A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Hematopoietic Malignancies
Leukemia
Unknown Primary
18 Years and older, Male and Female
CDAK539A12303 (primary)
NCI-2026-03479
2025
2025-523555-66-00
Summary
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.
Objectives
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.
Eligibility
- 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
Treatment Sites in Georgia
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