Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy
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|ClinicalTrials.gov Identifier: NCT02979873|
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : September 13, 2022
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:
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
|Condition or disease||Intervention/treatment||Phase|
|Severe Aplastic Anemia||Drug: Sirolimus||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||118 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Trial of Sirolimus (Rapamune(R)) for Relapse Prevention in Patients With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy|
|Actual Study Start Date :||December 19, 2016|
|Estimated Primary Completion Date :||August 31, 2023|
|Estimated Study Completion Date :||August 31, 2023|
Sirolimus will be started on day 1 for subjects in the Sirolimus arm. A baseline CBC will be obtained within one week of randomization, or on Day 0. Thereafter, CBC will be monitored on a weekly basis for subjects in both arms. In the event of relapse (see definition of outcomes Section 6.7), the patient shall return to the NIH CRC for evaluation to include bone marrow biopsy and aspirate to exclude clonal evolution to MDS. Assessment will include (i) flow cytometry phenotyping of peripheral blood mononuclear cells for regulatory T-cells (Tregs, e.g. CD4+ CD25high FOXP3+) and regulatory dendritic cells (DCregs) and (ii) proteomics assay (research labs).
No Intervention: Standard of Care
- To determine if the rate of relapse at 24 months after CSA discontinuation can be improved by conversion to sirolimus in severe aplastic anemia patients who have responded to IST. [ Time Frame: 24 months ]Rate of relapse in both arms
- Safety and tolerability of sirolimus. [ Time Frame: 3 mo ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02979873
|Contact: Ivana Darden, R.N.||(301) email@example.com|
|Contact: Bhavisha A Patel, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Bhavisha A Patel, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|