A Phase 3 interventional study of Pelabresib and Ruxolitinib in Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF) and Post-essential Thrombocythemia Myelofibrosis (PET-MF), sponsored by Novartis Pharmaceuticals. Recruiting at 165 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
Czechia, Germany, Netherlands, Canada, Belgium, Mexico
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.
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.
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.
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.
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.
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.
625 studies on the registry are indexed under Primary Myelofibrosis; 124 are open to participants now.
This study's planned enrollment of 460 is above the median of 43 across 489 interventional studies indexed under Primary Myelofibrosis.
Browse Primary Myelofibrosis studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this arm receive pelabresib (DAK539) orally once daily for 14 days of each 21-day cycle, in combination with ruxolitinib, which is taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.
Drug: Pelabresib · Drug: Ruxolitinib
Participants in this arm receive a matching placebo orally once daily for 14 days of each 21-day cycle, together with ruxolitinib, which is also taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.
Drug: Ruxolitinib · Drug: Placebo
Pelabresib monohydrate tablets
Also known as: DAK539
Ruxolitinib phosphate tablets
Also known as: INC424
Matches pelabresib
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline total symptom score (TSS) ≥ 25
Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 25.
Time frame: Week 24
Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 25
Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 25.
Time frame: Baseline, Week 24
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline TSS ≥ 15
Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 15.
Time frame: Week 24
Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 15
Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 15.
Time frame: Baseline, Week 24
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads over time
Spleen Response (SVR35) over time is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 12, Week 36, Week 48 and thereafter, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review.
Time frame: Week 12, Week 36, Week 48 and every 12 weeks thereafter till End of Study (an average of 3 years)
Absolute change from baseline and percentage change from baseline in spleen volume over time
Absolute and percentage change from baseline in spleen volume over time will be summarized using descriptive summary statistics
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Time to first SVR35 response
Time to first SVR35 response defined as the time from date of randomization to the date of first SVR35 response as measured by MRI (or CT scan) will be summarized by treatment arm.
Time frame: From date of randomization to the date of first SVR35 response, assessed up to approximately 3 years
Duration of first SVR35 response
Duration of first SVR35 response defined as the time from first SVR35 response to loss of response for any participant who reaches SVR35 at any time.
Time frame: From first SVR35 response to loss of response, assessed up to approximately 3 years
Number of Participants with TSS50 response at Week 24
Symptom response defined as achieving ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 24 as measured by the MFSAF v4.0
Time frame: Week 24
Number of Participants with TSS50 response over time
Symptom response defined as achieving ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 12, Week 36, Week 48 and thereafter as measured by the MFSAF v4.0
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Absolute and percentage change from baseline in TSS over time
Absolute change from baseline and percentage change from baseline in TSS over time
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Time to first TSS50 response
Time to first TSS50 response defined as the time from date of randomization to the date of first TSS50 response as measured by the MFSAF v4.0.
Time frame: From date of randomization till date of first TSS50 response, assessed up to approximately 3 years
Duration of TSS50 response
Duration of TSS50 response defined as the time from first TSS50 response to loss of response for any participant who reaches TSS50 at any time.
Time frame: From first TSS50 response to loss of response, assessed up to approximately 3 years
Dual Response (SVR35 + TSS50)
Dual response is defined as achieving both ≥ 35% reduction in spleen volume (SVR35) and ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 12, 24, 36, 48 and every 12 weeks thereafter, with SVR measured by MRI (or CT scan) and assessed by central radiology read and TSS measured by MFSAF v4.0.
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Hemoglobin response
Hemoglobin response defined as a ≥1.5 g/dL average increase in hemoglobin from baseline in any 12-week mean hemoglobin concentration.
Time frame: 12 consecutive weeks (rolling window) up to 7 days following last dose of pelabresib/placebo
Change from baseline in hemoglobin over time
Change from baseline in hemoglobin over time will be summarized using descriptive summary statistics.
