Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder
To learn about the safety and effects of low-dose sirolimus in participants with RUNX1-FPD.
- EligibilityCriteria: Inclusion Criteria:  Participants has provided signed, informed consent before initiation of any study specific procedures Aged ≥18 years at the time of signing the informed consent Confirmed P/LP germline RUNX1 variant per ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) RUNX1-specific variant curation rules80 Participants must be willing to provide bone marrow sample at time of screening and at the end of treatment with sirolimus Platelet count of ≥50,000/µL Adequate renal function: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation, >30 mL/min/1.73m2 Adequate hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × upper limit of normal (ULN) and total bilirubin <1.5 × ULN Adequate cardiac function: left ventricular ejection fraction >50%  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 - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult