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

A vizsgálat adatai

Ki végzi

National Heart, Lung, and Blood Institute (NHLBI)

Azonosító

NCT02979873

A regiszteradat frissítve

2026. október 6.

Eredeti leírás

Background:A teljes eredeti leírásKevesebb

A Randomized Trial of Sirolimus (Rapamune(R)) for Relapse Prevention in Patients With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy

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. Immunosuppression (IST) with anti-thymocyte globulin (ATG) and cyclosporine (CSA) leads to better blood counts. But when cyclosporine is stopped, the disease may return in 1 in 3 people. The drug sirolimus (SRL) may help by suppressing the immune system to prevent the return of aplastic anemia.

Objective:

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

Eligibility:

1. People ages 2 and older with SAA who: 2. Have responded to IST and continue to take cyclosporine 3. Are not taking drugs with hematologic effects

Study Design:

Participants will be screened with:

• Medical history, physical exam, blood and urine tests, bone marrow biopsy and aspirate.

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 12 weeks with close monitoring. Group 2 will not receive the study drug but will be monitored closely (Observation arm).

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.

Bevonási feltételek: 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).

Kizáró feltételek: 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; 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; 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; 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; 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); Anaphylactic or hypersensitivity reaction to 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; 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.

ClinicalTrials.gov NCT02979873