RecruitingPhase 3NCT06079879

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)

A Phase 3, Randomized, Open-label, Active-Comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543/IMG-7289) Versus Best Available Therapy (BAT) in Participants With Essential Thrombocythemia Who Have an Inadequate Response to or Are Intolerant of Hydroxyurea


Sponsor

Merck Sharp & Dohme LLC

Enrollment

340 participants

Start Date

Dec 31, 2023

Study Type

INTERVENTIONAL

Conditions

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).


Eligibility

Min Age: 18 Years

Inclusion Criteria7

  • 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 Criteria5

  • 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

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Interventions

DRUGBomedemstat

Oral Capsule

DRUGAnagrelide

Oral Capsule

DRUGBusulfan

Oral Tablet

DRUGInterferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b

Subcutaneous Solution

DRUGRuxolitinib

Oral Tablet


Locations(161)

Palo Verde Hematology/ Oncology Center, Ltd. ( Site 3496)

Glendale, Arizona, United States

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

Optum Care Cancer Center ( Site 3497)

Las Vegas, Nevada, 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

Medical University of South Carolina-Hollings Cancer Center ( Site 3426)

Charleston, South Carolina, United States

University of Virginia ( Site 3422)

Charlottesville, Virginia, United States

VCU Health Adult Outpatient Pavillion ( Site 3416)

Richmond, Virginia, United States

Hospital Universitario Austral ( Site 0104)

Pilar, Buenos Aires, Argentina

Hospital Italiano de Buenos Aires ( Site 0105)

ABB, Buenos Aires F.D., Argentina

C.I.C.E. 9 de Julio ( Site 1001)

San Miguel de Tucumán, Tucumán Province, Argentina

Royal Prince Alfred Hospital ( Site 1100)

Camperdown, New South Wales, Australia

Liverpool Hospital-Haematology ( Site 0501)

Liverpool, New South Wales, Australia

Royal North Shore Hospital ( Site 0003)

St Leonards, New South Wales, Australia

Calvary Mater Newcastle ( Site 0505)

Waratah, New South Wales, Australia

Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0001)

Adelaide, South Australia, Australia

Monash Health-Haematology Research ( Site 0006)

Clayton, Victoria, Australia

Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0502)

Melbourne, Victoria, Australia

Royal Perth Hospital-Haematology ( Site 0504)

Perth, Western Australia, Australia

ZAS Cadix ( Site 1200)

Antwerp, Belgium

The Moncton Hospital-Oncology ( Site 1500)

Moncton, New Brunswick, Canada

The First Afflilated Hospital of Bengbu Medical College ( Site 3509)

Bengbu, Anhui, China

Anhui Provincial Hospital ( Site 3513)

Hefei, Anhui, China

Peking University Third Hospital-Hematology ( Site 3502)

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital ( Site 3531)

Beijing, Beijing Municipality, China

The Second Affiliated Hospital Of Fujian Medical University ( Site 3525)

Quanzhou, Fujian, China

The First Affiliated hospital of Xiamen University ( Site 3515)

Xiamen, Fujian, China

Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 3524)

Guangzhou, Guangdong, China

Southern Medical University Nanfang Hospital-Department of Hematopathology ( Site 3511)

Guangzhou, Guangdong, China

The First Hospital of Hebei Medical University ( Site 3510)

Shijiazhuang, Hebei, China

Henan Cancer Hospital-hematology department ( Site 3504)

Zhengzhou, Henan, China

Wuhan Union Hospital ( Site 3500)

Wuhan, Hubei, China

Jiangsu Province Hospital ( Site 3507)

Nanjing, Jiangsu, China

Affiliated Hospital of Nantong University ( Site 3527)

Nantong, Jiangsu, China

The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 3505)

Nanchang, Jiangxi, China

The First Hospital of Jilin University-Hematology ( Site 3526)

Changchun, Jilin, China

Shaanxi provincial people's hospital ( Site 3516)

Xi'an, Shaanxi, China

Jinan Central Hospital ( Site 3523)

Jinan, Shandong, China

Zhongshan Hospital,Fudan University-Hematology ( Site 3530)

Shanghai, Shanghai Municipality, China

Huashan Hospital, Fudan University ( Site 3529)

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuan University ( Site 3518)

Chengdu, Sichuan, China

Institute of hematology&blood disease hospital ( Site 3501)

Tianjin, Tianjin Municipality, China

The first Affiliated Hospital, Zhejiang University School of Medicine ( Site 3508)

Hangzhou, Zhejiang, China

Zhejiang University School of Medicine-The Fourth Affiliated Hospital ( Site 3517)

Yiwu, Zhejiang, China

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1403)

Medellín, Antioquia, Colombia

Los Cobos Medical Center ( Site 1404)

Bogotá, Bogota D.C., Colombia

IMAT S.A.S ( Site 1401)

Montería, Departamento de Córdoba, Colombia

Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou ( Site 0417)

