Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007)
- Conditions
- Essential Thrombocythemia
- Interventions
- Registration Number
- NCT06456346
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of bomedemstat compared with hydroxyurea in cytoreductive therapy naïve essential thrombocythemia (ET) participants for whom cytoreductive therapy is indicated. Its primary objective is to compare bomedemstat to hydroxyurea with respect to durable clinicohematologic response (DCHR). The primary hypothesis is that bomedemstat is superior to hydroxyurea with respect to DCHR.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Diagnosis of Essential Thrombocythemia (ET) based on World Health Organization Criteria for myeloproliferative neoplasms, and an indication for cytoreductive therapy regardless of age or risk status
- 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 received no prior cytoreductive treatment for their ET
- Human Immunodeficiency Virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy
- Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load
- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable
- History of any illness/impairment of gastrointestinal function that might interfere with drug absorption
- History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has an active infection requiring systemic therapy
- Has had a major surgery <4 weeks prior to first dose of study intervention or has not recovered from side effects of major surgery >4 weeks prior to first dose
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bomedemstat Hydroxyurea placebo Participants will receive active bomedemstat and hydroxyurea placebo daily for up to approximately 52 weeks. 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. Participants who complete treatment at Week 52 will be eligible to continue treatment in the extended treatment phase. Unblinding will occur and placebo discontinued once all participants have completed at least 52 weeks of therapy or otherwise discontinued. Bomedemstat Bomedemstat Participants will receive active bomedemstat and hydroxyurea placebo daily for up to approximately 52 weeks. 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. Participants who complete treatment at Week 52 will be eligible to continue treatment in the extended treatment phase. Unblinding will occur and placebo discontinued once all participants have completed at least 52 weeks of therapy or otherwise discontinued. Hydroxyurea Hydroxyurea Participants will receive active hydroxyurea and bomedemstat placebo daily for up to 52 weeks. 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. Participants who complete treatment at Week 52 will be eligible to continue treatment in the extended treatment phase. Unblinding will occur and placebo discontinued once all participants have completed at least 52 weeks of therapy or otherwise discontinued. Hydroxyurea Bomedemstat placebo Participants will receive active hydroxyurea and bomedemstat placebo daily for up to 52 weeks. 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. Participants who complete treatment at Week 52 will be eligible to continue treatment in the extended treatment phase. Unblinding will occur and placebo discontinued once all participants have completed at least 52 weeks of therapy or otherwise discontinued.
- Primary Outcome Measures
Name Time Method Durable Clinicohematologic Response (DCHR) Rate Up to Week 52 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, starting by Week 24 and maintained for at least 24 weeks, 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 version 4.0 (MFSAF v4.0) Individual Fatigue Symptom Item Score Baseline and pre-specified timepoints up to Week 52 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.
Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score Baseline and pre-specified timepoints up to Week 52 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 MFSAF v4.0 Total Symptom Score Baseline and Week 52 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. The change from baseline in MFSAF total score for all symptoms will be presented.
Duration of Hematologic Remission (DOHR) Up to Week 52 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.
Number of Participants Who Experience Thrombotic Events Up to approximately 52 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.
Number of Participants Who Experience Major Hemorrhagic Events Up to approximately 52 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 Week 52 Disease progression rate is the percentage of participants with disease progression, defined as the transformation to post-essential thrombocythemia myelofibrosis, myelodysplastic syndrome, or AML as assessed by the adjudication committee.
