A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment

Myelofibrosis Clinical Trial

Official title:

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04576156
• Other study ID #: MYF3001
• Secondary ID: 2020-003288-24
• Status: Recruiting
• Phase: Phase 3
• Start date: April 12, 2021
• Est. completion date: April 27, 2027

Study information

• Verified date: June 2024
• Source: Geron Corporation
• Contact: Vivian Rodolf, MD
• Phone: +1 (650) 473-7793
• Email: myf3001-info[@]Geron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory to Janus Kinase (JAK)-Inhibitor treatment.

Description:

This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT). Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: April 27, 2027
• Est. primary completion date: April 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria
• Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF
• Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at

screening:

• (i) Treatment with JAK-inhibitor for >= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant

and at least one of the following:

1. no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor

2. no decrease in spleen size (< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor

3. no decrease in symptoms (< 20% by Myelofibrosis Symptom Assessment Form [MFSAF] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor

4. a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.

• (ii) Treatment with JAK-inhibitor treatment for>= 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i [a, b, or c]).
• (iii) Following maximum tolerated doses of JAK inhibitor therapy for =3 months duration, having documented relapsed disease defined as either

1. Increase in spleen volume from time of best response by 25% measured by MRI or CT, or

2. Increase in spleen size by palpation, CT, or ultrasound

• (b.i) For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response;
• (b.ii) For splenomegaly of > 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response; AND not a candidate for further JAK inhibitor at screening per investigator.
• Measurable splenomegaly demonstrated by a palpable spleen measuring >= 5 cm below the left costal margin or a spleen volume >= 450 cm^3 by MRI or CT
• Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)
• Hematology laboratory test values within the protocol defined limits
• Biochemical laboratory test values must be within protocol defined limits
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
• Participants should follow protocol defined contraceptives procedures
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening

Exclusion Criteria:

• Peripheral blood blast count of >= 10% or bone marrow blast count of >=10%
• Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
• Prior treatment with imetelstat
• Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization
• Diagnosis or treatment for malignancy other than MF except:
• Malignancy treated with curative intent and with no known active disease present for >= 3 years before randomization
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics
• Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease requiring treatment unless related to underlying hepatosplenomegaly due to MF
• Major surgery within 28 days prior to randomization
• Any life-threatening illness (e.g., coronavirus disease-2019), medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Imetelstat
Imetelstat will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.
• Best Available Therapy (BAT)
Non-JAK-inhibitor treatment will be given, which may include but is not limited to hydroxyurea, thalidomide or an analog of thalidomide, interferon, danazol, hypomethylating agents, chemotherapy or radiotherapy.

