Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder

Exclusion Criteria

• •Known allergy to sirolimus
• •History of lymphoma or other hematologic malignancies
• •Uncontrolled bleeding
• •Any prior diagnosis of myelodysplastic syndrome or other hematologic malignancy using International Working Group criteria
• •Prior treatment with sirolimus or a rapalog, mTOR inhibitor, or B-cell-depleting therapy within 28 days before study day 1
• •Treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4; eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, and clarithromycin), strong inducers of CYP3A4 (eg, rifampin and rifabutin), other drugs that could increase sirolimus blood concentrations (eg, bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors \[eg, ritonavir, indinavir, boceprevir, and telaprevir\], metoclopramide, nicardipine, troleandomycin, and verapamil), other drugs that could decrease sirolimus blood concentrations (eg, carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort \[Hypericum perforatum\]), or drugs with blood concentrations that could increase (eg, verapamil) within 7 days before study day 1
• •Use of cannabidiol, which can increase blood levels of sirolimus, within 7 days before study day 1
• •Myocardial infarction within 6 months before study day 1, congestive heart failure (New York Heart Association \> class II)
• •Total cholesterol \>300 mg/dL or triglyceride \>400 mg/dL
• •Arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months before study day 1
• •Infection requiring intravenous anti-infective treatment within 1 week of study day 1
• •Live vaccines (eg, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid) within 28 days before study day 1
• •Known diagnosis of chronic viral infection (eg, hepatitis B or C or HIV, and Epstein-Barr) or tuberculosis
• •Women who are pregnant, may become pregnant, or who are breastfeeding