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A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
399 patients around the world
Available in Brazil, United States
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.
Swedish Orphan Biovitrum
14Research sites
399Patients around the world
This study is for people with
Myeloproliferative syndromes
Myelofibrosis
Requirements for the patient
From 18 Years
All Gender
Medical requirements
- Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF as defined by Tefferi and Vardiman 2008.Platelet count of <50,000/μL at Screening (Day -35 to Day -3).Dynamic International Prognostic Scoring System Intermediate-1, Intermediate-2, or High-Risk as per Passamonti et al 2010.Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination.TSS of ≥10 on the MPN-SAF TSS 2.0 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats.The TSS criteria need only to be met on a single day.Age ≥18 years.Eastern Cooperative Oncology Group performance status 0 to 2.Peripheral blast count of <10% throughout the Screening period prior to randomization.Absolute neutrophil count of ≥500/µL.Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition scan.Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) ≤3 × the upper limit of normal (ULN) (AST/ALT ≤5 × ULN if transaminase elevation is related to MF), total bilirubin ≤4 x ULN (in cases where total bilirubin is elevated, direct bilirubin ≤4 × ULN, is required) and creatinine ≤2.5 mg/dLAdequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN.If fertile, willing to use highly effective birth control methods during the study.Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study.Able to understand and willing to complete symptom assessments using a patient-reported outcome instrument.Provision of signed informed consent.
- Life expectancy <6 months.Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete other approved available therapy including allogeneic stem cell.History of splenectomy or planning to undergo splenectomy.Splenic irradiation within the last 6 months.Previously treated with pacritinib.Treatment with any MF-directed therapy within 14 days prior to treatment Day 1.Prior treatment with more than one JAK2 inhibitor.Prior treatment with ruxolitinib, if BOTH of the following conditions are met:Exposure to higher-dose ruxolitinib (>10 mg daily) within 120 days prior to treatment Day 1.Total duration of treatment with higher-dose ruxolitinib (>10 mg daily) was >90 days, from first to last exposure.Prior treatment with any JAK2 inhibitor other than ruxolitinib, irrespective of dose, with a duration of >90 days. The 90-day period starts on the date of first administration of JAK2 inhibitor therapy and continues for 90 calendar days, regardless of whether therapy is administered continuously or intermittently.Treatment with an experimental therapy, including MF-directed experimental therapies within 28 days prior to treatment Day 1.Systemic treatment with a strong CYP 3A4 inhibitor or a strong CYP 3A4 inducer within 14 days prior to treatment Day 1. Shorter washout periods may be permitted with approval of the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (eg, surgery, trauma, or injury)Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day),and daily use of cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1. Treatment with systemic anti-vascular endothelial growth factor (anti-VEGF) agents within 28 days prior to treatment Day 1.Systemic treatment with medications that can prolong the QT interval within 14 days prior to treatment Day 1. Shorter washout periods may be permitted with approval of the Medical Monitor, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within 6 months prior to treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the Medical Monitor, if stable and unlikely to affect patient safety.Any history of CTCAE grade ≥2 cardiac dysrhythmias within 6 months prior to treatment Day 1. Patients with non-corrected QT interval CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the Medical Monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.QT corrected by the Fridericia method (QTcF) prolongation >450 ms or other factors that increase the risk for QT interval prolongation (eg, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or history of long QT interval syndrome).New York Heart Association Class II, III, or IV congestive heart failure.Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication.Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation.Other malignancy within 3 years prior to treatment Day 1.Uncontrolled intercurrent illness, including ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements.Known seropositivity for human immunodeficiency (HIV) virus.Known active hepatitis A, B, or C virus infection.Women who are pregnant or lactating.Concurrent enrollment in another interventional trial.Severe thrombocytopenia due to vitamin B12 deficiency, folate deficiency, or viral infection in the opinion of the investigator.Known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate; any contraindication to the "physician's choice" medicinal product selected by the investigator to be used as the comparator or to loperamide or equivalent antidiarrheal medicationPersons deprived of their liberty by a judicial or administrative decision.Persons subject to legal protection measures or unable to express their consent.Temporarily incapacitated persons.
Sites
Hospital São Lucas de Copacabana
Recruiting
Hospital São Rafael
Hospital das Clínicas da Universidade Federal de Goiás - UFG
Recruiting
CETUS Hospital Dia Oncologia - Belo Horizonte
Recruiting
Hospital De Clínicas Da Universidade Federal Do Paraná
Instituto Atena de Pesquisa Clínica
Recruiting
Hospital Moinhos de Vento
Recruiting
Hospital Mãe de Deus - Porto Alegre
Recruiting
CEPEN - CENTRO DE PESQUISA E ENSINO DE SANTA CATARINA
Recruiting
Hospital de Clínicas - Universidade Estadual de Campinas - UNICAMP
StudyPACIFICA
SponsorSwedish Orphan Biovitrum
Study typeInterventional
Conditions
Myelofibrosis
Requirements
From 18 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT03165734