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Ciudad de Buenos Aires	Buenos Aires
Argentina	Sanatorio Allende	Córdoba
Argentina	Sanatorio de la Mujer	Rosario	Santa Fe
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Epworth Healthcare	Richmond	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Austria	Kepler Universitätsklinikum Gm	Linz	Oberösterreich
Austria	Krankenhaus der Elisabethinen	Linz	Oberösterreich
Austria	Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel	Wein	Burgenland
Austria	Klinikum Wels-Grieskirchen GmbH	Wels	Oberösterreich
Belgium	AZ Klina	Antwerpen
Belgium	Zna - Campus Middelheim	Antwerpen
Belgium	ZNA Stuyvenberg Antwerpen	Antwerpen
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Centre Hospitalier de Jolimont	Haine-Saint-Paul	Hainaut
Belgium	Universitair Ziekenhuis Brussel - Myeloom Centrum Brussel (MCB)	Jette
Belgium	CHU De Liège	Liege	Liège
Brazil	Hospital Erasto Gaertner	Curitiba	Paraná
Brazil	CEPON Centro de Pesquisas Oncologicas SC	Florianópolis
Brazil	Centro de oncologia Leonardo da Vinci	Fortaleza	Ceará
Brazil	Hospital das Clínicas UFG	Goiânia	Goiás
Brazil	Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa LTDA	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Clinicas de Porto Alegre - UFRGS	Porto Alegre	Rio Grande Do Sul
Brazil	Fundacao Doutor Amaral Carvalho / Hospital Amaral Carvalho	São Paulo
Brazil	Hospital A.C.Camargo Cancer Center - Clinical Oncology	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo
Brazil	Instituto de Educação, Pesquisa e Gestão em Saúde	São Paulo
Bulgaria	UMHAT "Dr. Georgi Stranski"	Pleven
Bulgaria	UMBAL Sveti Georgi	Plovdiv
Bulgaria	Specialized Hospital for Active Therapy of Hematological dis	Sofia
Colombia	Hospital Pablo Tobon Uribe	Antioquia
Colombia	Centro Medico Imbanaco de Cali S.A.	Cali
Colombia	FOSCAL	Floridablanca
Colombia	Oncologos del Occidente S.A	Pereira	Risaralda
Denmark	Odense University Hospital - Hematology	Odense
France	Hospital CENTRE HOSPITALIER AVIGNON	Avignon cedex	Provence-Alpes-Côte-d'Azur
France	Hopital Avicenne - Hématologie Clinique	Bobigny	Seine-Saint-Denis
France	CHRU Brest - Hôpital Morvan	Brest cedex
France	CHU de Limoges Dupuytren	Haute-Vienne	Limoges
France	Centre Hospitalier Du Mans - Cancérologie Médicale	Le Mans	Sarthe
France	CHU de Saint Etienne	Loire	Saint Priest En Jarez
France	CHU De Nantes - Hématologie C	Nantes	Loire-Atlantique
France	CHU de Nice - Hopital de l'Archet II - Pharmacie	Nice	Nice Cedex 3
France	Institut de cancérologie du Gard - Hematologie clinique	Nimes Cedex 09	Gard
France	CHU - Hôpital Saint Louis - Centre D'Investigations Cliniq	Paris
France	Hopital Bicetre	Paris	Le Kremlin-Bicêtre
France	Hopital Cochin - Aphp Hôpitaux Universitaires Paris Centre	Paris	Île-de-France
France	Centre Hospitalier Lyon	Pierre-benite	Rhône-Alpes
France	CHU Bretonneau	Tours	Indre-et-Loire
Georgia	J.S.C."K.Eristavi National Cen	Tbilisi
Georgia	Ltd "Medinvest" Institute of H	Tbilisi
Georgia	LTD Israeli-Georgian Medical R	Tbilisi
Georgia	M.Zodelava Hematology Center L	Tbilisi
Georgia	Multi Profile Clinic Consilium	Tbilisi
Germany	Universitätsklinikum Carl Gust	Dresden	Hamburg
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle (Saale)	Sachsen-Anhalt
Germany	Klinikum Kempten-Oberallgaeu GmbH	Kempten	Rheinland-Pfalz
Germany	Universitätsklinikum Schleswig	Kiel	Schleswig-Holstein
Germany	Universitätsklinikum Leipzig AöR	Leipzig	Sachsen
Germany	Universitätsklinikum Mannheim - University of Heidelberg	Mannheim	Baden-Württemberg
Germany	Universitätsklinikum Tübingen	Tübingen	Baden-Württemberg
Hungary	Dél-pesti Centrumkórház Ország	Budapest
Hungary	Semmelweis Egyetem - III. sz.	Budapest
Hungary	Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András	Nyíregyháza
Hungary	Fejer Megyei Szent Gyorgy Egye	Székesfehérvár
India	St. John's Medical College Hospital	Bangalore	Karnataka
India	Fortis Hospital 154/9	Bengaluru	Karnataka
India	All India Institute of Medical Sciences	Bhubaneswar	Orissa
India	Fortis Memorial Research Institute	Gurgaon	New Delhi
India	Narayana Hrudayalaya Hospital	Hyderabad
India	Nilratan Sircar Medical College	Kolkata	West Bengal
India	All India Institute of Medical Sciences, Dept. of Hematology, New Delhi (All India Institute Of Medical Sciences)	New Delhi	Delhi
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Deenanath Mangeshkar Hospital & Research Center	Pune
India	Sahyadri Specialty Hospital	Pune
India	Nirmal Hospital - Hematology	Surat	Gujarat
Israel	Assuta Ashdod University Hospi	Ashdod	HaDarom
Israel	Barzilai Medical Center	Ashkelon	HaDarom
Israel	Soroka Medical Center - Hematology Institute	Beersheba
Israel	Bnai Zion Medical Center	Haifa
Israel	Carmel MC	Haifa
Israel	Hadassah Medical Organization	Jerusalem	Yerushalayim
Israel	Western Galilee Hospital - Nahariya	Nahariya	HaZafon
Israel	Kaplan Medical Center	Rehovot	HaMerkaz
