Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

Inclusion Criteria: * Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010) * Palpable splenomegaly ≥ 5 cm on physical examination * Total Symptom Score \>13 on the MPN-SAF TSS 2.0, not including the inactivity question * Patients who are platelet or red blood cell transfusion-dependent are eligible * Adequate white blood cell counts (with low blast counts), liver function, and renal function * No spleen radiation therapy for 6-12 months * Last therapy for myelofibrosis was 2-4 weeks ago, including any erythropoietic or thrombopoietic agent * Not pregnant, not lactating, and agree to use effective birth control Exclusion Criteria: * Prior treatment with a JAK2 inhibitor * History of (or plans to undergo) spleen removal surgery or allogeneic stem cell transplant * Ongoing gastrointestinal medical condition such as Crohn's disease, Inflammatory bowel disease, chronic diarrhea, or constipation * Cardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction * Other malignancy within last 3 years other than certain limited skin, cervical, prostate, breast, or bladder cancers * Other ongoing, uncontrolled illnesses (including HIV infection and active hepatitis A, B, or C), psychiatric disorder, or social situation that would prevent good care on this study * Life expectancy \< 6 months