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To receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food

The Physician's Choice (P/C) therapy (limited to single drugs from the following list: corticosteroids, hydroxyurea, danazol, or low-dose ruxolitinib). The proposed P/C regimen for a patient must be selected prior to randomization.

Oral administration. Supplied in capsules containing 100 mg (as the free base) in red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000. Each capsule contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base

Pacritinib

Physician's Choice medications will be selected and administered according to the investigator's judgement. Investigators can select individual P/C agents but cannot combine agents or give them sequentially.

Physician's Choice medications

Simran Bedi Singh

This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count \<50,000/μL). Approximately 399 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 266 patients) or to P/C therapy (approximately 133 patients)

Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis

Intervention/treatment: Drug-Pacritinib

The study is a randomized, controlled phase 3 study comparing the efficacy of pacritinib with P/C therapy in patients with PMF, PPV-MF, or PET-MF (Dynamic International Prognostic Scoring System \[DIPSS\] risk score of Intermediate-1 to High-Risk), who have had had no or limited exposure to any JAK2 inhibitor or are JAK2 inhibitor-naive, and who have severe thrombocytopenia (platelet count \<50,000/µL). This study was designed to use the pacritinib 200 mg BID dose, which was determined to be the optimal dose based on dose- and exposure-response analyses conducted using all available data, including the dosing data from the previous portion of this study. Patients will be randomized 2:1 to receive pacritinib 200 mg BID or the P/C therapy (limited to single drugs from the following list: corticosteroids, hydroxyurea, danazol, or low-dose ruxolitinib). The proposed P/C regimen for a patient must be selected prior to randomization. Randomization will be stratified by prior JAK2 inhibitor therapy (yes/no) and P/C therapy selected prior to randomization. Prior JAK2 inhibitor therapy will be defined as any duration of treatment with a JAK2 inhibitor, such as ruxolitinib, fedratinib, or momelotinib. To be eligible, patients are not allowed to have been treated with more than one JAK2 inhibitor. Assigned treatment will continue until the patient experiences progressive disease or intolerable AEs, withdraws consent, or initiates new MF-directed therapy. No study treatment crossover will be allowed at any time. All patients should complete all visit procedures through Week 24, including patients who stop treatment or have protocol-defined progressive disease prior to Week 24, unless the patient withdraws consent for study procedures, dies, undergoes splenic irradiation or splenectomy, initiates any non-protocol-directed anti-MF treatment, or the study is terminated. In addition to the above, patients will be considered to have discontinued treatment if pacritinib or P/C therapy is held for \>28 consecutive days due to treatment toxicity, or if treatment is discontinued for lack of efficacy, or at the request of the principal investigator or the patient. Following the Week 24 assessment, patients who are benefiting from therapy will be allowed to continue receiving the assigned treatment (pacritinib or P/C) until the patient experiences progressive disease, intolerable AEs, withdraws consent, or initiates new MF-directed therapy. All randomized patients will be followed for survival for 2.5 years from the date of randomization unless consent for follow-up is withdrawn.

A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

A Randomized, Controlled Phase 3 Study of Pacritinib Versus Physician's Choice in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Severe Thrombocytopenia (Platelet Count <50,000/μL)(PACIFICA)

Proportion of patients achieving \>25% SVR

Achievement of red blood cell (RBC) transfusion independence at Weeks 12 and 24

Improvement in hemoglobin level without transfusion at Weeks 12 and 24

Improvement in platelet count at Weeks 12 and 24

Frequency of platelet transfusions at Weeks 12 and 24

Improvement in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) v.1.0 - Fatigue from Baseline through Week 24

Leukemia-free survival (LFS) of patients treated with pacritinib versus P/C therapy

The percentage of red blood cell transfusion-independent patients at baseline achieving a 1 g/dL and a 2 g/dL increase in hemoglobin at week 24

The percentage of platelet transfusion-independent patients at baseline with improvement in grade of thrombocytopenia at week 24

The percentage of transfusion-dependent patients at baseline achieving transfusion independence and achieving 50% reduction in transfusion rate at week 24

Changes in mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers

MACE is a composite endpoint that is considered to occur if any of the following TEAEs occur:

* cardiovascular death, defined as death due to acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular procedures, death due to cardiovascular hemorrhage, or death due to peripheral artery disease
* non-fatal myocardial infarction
* non-fatal stroke of any classification, including reversible focal neurological defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage

To compare the efficacy of pacritinib with that of physician's choice (P/C) therapy, as assessed by the proportion of patients achieving a ≥35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans

To compare the efficacy of pacritinib compared to P/C therapy, as assessed by the proportion of patients achieving a ≥50% reduction in Total Symptom Score (TSS). The TSS is the sum of the individual symptom scores for tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under ribs on the left side. Symptoms are ranked 0 (absent) to 10 (worst imaginable)

To compare the overall survival (OS) of patients treated with pacritinib versus those treated with P/C

To compare the percentage of patients who self-assess as "very much improved" or "much improved" as measured by the Patient Global Impression of Change (PGIC) in patients treated with pacritinib versus those treated with P/C

Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment with pacritinib and/or physician's choice therapy.

PSI CRO

CTI BioPharma

Cytopenia

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.

Best Available Therapy

Simran Singh

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.

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.

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

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

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).

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.

All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).

Pacritinib, Once Daily

Pacritinib, Twice Daily

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis	NCT03165734	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Physician's Cho...	18 Years -	CTI BioPharma
Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia	NCT02055781	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Best Available ...	18 Years -	CTI BioPharma
Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia	NCT02055781	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Best Available ...	18 Years -	CTI BioPharma
A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis	NCT03165734	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Physician's Cho...	18 Years -	CTI BioPharma

Spots Global Cancer Trial Database for spleen volume