Number of Participants Who Experience One or More Adverse Events (AEs) Up to approximately 52 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 Who Discontinue Study Intervention Due to an AE Up to approximately 52 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.
Trial Locations
- Locations (114)
Clinica Universidad de Navarra-Hematology Department ( Site 0485)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario Ramón y Cajal-Hematology ( Site 0484)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Costa del Sol-Hematology Service ( Site 0493)
🇪🇸Marbella, Malaga, Spain
Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0489)
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre ( Site 0494)
🇪🇸Madrid, Spain
Los Angeles Cancer Network ( Site 0025)
🇺🇸Glendale, California, United States
Stanford Cancer Center ( Site 0024)
🇺🇸Palo Alto, California, United States
Exempla Lutheran Medical Center ( Site 0014)
🇺🇸Golden, Colorado, United States
Parkview Research Center at Parkview Regional Medical Center ( Site 0006)
🇺🇸Fort Wayne, Indiana, United States
Duke University Health System (DUHS) ( Site 0012)
🇺🇸Durham, North Carolina, United States
Oregon Health & Science University ( Site 0018)
🇺🇸Portland, Oregon, United States
University of Texas Health Science Center at San Antonio ( Site 0021)
🇺🇸San Antonio, Texas, United States
University of Virginia ( Site 0020)
🇺🇸Charlottesville, Virginia, United States
VCU Health Adult Outpatient Pavillion ( Site 0008)
🇺🇸Richmond, Virginia, United States
Hospital Universitario Austral ( Site 0101)
🇦🇷Pilar, Buenos Aires, Argentina
Hospital Italiano de Buenos Aires ( Site 0102)
🇦🇷ABB, Caba, Argentina
C.I.C.E. 9 de Julio ( Site 0104)
🇦🇷San Miguel de Tucumán, Tucuman, Argentina
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares ( Site 0105)
🇦🇷Santa Fe, Argentina
Westmead Hospital ( Site 0201)
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0203)
🇦🇺Adelaide, South Australia, Australia
Monash Health-Haematology Research ( Site 0202)
🇦🇺Clayton, Victoria, Australia
Austin Health-Cancer Clinical Trials Centre ( Site 0206)
🇦🇺Heidelberg, Victoria, Australia
Royal Perth Hospital-Haematology ( Site 0204)
🇦🇺Perth, Western Australia, Australia
Ordensklinikum Linz GmbH Elisabethinen ( Site 0562)
🇦🇹Linz, Oberosterreich, Austria
Biocenter ( Site 0149)
🇨🇱Concepcion, Biobio, Chile
IC La Serena Research ( Site 0150)
🇨🇱La Serena., Coquimbo, Chile
FALP-UIDO ( Site 0148)
🇨🇱Santiago, Region M. De Santiago, Chile
Clínica Inmunocel ( Site 0147)
🇨🇱Santiago, Region M. De Santiago, Chile
Clínica Alemana de Santiago ( Site 0143)
🇨🇱Santiago, Region M. De Santiago, Chile
Bradfordhill-Clinical Area ( Site 0142)
🇨🇱Santiago, Region M. De Santiago, Chile
Fundacion Colombiana de Cancerología Clinica Vida ( Site 0164)
🇨🇴Medellín, Antioquia, Colombia
IMAT S.A.S ( Site 0162)
🇨🇴Monteria, Cordoba, Colombia
Los Cobos Medical Center ( Site 0165)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Rigshospitalet-Hematology - CTU ( Site 0321)
🇩🇰Copenhagen, Hovedstaden, Denmark
Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 0324)
🇩🇰Aarhus, Midtjylland, Denmark
Roskilde Sygehus-Department of Hematology ( Site 0323)
🇩🇰Roskilde, Sjaelland, Denmark
Odense Universitetshospital-Department of Hematology ( Site 0325)
🇩🇰Odense C, Syddanmark, Denmark
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet-Hematology ( Site 0349)
🇫🇷Nice, Alpes-Maritimes, France
CHU Bordeaux Haut-Leveque-service de mèdecine interne et maladies infectieuses ( Site 0346)
🇫🇷Pessac, Aquitaine, France
Hôpital de la Conception ( Site 0351)
🇫🇷Marseille, Bouches-du-Rhone, France
Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE ( Site 0352)
🇫🇷Toulouse, Haute-Garonne, France
Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren ( Site 0344)
🇫🇷Limoges, Haute-Vienne, France
Centre Hospitalier Régional Universitaire de Tours - Hôpital-Hématologie et Thérapie Cellulaire ( Site 0342)
🇫🇷Tours, Indre-et-Loire, France
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu ( Site 0347)
🇫🇷Nantes, Loire-Atlantique, France
centre hospitalier lyon sud ( Site 0343)
🇫🇷Pierre-Bénite, Rhone, France
HENRI MONDOR HOSPITAL ( Site 0348)
🇫🇷Creteil, Val-de-Marne, France
Hopital Saint-Louis ( Site 0341)
🇫🇷Paris, France
VK&K Studien GbR ( Site 0370)
🇩🇪Landshut, Bayern, Germany
Medizinische Hochschule Hannover-Department of Hematology, Hemostasis, Oncology and Stem Cell Trans ( Site 0371)
🇩🇪Hannover, Niedersachsen, Germany
Universitätsklinikum Aachen ( Site 0367)
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Universitaetsklinikum Essen ( Site 0366)
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz-3. Medizinische Klinik und Poliklinik ( Site 0365)
🇩🇪Mainz, Rheinland-Pfalz, Germany
Universitätsklinikum Halle ( Site 0361)
