Inclusion Criteria:

• PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008).
• Platelet count of <50,000/μL at Screening (Day -35 to Day -3) (based on two measurements taken on different days; both measurements must be <50,000/μL)
• DIPSS Intermediate-1, Intermediate -2, or High risk (Passamonti et al 2010).
• Palpable splenomegaly ≥5 cm below the lower costal margin in the midclavicular line as assessed by physical examination
• TSS of ≥10 on the MPN-SAF TSS 2.0 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats
• If the patient has received prior JAK2 inhibitor treatment, this treatment must meet at least one of the following criteria:
  • a. Prior treatment with any JAK2 inhibitor, irrespective of dose, with a duration of 90 days orless. The 90-day period starts on the date of first administration of JAK2 inhibitor therapy and continues for 90 calendar days, regardless of whether therapy is administered continuously or intermittently during that interval.
  • b. Prior treatment with ruxolitinib, at no more than 10 mg total daily dose on any day, with a duration of 180 days or less. The 180-day period starts on the date of first ruxolitinib administration and continues for 180 calendar days, regardless of whether therapy is administered continuously or intermittently during that interval.The patient may not have received >10 mg of ruxolitinib on any day during that interval.
• Age ≥18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Peripheral blast count of <10% throughout the Scrrening period and prior to randomization.
• Absolute neutrophil count of >500/µL.
• Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition (MUGA) scan.
• 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.
• Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), international normalized ration (INR) and partial thromboplastin time of ≤1.5 × ULN.
• If fertile, willing to use effective birth control methods during the study.
• Willing to undergo and able to tolerate frequent MRI or CT assessments during the study.
• Able to understand and willing to complete symptom assessments using a patient reported outcomes instrument.
• Provision of informed consent.

Exclusion Criteria:

• Life expectancy <6 months.
• Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete other approved available therapy including allo-SCT.
• History of splenectomy or planning to undergo splenectomy.
• Splenic irradiation within the last 6 months.
• Previously treated with pacritinib.
• Treatment with any MF-directed therapy within 14 days prior to treatment Day 1
• Any prior treatment with more than one JAK2 inhibitor
• Treatment with an experimental therapy within 28 days prior to treatment Day 1
• Systemic treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) inducer within 14 days prior to treatment Day 1.
• Significant recent bleeding history defined as NCI CTCAE grade ≥2 within months prior to treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, injury)
• Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), anti-vascular endothelial growth factor (anti-VEGF) agents, and daily use of COX-1 inhibiting Nonsteroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1. 
• Treatment with medications that can prolong the QTc interval within 14 days priot to treatment Day 1. Shorter washout periods may be permitted with approval of the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1. 
• Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety.
• 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.
• QT corrected by the Fridericia method QTcF prolongation >450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or history of long QT interval syndrome
• New York Heart Association Class II, III, or IV congestive heart failure.
• Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication.
• Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or constipation.
• Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin or corneal cancer; curatively treated carcinoma in situ of the cervix; organ-confined prostate cancer with prostate-specific antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low, Low, or Favorable Intermediate; curatively treated non-metastatic prostate cancer with negative PSA; or in situ breast carcinoma after complete surgical resection.
• 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.
• Known seropositivity for human immunodeficiency virus.
• Known active hepatitis A, B, or C virus infection.
• Women who are pregnant or lactating.
• Concurrent enrollment in another interventional trial.