A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis (PACIFICA)
Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
About this trial
This is an interventional treatment trial for Primary Myelofibrosis focused on measuring myelofibrosis, pacritinib, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Ruxolitinib, Bone Marrow Disease, Hematologic Diseases, Blood Platelet Disorders, Hemorrhagic Disorders, Splenomegaly, Anemia, Spleen volume, Spleen
Eligibility Criteria
Diagnosis and Inclusion Criteria
- PMF (including pre-fibrotic MF), PPV-MF, or PET-MF (Tefferi and Vandiman 2008)
- Average platelet count of <50,000/µL at Screening (Day -35 to Day -3) based on two measurements taken on different days; both measurements must be <50,000/µL
- DIPSS Intermediate-1, Intermediate-2, or High risk (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
If the patient has received prior JAK2 inhibitor treatment, this treatment must meet at least one of the following criteria:
- Prior treatment with any JAK2 inhibitor, irrespective of dose, with a duration of 90 days or less. 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 during that interval.
- Prior treatment with ruxolitinib, at no more than 10 mg total daily dose on any day, with a duration of 270 days or less. The 270-day period starts on the date of first ruxolitinib administration and continues for 270 calendar days, regardless of whether therapy is administered continuously or intermittently during that interval.The patient may not have received >10 mg of ruxolitinib on any day during that interval
- Age ≥18 years
- Eastern Cooperative Oncology Group performance status 0 to 2
- Peripheral blast count of <10% throughout the Screening period and at baseline
- Absolute neutrophil count of ≥500/µL
- Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition (MUGA) 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/dL
- Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
- If fertile, willing to use 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
Exclusion Criteria
- Life expectancy <6 months
- Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete other approved available therapy including allo-SCT
- 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
- Any prior treatment with more than one JAK2 inhibitor
- Treatment with an experimental therapy within 28 days prior to treatment Day 1
- Systemic treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) 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 1
- Significant 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 (e.g., 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), anti-vascular endothelial growth factor (anti-vascular endothelial growth factor [anti-VEGF]) agents, and daily use of cyclooxygenase-1 (COX-1) inhibiting nonsteroidal anti- inflammatory drugs (NSAIDs) within 14 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 1
- Any 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-QTc 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 (e.g., 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. The following patients may be eligible despite having had a malignancy within the prior 3 years: patients with curatively treated squamous or basal cell carcinoma of the skin; patients with curatively treated non-invasive cancers; patients with organ-confined prostate cancer with prostate-specific antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low, Low, or Favorable Intermediate; and patients with curatively treated non-metastatic prostate cancer with negative PSA.
- Uncontrolled intercurrent illness, including, but not limited to, 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 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 medication.
Sites / Locations
- University of Alabama at Birmingham, (UAB) Hospital, Comprehensive Cancer Center
- Mayo Clinic Hospital
- City of Hope
- USC Norris Comprehensive Cancer Center
- UCLA David Geffen School of Medicine
- University of Colorado Cancer Center
- Rocky Mountain Cancer Centers (US Oncology/McKesson)
- Yale School of Medicine
- Georgetown University Hospital
- George Washington University-Medical Faculty Associates
- Cleveland Clinic Florida
- Northwestern Memorial Hospital
- Rush University Medical Center
- The University of Chicago Medical Center
- University of Kansas Cancer Center and Medical Pavilion
