A Study of Ruxolitinib in Combination With Ulixertinib in People With Myelofibrosis

Exclusion Criteria

• •Use of experimental drug therapy for MF or any other standard drug with the exception of hydroxyurea or ruxolitinib within 2 weeks of starting combination therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better. Hydroxyurea may be utilized to control leukocytosis for up to 4 weeks during study
• •Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• •Unwilling to receive red blood cell transfusion to treat low hemoglobin.
• •Participants who are receiving any other investigational agents.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib and ulixertinib.
• •Participants requiring any medications or substances that are strong inhibitors or inducers of 3A4, strong inhibitors of CYP1A2 and CYP2D6, and inhibitors of Pglycoprotein (P-gp). Strong inhibitors or inducers of 3A4, strong inhibitors of CYP1A2 and CYP2D6, and inhibitors of P-gp must be stopped within 14 days (or 5 half-lives) of study commencement. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• •Participants who are pregnant or breastfeeding.
• •Pregnant women are excluded from this study because ruxolitinib and ulixertinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib and ulixertinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib and ulixertinib.
• •Active bacterial, fungal, or viral infection requiring treatment.
• •Participants with chronic Human immunodeficiency virus (HIV) or hepatitis B or C viral infection.
• •* HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: testing does not have to be performed during screening unless participant has known or suspected history of HIV.
• •* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• •Presence of active interstitial lung disease or pneumonitis.
• •History of cardiovascular risk factors:
• •* Clinically significant, uncontrolled arrythmias and/or conduction abnormalities. Participants with controlled atrial fibrillation \>30 days prior to study initiation are eligible.
• •* QTc \> 480 msec.
• •* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study entry;
• •* Class II congestive heart failure or greater or ejection fraction ≤50% on baseline echocardiogram.
• •* History of uncontrolled hypertension.
• •A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
• •Psychiatric illness/social situations, active drug, alcohol or substance use that would interfere with study compliance.
• •Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending study visits; pose a significant risk to the participant; or interfere with interpreting study data.
• •Participants eligible for allogeneic stem cell transplantation in the opinion of the treating physician at the time of enrollment.
• •Inability to comprehend or unwilling to sign the informed consent form.
• •Transformation to accelerated or blast phase disease, including myeloid sarcoma.