Testing Momelotinib with Luspatercept for primary myelofibrosis

Exclusion

• −Known positive status for human immunodeficiency virus (HIV).
• −Hepatitis A, B, or C status as defined below:
• −Chronic active or acute viral hepatitis A.
• −Active Hepatitis B infection indicated by the presence of hepatitis B surface antigen (HBsAg) at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → or within 3 months prior to the first dose of study intervention.
• −Positive hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more →, only if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.
• −Participants with an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years.
• −Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
• −Uncontrolled intercurrent illness:
• −Active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under controlControl groupThe group a new treatment is measured against.Read more → or as infection prophylaxis may be included in the trial);
• −Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology Criteria for Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → (CTCAE) v5.0, within 4 weeks prior to the first dose of study treatment; or
• −Uncontrolled acute and chronic liver disease (e.g., Child-Pugh score ≥10) OR has current unstable liver or biliary disease per investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
• −Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, that is not resolved at the time of the first dose of study treatment.
• −Any of the following in conditions within 6 months prior to the first dose of study intervention:
• −Unstable angina pectoris; OR
• −Symptomatic congestive heart failure; OR
• −Uncontrolled cardiac arrhythmia
• −QTc interval \>450 msec or QTc \>480 msec for participants with bundle branch block.
• −Participants with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to the first dose of study intervention.
• −History of porphyria.
• −Presence of peripheral neuropathy ≥Grade 2 per CTCAE v5.0.
• −Use of the following treatments within the time periods noted NOTE: All active anti-MF therapy must discontinue at least 1 week prior to the start of baselineBaselineYour starting measurements, taken before treatment begins.Read more → MFSAF recording (Study Day -7):
• −Active anti-MF therapy within 28 days or 5 half-lives, whichever is shorter (exception is prior JAKi therapy).
• −Steroid use for the treatment of myelofibrosis is prohibited within 14 days prior to the first dose of study treatment until discontinuation of study treatment. Supportive care including steroids for non-myelofibrosis indications may be used.
• −Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of study intervention.
• −Any prior investigational agent for myelofibrosis within 4 weeks prior to the first dose of study treatment.
• −Erythropoiesis stimulating agent (ESA) within 4 weeks prior to the first dose of study treatment.
• −Prior treatment with MMB.
• −Prior treatment with TGF-β pathway ligand traps (e.g., luspatercept or sotatercept).
• −Prior splenectomy.
• −Inability or unwillingness to comply with the protocolProtocolThe detailed plan a study must follow.Read more → restrictions on myelofibrosis therapy and other medications prior to and during study treatment.
• −Unresolved non-hematologic toxicities from prior therapies that are \>Grade 1 per CTCAE v5.0 unless otherwise specified.
• −Women who are already pregnant or lactating.
• −History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study intervention or result in inability to swallow oral medications.
• −Splenic irradiation within 3 months prior to the first dose of study treatment.