A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
- Conditions
- Post-essential Thrombocythemia MyelofibrosisPost-polycythemia Vera MyelofibrosisPrimary Myelofibrosis
- Interventions
- Drug: PacritinibDrug: Physician's Choice medications
- Registration Number
- NCT03165734
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 399
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pacritinib 200 mg BID Pacritinib To receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food Physician's Choice (P/C) therapy Physician's Choice medications 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.
- Primary Outcome Measures
Name Time Method Spleen volume From baseline at 24 weeks 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
Total Symptom Score (TSS) (excluding tiredness) From baseline at Week 24 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)
- Secondary Outcome Measures
Name Time Method Patient Global Impression of Change (PGIC) assessed at Week 24 End of Week 12 to 2 years following Week 24 visit 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
To compare the safety of pacritinib versus P/C therapy Randomization through 30 after last treatment 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.
Overall Survival (OS) until 2.5 years after the date of randomization To compare the overall survival (OS) of patients treated with pacritinib versus those treated with P/C
Trial Locations
- Locations (181)
The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Shri Ram Cancer Centre, Mahatma Gandhi Medical College & Hospital
🇮🇳Jaipur, Rajasthan, India
Gauhati Medical College and Hospital
🇮🇳Guwahati, Assam, India
Tata Medical Center
🇮🇳Kolkata, West Bengal, India
University of Alabama at Birmingham, (UAB) Hospital, Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers (US Oncology/McKesson)
🇺🇸Boulder, Colorado, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
George Washington University-Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Kansas Cancer Center and Medical Pavilion
🇺🇸Westwood, Kansas, United States
Saint Agnes Hospital
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
American Oncology Partners of Maryland, PA
🇺🇸Bethesda, Maryland, United States
Regional Cancer Care Associates LLC - CCBD Division
🇺🇸Bethesda, Maryland, United States
Maryland Oncology Hematology, PA- Columbia
🇺🇸Columbia, Maryland, United States
Dana Farber Cancer Institute, Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Michigan Medicine Hematology Clinic-Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine-Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada- Twain Office
🇺🇸Las Vegas, Nevada, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan -Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
The Sarah Cannon Research Institute-Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Texas Oncology- San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah - Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Alfred Hospital, Malignant Hematology and Stem Cell Transplantation Service
🇦🇺Melbourne, Victoria, Australia
The Perth Blood Institute
🇦🇺Perth, Western Australia, Australia
Republican Research Center for Radiation Medicine and Human Ecology
🇧🇾Gomel, Belarus
Grodno University Hospital
🇧🇾Grodno, Belarus
Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
🇧🇾Minsk, Belarus
University Clinical Centre of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
University Clinical Center of Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
🇧🇬Pleven, Bulgaria
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
🇧🇬Plovdiv, Bulgaria
Multiprofile Hospital for Active Treatment - Sofia, part of Military Medical Academy
🇧🇬Sofia, Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases
🇧🇬Sofia, Bulgaria
Multiprofile Hospital for Active Treatment "Sveta Marina"
🇧🇬Varna, Bulgaria
Tom Baker Cancer Center, Internal Medicine/Hematology
🇨🇦Calgary, Alberta, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Providence Hematology - Vancouver
