Danazol for Treatment of Cytopenias in Patients With Cirrhosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Southern California
About this trial
This is a phase II pilot study designed to assess the safety and efficacy of danazol for treatment of cytopenias in patients with CPC A/B cirrhosis. Subjects with or without telomere mutations and/or shortened telomeres will be treated with danazol 600 mg per day by mouth for a duration of 24 months. The goal will be to treat a total of 10 patients.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 years or older and able to provide informed consent
ECOG 0-2
Compensated Child-Pugh class A of any etiology with the exception of chronic hepatitis B with one or more of the following cytopenias
Leukopenia defined as white blood cell count <2000/mm3 or absolute neutrophil count <1000/mm3 along with thrombocytopenia <150,000/mm3 measured on two separate occasions at least 3 months apart within 6 months of enrollment
Disqualifiers
Cirrhosis secondary to chronic hepatitis B or any history of hepatitis B
Patients with telomere related mutations know to confer gain of function will be excluded
Patients known to be infected with HIV
History of any hormone sensitive malignancy, including breast cancer, prostate cancer, hepatocellular carcinoma or liver adenoma as well as any patient considered high risk for developing malignancy (i.e. history of familial cancers including a first degree relative)
Trial design
Design model
Single group
Treatments tested in this trial
Danazol Pill
DrugDanazol is a synthetic steroid derived from ethisterone, It suppresses the pituitary-ovarian axis by inhibiting the pituitary output of gonadotropins. The pituitary-suppressive action of danazol is reversible. Danazol has been approved in treating endometriosis, fibrocystic breast disease, hereditary angioedema, thrombocytopenic purpura, and other conditions. It is metabolized and eliminated by renal and fecal pathways. The mean half-life of danazol in healthy males is 9.7 hours. After 6 months of 200 mg three times a day dosing in endometriosis patients, the half-life of danazol was reported as 23.7 hours. Adverse reactions from danazol include androgen like effects (i.e. weight gain, acne, mild hirsutism, edema, hair loss, voice change) and menstrual disturbances. The use of danazol in pregnancy is contraindicated. Other side effects include elevations in liver-enzyme levels and lipid abnormalities.
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Danazol in Treatment of CytopeniasExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Hematologic Response
Defined as normalization of WBC to ≥ 4000/µL or doubling of WBC from baseline, AND/OR normalization of platelet count to ≥150,000/µL or doubling of platelet count from baseline, from study entry to three months.
Time frame
2 years2
Occurrence of grade 3+ adverse events
Adverse events will be measured using CTCAE v5 .
Time frame
Up to 2 yearsSecondary outcomes
1
Change in blood cell counts
Complete blood cell counts will be measured every 3 months for a total of 24 months
Time frame
2 years2
Change in peripheral blood telomere lengths
Telomere length will be measured at baseline and 24 months. Rate of telomere attrition will be measured and compared to age and sex matched controls.
Time frame
2 years3
Change in liver fibrosis
Liver fibrosis will be measured using transient elastrography (fibroscan) at baseline and 24 months
Time frame
2 years4
Change in liver function - Albumin
Albumin level will be measured by blood test every 3 months from baseline to 24 months
Time frame
Up to 2 yearsSponsors and contacts
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Source ClinicalTrials.gov