Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis

Intervention / Treatment
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* Drug: Pacritinib
* Drug: Best Available Therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pacritinib<br>Pacritinib 400 mg QD | Drug: Pacritinib<br> <br> |
| Active Comparator: Best Available Therapy<br>BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases) | Drug: Best Available Therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spleen Volume Reduction | Number 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) | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Symptom Score (TSS) Reduction | Number of patients with >= 50% reduction in total score from baseline to week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 [absent] to 10 [worst imaginable]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, Primary Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, Bone Marrow Disease, Hematologic Disease, Splenomegaly, Pacritinib, MPN-SAF, MPN-SAF TSS, Anemia, Myeloproliferative Neoplasm, Spleen volume, Thrombocytopenia, SB1518