Phase 2 Study: An Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post- Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib

Inclusion Criteria: 1. PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008) 2. DIPSS Intermediate-1, Intermediate -2, or High-risk (Passamonti et al 2010) 3. Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following: 1. Treatment for ≥3 months with inadequate efficacy response defined as \<10% SVR by MRI or \<30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response; and/or 2. Treatment for ≥28 days complicated by either i. Development of a red blood cell (RBC) transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (NCI) CTCAE grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \<20 mg BID 4. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination 5. TSS of ≥10 on the MPN-SAF TSS 2.0 or patients with a single symptom score of ≥5 or 2 symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats 6. Age ≥18 years old 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 8. Peripheral blast count of \<10% throughout the Screening period 9. Absolute neutrophil count of \>500/μL 10. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase \[AST\]/serum glutamic-oxaloacetic transaminase \[SGOT\] and alanine aminotransferase \[ALT\]/serum glutamic-pyruvic transaminase \[SGPT\]), ≤3 × the upper limit of normal (ULN) (AST/ALT ≤5 × ULN, if transaminase elevation is related to MF), direct bilirubin ≤4× ULN, and creatinine ≤2.5 mg/dL 11. Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN 12. Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan 13. If fertile, willing to use effective birth control methods during the study 14. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study 15. Able to understand and willing to complete symptom assessments using a PRO instrument 16. Provision of informed consent Exclusion Criteria: 1. Life expectancy \<6 months 2. Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete allo-SCT 3. History of splenectomy or planning to undergo splenectomy 4. Splenic irradiation within the last 6 months 5. Previously treated with pacritinib 6. Patients receiving high-dose ruxolitinib (more than 10 mg BID or 20 mg QD) who cannot tolerate tapering down ruxolitinib to 10 mg BID or less prior to the first dose of pacritinib 7. Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ≤100 mg per day, within the last 2 weeks 8. Treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 inducer within the last 2 weeks 9. Treatment with medications that can prolong the QTc interval within the last 2 weeks 10. Treatment with an experimental therapy within the last 28 days 11. Significant recent bleeding history defined as NCI CTCAE grade ≥2 within the last 3 months, unless precipitated by an inciting event (eg, surgery, trauma, or injury) 12. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety. 13. New York Heart Association Class II, III, or IV congestive heart failure 14. Any history of CTCAE grade ≥2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the medical monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety. 15. QTc prolongation \>450 ms based on the mean of triplicate ECGs or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia \[defined as serum potassium \<3.0 mEq/L that is persistent and refractory to correction\], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval) 16. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication 17. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or constipation 18. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma 19. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection or psychiatric illness or social situation that, in the judgment of the treating physician, would limit compliance with study requirements 20. Known seropositivity for human immunodeficiency virus 21. Known active hepatitis A, B, or C virus infection 22. Women who are pregnant or lactating 23. Concurrent enrollment in another interventional trial