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

April 4, 2024 updated by: CTI BioPharma

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

399

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia
        • Recruiting
        • Westmead Hospital
    • Victoria
      • Melbourne, Victoria, Australia
        • Recruiting
        • Alfred Hospital, Malignant Hematology and Stem Cell Transplantation Service
    • Western Australia
      • Perth, Western Australia, Australia
        • Recruiting
        • The Perth Blood Institute
  • Belarus
      • Gomel, Belarus
        • Recruiting
        • Republican Research Center for Radiation Medicine and Human Ecology
      • Grodno, Belarus
        • Completed
        • Grodno University Hospital
      • Minsk, Belarus
        • Recruiting
        • Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
  • Bosnia and Herzegovina
      • Banja Luka, Bosnia and Herzegovina
        • Recruiting
        • University Clinical Centre of the Republic of Srpska
      • Sarajevo, Bosnia and Herzegovina
        • Recruiting
        • University Clinical Center of Sarajevo
  • Bulgaria
      • Pleven, Bulgaria
        • Recruiting
        • University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
      • Plovdiv, Bulgaria
        • Recruiting
        • University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
      • Sofia, Bulgaria
        • Recruiting
        • Multiprofile Hospital for Active Treatment - Sofia, part of Military Medical Academy
      • Sofia, Bulgaria
        • Recruiting
        • Specialized Hospital for Active Treatment of Hematological Diseases
      • Varna, Bulgaria
        • Recruiting
        • Multiprofile Hospital for Active Treatment "Sveta Marina"
  • Canada
    • Alberta
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 2A5
    • Newfoundland and Labrador
      • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Recruiting
        • Eastern Regional Health Authority
        • Contact:
          • Esther Pope
          • Phone Number: (709) 777-2951
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Recruiting
        • Nova Scotia Health Authority, Centre for Clinical Research
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
  • Czechia
      • Brno, Czechia
        • Recruiting
        • University Hospital Brno
      • Olomouc, Czechia
        • Recruiting
        • University Hospital Olomouc
      • Pilsen, Czechia
        • Recruiting
        • University Hospital Plzen
      • Prague, Czechia
        • Recruiting
        • University Hospital Kralovske Vinohrady, Clinic of Internal Hematology
  • France
      • Amiens, France, 80054
        • Recruiting
        • CHU Hôpital Amiens Sud
      • Marseille, France
        • Recruiting
        • La Conception Hospital
      • Nîmes, France, 30900
        • Recruiting
        • CHU de Nimes - Hopital Universitaire Caremeau
      • Paris, France
        • Recruiting
        • Hôpital Saint-Louis
      • Pessac, France, 33604
        • Recruiting
        • CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
      • Pierre Benite, France
        • Recruiting
        • Centre Hospitalier Lyon-Sud
      • Poitiers, France
        • Recruiting
        • University Hospital Center of Poitiers
      • Strasbourg, France
        • Withdrawn
        • Hautepierre Hospital
      • Toulouse, France
        • Withdrawn
        • Centre Hospitalier de Toulouse- Hôpital Purpan
  • Georgia
      • Tbilisi, Georgia
        • Recruiting
        • JSC K. Eristavi National Center For Experimental and Clinical Surgery
      • Tbilisi, Georgia
        • Recruiting
        • LTD M.Zodelava's Hematology Center, Department of Hematology
      • Tbilisi, Georgia
        • Completed
        • LTD S.Khechinashvili University Hospital
      • Tbilisi, Georgia
        • Recruiting
        • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTD
      • Tbilisi, Georgia
        • Withdrawn
        • LTD National Institute of Endocrinology
      • Tbilisi, Georgia
        • Recruiting
        • Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
  • Germany
      • Cologne, Germany
        • Withdrawn
        • University Hospital Cologne, Department of Internal Medicine I,
      • Halle, Germany
        • Withdrawn
        • University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
      • Minden, Germany
        • Withdrawn
        • Johannes Wesling Hospital Minden, Department of Oncology and Hematology
      • Munich, Germany
        • Withdrawn
        • Hospital rechts der Isar, Department of Internal Medicine III, Hematology and Oncology
      • Ulm, Germany
        • Withdrawn
        • University Hospital Ulm, Center for Internal Medicine,
  • Hungary
      • Budapest, Hungary
        • Recruiting
        • Semmelweis University SE ÁOK I. sz. Belgyógyászati Klinika
      • Debrecen, Hungary
        • Recruiting
        • University of Debrecen Clinical Center (Debreceni Egyetem Klinikai Központ)
      • Kaposvár, Hungary
        • Recruiting
        • Somogy Megyei Kaposi Mór Oktató Kórház
      • Kecskemét, Hungary
