Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia (PAC326)

Inclusion Criteria:

• Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
• Thrombocytopenia (platelet count ≤ 100,000/µL) at any time after signing informed consent
• 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
• At least 6 months from prior splenic irradiation
• At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent
• Not pregnant, not lactating, and agree to use effective birth control
• Able and willing to undergo frequent MRI or CT assessments and complete symptom assessments using a patient-reported outcome instrument

Exclusion Criteria:

• Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
• There is no maximum cumulative prior JAK2 inhibitor treatment
• 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
• Active bleeding that requires hospitalization during the screening period
• 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