Rennes, Brittany Region, France

Centre Hospitalier Régional Universitaire de Tours - Hôpital-Hématologie et Thérapie Cellulaire ( Site 0413)

Tours, Indre-et-Loire, France

Centre Hospitalier Universitaire de Limoges - Hôpital Dupuyt-Hématologie Clinique et Thérapie Cellu ( Site 1701)

Limoges, Limousin, France

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois-HEMATOLOGY ( Site 0407)

Vandœuvre-lès-Nancy, Lorraine, France

Centre Hospitalier de Roubaix ( Site 1703)

Roubaix, Nord, France

centre hospitalier lyon sud ( Site 0406)

Pierre-Bénite, Rhone, France

Hôpital Saint-Louis-Centre d'Investigations Cliniques ( Site 0405)

Paris, France

Hôpital Saint Antoine-Service d'Hématologie et de Thérapie Cellulaire ( Site 1702)

Paris, Île-de-France Region, France

Universitätsklinikum Aachen ( Site 1801)

Aachen, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0402)

Dresden, Saxony, Germany

Universitätsklinikum Halle ( Site 0401)

Halle, Saxony-Anhalt, Germany

Queen Mary Hospital ( Site 1901)

Hksar, Hong Kong

Petz Aladar Egyetemi Oktato Korhaz ( Site 2000)

Győr, Győr-Moson-Sopron, Hungary

Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 0706)

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 0708)

Budapest, Hungary

Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0707)

Debrecen, Hungary

Soroka Medical Center ( Site 2100)

Beersheba, Israel

Rambam Health Care Campus ( Site 2102)

Haifa, Israel

Carmel Hospital ( Site 0906)

Haifa, Israel

Hadassah Medical Center ( Site 0904)

Jerusalem, Israel

Rabin Medical Center ( Site 0905)

Petah Tikva, Israel

Sheba Medical Center ( Site 2101)

Ramat Gan, Israel

Sourasky Medical Center ( Site 0902)

Tel Aviv, Israel

Yitzhak Shamir Medical Center. ( Site 0901)

Ẕerifin, Israel

Azienda Ospedaliero Universitaria di Ferrara ( Site 0304)

Cona, Ferrara, Italy

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0308)

Meldola, Forli-Cesena, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 2201)

Milan, Lombardy, Italy

Azienda Ospedaliera Universitaria Careggi ( Site 0030)

Florence, Tuscany, Italy

Azienda Ospedaliero Universitaria Pisana-UO Ematologia UNIV ( Site 0309)

Pisa, Tuscany, Italy

Istituto Oncologico Veneto IRCCS-Oncoematologia ( Site 0306)

Castelfranco Veneto, Veneto, Italy

Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 0034)

Alessandria, Italy

Azienda Ospedaliero Universitaria delle Marche ( Site 0302)

Ancona, Italy

Arcispedale Santa Maria Nuova ( Site 0301)

Reggio Emilia, Italy

Ospedale Mauriziano ( Site 0305)

Torino, Italy

Ospedale di Circolo e Fondazione Macchi Varese ( Site 2200)

Varese, Italy

Fujita Health University Hospital ( Site 3613)

Toyoake, Aichi-ken, Japan

National Cancer Center Hospital East ( Site 3610)

Kashiwa, Chiba, Japan

Ehime University Hospital ( Site 3612)

Tōon, Ehime, Japan

Hokkaido University Hospital ( Site 3601)

Sapporo, Hokkaido, Japan

Kobe City Medical Center General Hospital ( Site 3603)

Kobe, Hyōgo, Japan

Kanazawa University Hospital ( Site 3614)

Kanazawa, Ishikawa-ken, Japan

Mie University Hospital ( Site 3615)

Tsu, Mie-ken, Japan

National Hospital Organization Sendai Medical Center ( Site 3617)

Sendai, Miyagi, Japan

Kansai Medical University Hospital ( Site 3607)

Hirakata, Osaka, Japan

Kindai University Hospital ( Site 3600)

Sakai, Osaka, Japan

Juntendo University Hospital ( Site 3611)

Bunkyo-ku, Tokyo, Japan

Nippon Medical School Hospital ( Site 3608)

Bunkyo-ku, Tokyo, Japan

University of Yamanashi Hospital ( Site 3606)

Chūō, Yamanashi, Japan

Kyushu University Hospital ( Site 3605)

Fukuoka, Japan

Fukushima Medical University Hospital ( Site 3616)

Fukushima, Japan

University of Miyazaki Hospital ( Site 3609)

Miyazaki, Japan

Okayama University Hospital ( Site 3604)

Okayama, Japan

Spaarne Gasthuis - Hoofddorp-Oncology ( Site 2301)

Hoofddorp, North Holland, Netherlands

Albert Schweitzer Ziekenhuis, locatie Dordwijk-Internal Medicine ( Site 2302)

