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

NCT07071155 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: J2586IRB00509021
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes; Myeloproliferative Overlap Neoplasms; Chronic Neutrophilic Leukemia

Keywords

momelotinib; chronic neutrophilic leukemia; myelodysplastic; myeloproliferative

Outcome Measures

Primary Outcomes (3)

• Number of participants who achieve a complete response

  Efficacy determination - complete response: number of participants who achieve a complete response as defined by international consortium response criteria for MDS/MPN in adults

  24 weeks

• Number of participants who achieve a partial response

  Efficacy determination - partial response: number of participants who achieve a partial response as defined by international consortium response criteria for MDS/MPN in adults

  24 weeks

• Number of participants who achieve a clinical benefit

  Efficacy determination - clinical benefit: number of participants who achieve a clinical benefit per MDS/MPN IWG criteria4

  24 weeks

Secondary Outcomes (11)

• Number of participants who experience a grade 3 or higher adverse events or severe event

  2 years

• Number of Participants Who Achieve Erythroid Response

  12 weeks

• Number of Participants Who Achieve Erythroid Response

  24 weeks

• Proportion of Participants Who Achieve Spleen Size Reduction

  12 weeks

• Proportion of participants Who Achieve Spleen Size Reduction

  24 weeks

Study Arms (1)

Combination therapy (MMB-HMA)

EXPERIMENTAL

Combination of once daily oral momelotinib plus hypomethylating agents (HMA), e.g. azacitidine) starting cycle 1. Azacitidine will be administered as an injection at 75 mg/m2 for days 1-5 in a 28-day cycle. Dose escalation Phase: The first 3 patients will receive MMB 150 mg daily in combination with azacitidine. Depending on the number of dose limiting toxicities (DLTs) experienced during this period, participants in this phase of the study will receive either 150mg daily or have an escalated dose of 200mg daily. Depending on DLT assessment during this phase of the study, the maximum tolerated dose (MTD) of either 150mg or 200mg will be determined. Expansion Phase: Once the MTD is determined (either 150 mg or 200 mg), all remaining patients up to the total of 18 evaluable patients will be treated at the MTD.

Drug: Momelotinib; Drug: Azacitidine

Interventions

Momelotinib DRUG

Capsules of Momelotinib will be administered orally once a day by all participants for up to 24 months, depending on response to treatment. Dose escalation will include the first 3 patients who will receive either 150 mg or 200mg of momelotinib daily, depending on the number of dose limiting toxicities (DLTs) experienced during this period. Dose expansion will include up to 18 evaluable participants who will receive the maximum tolerated dose (either 150mg or 200 mg) daily as will be determined during the dose escalation phase.

Also known as: OJJAARA

Combination therapy (MMB-HMA)

Azacitidine DRUG

75 mg/m2, days 1-5 in a 28-day cycle

Also known as: Vidaza

Combination therapy (MMB-HMA)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia, Neutrophilic, Chronic

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Tania Jain, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania Jain, MD

CONTACT

410-955-7035; tjain2@jhmi.edu

Amanda Stevens, MD CCRA

CONTACT

msteve35@jhmi.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label study of MMB-HMA in MDS/MPN and CNL. The investigators will enroll a total of 18 evaluable patients using a modified 3+3 dose escalation design followed by expansion.

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 17, 2025
• Study Start: March 19, 2026
• Primary Completion (Estimated): March 5, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)