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

INCLUSION CRITERIA:

• 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 withlymphodepleting therapy ATG, cyclophosphamide or alemtuzumab that includedcyclosporine. The lymphodepleting therapy must have been administered at least 12months prior.

• Continuous treatment with cyclosporine for the previous 6 months (excluding minordose delays not exceeding more than 30 days).

• Evidence of a hematologic response to an lymphodepletion-based regimen as evidenceof 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)

EXCLUSION CRITERIA:

• Evidence of relapse of aplastic anemia due to cyclosporine withdrawal during theprevious 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 diagnosticcriteria (if baseline BM consistent with MDS after enrollment, patients will beconsidered ineligible and immediately exit the study, and the subject can bereplaced with another subject)

• Patients that are on CYP3A4 inhibitors and cannot replace these medications withother 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 asevidenced by persistence of a clear source of infection that, in the view of theinvestigator, would preclude safe treatment with sirolimus.

• Current pregnancy, or unwillingness to take oral contraceptives or use the barriermethods of birth control or practice abstinence to refrain from pregnancy if ofchildbearing potential during the course of the study 8. Lactating women, due to thepotentially 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 whotake drugs with hematological effects such as thrombopoietin receptor agonists (suchas eltrombopag), granulocyte-colony stimulating factor or erythroid stimulatingagents.

• Moribund status such that death within 7 to 10 days is likely. Comorbidities of suchseverity that in the view of the Investigator it would likely preclude the patient'sability to tolerate sirolimus.

• Inability to understand the investigational nature of the study or to give informedconsent or without a legally authorized representative or surrogate that can provideinformed consent.