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

NCT02979873 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 17001917-H-0019
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Severe Aplastic Anemia

Keywords

Rapamycin; Relapse Prevention; Immune Tolerance

Outcome Measures

Primary Outcomes (1)

• 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.

  Rate of relapse in both arms

  24 months

Secondary Outcomes (1)

• Safety and tolerability of sirolimus.

  3 mo

Study Arms (2)

Sirolimus

EXPERIMENTAL

sirolimus

Drug: Sirolimus

Standard of Care

NO INTERVENTION

no intervention

Interventions

Sirolimus DRUG

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).

Sirolimus

Eligibility Criteria

• Age: 2 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 2 years old
• Weight greater than 12 kg
• Previous diagnosis of SAA by bone marrow biopsy and cytogenetics, treated with lymphodepleting therapy ATG, cyclophosphamide or alemtuzumab that included cyclosporine. The lymphodepleting therapy must have been administered at least 12 months prior.
• Continuous treatment with cyclosporine for the previous 6 months (excluding minor dose delays not exceeding more than 30 days).
• Evidence of a hematologic response to an lymphodepletion-based regimen as evidence of at least two of the following:
• Absolute neutrophil count greater than or equal to 500/uL
• Platelet count greater than or equal to 20,000/uL (without transfusion support)
• Absolute reticulocyte count greater than or equal to 60,000/uL (or hemoglobin 10 gm/dL without transfusion support)

You may not qualify if:

• Evidence of relapse of aplastic anemia due to cyclosporine withdrawal during the previous 6 months
• Prior use of sirolimus or other mTOR inhibitor within 12 weeks of study entry
• Myelodysplastic syndrome or acute myeloid leukemia, according to WHO diagnostic criteria (if baseline BM consistent with MDS after enrollment, patients will be considered ineligible and immediately exit the study, and the subject can be replaced with another subject)
• Patients that are on CYP3A4 inhibitors and cannot replace these medications with other equivalent medications for the period of study: protease inhibitors (ritonavir, indinavir, nelfinavir, saquinavir), some macrolide antibiotics (clarithromycin, telithromycin, erythromycin), azole anti-fungals (fluconazole, itraconazole, ketoconazole), metroclopramide, felodipine, nifedipine, carbamazepine, phenobarbital, grapefruit juice and St. John s Wort.
• Anaphylactic or hypersensitivity reaction to sirolimus
• Patients with infections not adequately responding to appropriate therapy as evidenced by persistence of a clear source of infection that, in the view of the investigator, would preclude safe treatment with sirolimus.
• Current pregnancy, or unwillingness to take oral contraceptives or use the barrier methods of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during the course of the study 8. Lactating women, due to the potentially harmful effects on the nursing child.
• \. Patients who have received live vaccines within the past 30 days
• \. Patients with cancer who are actively receiving chemotherapeutic treatment or who take drugs with hematological effects such as thrombopoietin receptor agonists (such as eltrombopag), granulocyte-colony stimulating factor or erythroid stimulating agents.
• \. Moribund status such that death within 7 to 10 days is likely. Comorbidities of such severity that in the view of the Investigator it would likely preclude the patient's ability to tolerate sirolimus.
• \. Inability to understand the investigational nature of the study or to give informed consent or without a legally authorized representative or surrogate that can provide informed consent.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Bhavisha A Patel, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 2, 2016
• Study Start: December 19, 2016
• Primary Completion: September 4, 2025
• Study Completion (Estimated): June 30, 2030
• Last Updated: January 16, 2026

Record last verified: 2026-01-06

Locations

US (1)