Study Description
The purpose of this trial is to evaluate whether treatment with pelabresib in combination with ruxolitinib leads to improved clinical outcomes compared to ruxolitinib alone in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) who have not previously received Janus kinase (JAK) inhibitor therapy. The study for each participant is composed of several distinct periods: a screening period, a study treatment period, and a post-treatment follow-up phase.
1. Screening Period:
The screening period lasts for up to 28 days prior to Cycle 1 Day 1, which marks the beginning of treatment. During this time, the participant's eligibility for the study is confirmed, informed consent is obtained, and all required baseline assessments are completed.
2. Treatment Period:
The treatment period begins on Cycle 1 Day 1, which is the point of randomization and the start of study treatment. This period continues until the participant permanently discontinues study treatment, which may occur due to disease progression, unacceptable toxicity, participant withdrawal, or other reasons specified in the protocol. Throughout this period, participants receive study drugs in 21-day cycles, with pelabresib or placebo administered for 14 days and ruxolitinib given continuously. Regular site visits and assessments are conducted according to the Schedule of Activities.
3. Safety Follow-up Period:
The safety follow-up period extends for 30 days (with a window of plus or minus 3 days) after the participant receives their last dose of pelabresib or placebo. During this period, participants are monitored for any late-onset adverse events or safety concerns that may arise after discontinuing the study treatment.
4. Efficacy Follow-up Period:
Following the safety follow-up, efficacy follow-up visits are scheduled every 12 weeks for participants who have not shown evidence of disease progression, meaning there is no documented progression of splenomegaly or leukemic transformation and no new therapy for myelofibrosis has been started. The purpose of this follow-up is to continue monitoring efficacy endpoints, such as spleen imaging, laboratory assessments, and bone marrow biopsies, until either disease progression occurs or a new therapy is initiated.
5. Survival Follow-up Period:
Once a participant enters the survival follow-up phase, follow-up visits are conducted every 12 weeks and may be performed remotely. This phase applies to participants who have experienced documented disease progression or have started a new therapy for myelofibrosis. The aim of survival follow-up is to monitor overall survival and to collect ongoing data regarding disease status and any subsequent therapies the participant may receive.
Interventions
Pelabresib
Placebo
Ruxolitinib
Eligibility Criteria
Key Inclusion Criteria:
* Participants have diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocythemia myelofibrosis (post-ET MF) according to the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias 2022
* DIPSS risk category of intermediate-1, intermediate-2 or high-risk
* Spleen volume ≥ 450 cm3 by CT or MRI scan (local read sufficient if no central read available)
* Have an average TSS of ≥15 within 7 days prior to randomization, using MFSAF v. 4.0 (at least 4 out of 7 TSS assessments required for average calculation)
* Participants with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Blasts \<5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening
* Platelet count ≥ 100 x 10\^9/L in the absence of growth factors or transfusions for the previous 4 weeks
Key Exclusion Criteria:
* Prior splenectomy at any time or splenic irradiation in the previous 6 months
* Prior hematopoietic cell transplant or participant anticipated to receive a hematopoietic cell transplant within 24 weeks from the date of randomization
* Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase (AP) or leukemic transformation
* History of a malignancy (other than MF, PPV-MF or PET-MF) in the past 3 years in need of systemic treatment
* Received any approved or investigational agent other than hydroxyurea or anagrelide for the treatment of MF within 14 days of first dose of study treatment or within 5 half-lives of the approved or investigational agent, whichever is longer
* Prior treatment with any JAK inhibitor or Bromodomain and extraterminal domain (BET) inhibitor
Other protocol-defined inclusion/exclusion criteria may apply.
Hospital de Clinicas Jose de San Martin
Recruiting
Buenos Aires,Buenos Aires F.D.,1221,Argentina
Francisca Rojas
Hospital Italiano de Buenos Aires
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CABA,C1181ach,Argentina
Georgina Bendek
FUNDALEU
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Capital Federal,C1114aan,Argentina
Federico Sackmann, Dr
Hospital Privado de Cordoba
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Córdoba,X5016keh,Argentina
Ana Lisa Basquiera
Novartis Investigative Site
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Clayton,Victoria,3168,Australia
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Adelaide,South Australia,5000,Australia
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Sankt Pölten,3100,Austria
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Graz,8036,Austria
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Woluwe-Saint-Lambert,Brussels Capital,1200,Belgium
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Barretos,São Paulo,14784-400,Brazil
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Goiânia,Goiás,74605-050,Brazil
Grupo ELORA
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Florianópolis,Santa Catarina,88020-210,Brazil
Jaisson Bortolini
Jewish General Hospital
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Montreal,Quebec,H3t 1e2,Canada
Shireen Sirhan
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Nantong,Jiangsu,226000,China
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Beijing,100730,China
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Wenzhou,Zhejiang,325000,China
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Fuzhou,350001,China
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Guangzhou,Guangdong,510515,China
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Yantai,Shandong,264000,China
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Chongqing,400016,China
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Shenyang,110004,China
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Hefei,Anhui,230001,China
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Guangzhou,Guangdong,510080,China
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Wuhan,Hubei,430022,China
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Nanjing,Jiangsu,210029,China
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Changchun,Jilin,130021,China
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Kunming,Yunnan,650101,China
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Hangzhou,Zhejiang,310003,China
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Shanghai,200025,China
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Tianjin,300020,China
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Wuhan,Hubei,430030,China
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Jinan,Shandong,250012,China
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Nanchang,Jiangxi,330006,China
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Ostrava,Poruba,708 52,Czechia
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Brno,625 00,Czechia
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Hradec Králové,500 05,Czechia
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Olomouc,779 00,Czechia
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Poitiers,86021,France
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Brest,29200,France
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Nîmes,30029,France
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Lens,62307,France
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Pessac,33604,France
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Le Kremlin-Bicêtre,94275,France
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Rennes,35033,France
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Toulouse,31059,France
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Mannheim,Baden-Wurttemberg,68305,Germany
