This phase II trial studies how well LSD1 inhibitor MK-3543 works for the treatment of essential thrombocythemia. LSD1 inhibitor MK-3543 works by turning off the activity of an enzyme called LSD1 (lysine-specific demethylase 1) which is present at low levels in cells of all people. High levels of LSD1 inside the abnormal stem cells of essential thrombocythemia patients are believed to block the cells from becoming mature cells that function normally; instead, the abnormal cells continue to be made. This, in turn, lowers the abnormal red cell and platelet counts seen in patients with essential thrombocythemia. LSD1 inhibitor MK-3543 may decrease spleen size and other inflammatory markers which are believed to cause symptoms in these diseases.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04081220.
PRIMARY OBJECTIVES:
I. To assess the hematologic effects of LSD1 inhibitor MK-3543 (MK-3543) in a population of essential thrombocythemia (ET) patients requiring platelet control who are resistant to or intolerant of hydroxyurea per European Leukemia Net (ELN) criteria.
II. To qualitatively examine markers of disease burden including patient-reported symptom burden, standard ARUP testing of mutant (variant) allele burden in granulocytes (baseline and week 24), spleen size, and bone marrow histology.
OUTLINE:
Patients receive LSD1 inhibitor MK-3543 orally (PO) once daily (QD). Treatment continues for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit receive LSD1 inhibitor MK-3543 for an additional 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy (BMB) and bone marrow aspiration (BMA) throughout the study.
After completion of study treatment, patients are followed up at 28 days.
Lead OrganizationCancer Therapy and Research Center at The UT Health Science Center at San Antonio
Principal InvestigatorZohra Nooruddin
