Sirolimus and Cyclosporine for Treatment-Resistant Aplastic Anemia

• Status: Unknown status
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Aplastic anemia is a rare autoimmune disorder in which the bone marrow production of blood cells is greatly decreased or absent. Symptoms include fatigue, weakness, tiny reddish-purple marks on the skin, abnormal bruising, and bleeding from the gums, nose, or intestine. While some cases of aplastic anemia are caused by medications, toxic exposures, or inherited genes, most often the cause remains unknown. The purpose of this study is to determine the safety and efficacy of combining two drugs, sirolimus and cyclosporine, for treating individuals with aplastic anemia that has not responded to other treatments.

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

Details

• Lead Sponsor: Office of Rare Diseases (ORD)
• Collaborator: Rare Diseases Clinical Research Network
• Treatments: Cyclosporine; Cyclosporins; Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• Diagnosis of moderate or severe aplastic anemia with bone marrow cellularity of less than 25%

• Falls within one of the following descriptions at the time of the original diagnosis:

1. For severe aplastic anemia, fulfills any two of the following three criteria:

absolute neutrophil count less than 500/uL; absolute reticulocyte count less than 60,000/uL; and platelet count less than 20,000/uL

2. For moderate aplastic anemia, fulfills any two of the following three criteria:

absolute neutrophil count less than 1200/ul; hemoglobin less than 8 g/dL with corrected reticulocyte count less than 1%; and platelet count less than 60,000/uL (Note: Participants who have progressed from moderate to severe aplastic anemia prior to study entry will be classified as having severe aplastic anemia)

• Diagnosis of refractory aplastic anemia, as defined by a failure to achieve at least a partial response to ATG within 6 months of treatment. Individuals who had a prior response to ATG but who have relapsed and not responded to salvage ATG are eligible. Individuals with relapsed disease who are not candidates for salvage ATG because they experienced a serious or life-threatening complication prior to ATG are also eligible.

• A Karnofsky performance status of at least 60%

• Adequate organ function, as defined by creatine levels less than 1.5 times the upper limit normal (ULN), and liver function tests (AST, bilirubin) less than 2 times the ULN

• Women of childbearing age must be willing to use effective contraception throughout the study

Exclusion Criteria:

• Received ATG treatment less than 6 months prior to study entry

• Candidate for related allogeneic stem cell transplantation

• Active uncontrolled infection

• History of myelodysplastic syndrome or bone marrow cytogenetic abnormalities

• History of Fanconi's anemia or other congenital form of aplastic anemia

• Treatment with an investigational agent within 1 month of study entry

• HIV infection

• Pregnant or breastfeeding