An Enzyme Inhibitor, Bomedemstat, for the Treatment of Essential Thrombocythemia or Polycythemia Vera That Has Failed at Least One Standard Therapy

Inclusion Criteria

• Diagnosis of essential thrombocythemia or polycythemia vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms
• Patients that have failed at least one standard therapy (failure is the equivalent of inadequate response or intolerance)
• Platelet count > 450 x 10^9/L pre-dose day 1 for patients with essential thrombocytopenia
• Platelet count > 150 x 10^9/L pre-dose day 1 for patients with polycythemia vera
• Peripheral blast count < 10% pre-dose day 1
• Absolute neutrophil count (ANC) >= 0.5 x 10^9/L pre-dose day 1
• Fibrosis score =< grade 2, as per a slightly modified version of the European Consensus Criteria for Grading Myelofibrosis
• Life expectancy > 36 weeks
• Able to swallow capsules
• Amenable to blood draws, spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study
• Must have discontinued prior therapy for condition under study for 2 weeks (4 weeks for interferon) prior to study drug initiation
• Agrees to use an approved method of contraception from Screening until 28 days after last administration of the study drug
• If male, agrees not to donate sperm or father a child for at least one month after the last dose of the study medication

Exclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater
• Currently pregnant, planning on being pregnant in the following 6 months or currently breastfeeding
• Currently residing outside the United States
• History of splenectomy
• Unresolved treatment related toxicities from prior therapies (unless resolved to =< grade 1)
• Uncontrolled active infection
• Known positive for human immunodeficiency virus (HIV) if not well-controlled (i.e., undetectable viral load), or infectious hepatitis, type A, B or C
• Current use of monoamine oxidase A and B inhibitors (MAOIs)
• Evidence at the time of screening of increased risk of bleeding, including any of the following: * Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal * International normalized ratio (INR) > 1.3 x the local upper limit of normal * History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment * Known bleeding disorder (e.g., dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand’s disorder, disseminated intravascular coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency)
• Evidence at the time of screening of significant renal or hepatic insufficiency (unless due to hemolysis, or leukemic infiltration) as defined by any of the following local lab parameters: * Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) < 40 mL/min or serum creatinine > 1.5 x the local upper limit of normal * Aspartate transaminase (AST) or alanine aminotransferase (ALT) >= 2 x the local upper limit of normal
• Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to MK-3543 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation
• Patients with impaired decision-making capacity