Low-Dose Danazol for the Treatment of Telomere Related Diseases

Launched by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) · Oct 14, 2017

Keywords

ClinConnect Summary

This clinical trial is studying a medication called danazol to see if it can help people with telomere-related diseases, which can affect the bone marrow, lungs, and liver. Telomeres are protective caps on our DNA that shorten as we age, and some people have very short telomeres due to genetic changes, leading to serious health issues. The trial is open to individuals aged 3 and older who have been diagnosed with telomere disease and show signs of certain related conditions, like low blood counts or lung and liver problems.

Participants in the trial will undergo various tests to assess their health before starting the medication. If eligible, they will take danazol by mouth twice a day for one year and attend follow-up visits at 6 and 12 months during treatment, as well as 6 months after stopping. These visits will include blood tests, lung exams, and imaging studies to monitor their progress. It’s important for potential participants to discuss their health history with their doctor to determine if this trial is a good fit for them.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• • 1. Age-adjusted telomere length less than or equal to the first percentile by flow-FISH method. In patients with a known pathogenic or likely pathogenic mutation in a telomere maintenance gene, age adjusted telomere length less than or equal to the 10th percentile is sufficient.
• • 2. A mutation in telomere maintenance genes (TERT, TERC, DKC1, TINF2, NHP2, NOP10, WRAP53, TERF2, PARN, RTEL1, ACD, CTC1, USB1) as tested in a CLIA (or international equivalent) certified laboratory
• • 3. Age greater than or equal to 3 years
• • 4. Weight greater than or equal to 12 Kg
• • AND
• 5. At least one of the following criteria:
• • 1. Anemia with a hemoglobin less than or equal to 10 g/dL without red blood cell transfusion
• • 2. Thrombocytopenia with a platelet count less than or equal to 50,000/microliter without transfusion
• • 3. Neutropenia with an absolute neutrophil count less than or equal to 1,000/ microliter
• • OR
• • Pulmonary fibrosis diagnosed by either a lung biopsy or computed tomography scan of the chest according to guidelines from the American Thoracic Society and European Respiratory Society.
• • OR
• • 6. Hepatic fibrosis diagnosed by Transient Elastography by Fibroscan value greater than 10 kpa or US evidence of cirrhotic liver or splenomegaly, or transjugular liver biopsy demonstrating fibrosis.
• EXCLUSION CRITERIA:
• • 1. Patients on androgen hormones to include testosterone or high dose estrogen (estradiol 0.5 mg/day or greater) for the12 months prior to enrollment
• • 2. Patients with active thrombosis or thromboembolic disease and history of such events, undiagnosed abnormal genital bleeding, porphyria, androgendependent tumor, or prostatic hypertrophy
• • 3. Patients with pulmonary fibrosis who are receiving anti-fibrotic drug treatment, such as pirfenidone or nintedanib unless stable on anti-fibrotic drug for at least 6 months prior to starting on danazol as demonstrated by PFTs.
• • 4. Patients with active hepatitis B or C
• • 5. Patients who have received a bone marrow transplant
• • 6. Patient with other hereditary bone marrow failure syndromes such as Fanconi anemia or Diamond Blackfan anemia
• • 7. Patients with infections not adequately responding to appropriate therapy
• • 8. Current pregnancy, or unwillingness to take oral contraceptives or use the barrier methods of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during the course of the study
• • 9. Lactating women, due to the potentially harmful effects on the nursing child
• • 10. Patients with cancer who are actively receiving systemic chemotherapeutic treatment or who take drugs with hematological effects
• • 11. Patients with decompensated liver disease to include persistent ascites, encephalopathy, variceal hemorrhage, or MELD score of 10 or greater
• • 12. Inability to understand the investigational nature of the study or to give informed consent or without a legally authorized representative or surrogate that can provide informed consent
• • 13. Inability to swallow a capsule