Familial Platelet Disorder Clinical Trial
Official title:
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.
Primary Objective: • Evaluate the safety and tolerability of low-dose sirolimus in participants with RUNX1 familial platelet disorder (RUNX1-FPD) Secondary Objectives: - Evaluate increases in platelet counts during and after treatment with low-dose sirolimus - Evaluate changes in somatic mutation variant allele frequency (VAF) - Monitor the rate of somatic mutation acquisition (ie, mutation burden) - Assess change in platelet aggregation score - Measure the change from baseline in bleeding score (ISTH-BAT) - Evaluate change in mTORC1 downstream signaling (pS6/EBP) Exploratory Objectives: - Measure rescue of elevated cytokine profiles - Evaluate reversal of myeloid skewing using flow cytometry - Determine changes in bone marrow (eg, megakaryocytic atypia and cellularity) - Assess changes in patient-reported outcomes measures (eg, EORTC and PRO-CTCAE) - Describe the pharmacokinetics of sirolimus in patients with RUNX1-FPD - Determine the correlation between sirolimus trough levels and each endpoint ;