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.
Patients of age 18 or older
Chronic myelomonocytic leukemia
MDS/MPN with neutrophilia, previously known as atypical chronic myeloid leukemia
Chronic neutrophilic leukemia
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
Single group
Momelotinib
DrugCapsules 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.
Azacitidine
Drug75 mg/m2, days 1-5 in a 28-day cycle
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
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
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
Number of participants who experience a grade 3 or higher adverse events or severe event
Safety and tolerability evaluation: number of participants who experience a grade 3 or higher adverse event events or severe adverse events as defined by CTCAE v.5.0
Number of Participants Who Achieve Erythroid Response
Number of patients who achieve erythroid response at week 12 per international consortium criteria
Number of Participants Who Achieve Erythroid Response
Number of participants who achieve erythroid response at week 24 per international consortium criteria
Proportion of Participants Who Achieve Spleen Size Reduction
Determine the proportion of participants who achieve a spleen volume reduction of ≥ 35% from baseline at week 12
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
GlaxoSmithKline
Collaborator