Dordrecht, South Holland, Netherlands

University Medical Center Groningen ( Site 2304)

Groningen, Netherlands

Martini Ziekenhuis ( Site 2300)

Groningen, Netherlands

North Shore Hospital-Department of Haematology ( Site 0051)

Auckland, New Zealand

Aotearoa Clinical Trials ( Site 0050)

Auckland, New Zealand

Pratia Onkologia Katowice ( Site 0702)

Katowice, Silesian Voivodeship, Poland

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 2504)

Kielce, Świętokrzyskie Voivodeship, Poland

Unidade Local de Saude de Braga - Hospital de Braga ( Site 0415)

Braga, Portugal

Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 2600)

Lisbon, Portugal

Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 0414)

Porto, Portugal

Seoul National University Bundang Hospital-Hematology ( Site 0605)

Seongnam, Kyonggi-do, South Korea

Korea University Anam Hospital ( Site 0604)

Seoul, South Korea

Asan Medical Center ( Site 0603)

Seoul, South Korea

The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 0606)

Seoul, South Korea

Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0409)

Badalona, Barcelona, Spain

Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 2801)

L'Hospitalet Del Llobregat, Barcelona, Spain

Hospital del Mar ( Site 2807)

Barcelona, Catalonia, Spain

HOSPITAL CLÍNIC DE BARCELONA ( Site 2800)

Barcelona, Catalonia, Spain

CHUS - Hospital Clinico Universitario ( Site 0421)

Santiago de Compostela, La Coruna, Spain

Hospital Universitario Ramón y Cajal-Hematology ( Site 2803)

Madrid, Madrid, Comunidad de, Spain

Hospital Costa del Sol-Hematology Service ( Site 0412)

Marbella, Malaga, Spain

Hospital General Universitario de Albacete ( Site 0408)

Albacete, Spain

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0404)

Barcelona, Spain

Hospital Universitario 12 de Octubre ( Site 2806)

Madrid, Spain

Hospital Universitario Virgen de la Victoria ( Site 0418)

Málaga, Spain

Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0419)

Salamanca, Spain

Hospital Universitario Doctor Peset ( Site 0411)

Valencia, Spain

Karolinska Universitetssjukhuset Huddinge ( Site 2900)

Huddinge, Stockholm County, Sweden

Universitetssjukhuset Örebro ( Site 0403)

Örebro, Örebro County, Sweden

Chang Gung Memorial Hospital- Chiayi ( Site 3102)

Chiayi City, Chiayi, Taiwan

Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 3104)

Kaohsiung City, Taiwan

National Cheng Kung University Hospital-Clinical Trial Center ( Site 3105)

Tainan, Taiwan

National Taiwan University Hospital ( Site 3101)

Taipei, Taiwan

Chang Gung Medical Foundation-Linkou Branch ( Site 3103)

Taoyuan District, Taiwan

Ege Universitesi Hastanesi ( Site 3202)

Bornova, İzmir, Turkey (Türkiye)

Hacettepe Universite Hastaneleri-Department of Hematology ( Site 3204)

Ankara, Turkey (Türkiye)

Ankara UTF Cebeci Arastırma ve Uygulama Hastanesi ( Site 3210)

Ankara, Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi ( Site 3201)

Ankara, Turkey (Türkiye)

Antalya Egitim ve Arastırma Hastanesi ( Site 3207)

Antalya, Turkey (Türkiye)

Trakya University Medical Faculty Hospital-Hematology ( Site 3200)

Edirne, Turkey (Türkiye)

Medipol Mega Universite Hastanesi-oncology ( Site 3203)

Istanbul, Turkey (Türkiye)

Kocaeli Üniversitesi-Hematology ( Site 3205)

Kocaeli, Turkey (Türkiye)

VM Medical Park Mersin Hastanesi ( Site 3208)

Mersin, Turkey (Türkiye)

Ondokuz Mayıs Universitesi-hematology ( Site 3206)

Samsun, Turkey (Türkiye)

Addenbrooke's Hospital ( Site 3303)

Cambridge, Cambridgeshire, United Kingdom

Gloucestershire Royal Hospital ( Site 3302)

Gloucester, Gloucestershire, United Kingdom

Lincoln County Hospital ( Site 3310)

Lincoln, Great Britain, United Kingdom

Boston Pilgrim Hospital ( Site 3301)

Boston, Lincolnshire, United Kingdom

University College London Hospital ( Site 3300)

London, London, City of, United Kingdom

Guy's & St Thomas' NHS Foundation Trust ( Site 3305)

London, London, City of, United Kingdom

King's College Hospital ( Site 3308)

London, London, City of, United Kingdom

Royal Gwent Hospital ( Site 3304)

Gwent, Newport, United Kingdom

GenesisCare - Windsor ( Site 3309)

Windsor, Windsor And Maidenhead, United Kingdom

The Christie NHS Foundation Trust ( Site 3307)

Manchester, United Kingdom

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NCT06079879


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