Clinical trial NCT06079879: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Essential Thrombocythemia
Keywords: essential thrombocythemia
ET
bomedemstat
IMG-7289
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-10-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Durable Clinicohematologic Response (DCHR) Rate
timeFrame: Up to approximately 52 weeks
Secondary outcomes:
measure: Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score
timeFrame: Baseline and pre-specified timepoints through Week 156
measure: Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score
timeFrame: Baseline and pre-specified timepoints through Week 156
measure: Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0
timeFrame: Baseline and pre-specified timepoints through Week 156
measure: Duration of Clinicohematologic Response (DOCHR)
timeFrame: Up to approximately 52 weeks
measure: Duration of Hematologic Remission (DOHR)
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants with Thrombotic Events
timeFrame: Up to 156 weeks
measure: Percentage of Participants with Major Hemorrhagic Events
timeFrame: Up to 156 weeks
measure: Disease Progression Rate
timeFrame: Up to approximately 52 weeks
measure: Number of Participants with An Adverse Event (AE)
timeFrame: Up to 180 weeks
measure: Number of Participants Discontinuing From Study Therapy Due to an AE
timeFrame: Up to 152 weeks
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Los Angeles Cancer Network ( Site 3491)
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute ( Site 0107)
state: California
city: Torrance
country: United States
facility: The Lundquist Institute ( Site 3423)
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus ( Site 3425)
state: Colorado
city: Boston
country: United States
facility: Tufts Medical Center ( Site 3408)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 0008)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 3413)
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute ( Site 3421)
state: New York
city: Durham
country: United States
facility: Duke University Health System (DUHS) ( Site 0016)
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health-Internal Medicine, Section on Hematology & Oncology ( Site 3400)
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina-Hollings Cancer Center ( Site 3426)
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia ( Site 3422)
state: Virginia
city: Richmond
country: United States
facility: VCU Health Adult Outpatient Pavillion ( Site 3416)
state: Virginia
city: Pilar
country: Argentina
facility: Hospital Universitario Austral ( Site 0104)
state: Buenos Aires
city: ABB
country: Argentina
facility: Hospital Italiano de Buenos Aires ( Site 0105)
state: Caba
city: San Miguel de Tucumán
country: Argentina
facility: C.I.C.E. 9 de Julio ( Site 1001)
state: Tucuman
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital ( Site 1100)
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital-Haematology ( Site 0501)
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital ( Site 0003)
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle ( Site 0505)
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0001)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health-Haematology Research ( Site 0006)
state: Victoria
city: Melbourne
country: Australia
facility: Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0502)
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital-Haematology ( Site 0504)
state: Western Australia
city: Antwerpen
country: Belgium
facility: ZAS Cadix ( Site 1200)
city: Moncton
country: Canada
facility: The Moncton Hospital-Oncology ( Site 1500)
state: New Brunswick
city: Bengbu
country: China
facility: The First Afflilated Hospital of Bengbu Medical College ( Site 3509)
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital ( Site 3513)
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital-Hematology ( Site 3502)
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 3531)
state: Beijing
city: Quanzhou
country: China
facility: The Second Affiliated Hospital Of Fujian Medical University ( Site 3525)
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated hospital of Xiamen University ( Site 3515)
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital of Sun Yat-sen University ( Site 3524)
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital-Department of Hematopathology ( Site 3511)
state: Guangdong
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University ( Site 3510)
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-hematology department ( Site 3504)
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital ( Site 3500)
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital ( Site 3507)
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University ( Site 3527)
state: Jiangsu
city: Nanchang
country: China
facility: The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 3505)
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University-Hematology ( Site 3526)
state: Jilin
city: Xian
country: China
facility: Shaanxi provincial people's hospital ( Site 3516)
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital ( Site 3523)
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital,Fudan University-Hematology ( Site 3530)
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University ( Site 3529)
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital, Sichuan University ( Site 3518)
state: Sichuan
city: Tianjin
country: China
facility: Institute of hematology&blood disease hospital ( Site 3501)
state: Tianjin
city: Hangzhou
country: China
facility: The first Affiliated Hospital, Zhejiang University School of Medicine ( Site 3508)
state: Zhejiang
city: Yiwu
country: China
facility: Zhejiang University School of Medicine-The Fourth Affiliated Hospital ( Site 3517)
state: Zhejiang
city: Medellin
country: Colombia
facility: Fundacion Colombiana de Cancerología Clinica Vida ( Site 1403)
state: Antioquia
city: Monteria
country: Colombia
facility: IMAT S.A.S ( Site 1401)
state: Cordoba
city: Bogota
country: Colombia
facility: Los Cobos Medical Center ( Site 1404)
state: Distrito Capital De Bogota
city: Paris
country: France
facility: Hôpital Saint Antoine-Service d'Hématologie et de Thérapie Cellulaire ( Site 1702)
state: Ile-de-France
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou ( Site 0417)
state: Ille-et-Vilaine
city: Tours
country: France
facility: Centre Hospitalier Régional Universitaire de Tours - Hôpital-Hématologie et Thérapie Cellulaire ( Site 0413)
state: Indre-et-Loire
city: Limoges
country: France
facility: Centre Hospitalier Universitaire de Limoges - Hôpital Dupuyt-Hématologie Clinique et Thérapie Cellu ( Site 1701)
state: Limousin
city: Vandoeuvre lès Nancy
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois-HEMATOLOGY ( Site 0407)
state: Lorraine
city: Roubaix
country: France
facility: Centre Hospitalier de Roubaix ( Site 1703)
state: Nord
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud ( Site 0406)
state: Rhone
city: Paris
country: France
facility: Hôpital Saint-Louis-Centre d'Investigations Cliniques ( Site 0405)
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen ( Site 1801)
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Universitätsklinikum Halle ( Site 0401)
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0402)
state: Sachsen
city: Hksar
country: Hong Kong
facility: Queen Mary Hospital ( Site 1901)
city: Győr
country: Hungary
facility: Petz Aladar Egyetemi Oktato Korhaz ( Site 2000)
state: Gyor-Moson-Sopron
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 0706)
