Danazol for Genetic Bone Marrow and Lung Disorders

• Status: Completed
• Trial end date: 2016-11-14
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Some people have bone marrow and lung disorders that are caused by genetic problems. These problems often involve damage to the ends of the chromosomes that pass down genes. One of these disorders is aplastic anemia. This is a disorder in which the bone marrow does not make enough blood cells. Currently, doctors use a male hormone-based drug called Danazol to improve bone marrow function and treat aplastic anemia. More information is needed on whether Danazol can help repair the damaged chromosomes that cause aplastic anemia and similar disorders that cause low blood cell counts or lung problems.

Objectives:

• To study the safety and effectiveness of Danazol for bone marrow and lung disorders caused by damaged genes.

Eligibility:

• Individuals at least 2 years of age who have low blood cell counts or lung fibrosis caused by damaged genes.

Design:

• Participants will be screened with a physical exam and medical history. Then they will have blood and urine tests, imaging studies, and a lung function test. They will also take a 6-minute walking test and have a bone marrow biopsy.

• Participants will receive Danazol to take twice a day for the duration of the study.

• Participants will have regular study visits at 6, 12, and 24 months, with blood tests, imaging studies, a lung function test, and a 6-minute walking test. A bone marrow sample will be collected at the 12-month visit.

• Participants will remain on the study for up to 2 years. Researchers will follow up with them for 2 years after the end of the study.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Danazol

Criteria

• INCLUSION CRITERIA:

1. Short age-adjusted telomere length in the first percentile and/or a mutation in telomerase genes

2. One or more of the following cytopenia(s).

• Anemia

1. Symptomatic anemia with a hemoglobin < 9.5 g/dL or red cell transfusion requirements > 2 units/month for at least 2 months

2. Reticulocyte count < 60,000 /microL

• Thrombocytopenia

1. Platelet count < 30,000 /microL or < 50,000 /microL associated with bleeding

2. Decreased megakaryocytic precursors in the bone marrow

• Neutropenia

1. Absolute neutrophil count < 1,000 /microL

OR

3. Idiopathic pulmonary fibrosis diagnosed by either a lung biopsy of high resolution computed tomography scan of the chest according to guidelines from the American Thoracic Society and European Respiratory Society

4. Age greater than or equal to 2 years

5. Weight > 12 kg

EXCLUSION CRITERIA:

1. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy, or that death within 30 days is likely

2. Potential subjects with cancer who are on active chemotherapeutic treatment

3. Current pregnancy, or unwillingness to avoid pregnancy if of childbearing potential

4. Not able to understand the investigational nature of the study or give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent.