Name

Location

Children's Hospital BostonBoston, Massachusetts  02115