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

• PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)
• DIPSS Intermediate-1, Intermediate -2, or High-risk (Passamonti et al 2010)
• Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following:
• Treatment for ≥3 months with inadequate efficacy response defined as 500/μL
• 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), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN
• Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan
• If fertile, willing to use effective birth control methods during the study
• Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study
• Able to understand and willing to complete symptom assessments using a PRO instrument
• Provision of informed consent

Exclusion Criteria

• Life expectancy 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)
• 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 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
• 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