Time frame: Up to 7 days following last dose of pelabresib/placebo
Anemia response over time
Anemia response (major response, minor response, stable anemia, progressive anemia) as per proposed 2024 IWG-ELN criteria in participants with transfusion dependent and non-transfusion dependent anemia (Tefferi et al 2024).
Time frame: Up to 7 days following last dose of pelabresib/placebo
Overall survival (OS)
Overall survival (OS) defined as the time from date of randomization to date of death due to any cause.
Time frame: From date of randomization till date of death due to any cause, assessed up to approximately 3 years
Progression-free survival (PFS)
Progression-free survival (PFS) defined as the time from date of randomization to date of documented disease progression, or death due to any cause whichever comes first.
Time frame: From date of randomization till date of documented disease progression, or death due to any cause whichever comes first, assessed up to approximately 3 years
Leukemia-free survival (LFS)
Leukemia-free survival (LFS) is defined as the time from date of randomization to date of leukemic transformation, or death due to any cause whichever comes first.
Time frame: From date of randomization till date of leukemic transformation, or death due to any cause whichever comes first, assessed up to approximately 3 years
Exposure-Adjusted Incidence Rate (EAIR) of Participants with Leukemic Transformation
The EAIR of participants with leukemic transformation is the rate at which this event occurs, adjusted for the actual time participants were exposed to the study drug(s).
Time frame: Throughout study completion (an average of 3 years)
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Time frame: Up to 30 days following last dose of pelabresib/placebo
Pelabresib plasma concentrations
Blood samples for pelabresib pharmacokinetics (PK) will be obtained and evaluated in all participants at all dose levels and summarized using descriptive statistics.
Time frame: Cycle 1: Day 1 (0/Pre-dose and 0.5 post dose), Day 7 (0/Pre-dose), Day 14 (0/Pre-dose, 2, and 5 hours post-dose). 1 cycle = 21 days.
Maximum observed plasma Concentration (Cmax) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. Cmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Time to Maximum observed plasma Concentration (Tmax) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. Tmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Area Under the Concentration-Time Curve over a dosing interval (AUCtau) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. AUCtau will be listed and summarized using descriptive statistics.
Time frame: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Change from baseline over time in fatigue as measured by PROMIS SF v1.0 Fatigue 7a
The PROMIS Short Form version 1.0 Fatigue 7a is a seven-question survey that measures how much fatigue has affected a person over the past week. Each question is rated from "Never" to "Always" on a five-point scale. The total score is converted to a standardized score, where the average is 50 and the standard deviation is 10. A lower score means less fatigue and minimal impact on daily life, while a higher score indicates more severe fatigue and greater disruption of daily activities.
Time frame: Baseline, once per week from Cycles 1 to 9 (each cycle is 21 days), day 1 of every odd cycle thereafter, within 7 days of last dose of pelabresib/placebo and at 12 weeks following last dose of pelabresib/placebo
Change from baseline over time in overall QOL and functional scales as measured by the EORTC QLQ-C30
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) measures overall quality of life and key functional areas in people with cancer, including physical, role, emotional, cognitive, and social functioning. Items are rated from 1 (not at all) to 4 (very much), except for the global quality of life scale, which uses a 1 to 7 scale. Scores are converted to a 0 to 100 scale. Higher scores indicate better functioning and quality of life, while lower scores reflect poorer functioning and well-being.
Time frame: Baseline, day 1 of every cycle from Cycle 1 to 9 (each cycle is 21 days), day 1 of every odd cycle thereafter, within 7 days of last dose of pelabresib/placebo and at 12 weeks following last dose of pelabresib/placebo
Showing the first 100 of 165 sites across 23 countries. Choose a country and city above to see the rest.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
No publications or documents are linked to this record.
Started May 2026 (actual). Primary completion is estimated for May 2028, 23 months after the start.
Of 22 phase 3 interventional studies under Primary Myelofibrosis, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 68. This study's planned 23 months is below that.
How these figures are worked out, and which studies are left out of them.
Czechia, Germany, Netherlands, Canada, Belgium, Mexico
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: CPI-0610