Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia

Recruiting now · Early Phase 1

Conditions studied: Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Myeloproliferative Overlap Neoplasms, Chronic Neutrophilic Leukemia

In brief

This research is being done to evaluate effectiveness, safety, and tolerability of a study drug called momelotinib in participants with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), MDS/MPN-not otherwise specified (MDS/MPN-NOS), MDS/MPN with neutrophilia (MDS/MPN-N), also called as atypical chronic myeloid leukemia, or chronic neutrophilic leukemia. Momelotinib will be added to standard treatment which usually includes a hypomethylating agent like azacitidine. Treatment options for this diagnosis remain limited and investigators need better treatments to help control the disease, improve symptoms, and potentially help more patients become eligible for transplant. Participants for this study will be asked to take some screening tests which will include routine physical examination, blood tests, and imaging scans to determine eligibility for the study. Those who continue to qualify for this study will begin treatment and may be asked to remain on the study drug for up to 24 months, depending upon how they are responding to treatment. After the study drug is completed, patients will have one additional clinic visit to evaluate overall health and response to study drug. The study drug treatment on this study will include taking momelotinib by mouth in combination with azacitidine, which is given by injection for all patients for the first 5 days of each 28-day cycle. The most common side effect that may be related to participation in this study can include (i) infections which can present as fever, chills, cough, breathing problems, diarrhea, vomiting, pain or burning with urination; or (ii) low blood platelet count which can result in bruising or bleeding for longer than usual if the participant hurts themself.

Key facts

Study ID: NCT07071155
Run by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
People needed: 18
Starts: 2026-03-19
Expected to finish: 2028-07-30
Last updated by the study team: 2026-03-27

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

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:
Momelotinib at any time prior to screening
Erythropoietic stimulating agents within 4 weeks of treatment
Investigational agent within 4 weeks of the first dose of study treatment
Immunosuppressive agents within 28 days (low dose steroids ≤10 mg daily prednisone or equivalent is allowed)
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:
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.
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
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.

Where it is running

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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