APEX-MF, A Randomized Trial Comparing Momelotinib vs Dose-Adjusted Ruxolitinib for Treatment-Naive, Cytopenic Myelofibrosis

Inclusion Criteria:

- Participants must be greater than or equal to 18 years old at the time of registration.
- Participants must have Zubrod/ECOG Performance Status of 0-2.
- Participants must have a complete medical history and physical exam within 28 days prior to registration.
- Participants must have confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PV) MF or post-essential thrombocythemia (ET) MF as assessed by the treating physician per 2022 WHO classification, and confirmed by a bone marrow biopsy within four years.
- Participants must have a spleen measuring greater than or equal to 450 cm3 by MRI within 14 days prior to registration.
- Participants must have DIPSS risk category of Intermediate-1, Intermediate-2 or High per Dynamic International Prognostic Scoring System (DIPSS) for MF.
- Participants must have blasts less than 10% in peripheral blood within 28 days of registration. If bone marrow biopsy is performed within 28 days prior to registration blasts must be less than 10% as well.
- Participants must have discontinued all drugs used to treat MF, including hydroxyurea, peginterferon alfa-2a, ropeginterferon alfa-2b, anagrelide or busulfan greater than or equal to 14 days prior to registration.
- Participants must meet the following hematologic parameters within 28 days prior to registration:
* platelets 50 - 200 x 103/uL
* Hemoglobin less than 10 g/dL
- Participants must have a calculated creatinine clearance greater than or equal to 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration.
- Participants must be able to take orally administered medication and comply with the oral regimen.
- Participants with a history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration.
- Participants with a history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated.
- Participants must be offered the opportunity to participate in specimen banking.
- Participants who can complete PRO and QOL questionnaires in English or Spanish languages must agree to participate in the patient-reported outcomes and quality of life questionnaires.

Exclusion Criteria:

- Participants must not be considered immediately eligible for hematopoietic stem cell transplantation (HSCT) or have prior HSCT for MF.
- Participants must not have received prior JAK or ACVR1 inhibitor treatment.
- Participants must not have received investigational therapy within 14 days prior to registration.
- Participants must not have had a prior splenectomy.
- Participants must not have had splenic irradiation within 90 days prior to registration.
- Participants must not have received prior chemotherapy for their MF (e.g., hypomethylating agent, hypomethylating agent and venetoclax).
- Participants must not have had major surgery within 21 days prior to registration.
- Participants must not have received a live vaccine within 14 days prior to registration.
- Participants must not have grade 2 or higher peripheral neuropathy.
- Participants must not have clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; or unstable angina pectoris.
- Participants must not have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Participants must not have history of stroke, reversible ischemic neurologic deficit, or transient ischemic attack within 90 days prior to registration.
- Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Participants with curatively treated basal or squamous cell skin cancer, superficial bladder cancer, in situ cervical cancer and/or in situ breast cancer may be enrolled.
- Participants must not have uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) as determined by the local investigator.
- Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process.