Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia

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 thrombocytopenia and 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 thrombocytopenia and primary or secondary myelofibrosis. Approximately 300 eligible patients will be randomized in a 1:1:1 allocation to pacritinib 400 mg dosed QD, pacritinib 200 mg dosed BID, or BAT (includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry). 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 Thrombocytopenia and 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) 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

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, Once Daily<br>Pacritinib 400 mg QD | Drug: Pacritinib<br> <br> |
| Experimental: Pacritinib, Twice Daily<br>Pacritinib 200 mg BID | Drug: Pacritinib<br> <br> |
| Active Comparator: Best Available Therapy<br>BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry. | 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 | 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). | Baseline to Week 24 | 
| Total Symptom Score (TSS) Reduction | 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 (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 Diseases, Hemorrhagic Disorders, Splenomegaly, Pacritinib, MPN-SAF, MPN-SAF TSS, Anemia, Myeloproliferative Neoplasm, Spleen volume, Thrombocytopenia, SB1518