NCT07071155

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

A Pilot Study of Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia (M-HArbOr)

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is an open-label study of MMB-HMA in MDS/MPN and CNL that will enroll up to 18 patients. Momelotinib will be administered using modified 3+3 dose escalation design followed by expansion. The first three patients will be treated at 150mg daily and if DLT criteria are not met, the remaining patients will be treated at 200mg daily to a total of 18 evaluable patients (all in combination with azacitidine). If DLTs are met within the dose escalation phase (first three patients), then the patients will be treated at 150mg daily (in combination with azacitidine) Key Eligibility Criteria: 1. Patients with a WHO diagnosis of chronic myelomonocytic leukemia (CMML), MDS/MPN-not otherwise specified (MDS/MPN-NOS), MDS/MPN with neutrophilia (MDS/MPN-N), CNL. 2. Age greater than or equal to 18 years 3. Blood counts with platelets greater than 25,000/microL, ANC greater than or equal to 0.75 x 10\^9/L (without transfusion or growth factor support) 4. Baseline splenomegaly with greater than or equal to 5 cm below costal margin or greater than or equal to 450 cm3 on imaging (ultrasound, CT or MRI)

Conditions

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

Interventions

Type	Name	Description
DRUG	Momelotinib	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.
DRUG	Azacitidine	75 mg/m2, days 1-5 in a 28-day cycle

Timeline

• Start date: 2026-03-19
• Primary completion: 2028-03-05
• Completion: 2028-07-30
• First posted: 2025-07-17
• Last updated: 2026-03-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study