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)
- Conditions
- Essential Thrombocythemia
- Interventions
- Drug: Interferon alfa/pegylated interferon alfa
- Registration Number
- NCT06079879
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Best Available Therapy Anagrelide Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, 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 152 weeks at the investigators discretion. Best Available Therapy Interferon alfa/pegylated interferon alfa Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, 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 152 weeks at the investigators discretion. Best Available Therapy Busulfan Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, 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 152 weeks at the investigators discretion. Bomedemstat 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 152 weeks. Best Available Therapy Ruxolitinib Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, 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 152 weeks at the investigators discretion.
- Primary Outcome Measures
Name Time Method Durable Clinicohematologic Response (DCHR) Rate Up to approximately 52 weeks DCHR rate is the percentage of participants with DCHR, defined as a confirmed reduction of platelet count to ≤400 × 10\^9/L, absence of white blood cell (WBC) count elevation to \>10 × 10\^9/L locally assessed to be due to ET, and the absence of any thrombotic or major hemorrhagic events or disease progression to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) by Week 52.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score Baseline and pre-specified timepoints through Week 156 The MFSAF v4.0 is a 7-item participant-reported myelofibrosis symptom assessment which asks respondents to report symptom severity at its worst for each of the 7 items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. For this outcome measure, the change from baseline through Week 156 in scores for the individual item of fatigue severity will be presented.
Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score Baseline and pre-specified timepoints through Week 156 The PROMIS F SF-7a is a 7-item participant-reported assessment that measures both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 = never to 5 = always. Change from baseline in PROMIS Fatigue SF-7a through Week 156 will be presented.
Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0 Baseline and pre-specified timepoints through Week 156 The MFSAF v4.0 is a 7-item participant-reported myelofibrosis symptom assessment which asks respondents to report symptom severity at its worst for each of the 7 items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. MFSAF total score for all symptoms at baseline through Week 156 will be presented.
Duration of Clinicohematologic Response (DOCHR) Up to approximately 52 weeks For participants who demonstrate DCHR, duration of clinicohematologic response is defined as the time from the first documented evidence of confirmed reduction of platelet and WBC count until confirmed increase of platelet and WBC counts to above acceptable threshold, thrombotic or major hemorrhagic events or disease progression to MF, MDS or AML.
Duration of Hematologic Remission (DOHR) Up to approximately 52 weeks For participants who demonstrate hematologic remission, DOHR is defined as the time from the first documented evidence of platelet and WBC counts reduction until platelet or WBC counts increase to above acceptable threshold.
Percentage of Participants with Thrombotic Events Up to 156 weeks Thrombotic events include but are not limited to new or recurrent acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, thrombotic digital ischemia, or other thrombotic events.
Percentage of Participants with Major Hemorrhagic Events Up to 156 weeks Major hemorrhagic events include but are not limited to fatal bleeding, and/or symptomatic bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a decrease in hemoglobin level of 2 g/dL or more, or leading to transfusion of 2 or more units of whole blood or red cells.
Disease Progression Rate Up to approximately 52 weeks Disease progression rate is the percentage of participants with disease progression, defined as the transformation to post-essential thrombocythemia myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia as assessed by the adjudication committee. The disease progression rate of participants in each arm will be presented.
Number of Participants with An Adverse Event (AE) Up to 180 weeks An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Discontinuing From Study Therapy Due to an AE Up to 152 weeks An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an adverse event will be presented.
Trial Locations
- Locations (159)
Los Angeles Cancer Network ( Site 3491)
🇺🇸Glendale, California, United States
Stanford Cancer Institute ( Site 0107)
🇺🇸Stanford, California, United States
The Lundquist Institute ( Site 3423)
🇺🇸Torrance, California, United States
University of Colorado Anschutz Medical Campus ( Site 3425)
🇺🇸Aurora, Colorado, United States
Tufts Medical Center ( Site 3408)
🇺🇸Boston, Massachusetts, United States
University of Michigan ( Site 0008)
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital ( Site 3413)
🇺🇸Detroit, Michigan, United States
Roswell Park Cancer Institute ( Site 3421)
🇺🇸Buffalo, New York, United States
Duke University Health System (DUHS) ( Site 0016)
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Health-Internal Medicine, Section on Hematology & Oncology ( Site 3400)
🇺🇸Winston-Salem, North Carolina, United States
Scroll for more (149 remaining)Los Angeles Cancer Network ( Site 3491)🇺🇸Glendale, California, United StatesStudy CoordinatorContact213-977-1214