A Phase 1/2 interventional study of Sirolimus and Cyclosporine in Anemia, Aplastic, sponsored by Office of Rare Diseases (ORD). Status unknown at 4 sites in United States. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2008-10-07.
Sponsored by Office of Rare Diseases (ORD) · Phase 1/2, Interventional, and Treatment
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.
The most successful treatment for aplastic anemia is bone marrow transplantation. However, few patients are eligible for this procedure. For others, treatment usually consists of immunosuppressive agents, such as antithymocyte globulin (ATG) and cyclosporine. Unfortunately, even with immunosuppressive therapy, relapse is common. New combinations of medications may offer alternative and more effective treatment options. Sirolimus and cyclosporine are two drugs routinely used to suppress the immune system and prevent rejection in patients who have received organ transplants. While cyclosporine has been proven effective for treating aplastic anemia, sirolimus has not been tested for this disease. This study will evaluate the safety and efficacy of sirolimus in combination with cyclosporine for treating individuals with aplastic anemia that has not responded to other treatments.
This study will last at least 6 months. Participants will first be screened to verify diagnosis of aplastic anemia. The screening will include a physical examination, blood test, bone marrow biopsy from the pelvic bone, and review of medications and medical history. Individuals who are eligible will then start the first treatment period. Participants will receive two medications: cyclosporine will be taken twice a day and sirolimus will be taken once a day. Depending on side effects, the doses of either drug may be temporarily stopped or lowered. On Day 1, blood will be drawn and females will undergo a pregnancy test. Subsequent study visits will occur weekly for the first month, every 2 weeks for 2 months, and then once a month for the remainder of the study. Each visit will include a physical examination, vital sign assessment, and review of side effects and medications. Blood tests will be performed weekly for the first 3 weeks, and then every 2 weeks.
After 6 months of treatment, if a participant has shown improvements in disease status without major side effects, the treatment will continue. Over time the doses may be lowered. If a participant has not improved while on the study medication, treatment will stop at 6 months. Whenever treatment is discontinued, the participant will again undergo a physical examination, blood tests, and bone marrow biopsy.
1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.
This study's planned enrollment of 52 is below the median of 94 across 1,291 interventional studies indexed under Anemia.
Browse Anemia studies →Office of Rare Diseases (ORD) is the lead sponsor of 6 studies on the registry; none are open to participants now.
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Falls within one of the following descriptions at the time of the original diagnosis:
Exclusion Criteria:
Participants will be treated with sirolimus and cyclosporine. In phase I, each dose cohort will initially enroll three patients. If no dose-limiting toxicity (DLT) is observed by Day 28 in any patient of a cohort, then 3 patients will be treated with the next highest sirolimus dose. If 1 out of 3 patients in any cohort experiences a DLT, then 3 more patients will be enrolled in that cohort. If no more patients have a DLT by Day 28, then sirolimus dose escalation will proceed. If one or more patients experience a DLT then that dose level will be considered to be the maximum tolerated sirolimus dose, and Phase II patients will be treated at the next lowest level. Cyclosporine will be given as a twice daily oral dose.
Drug: Sirolimus · Drug: Cyclosporine
Oral loading dose followed by a once daily dose: * Cohort 1: Loading Dose - 1.2 mg; Daily Dose - 0.4 mg * Cohort 2: % Dose Increase - 100%; Loading Dose - 2.4 mg; Daily Dose - 0.8 mg * Cohort 3: % Dose Increase - 67%; Loading Dose - 3.9 mg; Daily Dose - 1.3 mg * Cohort 4: % Dose Increase - 50%; Loading Dose - 6.0 mg; Daily Dose - 2.0 mg
Dose of 5 mg/kg divided as a twice daily oral dose
Safety and tolerability of sirolimus and cyclosporine in each stratum of participants
Time frame: Measured at Month 6
Response rate
Time frame: Measured at Months 3 and 6
Duration of hematologic response
Time frame: Measured at Month 6
Rate of clonal disease evolution
Time frame: Measured at Month 6
Survival
Time frame: Measured at Month 6
This study is status unknown, as verified in Oct 2008. You cannot join it, but the record below documents what was studied.
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Office of Rare Diseases (ORD)