Danazol for Treatment of Cytopenias in Patients With Cirrhosis

NCT04873102 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HS-20-00366
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cirrhosis, Liver; Cytopenia

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years

• Occurrence of grade 3+ adverse events

  Adverse events will be measured using CTCAE v5 .

  Up to 2 years

Secondary Outcomes (7)

• Change in blood cell counts

  2 years

• Change in peripheral blood telomere lengths

  2 years

• Change in liver fibrosis

  2 years

• Change in liver function - Albumin

  Up to 2 years

• Transplant-free survival

  2 years

Study Arms (1)

Danazol in Treatment of Cytopenias

EXPERIMENTAL

AGENT: Danazol 600mg, Oral, Daily for 24 months

Drug: Danazol Pill

Interventions

Danazol Pill DRUG

Danazol 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.

Also known as: Danocrine

Danazol in Treatment of Cytopenias

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Thrombocytopenia defined as platelet count \<50,000/mm3 along with white blood cell count \<4000/mm3 measured on two separate occasions at least 3 months apart within 6 months of enrollment
• Compensated Child-Pugh class B cirrhosis 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 ≤ 3500/mm3 measured on two separate occasions at least 3 months apart within 6 months of enrollment 3. Thrombocytopenia defined as platelet count ≤ 100,000/mm3 measured on two separate occasions at least 3 months apart within 6 months of enrollment
• Enrolled patients must have one or more of the following:
• Presence of a genetic variant (defined as a known mutation, variant likely to be pathogenic or variant of undetermined significance with likely deleterious effect on transcription or translation) in at least one of the following genes: TERT, TERC, RTEL1, DKC, NOP10, NHP2, TINF2, WRAP53
• Shortened telomere length in peripheral blood mononuclear cells (defined as age-adjusted telomere length at or below the 5th percentile)
• Of note, patient's found to have telomere mutations know to confer a gain of function will be excluded
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception

You may not qualify if:

• 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)
• Patients who are actively receiving anti-cancer therapy
• Liver decompensation event within the last 6 months (i.e. variceal bleed, ascites requiring paracentesis, hepatic encephalopathy)
• Active thrombosis or history of unprovoked thromboembolic disease, including cardiovascular events. If a patient has received and completed adequate anticoagulation for a provoked thrombosis, they can be included in the study.
• Pregnant or planning to become pregnant
• Females patients who are breast feeding
• Any contraindication to danazol use
• Uncontrolled co-morbid condition which would make the administration of danazol unsafe, including decompensated heart failure or known EF less than 40%, unstable angina pectoris, uncontrolled cardiac arrhythmia, decompensated liver failure, renal failure defined as creatinine greater than \>1.6 or psychiatric illness that would limit compliance with study requirements
• Alanine aminotransferase and/or aspartate aminotransferase \>3x upper limit of normal
• Alkaline phosphatase \>2.5 x upper limit of normal
• Total bilirubin or direct bilirubin \>2.5 x upper limit of normal
• Patients with known alcohol or drug abuse within the last year

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

Keck Hosital of USC

Los Angeles, California, 90033, United States

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Cytopenia

Interventions

Danazol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Casey O'Connell, MD

  Keck Hospital of USC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ibrahim Syed, MBBS

CONTACT

323-865-3000; isyed@med.usc.edu

Caitlin O'Neill, MD

CONTACT

323-865-3000; caitlin.oneill@med.uc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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 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 with telomere gene mutations and/or shortened telomere lengths.

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: May 5, 2021
• Study Start: August 1, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)