Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

The primary objective is to compare the efficacy of pacritinib with that of best available
therapy (BAT) in patients with primary myelofibrosis (PMF), post-polycythemia vera
myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF); the
efficacy measure for this analysis is the proportion of patients achieving a ≥ 35% reduction
in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or
computed tomography (CT) scan.

Inclusion Criteria:

- Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)

- 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

- No spleen radiation therapy for 6-12 months

- Last therapy for myelofibrosis was 2-4 weeks ago, including any erythropoietic or
thrombopoietic agent

- Not pregnant, not lactating, and agree to use effective birth control

Exclusion Criteria:

- Prior treatment with a JAK2 inhibitor

- 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

- 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