Israel	Tel Aviv Sourasky Medical Cent	Tel Aviv	Tel-Aviv
Israel	Shamir Medical Center (Assaf Harofeh)	Zerifin	HaMerkaz
Italy	PO Civile SS.Antonio e Biagio	Alessandria
Italy	A.O.di Bologna Policl.S.Orsola	Bologna
Italy	Presidio Ospedaliero Garibaldi	Catania
Italy	Arcispedale S.Anna - Ematologi	Cona	Ferrara
Italy	AOU Careggi	Firenze
Italy	Clinica Ematologica, Univ. Deg	Genova
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Irccs Irst	Meldola
Italy	ASST Grande Ospedale Metropoli	Milano
Italy	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera San Gerard	Monza
Italy	AOU Federico II	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano	Torino
Italy	Ospedale Civile S.Maria delle	Ravenna
Italy	Arcispedale S Maria Nuova, AO di Reggio Emilia	Reggio Calabria
Italy	Azienda Ospedaliera Bianchi-Me	Reggio Calabria
Italy	AUSL di Rimini Ospedale Inferm	Rimini
Italy	ASL Roma 2 - PO "S. Eugenio"	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Istituto Clinico Humanitas Roz	Rozzano	Milano
Italy	AOU Città della Salute e della Scienza di Torino	Torino
Italy	Ospedale di Circolo, PO Varese	Varese
Italy	Ospedale S.Bortolo, AULSS n.6	Vicenza
Korea, Republic of	Inje University Busan Paik Hos	Busan	Busan Gwang'yeogsi [Pusan-Kwangyokshi]
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan	Busan Gwang'yeogsi [Pusan-Kwangyokshi]
Korea, Republic of	Pusan National University Hospital - Hematology and Oncology	Busan
Korea, Republic of	Kyungpook National University	Daegu	Daegu Gwang'yeogsi [Taegu-Kwan]
Korea, Republic of	National Cancer Institute Center for Cancer Research	Goyang-Si	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Incheon Gwang'yeogsi [Inch'n-Kwangyokshi]
Korea, Republic of	The Catholic University of Korea	Seongdong
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Korea University Anam Hospital	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Korea University Guro Hospital	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Seoul National University Hospital - Department of Internal	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp
Korea, Republic of	Severance Hospital, Yonsei Uni	Seoul
Malaysia	Hospital Ampang	Ampang	Selangor
Malaysia	Hospital Sultanah Aminah Johor Bahru	Johor Bahru	Johor
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	Sarawak General Hospital	Kuching	Sarawak
Malaysia	Hospital Pulau Pinang	Pulau Pinang	Georgetown
Poland	Wojewodzki Szpital Specjalistyczny	Biala Podlaska
Poland	Pratia Onkologia Katowice	Katowice	Slaskie
Poland	Ars Medical Sp. z o.o.	Pila	Wielkopolskie
Poland	Centrum Medyczne Pratia Poznan	Skorzewo	Wielkopolskie
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Sl	Slupsk	Pomorskie
Portugal	CCA-Braga. Centro Clínico Académico - Hospital Braga	Braga
Portugal	CHUC - Centro Hospitalar e Uni	Coimbra
Portugal	Centro Clinico Fundacao Champalimaud	Lisboa
Portugal	H. Santa Maria. Centro Hospita	Lisboa
Portugal	H. São Francisco Xavier-Centro	Lisboa
Portugal	Instituto Português de Oncologia de Lisboa	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto	Porto
Russian Federation	MONIKI - Oncology	Moscow	Moskovskaya Oblast'
Russian Federation	MUZ City Clinical Hospital # 2	Novosibirsk	Novosibirskaya Oblast'
Russian Federation	Budgetary Healthcare Institution of Omsk Region	Omsk
Russian Federation	V.A. Almazov National Medical Research Center	Saint Petersburg
Russian Federation	First Saint-Petersburg State Medical University n.	Saint-Petersburg
Russian Federation	GOU VPO Saratov State Medical University n.a. V.I.	Saratov
Russian Federation	Tula Regional Clinical Hospital	Tula	Tul'skaya Oblast'
Singapore	National University Cancer Institute (NCIS)	Singapore	Central Singapore
Singapore	Singapore General Hospital	Singapore	Central Singapore
Spain	H.G.U. Alicante	Alicante
Spain	H.U. Ribera de Alzira	Alzira	Valencia
Spain	Institut Català d'Oncologia-Ho	Badalona	Barcelona
Spain	H. San Pedro de Alcántara	Cáceres
Spain	ICO-Hospital Universitari de G	Girona
Spain	Hospital Universitario Virgen	Granada
Spain	Hospital Universitario de Gran	Las Palmas de Gran Canaria	Canarias
Spain	H.U. La Paz	Madrid
Spain	Hospital U. 12 Octubre	Madrid
Spain	Hospital Universitario Fundaci	Madrid
Spain	H. Comarcal Costa del Sol	Málaga	Marbella
Spain	H.U.V. de la Victoria	Málaga
Spain	C.S. Parc Tauli	Sabadell	Barcelona
Spain	Complejo Asistencial Universit	Salamanca
Spain	Hospital Universitario Doctor	Valencia
Spain	H. Quirón Zaragoza	Zaragoza
Taiwan	Chang Gung Medical Foundation	Chiayi City	Chiayi
Taiwan	China Medical University Hospital - Hematology/Onc	Taichung City
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Turkey	Sakarya Research and Training Hospital - Medical Oncology	Adapazari
Turkey	Ankara University Medical Facu	Ankara
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Istanbul Üniversitesi Cerrahpasa	Istanbul
