A Phase I/II Trial of Sirolimus (Rapamune) and Cyclosporine in Patients With Refractory Aplastic Anemia
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability of sirolimus and cyclosporine in each stratum of participants
Measured at Month 6
United States: Federal Government
|UCLA Center for Health Sciences||Los Angeles, California 90095|
|Lee Moffitt Cancer Center||Tampa, Florida 33606|
|Taussig Cancer Center, Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|Penn State University Cancer Center||Hershey, Pennsylvania 17033|