- Ochsner Medical Center
- Saint Agnes Hospital
- Johns Hopkins University
- American Oncology Partners of Maryland, PA
- Regional Cancer Care Associates LLC - CCBD Division
- Maryland Oncology Hematology, PA- Columbia
- Dana Farber Cancer Institute, Massachusetts General Hospital
- Michigan Medicine Hematology Clinic-Rogel Cancer Center
- Cancer and Hematology Centers of Western Michigan
- Washington University School of Medicine-Siteman Cancer Center
- Comprehensive Cancer Centers of Nevada- Twain Office
- Hackensack University Medical Center
- Memorial Sloan-Kettering Cancer Center- Commack
- Columbia University Medical Center
- Weill Cornell Medical College
- Icahn School of Medicine at Mount Sinai
- Memorial Sloan -Kettering Cancer Center
- University of Rochester
- Duke University Hospital
- Cleveland Clinic
- Ohio State University Comprehensive Cancer Center
- Oregon Health and Science University
- UPMC Hillman Cancer Center
- The Sarah Cannon Research Institute-Tennessee Oncology
- The University of Texas MD Anderson Cancer Center
- Mays Cancer Center
- Texas Oncology- San Antonio
- University of Utah - Huntsman Cancer Institute
- Fred Hutchinson Cancer Research Center
- Westmead HospitalRecruiting
- Alfred Hospital, Malignant Hematology and Stem Cell Transplantation ServiceRecruiting
- The Perth Blood InstituteRecruiting
- Republican Research Center for Radiation Medicine and Human EcologyRecruiting
- Grodno University Hospital
- Minsk Scientific and Practical Center of Surgery, Transplantology and HematologyRecruiting
- University Clinical Centre of the Republic of SrpskaRecruiting
- University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"Recruiting
- University Multiprofile Hospital for Active Treatment "Sveti Georgi", PlovdivRecruiting
- Multiprofile Hospital for Active Treatment - Sofia, part of Military Medical AcademyRecruiting
- Specialized Hospital for Active Treatment of Hematological DiseasesRecruiting
- Multiprofile Hospital for Active Treatment "Sveta Marina"Recruiting
- Tom Baker Cancer Center, Internal Medicine/HematologyRecruiting
- University of AlbertaRecruiting
- Providence Hematology - VancouverRecruiting
- Eastern Regional Health AuthorityRecruiting
- Nova Scotia Health Authority, Centre for Clinical ResearchRecruiting
- Princess Margaret Cancer CentreRecruiting
- Jewish General Hospital; Clinical Research UnitRecruiting
- University Hospital BrnoRecruiting
- University Hospital OlomoucRecruiting
- University Hospital PlzenRecruiting
- University Hospital Kralovske Vinohrady, Clinic of Internal HematologyRecruiting
- CHU Hôpital Amiens SudRecruiting
- La Conception HospitalRecruiting
- CHU de Nimes - Hopital Universitaire CaremeauRecruiting
- Hôpital Saint-LouisRecruiting
- CHU Hopitaux de Bordeaux - Hôpital Haut-LévêqueRecruiting
- Centre Hospitalier Lyon-SudRecruiting
- University Hospital Center of PoitiersRecruiting
- Hautepierre Hospital
- Centre Hospitalier de Toulouse- Hôpital Purpan
- JSC K. Eristavi National Center For Experimental and Clinical SurgeryRecruiting
- LTD M.Zodelava's Hematology Center, Department of HematologyRecruiting
- LTD National Institute of Endocrinology
- LTD S.Khechinashvili University Hospital
- Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTDRecruiting
- Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLCRecruiting
- University Hospital Cologne, Department of Internal Medicine I,
- University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
- Johannes Wesling Hospital Minden, Department of Oncology and Hematology
- Hospital rechts der Isar, Department of Internal Medicine III, Hematology and Oncology
- University Hospital Ulm, Center for Internal Medicine,
- Semmelweis University SE ÁOK I. sz. Belgyógyászati KlinikaRecruiting
- University of Debrecen Clinical Center (Debreceni Egyetem Klinikai Központ)Recruiting
- Somogy Megyei Kaposi Mór Oktató KórházRecruiting
- Bacs-Kiskun County Hospital, 2nd Department of Internal Medicine
- Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of HematologyRecruiting
- Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine IRecruiting
- Lady Davis Carmel Medical Center, Department of Hematology,Recruiting
- Hadassah Medical Center, Department of Hematology,Recruiting
- Meir Medical Center, Hematology Institute and Blood BankRecruiting
- Rabin Medical Center, Clinic for Myeloproliferative DisordersRecruiting