Turkey	Marmara university pendik training and research hospital	Istanbul
Turkey	Medipol Bagcilar Mega Hospital	Istanbul
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Medical Park Mersin Hastanesi	Mersin	Içel
Turkey	Mersin University Medical Faculty	Yenisehir/Mersin
United Kingdom	Guys and St Thomas' Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	Maidstone Hospital	Maidstone	Kent
United Kingdom	Oxford University Hospitals	Oxford
United States	Aultman Medical Group	Canton	Ohio
United States	Gabrail Cancer Center	Canton	Ohio
United States	Ohio Health	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology-Oncology Associates of Central New York (HOACNY)	East Syracuse	New York
United States	Highlands Oncology	Fayetteville	Arkansas
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Bon Secours (Greenville) - St. Francis Cancer Center	Greenville	South Carolina
United States	Hartford Healthcare	Hartford	Connecticut
United States	Oncology Consultants	Houston	Texas
United States	The University of Texas MD	Houston	Texas
United States	University of California-San Diego/Moores UCSD Cancer Center	La Jolla	California
United States	Memorial Care	Long Beach	California
United States	UCLA david geffen school of medicine	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Smilow Cancer Center at YNHH	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	BRCR Medical Center Inc	Plantation	Florida
United States	Maryland Oncology Hematology	Rockville	Maryland
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Sharp HealthCare	San Diego	California
United States	Sanford Health	Sioux Falls	South Dakota
United States	Beacon Health System	South Bend	Indiana
United States	Oncology Hematology Associates	Springfield	Missouri
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	University of South Florida	Tampa	Florida
United States	Prairie Lakes Health Care System, Inc.	Watertown	South Dakota
United States	The Oncology Institute - Innovative Clinical Research Institute (ICRI)	Whittier	California
United States	Cancer Care Associates of York	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Geron Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Colombia,  Denmark,  France,  Georgia,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Portugal,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Overall survival is defined as the time interval from randomization date to date of death from any cause.	Baseline (Day 1) until End of Study (EOS) (approximately 3 years )]
Secondary	Symptom response rate	The proportion of participants achieving a =50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline	Baseline (Day 1), and at Week 24
Secondary	Progression-free survival	Progression-free survival is defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria) or death from any cause, whichever occurs first.	Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
Secondary	Spleen response rate	The proportion of participants who achieve a reduction in spleen volume of = 35% from baseline at Week 24.	Baseline (Day 1), and at Week 24
Secondary	Complete remission (CR), partial remission (PR), clinical improvement (CI), spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria	The proportion of participants achieving CR or PR, CI, spleen response, symptom response, and anemia response per modified 2013 IWG-MRT criteria.	Baseline (Day 1) until End of Treatment (approximately 3 years)
Secondary	Reduction in the degree of bone marrow fibrosis	Reduction in the degree of bone marrow fibrosis will be assessed.	Baseline (Day 1) until End of Treatment (approximately 3 years)
Secondary	Number of Participants with Adverse Events	Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment	Screening (Day -28 to -1) until End of Study (approximately 3 years)
Secondary	Assessment of Cmax	Maximum Observed Plasma Concentration (Cmax).	Day 1 of all cycles (each cycle is 21 days)
Secondary	Assessment of Tmax	Time to reach the maximum observed plasma concentration	Day 1 of all cycles (each cycle is 21 days)
Secondary	Assessment of t1/2	Elimination half-life.	Day 1 of all cycles (each cycle is 21 days)
Secondary	Assessment of AUC	Area under the drug concentration-plasma time curve (AUC) from time zero to last measurable concentration	Day 1 of all cycles (each cycle is 21 days)
Secondary	European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores	Patient-reported outcomes including health-related quality of life, pain, and overall change in participant's health will be assessed using the EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher scores indicated worse outcome.	Baseline to End of Study (approximately 3 years)
Secondary	EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores	EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline to End of Study (approximately 3 years)