🇨🇦Vancouver, British Columbia, Canada
Eastern Regional Health Authority
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Nova Scotia Health Authority, Centre for Clinical Research
🇨🇦Halifax, Nova Scotia, Canada
University Hospital Olomouc
🇨🇿Olomouc, Czechia
University Hospital Plzen
🇨🇿Pilsen, Czechia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital; Clinical Research Unit
🇨🇦Montreal, Quebec, Canada
University Hospital Brno
🇨🇿Brno, Czechia
University Hospital Kralovske Vinohrady, Clinic of Internal Hematology
🇨🇿Prague, Czechia
CHU Hôpital Amiens Sud
🇫🇷Amiens, France
La Conception Hospital
🇫🇷Marseille, France
CHU de Nimes - Hopital Universitaire Caremeau
🇫🇷Nîmes, France
Hôpital Saint-Louis
🇫🇷Paris, France
CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
🇫🇷Pessac, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre Benite, France
University Hospital Center of Poitiers
🇫🇷Poitiers, France
Hautepierre Hospital
🇫🇷Strasbourg, France
Centre Hospitalier de Toulouse- Hôpital Purpan
🇫🇷Toulouse, France
JSC K. Eristavi National Center For Experimental and Clinical Surgery
🇬🇪Tbilisi, Georgia
LTD M.Zodelava's Hematology Center, Department of Hematology
🇬🇪Tbilisi, Georgia
LTD National Institute of Endocrinology
🇬🇪Tbilisi, Georgia
LTD S.Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTD
🇬🇪Tbilisi, Georgia
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
🇬🇪Tbilisi, Georgia
University Hospital Cologne, Department of Internal Medicine I,
🇩🇪Cologne, Germany
University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
🇩🇪Halle, Germany
Johannes Wesling Hospital Minden, Department of Oncology and Hematology
🇩🇪Minden, Germany
Hospital rechts der Isar, Department of Internal Medicine III, Hematology and Oncology
🇩🇪Munich, Germany
University Hospital Ulm, Center for Internal Medicine,
🇩🇪Ulm, Germany
Semmelweis University SE ÁOK I. sz. Belgyógyászati Klinika
🇭🇺Budapest, Hungary
University of Debrecen Clinical Center (Debreceni Egyetem Klinikai Központ)
🇭🇺Debrecen, Hungary
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
Bacs-Kiskun County Hospital, 2nd Department of Internal Medicine
🇭🇺Kecskemét, Hungary
Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology
🇭🇺Nyíregyháza, Hungary
Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine I
🇭🇺Székesfehérvár, Hungary
Sahyadri Super Speciality Hospital
🇮🇳Pune, Maharashtra, India
St. John's Medical College Hospital
🇮🇳Bengaluru, India
Lady Davis Carmel Medical Center, Department of Hematology,
🇮🇱Haifa, Israel
Hadassah Medical Center, Department of Hematology,
🇮🇱Jerusalem, Israel
Meir Medical Center, Hematology Institute and Blood Bank
🇮🇱Kfar Saba, Israel
Rabin Medical Center, Clinic for Myeloproliferative Disorders
🇮🇱Petah-Tikva, Israel
The Tel Aviv Sourasky Medical Center, Department of Internal Medicine
🇮🇱Tel Aviv, Israel
Cancer Institute "Giovanni Paolo II", IRCCS
🇮🇹Bari, Italy
Polyclinic S. Orsola-Malpighi
🇮🇹Bologna, Italy
ASST Spedali Civili Brescia, Hematology Unit
🇮🇹Brescia, Italy
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Florence, Italy
Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS
🇮🇹Forlì, Italy
Maggiore Polyclinic Hospital, Fondazione IRCCS Ca' Granda
🇮🇹Milan, Italy
ASST Monza - Ospedale San Gerardo
🇮🇹Monza, Italy
University Hospital "Federico II"
🇮🇹Naples, Italy
University Hospital "Maggiore della Carita" of Novara
🇮🇹Novara, Italy
United Hospitals Villa Sofia Cervello
🇮🇹Palermo, Italy
Polyclinic San Matteo, IRCCS
🇮🇹Pavia, Italy
Hospital "Infermi" of Rimini
🇮🇹Rimini, Italy
Umberto I Polyclinic of Rome
🇮🇹Rome, Italy
University Polyclinic Foundation "Agostino Gemelli"
🇮🇹Rome, Italy
City of Health and Science of Turin
🇮🇹Turin, Italy
Santa Maria della Misericordia University Hospital of Udine
🇮🇹Udine, Italy
ASST Sette Laghi Hospital
🇮🇹Varese, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
University Teaching Hospital in Bialystok
🇵🇱Białystok, Poland
University Clinical Center in Gdansk