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Aachen,52074,Germany
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Erlangen,91054,Germany
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Pune,Maharashtra,411006,India
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Kolkata,West Bengal,700014,India
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Rishikesh,Uttarakhand,249203,India
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Delhi,110085,India
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Aurangabad,Maharashtra,431005,India
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Verona,VR,37134,Italy
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Padova,PD,35128,Italy
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Florence,FI,50134,Italy
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Roma,RM,00161,Italy
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Meldola,FC,47014,Italy
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Novara,28100,Italy
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Monza,MB,20900,Italy
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Sapporo,Hokkaido,0030006,Japan
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Shiwa-Gun,Iwate,0283695,Japan
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Chūō,Yamanashi,4093898,Japan
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Miyazaki,8891692,Japan
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Kobe,Hyōgo,6500047,Japan
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Fukuoka,8128582,Japan
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Bunkyo Ku,Tokyo,1138431,Japan
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Kamogawa,Chiba,2968602,Japan
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Bunkyo-ku,Tokyo,1138603,Japan
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Tsu,Mie-ken,5148507,Japan
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Kumamoto,8628655,Japan
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Johor Bahru,80100,Malaysia
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Kuala Selangor,68000,Malaysia
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George Town,Pulau Pinang,10450,Malaysia
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Kota Kinabalu,Sabah,88586,Malaysia
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Kuching,Sarawak,93586,Malaysia
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Amsterdam,North Holland,1081 hv,Netherlands
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Utrecht,3584 cx,Netherlands
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Katowice,40-519,Poland
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Skorzewo,60-185,Poland
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Lublin,20-090,Poland
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Warsaw,02-776,Poland
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Wałbrzych,58-309,Poland
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Torun,87-100,Poland
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Seoul,03080,South Korea
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Seoul,Yangcheon Gu,07985,South Korea
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Seoul,05505,South Korea
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Seoul,06591,South Korea
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Seoul,06351,South Korea
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Busan,49241,South Korea
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Jeonju,Jeollabuk-do,54907,South Korea
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Suwon,Gyeonggi-do,16247,South Korea
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Barcelona,08035,Spain
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Las Palmas GC,35010,Spain
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Madrid,28009,Spain
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El Palmar,Murcia,30120,Spain
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Málaga,29010,Spain
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Salamanca,37007,Spain
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Genolier,1272,Switzerland
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Basel,4058,Switzerland
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Geneva,1211,Switzerland
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Bern,3010,Switzerland
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Changhua,50006,Taiwan
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Kaohsiung City,80756,Taiwan
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Taipei,10002,Taiwan
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Tainan,704302,Taiwan
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Ankara,06000,Turkey (Türkiye)
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Samsun,55200,Turkey (Türkiye)
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Kocaeli,41380,Turkey (Türkiye)
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Istanbul,Fatih,34098,Turkey (Türkiye)
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Izmir,35060,Turkey (Türkiye)
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Ankara,Sihhiye Altindag,06230,Turkey (Türkiye)
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Sakarya,Adapazari,54290,Turkey (Türkiye)
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Ankara,Kecioren,06010,Turkey (Türkiye)
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Istanbul,Pendik,34899,Turkey (Türkiye)
Summit Medical Group Oncology
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Berkeley Heights,New Jersey,07922,United States
Dipen Patel
The Ohio State University Comprehensive Cancer Center
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Columbus,Ohio,43221,United States
Andrew Srisuwananukorn
Hannah Davis
Yale University School Of Medicine
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New Haven,Connecticut,06520,United States
Farah Fasihuddin
Nikolai Podoltsev
Winship Cancer Institute of Emory University
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Atlanta,Georgia,30322,United States
Anthony Michael Hunter
Danielle Alexander
The Anderson Family Cancer Institute
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Jupiter,Florida,33458,United States
Christine Leonard
Ryan Devine
MD Anderson Cancer Center
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Houston,Texas,77030,United States
Maria Pinsoy
Prithviraj Bose
Franciscan Health Indianapolis
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Indianapolis,Indiana,42637,United States
Melanie Coleman
Waled Bahaj
New York Oncology Hematology P C
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Albany,New York,12206,United States
Josephine Faruol
Lawrence Garbo
Fred Hutch Cancer Research
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Seattle,Washington,98109,United States
Bart Scott
Lisa Grimm
Miami NS Ins Baptist Health S FL
Recruiting
Miami,Florida,33176,United States
Firas El Chaer
Florida Cancer Specialists-North
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St. Petersburg,Florida,33705,United States
Kelly Whitehead
Viralkumar Bhanderi
Florida Cancer Specialist South Reg
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Fort Myers,Florida,33916,United States
Christina Caruso
Fadi Kayali
Texas Oncology PA Dallas Presbyterian Hospital
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Dallas,Texas,75231,United States
Khoan Vu
Florida Cancer Specialists East
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Stuart,Florida,34994,United States
Judah Friedman
Mary Jo Luser
SCRI Texas Oncology Northeast Texas
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Tyler,Texas,75702,United States
Shail Dalal
Shelly Maxfield
American Oncology Partners PA Center for Cancer and Blood Disorders
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Bethesda,Maryland,20817,United States
Raissa Toure
Ralph Boccia
TxO Austin Midtown
Recruiting
Austin,Texas,78705,United States
Jason M Melear
Marian Heaven
University of Chicago Hospital
Recruiting
Chicago,Illinois,60637,United States
Anand Patel
Leigha Hughes
Columbia University Medical Center New York Presbyterian
Recruiting
New York,New York,10032,United States
Monica Kasbekar
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