* Patients of age 18 or older
* Has a diagnosis of MDS/MPN or CNL by WHO or ICC diagnostic criteria:
1. Chronic myelomonocytic leukemia
2. MDS/MPN with neutrophilia, previously known as atypical chronic myeloid leukemia
3. Chronic neutrophilic leukemia
4. MDS/MPN -not otherwise specified
* Chronic phase disease with \<10% blasts in peripheral blood and marrow within 1 month from planned start of treatment
* Eastern Cooperative Oncology Group (ECOG) Performance Score44 of 0-2
* Patients can be treatment naïve or could have undergone prior treatments for MDS/MPN as below:
1. Prior treatment with non-JAK inhibitors or hypomethylating agents are allowed (e.g., hydroxyurea, immunomodulatory agents, steroids). Hydroxyurea can be continued until or even beyond initiation of treatment for 2 months if needed for cytoreduction
2. If non-MMB JAK inhibitors were used for treatment and stopped due to side effects (e.g., anemia from ruxolitinib, gastrointestinal toxicity from fedratinib, etcetera), these patients will be allowed to enroll on this study as long as JAK inhibitor was stopped at least 2 weeks prior to anticipated start date of treatment
3. If prior hypomethylating agent was used and stopped longer than 3 months prior to anticipated start date of treatment due to side effects, these patients will be eligible. However, if hypomethylating agents were stopped due to lack of clinical benefit, these patients will not be deemed eligible
4. Prior treatment with erythropoietic stimulating agents is allowed if last treatment was more than 4 weeks prior to anticipated start date of treatment
5. Splenic radiation should have been performed more than 2 months before anticipated start date of treatment
6. Any prior or ongoing investigation therapy or agents should be stopped longer than 4 weeks of anticipated start date of treatment
* Blood counts with platelets ≥25,000/microL, ANC ≥0.75 x 10\^9/L (without transfusion or growth factor support)
* Baseline splenomegaly with ≥5 cm below costal margin or ≥450 cm3 on imaging (ultrasound, CT or MRI)
* Adequate organ function with creatinine clearance measured by Cockcroft-Gault calculation ≥30 mL/min, total bilirubin ≤1.5×ULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%), INR ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants, albumin ≥2.5 g/dL.
* Willing and able to sign the informed consent form
* Life expectancy \> 24 weeks
* Willing and able to complete patient-reported outcome assessments using an ePRO device according to protocol
* Patients of child-bearing potential, or those with partners of child-bearing potential or pregnant or lactating partners, who are willing to follow highly effective contraceptive requirements. Females of reproductive potential should use effective contraception during study treatment and for 6 months following the last dose for HMA-MMB and 1 week following the last dose for MMB monotherapy. Males with female partners of reproductive potential should use effective contraception during study treatment and for 3 months following the last dose for HMA-MMB and 1 week following the last dose for MMB monotherapy. Patients should not breastfeed during treatment and for 1 week after the last dose.
* Patients of child-bearing potential with a negative highly sensitive serum pregnancy test within 24 hours before the first dose of momelotinib.
Exclusion criteria
* Diagnosis of MDS/MPN with SF3B1 gene mutation and thrombocytosis (excluded due to unclear role of ACRV1 in the development of anemia)
* Peripheral blood or marrow (by immunohistochemistry) blast percentage \>10%
* Prior lack of response to MMB or hypomethylating agents.
* Known history of allergic reaction to momelotinib
* AST or ALT above 2.5 x ULN (above 5 X ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
* The following treatments within the time periods as specified:
1. Momelotinib at any time prior to screening
2. Erythropoietic stimulating agents within 4 weeks of treatment
3. Investigational agent within 4 weeks of the first dose of study treatment
4. Immunosuppressive agents within 28 days (low dose steroids ≤10 mg daily prednisone or equivalent is allowed)
5. Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of momelotinib. Strong CYP3A4 inducers can lead to decreased MMB exposure and risk a lack of efficacy. Therefore, alternative medicinal product to strong CYP3A4 inducer should be considered.
* Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo any imaging (ultrasound, CT without contrast or MRI without contrast) for spleen volume measurement per requirements
* Patients with an active invasive concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
* Localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured is allowed.
* History of non-melanoma skin cancers such as basal cell carcinoma or squamous cell carcinoma are also allowed.
* Completely resected intraepithelial carcinoma of cervix or papillary thyroid or follicular thyroid cancers are also allowed at the investigator's discretion.
* Untreated or active infections are excluded as below:
1. Chronic active or acute viral hepatitis A, B, or C infection. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained.
2. HIV with CD4+ cell count under 400 cells/ μL or on treatment with anti-retroviral therapy that is specifically excluded per the criteria above. HIV patients on established anti-retroviral therapy allowed per protocol for at least 4 weeks and CD4+ count above or equal to 400 cells/ μL
3. Infections requiring intravenous antibiotics
* Nonhematologic toxicities from prior therapies that are unresolved and are of grade \>1
* Presence of peripheral neuropathy of grade ≥2
* Pregnant women are excluded from this study because the effects of momelotinib on embryotoxicity, survival, and teratogenicity remain unclear.
* Patients unable to swallow medications
* Patient has any medical condition that puts the patient at an acceptable high risk with participation in the study per physician assessment or has any condition that confounds the ability to interpret data from the study.
* Any major surgery or radiation or intervention that interferes with safety or feasibility of enrollment per investigator assessment