🇵🇱Gdańsk, Poland
Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice, Department of Hematology and Bone Marrow Transplantation
🇵🇱Katowice, Poland
Pratia Oncology Katowice
🇵🇱Katowice, Poland
University Hospital in Krakow
🇵🇱Kraków, Poland
Independent Public Teaching Hospital No.1 in Lublin, Department of Hematooncology, Bone Marrow Transplantation and Chemotherapy
🇵🇱Lublin, Poland
Jedrzej Sniadecki Specialist Hospital in Nowy Sacz, Department of Hematology
🇵🇱Nowy Sącz, Poland
Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology,
🇵🇱Rzeszów, Poland
Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka
🇵🇱Toruń, Poland
Institute of Hematology and Transfusion Medicine, Teaching Department of Hematology
🇵🇱Warsaw, Poland
Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation
🇵🇱Wrocław, Poland
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
🇵🇱Łódź, Poland
Onco Card Srl
🇷🇴Braşov, Romania
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Prof. Dr. Ion Chiricuta" Institute of Oncology
🇷🇴Cluj-Napoca, Romania
City Clinical Hospital #40
🇷🇺Moscow, Russian Federation
City Clinical Hospital n.a. V.V. Veresaev of the Moscow City Health
🇷🇺Moscow, Russian Federation
S.P. Botkin City Clinical Hospital
🇷🇺Moscow, Russian Federation
Clinic UZI 4D, LLC
🇷🇺Pyatigorsk, Russian Federation
Research Institute of Hematology and Transfusiology
🇷🇺Saint Petersburg, Russian Federation
S.M. Kirov Military Medical Academy, Department and Clinic for Intermediate-Level Training in Internal Medicine, Hematology Division
🇷🇺Saint Petersburg, Russian Federation
V.A. Almazov North-West Federal Medical Research Center, Institute of Oncology and Hematology, Scientific Department of Clinical Oncology
🇷🇺Saint Petersburg, Russian Federation
V.D. Seredavin Samara Regional Clinical Hospital, Department of Hematology
🇷🇺Samara, Russian Federation
Bashkiria State Medical University, Department of Internal Medicine
🇷🇺Ufa, Russian Federation
Volgograd Regional Clinical Oncology Center
🇷🇺Volgograd, Russian Federation
Clinical Center of Serbia, Clinic of Hematology
🇷🇸Belgrade, Serbia
Clinical Center of Vojvodina, Clinic of Hematology
🇷🇸Novi Sad, Serbia
Hospital del Mar
🇪🇸Barcelona,, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
University Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
University Hospital 12 de Octubre, Department of Hematology
🇪🇸Madrid, Spain
Morales Meseguer University General Hospital, Department of Hematology and Hemotherapy
🇪🇸Murcia, Spain
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
University Clinical Hospital of Salamanca, Department of Hematology
🇪🇸Salamanca, Spain
University Hospital Virgen del Rocio (HUVR)
🇪🇸Seville, Spain
University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
🇪🇸Valencia, Spain
Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council, Regional Treatment and Diagnostic Hematology Center, Department of Hematology
🇺🇦Cherkasy, Ukraine
City Clinical Hospital #4" under Dnipro City Council
🇺🇦Dnipro, Ukraine
Regional Clinical Hospital, Department of Hematology,
🇺🇦Ivano-Frankivs'k, Ukraine
Communal Non-profit enterprise "Regional Center of Oncology", Department of Hematology
🇺🇦Kharkiv, Ukraine
Kyiv City Clinical Hospital #9, Hematology Department #1
🇺🇦Kyiv, Ukraine
Kyiv Regional Oncology Center, Department of Hematology,
🇺🇦Kyiv, Ukraine
Limited Liability Company "City Doctor"
🇺🇦Kyiv, Ukraine
Institute of Blood Pathology and Transfusion Medicine, Department of Hematology
🇺🇦Lviv, Ukraine
Poltava M.V. Sklifosovskyi Regional Clinical Hospital under Poltava Regional Council, Department of Hematology
🇺🇦Poltava, Ukraine
Royal Hallamshire Hospital, Department of Hematology
🇬🇧Sheffield, South Yorkshire, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, United Kingdom
Barts Health NHS Trust - The Royal London Hospital
🇬🇧London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Oxford University Hospitals NHS Trust - Churchill Hospital
🇬🇧Oxford, United Kingdom