Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia

The primary objective is to compare the efficacy of two dose-schedule arms(s) of pacritinib
(pooled once-daily [QD] and twice-daily [BID] dosing arms) with that of best available
therapy (BAT) in patients with thrombocytopenia and primary myelofibrosis (PMF),
post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia
myelofibrosis (PET-MF). The efficacy co-endpoints for this analysis are 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 and the proportion of
patients achieving a ≥ 50% reduction in total symptom score (TSS) from baseline to Week 24 as
measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).

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