OHSU Knight Cancer Institute
This phase I trial studies the safety and side effects of low-dose sirolimus in treating patients with RUNX1 familial platelet disorder (FPD). RUNX1-FPD is a rare inherited disorder with symptoms such as mild to moderately low platelet count, abnormal platelet function, and an increased risk of developing cancers like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is caused by changes (variants) in the RUNX1 gene that is passed down (inherited) from an affected parent. Sirolimus is typically given to help prevent organ rejection in patients receiving kidney transplants. However, sirolimus may also be able to prevent RUNX1-FPD from progressing to cancers like MDS and AML by targeting another protein called mTORC1. Sirolimus may be a safe treatment for patients with RUNX1-FPD.
PRIMARY OBJECTIVE: I. Evaluate the safety and tolerability of low-dose sirolimus in patients with RUNX1 familial platelet disorder (RUNX1-FPD). SECONDARY OBJECTIVES: I. Evaluate platelet counts. II. Evaluate changes in somatic mutation variant allele frequency (VAF). III. Evaluate somatic mutation acquisition (i.e., mutation burden). IV. Evaluate the change in platelet function. V. Evaluate the change from baseline in bleeding score (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool \[ISTH-BAT\]). VI. Evaluate the change in mTORC1 downstream signaling. EXPLORATO…
Inclusion Criteria: * Patient has provided signed, informed consent before initiation of any study specific procedures * Aged ≥ 18 years at the time of signing the informed consent * Confirmed pathogenic/likely pathogenic (P/LP) germline RUNX1 variant per ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) RUNX1-specific variant curation rules * Patient must be willing to provide a bone marrow sample at time of screening and at the end of treatment with sirolimus * Platelet count of ≥ 50,000/µL * Creatinine clearance (CrCl) of ≥ 60 mL/min; estimated using the Cockcroft Gault fo…
Undergo collection of blood
Undergo bone marrow biopsy/aspiration
Undergo bone marrow biopsy/aspiration
Ancillary studies
Given PO
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