🇩🇪Halle, Sachsen-Anhalt, Germany
Ehime University Hospital ( Site 0612)
🇯🇵Toon, Ehime, Japan
Universitätsklinikum Jena-Klinik für Innere Medizin II, Abt. Hämatologie und Internistische Onkolog ( Site 0364)
🇩🇪Jena, Thuringen, Germany
Queen Mary Hospital ( Site 0221)
🇭🇰Hksar, Hong Kong
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Belgyógyászati Klinika ( Site 0407)
🇭🇺Szeged, Csongrad, Hungary
Petz Aladar Egyetemi Oktato Korhaz-Hematológia ( Site 0405)
🇭🇺Gyor, Gyor-Moson-Sopron, Hungary
Somogy Vármegyei Kaposi Mór Oktató Kórház-Haematológiai osztály ( Site 0406)
🇭🇺Kaposvár, Somogy, Hungary
Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 0404)
🇭🇺Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary
Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0402)
🇭🇺Debrecen, Hungary
Soroka Medical Center ( Site 0427)
🇮🇱Be'er Sheva, Israel
Rambam Health Care Campus ( Site 0429)
🇮🇱Haifa, Israel
Carmel Hospital ( Site 0426)
🇮🇱Haifa, Israel
Hadassah Medical Center ( Site 0424)
🇮🇱Jerusalem, Israel
Rabin Medical Center ( Site 0425)
🇮🇱Petah Tikva, Israel
Sheba Medical Center ( Site 0428)
🇮🇱Ramat Gan, Israel
Sourasky Medical Center ( Site 0422)
🇮🇱Tel Aviv, Israel
Yitzhak Shamir Medical Center. ( Site 0421)
🇮🇱Zerifin, Israel
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 0443)
🇮🇹Alessandria, Ancona, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 0447)
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Universitaria Careggi ( Site 0441)
🇮🇹Firenze, Toscana, Italy
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0446)
🇮🇹Bologna, Italy
Fondazione IRCCS Policlinico San Matteo-Oncology ( Site 0444)
🇮🇹Pavia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0445)
🇮🇹Roma, Italy
Ospedale di Circolo e Fondazione Macchi Varese ( Site 0442)
🇮🇹Varese, Italy
Fujita Health University Hospital ( Site 0613)
🇯🇵Toyoake, Aichi, Japan
Hokkaido University Hospital ( Site 0601)
🇯🇵Sapporo, Hokkaido, Japan
Kobe City Medical Center General Hospital ( Site 0603)
🇯🇵Kobe, Hyogo, Japan
Kanazawa University Hospital ( Site 0614)
🇯🇵Kanazawa, Ishikawa, Japan
Mie University Hospital ( Site 0615)
🇯🇵Tsu, Mie, Japan
National Hospital Organization Sendai Medical Center ( Site 0617)
🇯🇵Sendai, Miyagi, Japan
Kansai Medical University Hospital ( Site 0607)
🇯🇵Hirakata, Osaka, Japan
Kindai University Hospital ( Site 0600)
🇯🇵Osakasayama, Osaka, Japan
Juntendo University Hospital ( Site 0611)
🇯🇵Bunkyo-ku, Tokyo, Japan
University of Yamanashi Hospital ( Site 0606)
🇯🇵Chuo, Yamanashi, Japan
Kyushu University Hospital ( Site 0605)
🇯🇵Fukuoka, Japan
Fukushima Medical University Hospital ( Site 0616)
🇯🇵Fukushima, Japan
University of Miyazaki Hospital ( Site 0609)
🇯🇵Miyazaki, Japan
Okayama University Hospital ( Site 0604)
🇯🇵Okayama, Japan
Nippon Medical School Hospital ( Site 0608)
🇯🇵Tokyo, Japan
Medivest Centro de Investigación Integral ( Site 0183)
🇲🇽Chihuahua City, Chihuahua, Mexico
Higiea Oncologia ( Site 0184)
🇲🇽Mexico City, Distrito Federal, Mexico
Centro de Investigacion Clinica de Oaxaca ( Site 0181)
🇲🇽Oaxaca de Juarez., Oaxaca, Mexico
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie-Oddział Hematoonkologii, Transplantacji Szp ( Site 0463)
🇵🇱Lublin, Lubelskie, Poland
Pratia Onkologia Katowice ( Site 0461)
🇵🇱Katowice, Slaskie, Poland
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 0466)
🇵🇱Kielce, Swietokrzyskie, Poland
Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0490)
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla-Haematology ( Site 0486)
🇪🇸Santander, Cantabria, Spain
HOSPITAL CLÍNIC DE BARCELONA ( Site 0481)
🇪🇸Barcelona, Cataluna, Spain
Institut Català d'Oncologia - L'Hospitalet ( Site 0482)
🇪🇸L'Hospitalet de Llobregat, Cataluna, Spain
Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca-Hematology ( Site 0488)
🇪🇸Salamanca, Spain
Universitetssjukhuset Örebro ( Site 0542)
🇸🇪Örebro, Orebro Lan, Sweden
Skånes Universitetssjukhus Lund-Department of Hematology ( Site 0544)
🇸🇪Lund, Skane Lan, Sweden
Karolinska Universitetssjukhuset Huddinge ( Site 0541)
🇸🇪Huddinge, Stockholms Lan, Sweden
Akademiska sjukhuset ( Site 0545)
🇸🇪Uppsala, Uppsala Lan, Sweden
Sahlgrenska Universitetssjukhuset-Department of hematology and coagulation ( Site 0543)
🇸🇪Gothenburg, Vastra Gotalands Lan, Sweden
Chang Gung Memorial Hospital- Chiayi ( Site 0242)
🇨🇳Chiayi City, Chiayi, Taiwan
National Cheng Kung University Hospital-Clinical Trial Center ( Site 0245)
🇨🇳Tainan, Taiwan
National Taiwan University Hospital ( Site 0241)
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch ( Site 0243)
🇨🇳Taoyuan, Taiwan
Glan Clwyd Hospital ( Site 0528)
🇬🇧Bodelwyddan, Denbighshire, United Kingdom
Hammersmith Hospital ( Site 0533)
🇬🇧London, London, City Of, United Kingdom
Royal Gwent Hospital ( Site 0524)
🇬🇧Gwent, Newport, United Kingdom