Inclusion Criteria:
* Participants must have pathologically confirmed primary myelofibrosis (PMF) according to WHO criteria or secondary myelofibrosis as defined by the IWG-MRT criteria.
* Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) Plus criteria OR
* Intermediate-1 risk disease with at least one of the following unfavorable features known to impact the survival adversely
* Red cell transfusion dependency
* Unfavorable Karyotype
* Platelet count ≤100 x 10\^9/L
* Presence of a high risk molecular marker associated with worsened overall survival (ASXL1, EZH2, IDH1/2, SRSF2, U2AF1, p53)
* Participants do not have to be receiving treatment with JAK inhibitors for MF at the time of enrollment. If participants are receiving JAK inhibitor therapy with agents other momelotinib, participants must agree to be switched to momelotinib to begin Cycle 1 Day 1 on Day -7 from HCT (at the initiation of conditioning).
* Age \>18 years
* Participants must be designated to undergo allogeneic HCT with:
* reduced intensity conditioning regimen, and
* peripheral blood stem cells as a graft source
* Participants who will undergo HCT from the following donor types are eligible:
* 6/6 (HLA-A, B, DR) fully matched related donor or
* 8/8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level
* ECOG performance status ≤2 (Karnofsky ≥60%)
* The effects of momelotinib on the developing human fetus are unknown. Female patients of childbearing potential must have a negative pregnancy test, as measured by serum or urine testing. Women of childbearing potential: must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 1 week after the last dose of momelotinib.
Male participants with women of child bearing potential partners must agree to use one of the forms of medically acceptable birth control at start of the first treatment, during the study, and for at least 6 months after the last dose. See Exclusion Criteria for effective contraception and birth control.
\- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Known intolerance or hypersensitivity to any JAK inhibitor, including ruxolitinib, fedratinib, pacritinib, momelotinib or any other JAK inhibitor, its metabolites or formulation excipients.
* Has had any major surgery within 28 days prior to randomization
* Has received treatment with an investigational agent within 4 weeks of the first dose of study intervention
* Has received immunosuppressive agents within 28 days
* Prior allogeneic transplant for any hematopoietic disorder
* Had accelerated phase or leukemic transformation (≥10% blasts in bone marrow any time prior to HCT)
* Has an active, uncontrolled infection
* Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
* Known diagnosis of active hepatitis B or hepatitis C.
* History of another malignancy(ies), unless:
* the participant has been disease-free for at least 2 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
* the cancer has been deemed indolent with no progression over the last 2 years, and deemed by the investigator to be at low risk for further progression during the course of study and follow-up
* the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
* Participants without normal organ function defined as follows:
* AST (SGOT), ALT (SGPT) and Alkaline Phosphatase \>3 × institutional Upper Limit of Normal (ULN)
* Total bilirubin \>1.5 mg/dL, with the exception of participants with Gilbert's Syndrome provided direct bilirubin is ≤1.5x ULN and participant otherwise meets entry criteria.
* Calculated creatinine clearance ≤60 mL/min (Cockcroft-Gault formula)
* Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 40%, as measured by MUGA scan or echocardiogram) or clinically significant arrhythmia not controlled by standard of care therapy.
* Not able to take oral medication or having any clinically significant gastrointestinal abnormalities that may alter absorption, e.g., malabsorption syndrome or major resection of the stomach and/or bowels.
* Grade 2 or greater peripheral neuropathy
* Pregnant or lactating women, or women planning to become pregnant or initiating breastfeeding.
* To exclude women of childbearing potential: who are unwilling or unable to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 1 week after the last dose. Highly effective contraceptive measures include:
* stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
* intrauterine device (IUD); intrauterine hormone-releasing system (IUS);
* sexual abstinence;
* intercourse with vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure).
* To exclude sexually active male participants with WOCBP partners who are unwilling to use the one of the following forms of medically acceptable birth control at start of the first treatment, during the study, and for at least 6 months after the last dose:
* vasectomy with medical assessment of surgical success OR consistent use of a condom.
* male participants must also agree not to donate sperm while receiving study drug and for at least 6 months after the last dose.
* Patients receiving strong CYP 3A4 inducers during study period
* Patients with major ABO mismatch donors only