state: Szabolcs-Szatmar-Bereg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 0708)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 0707)
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center ( Site 2100)
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 2102)
city: Haifa
country: Israel
facility: Carmel Hospital ( Site 0906)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 0904)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0905)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 2101)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0902)
city: Zerifin
country: Israel
facility: Yitzhak Shamir Medical Center. ( Site 0901)
city: Alessandria
country: Italy
facility: Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 0034)
state: Ancona
city: Cona
country: Italy
facility: Azienda Ospedaliero Universitaria di Ferrara ( Site 0304)
state: Ferrara
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0308)
state: Forli-Cesena
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 2201)
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi ( Site 0030)
state: Toscana
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana-UO Ematologia UNIV ( Site 0309)
state: Toscana
city: Castelfranco Veneto
country: Italy
facility: Istituto Oncologico Veneto IRCCS-Oncoematologia ( Site 0306)
state: Veneto
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria delle Marche ( Site 0302)
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova ( Site 0301)
city: Torino
country: Italy
facility: Ospedale Mauriziano ( Site 0305)
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi Varese ( Site 2200)
city: Toyoake
country: Japan
facility: Fujita Health University Hospital ( Site 3613)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 3610)
state: Chiba
city: Toon
country: Japan
facility: Ehime University Hospital ( Site 3612)
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 3601)
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital ( Site 3603)
state: Hyogo
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital ( Site 3614)
state: Ishikawa
city: Tsu
country: Japan
facility: Mie University Hospital ( Site 3615)
state: Mie
city: Sendai
country: Japan
facility: National Hospital Organization Sendai Medical Center ( Site 3617)
state: Miyagi
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital ( Site 3607)
state: Osaka
city: Osakasayama
country: Japan
facility: Kindai University Hospital ( Site 3600)
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital ( Site 3611)
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital ( Site 3608)
state: Tokyo
city: Chuo
country: Japan
facility: University of Yamanashi Hospital ( Site 3606)
state: Yamanashi
city: Fukuoka
country: Japan
facility: Kyushu University Hospital ( Site 3605)
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital ( Site 3616)
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital ( Site 3609)
city: Okayama
country: Japan
facility: Okayama University Hospital ( Site 3604)
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital-Hematology ( Site 0605)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital ( Site 0604)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0603)
city: Seoul
country: Korea, Republic of
facility: The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 0606)
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis - Hoofddorp-Oncology ( Site 2301)
state: Noord-Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, locatie Dordwijk-Internal Medicine ( Site 2302)
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen ( Site 2304)
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis ( Site 2300)
city: Auckland
country: New Zealand
facility: North Shore Hospital-Department of Haematology ( Site 0051)
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials ( Site 0050)
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice ( Site 0702)
state: Slaskie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 2504)
state: Swietokrzyskie
city: Braga
country: Portugal
facility: Unidade Local de Saude de Braga - Hospital de Braga ( Site 0415)
city: Lisboa
country: Portugal
facility: Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 2600)
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 0414)
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0409)
state: Barcelona
city: L'Hospitalet Del Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 2801)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar ( Site 2807)
state: Cataluna
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA ( Site 2800)
state: Cataluna
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario ( Site 0421)
state: La Coruna
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-Hematology ( Site 2803)
state: Madrid, Comunidad De
city: Marbella
country: Spain
facility: Hospital Costa del Sol-Hematology Service ( Site 0412)
state: Malaga
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete ( Site 0408)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0404)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 2806)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 0418)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0419)
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset ( Site 0411)
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro ( Site 0403)
state: Orebro Lan
city: Huddinge
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge ( Site 2900)
state: Stockholms Lan
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital- Chiayi ( Site 3102)
state: Chiayi
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 3104)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital-Clinical Trial Center ( Site 3105)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 3101)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch ( Site 3103)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-Department of Hematology ( Site 3204)
city: Ankara
country: Turkey
facility: Ankara UTF Cebeci Arastırma ve Uygulama Hastanesi ( Site 3210)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi ( Site 3201)
city: Antalya
country: Turkey
facility: Antalya Egitim ve Arastırma Hastanesi ( Site 3207)
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty Hospital-Hematology ( Site 3200)
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi-oncology ( Site 3203)
city: İzmir
country: Turkey
facility: Ege Universitesi Hastanesi ( Site 3202)
city: Kocaeli
country: Turkey
facility: Kocaeli Üniversitesi-Hematology ( Site 3205)
city: Mersin
country: Turkey
facility: VM Medical Park Mersin Hastanesi ( Site 3208)
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi-hematology ( Site 3206)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital ( Site 3303)
state: Cambridgeshire
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital ( Site 3302)
state: Gloucestershire
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital ( Site 3310)
state: Great Britain
city: Boston
country: United Kingdom
facility: Boston Pilgrim Hospital ( Site 3301)
state: Lincolnshire
city: London
country: United Kingdom
facility: University College London Hospital ( Site 3300)
state: London, City Of
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust ( Site 3305)
state: London, City Of
city: London
country: United Kingdom
facility: King's College Hospital ( Site 3308)
state: London, City Of
city: Gwent
country: United Kingdom
facility: Royal Gwent Hospital ( Site 3304)
state: Newport
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust ( Site 3307)
Study officials:
affiliation: Merck Sharpe & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: