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.
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)
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
Parallel
Pelabresib
DrugPelabresib monohydrate tablets
Ruxolitinib
DrugRuxolitinib phosphate tablets
Placebo
DrugMatches 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.
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.
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.
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.
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.
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 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.
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.
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