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

• Efficacy [ Time Frame: Baseline to Week 24 ]
  To compare the efficacy of once-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
• Efficacy [ Time Frame: Baseline to Week 24 ]
  To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.

• Primary Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Post-essential Thrombocythemia Myelofibrosis

• Drug: Pacritinib
• Drug: Best Available Therapy

• Experimental: Pacritinib, Once Daily
  Pacritinib 400 mg taken orally, once daily
  Intervention: Drug: Pacritinib
• Experimental: Pacritinib, Twice Daily
  Pacritinib 200 mg taken orally, twice daily
  Intervention: Drug: Pacritinib
• Active Comparator: Best Available Therapy
  Best Available Therapy includes any physician-selected treatment for primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis, such as approved JAK2 inhibitors, and may include any treatment received before study entry. Best Available Therapy may include ruxolitinib, other approved JAK2 inhibitors, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan, or other agents and may also include no treatment and symptom-directed treatment without myelofibrosis-specific treatment.
  Intervention: Drug: Best Available Therapy

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