Last updated on November 2018

Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy

Brief description of study


People with severe aplastic anemia (SAA) do not make enough red and white blood cells, and/or platelets. Their body's immune system stops the bone marrow from making these cells. The treatment cyclosporine leads to better blood counts. But when this treatment is stopped, the disease may return in 1 in 3 people. The drug sirolimus may help by suppressing the immune system.


To evaluate and compare the usefulness of sirolimus in preventing aplastic anemia from returning after cyclosporine is stopped, compared with stopping cyclosporine alone.


People ages 2 and older with SAA who:

Have responded to immunosuppressive therapy that includes cyclosporine, and continue to take cyclosporine

Are not taking drugs with hematologic effects


Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Bone marrow biopsy: The area above the hipbone will be numbed. A thin needle will remove

some bone marrow.

Participants will be randomly assigned to a group. All will stop cyclosporine. Group 1 will take sirolimus by mouth at the same time each day for 3 months with close monitoring. Group 2 will not receive the study drug but will be monitored closely.

Participants will have clinical tests for the first 3 months:

Weekly blood test

Monthly fasting blood test

For group 1, measurements of sirolimus in the blood every 1 2 weeks

Participants will have clinic visits at 3 months, 12 months, and annually for 5 years after the study starts. They may have another visit if their SAA returns. These will include:

Blood and urine tests

Bone marrow biopsy

Detailed Study Description

  • Most acquired aplastic anemia ensues from immune-mediated destruction of hematopoietic stem and progenitor cells
    • Immunosuppression is the definitive treatment of patients with acquired aplastic anemia who are not candidates for immediate hematopoietic stem cell transplantation.
    • Horse ATG combined with the calcineurin inhibitor, cyclosporine (CsA), remains standard as first-line immunosuppressive therapy (IST).
    • Hematologic responses to transfusion independence occur in about two thirds of patients with standard IST and in 80-90% of patients treated with IST in combination with the growth factor eltrombopag.
    • About 30% to 40% of patients relapse after discontinuation of cyclosporine. Many achieve disease control after the reinitiation of CSA, but remain CSA dependent indefinitely.
    • Evidence from mouse models of bone marrow failure indicates that conversion from cyclosporine to the mTOR inhibitor, sirolimus (SRL), results in immune tolerance which can endure the eventual withdrawal of SRL.
    • We hypothesize that CSA to SRL conversion will significantly decrease the relapse rate after immunosuppressive therapy for acquired aplastic anemia.
    • This study will investigate the safety and efficacy of SRL for preventing relapse in patients previously treated with IST who remain on CSA. The primary endpoint is rate of relapse at 2 years following conversion from CSA to SRL, versus stopping CSA.
    • Biological sampling of peripheral blood and bone marrow aspirates during treatment will be used to investigate changes to lymphocyte phenotypes and cytokine profiles.

Clinical Study Identifier: NCT02979873

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National Institutes of Health Clinical Center
Bethesda, MD United States
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Recruitment Status: Open

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