A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006)

Purpose

This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential thrombocythemia (ET) who have an inadequate response to or are intolerant of hydroxyurea. The primary study hypothesis is that bomedemstat is superior to the best available therapy with respect to durable clinicohematologic response (DCHR).

Condition

  • Essential Thrombocythemia

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms (confirmed by a central pathologist) - Has a centrally assessed bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the European Consensus Criteria for Grading Myelofibrosis - Has a history of inadequate response to or intolerance of hydroxyurea based on modified European LeukemiaNet (ELN) criteria for hydroxyurea resistance or intolerance - Has an inadequate or loss of response to their most recent prior ET therapy, requiring a change of cytoreductive therapy - Has a platelet count > 450 × 10^9/L (450k /μL) assessed up to 72 hours before first dose of study intervention - Has an absolute neutrophil count (ANC) ≥0.75 × 10^9/L assessed up to 72 hours before first dose of study intervention - Participants may have received up to 3 prior ET-directed cytoreductive agents including hydroxyurea

Exclusion Criteria

  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or lysine demethylase or monoamine oxidase inhibitor (LSDi or MAOi) or the chosen best available therapy (including anagrelide, interferon alfa/pegylated interferon, ruxolitinib, or busulfan) that contraindicates participation - History of any illness/impairment of GI function that might interfere with drug absorption (eg, chronic diarrhea or history of gastric bypass surgical procedure), confound the study results or pose an additional risk to the individual by participation in the study - Evidence at the time of Screening of increased risk of bleeding - History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder - Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Bomedemstat 		Participants will begin treatment at a dose of 50 mg of bomedemstat daily. Dosage will be adjusted either up or down within specified time parameters for each participant to the dose that provides sufficient exposure to safely inhibit thrombopoiesis to decrease platelet counts to the target range. All participants will be treated daily for up to 52 weeks, and are eligible for an extended treatment phase up to 156 weeks.
  • Drug: Bomedemstat
    Oral Capsule
    Other names:
    • MK-3543
    • IMG-7289
    • Bomedemstat tosylate
Active Comparator
Best Available Therapy 		Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 156 weeks at the investigators discretion.
  • Drug: Anagrelide
    Oral Capsule
  • Drug: Busulfan
    Oral Tablet
  • Drug: Interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b
    Subcutaneous Solution
  • Drug: Ruxolitinib
    Oral Tablet

Recruiting Locations

Los Angeles Cancer Network ( Site 3491)
Glendale 5352423, California 5332921 91206
Contact:
Study Coordinator
213-977-1214

Stanford Cancer Institute ( Site 0107)
Stanford 5398563, California 5332921 94305-5826
Contact:
Study Coordinator
650-497-6575

The Lundquist Institute ( Site 3423)
Torrance 5403022, California 5332921 90502
Contact:
Study Coordinator
323-457-1378

University of Colorado Anschutz Medical Campus ( Site 3425)
Aurora 5412347, Colorado 5417618 80045
Contact:
Study Coordinator
720-848-9260

Tufts Medical Center ( Site 3408)
Boston 4930956, Massachusetts 6254926 02111
Contact:
Study Coordinator
617-636-2675

University of Michigan ( Site 0008)
Ann Arbor 4984247, Michigan 5001836 48109
Contact:
Study Coordinator
734-615-3137

Henry Ford Hospital ( Site 3413)
Detroit 4990729, Michigan 5001836 48202
Contact:
Study Coordinator
313-556-8833

Roswell Park Cancer Institute ( Site 3421)
Buffalo 5110629, New York 5128638 14263
Contact:
Study Coordinator
317-966-5359

Duke University Health System (DUHS) ( Site 0016)
Durham 4464368, North Carolina 4482348 27710
Contact:
Study Coordinator
919-668-1608

Wake Forest Baptist Health-Internal Medicine, Section on Hematology & Oncology ( Site 3400)
Winston-Salem 4499612, North Carolina 4482348 27157
Contact:
Study Coordinator
336-713-5440

Medical University of South Carolina-Hollings Cancer Center ( Site 3426)
Charleston 4574324, South Carolina 4597040 29425
Contact:
Study Coordinator
843-792-9300

University of Virginia ( Site 3422)
Charlottesville 4752031, Virginia 6254928 22908
Contact:
Study Coordinator
434-310-0987

VCU Health Adult Outpatient Pavillion ( Site 3416)
Richmond 4781708, Virginia 6254928 23219
Contact:
Study Coordinator
804-828-2177

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com