Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with primary or secondary myelofibrosis.

Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with primary or secondary myelofibrosis. Approximately 322 eligible patients will be randomized in a 2:1 allocation to pacritinib (400mg QD) or BAT (includes any physician-selected treatment for myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)). Spleen volume will be measured by MRI or CT at baseline and every 12 weeks thereafter. An independent radiology facility (IRF), blind to treatment assignments, will measure spleen volumes. Patients will also be followed for safety, Leukemia Free Survival (LFS), Overall Survival (OS), frequency of red blood cell (RBC) and platelet transfusions, and other exploratory endpoints. An Independent Data Monitoring Committee (IDMC) will evaluate the safety of pacritinib.

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