- The Tel Aviv Sourasky Medical Center, Department of Internal MedicineRecruiting
- Cancer Institute "Giovanni Paolo II", IRCCSRecruiting
- Polyclinic S. Orsola-MalpighiRecruiting
- ASST Spedali Civili Brescia, Hematology UnitRecruiting
- Azienda Ospedaliero-Universitaria CareggiRecruiting
- Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCSRecruiting
- Maggiore Polyclinic Hospital, Fondazione IRCCS Ca' GrandaRecruiting
- ASST Monza - Ospedale San GerardoRecruiting
- United Hospitals Villa Sofia CervelloRecruiting
- Polyclinic San Matteo, IRCCSRecruiting
- Hospital "Infermi" of Rimini
- University Polyclinic Foundation "Agostino Gemelli"Recruiting
- ASST Sette Laghi HospitalRecruiting
- Pusan National University HospitalRecruiting
- Kyungpook National University HospitalRecruiting
- Severance HospitalRecruiting
- Samsung Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- The Catholic University of Korea, St. Mary's HospitalRecruiting
- University Clinical Center in GdanskRecruiting
- Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice, Department of Hematology and Bone Marrow TransplantationRecruiting
- Pratia Oncology KatowiceRecruiting
- University Hospital in KrakowRecruiting
- Jedrzej Sniadecki Specialist Hospital in Nowy Sacz, Department of HematologyRecruiting
- Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology,Recruiting
- Nasz Lekarz Medical Outpatient Clinics Slawomir JekaRecruiting
- Institute of Hematology and Transfusion Medicine, Teaching Department of HematologyRecruiting
- Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow TransplantationRecruiting
- Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in LodzRecruiting
- Onco Card SrlRecruiting
- Coltea Clinical HospitalRecruiting
- Fundeni Clinical InstituteRecruiting
- Prof. Dr. Ion Chiricuta" Institute of OncologyRecruiting
- City Clinical Hospital #40
- City Clinical Hospital n.a. V.V. Veresaev of the Moscow City Health
- S.P. Botkin City Clinical Hospital
- Clinic UZI 4D, LLC
- Research Institute of Hematology and Transfusiology
- S.M. Kirov Military Medical Academy, Department and Clinic for Intermediate-Level Training in Internal Medicine, Hematology Division
- V.A. Almazov North-West Federal Medical Research Center, Institute of Oncology and Hematology, Scientific Department of Clinical Oncology
- V.D. Seredavin Samara Regional Clinical Hospital, Department of Hematology
- Bashkiria State Medical University, Department of Internal Medicine
- Volgograd Regional Clinical Oncology Center
- Clinical Center of Serbia, Clinic of HematologyRecruiting
- Clinical Center of Vojvodina, Clinic of HematologyRecruiting
- Hospital del MarRecruiting
- Hospital Clínic de BarcelonaRecruiting
- Hospital Universitario Ramón y CajalRecruiting
- Morales Meseguer University General Hospital, Department of Hematology and HemotherapyRecruiting
- Clínica Universidad de Navarra
- University Clinical Hospital of Salamanca, Department of HematologyRecruiting
- University Clinical Hospital of Valencia, Department of Hematology and Medical OncologyRecruiting
- Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council, Regional Treatment and Diagnostic Hematology Center, Department of Hematology
- City Clinical Hospital #4" under Dnipro City Council
- Regional Clinical Hospital, Department of Hematology,
- Communal Non-profit enterprise "Regional Center of Oncology", Department of Hematology
- Kyiv City Clinical Hospital #9, Hematology Department #1
- Kyiv Regional Oncology Center, Department of Hematology,
- Limited Liability Company "City Doctor"
- Institute of Blood Pathology and Transfusion Medicine, Department of Hematology
- Poltava M.V. Sklifosovskyi Regional Clinical Hospital under Poltava Regional Council, Department of Hematology
- Royal Hallamshire Hospital, Department of HematologyRecruiting
- Beatson West of Scotland Cancer CentreRecruiting
- Gloucestershire Royal HospitalRecruiting
- Barts Health NHS Trust - The Royal London HospitalRecruiting
- Guy's and St Thomas' NHS Foundation Trust - Guy's HospitalRecruiting
- Imperial College Healthcare NHS Trust - Hammersmith HospitalRecruiting
- The Christie NHS Foundation Trust
- Oxford University Hospitals NHS Trust - Churchill HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pacritinib 200 mg BID
Physician's Choice (P/C) therapy
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.