        • Withdrawn
        • Bacs-Kiskun County Hospital, 2nd Department of Internal Medicine
      • Nyíregyháza, Hungary
        • Recruiting
        • Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology
      • Székesfehérvár, Hungary
        • Recruiting
        • Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine I
  • India
      • Bengaluru, India
        • Recruiting
        • St. John's Medical College Hospital
  • Israel
      • Haifa, Israel
        • Recruiting
        • Lady Davis Carmel Medical Center, Department of Hematology,
      • Jerusalem, Israel
        • Recruiting
        • Hadassah Medical Center, Department of Hematology,
      • Kfar Saba, Israel
        • Recruiting
        • Meir Medical Center, Hematology Institute and Blood Bank
      • Petah-Tikva, Israel
        • Recruiting
        • Rabin Medical Center, Clinic for Myeloproliferative Disorders
      • Tel Aviv, Israel
        • Recruiting
        • The Tel Aviv Sourasky Medical Center, Department of Internal Medicine
  • Italy
      • Bari, Italy
        • Recruiting
        • Cancer Institute "Giovanni Paolo II", IRCCS
      • Bologna, Italy
        • Recruiting
        • Polyclinic S. Orsola-Malpighi
      • Brescia, Italy
        • Recruiting
        • ASST Spedali Civili Brescia, Hematology Unit
      • Florence, Italy
        • Recruiting
        • Azienda Ospedaliero-Universitaria Careggi
      • Forlì, Italy
        • Recruiting
        • Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS
      • Milan, Italy
        • Recruiting
        • Maggiore Polyclinic Hospital, Fondazione IRCCS Ca' Granda
      • Monza, Italy
        • Recruiting
        • ASST Monza - Ospedale San Gerardo
      • Naples, Italy
        • Recruiting
        • University Hospital "Federico II"
      • Novara, Italy
        • Recruiting
        • University Hospital "Maggiore della Carita" of Novara
      • Palermo, Italy
        • Recruiting
        • United Hospitals Villa Sofia Cervello
      • Pavia, Italy
        • Recruiting
        • Polyclinic San Matteo, IRCCS
      • Rimini, Italy
        • Completed
        • Hospital "Infermi" of Rimini
      • Rome, Italy
        • Recruiting
        • University Polyclinic Foundation "Agostino Gemelli"
      • Rome, Italy
        • Recruiting
        • Umberto I Polyclinic of Rome
      • Varese, Italy
        • Recruiting
        • ASST Sette Laghi Hospital
  • Korea, Republic of
      • Busan, Korea, Republic of
        • Recruiting
        • Pusan National University Hospital
      • Daegu, Korea, Republic of
        • Recruiting
        • Kyungpook National University Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 3722
        • Recruiting
        • Severance Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • The Catholic University of Korea, St. Mary's Hospital
  • Poland
      • Białystok, Poland
        • Recruiting
        • University Teaching Hospital in Bialystok
      • Gdańsk, Poland
        • Recruiting
        • University Clinical Center in Gdansk
      • Katowice, Poland
        • Recruiting
        • Pratia Oncology Katowice
      • Katowice, Poland
        • Recruiting
        • Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice, Department of Hematology and Bone Marrow Transplantation
      • Kraków, Poland
        • Recruiting
        • University Hospital in Krakow
      • Lublin, Poland
        • Recruiting
        • Independent Public Teaching Hospital No.1 in Lublin, Department of Hematooncology, Bone Marrow Transplantation and Chemotherapy
      • Nowy Sącz, Poland
        • Recruiting
        • Jedrzej Sniadecki Specialist Hospital in Nowy Sacz, Department of Hematology
      • Rzeszów, Poland
        • Completed
        • Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology,
      • Toruń, Poland
        • Recruiting
        • Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka
      • Warsaw, Poland
        • Recruiting
        • Institute of Hematology and Transfusion Medicine, Teaching Department of Hematology
      • Wrocław, Poland
        • Recruiting
        • Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation
      • Łódź, Poland
        • Recruiting
        • Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
  • Romania
      • Braşov, Romania
        • Recruiting
        • Onco Card Srl
      • Bucharest, Romania
        • Recruiting
        • Fundeni Clinical Institute
      • Bucharest, Romania
        • Recruiting
        • Coltea Clinical Hospital
      • Cluj-Napoca, Romania
        • Recruiting
        • Prof. Dr. Ion Chiricuta" Institute of Oncology
  • Russian Federation
      • Moscow, Russian Federation
        • Completed
        • City Clinical Hospital #40
      • Moscow, Russian Federation
        • Completed
        • City Clinical Hospital n.a. V.V. Veresaev of the Moscow City Health
      • Moscow, Russian Federation
        • Active, not recruiting
        • S.P. Botkin City Clinical Hospital
      • Pyatigorsk, Russian Federation
        • Active, not recruiting
        • Clinic UZI 4D, LLC
      • Saint Petersburg, Russian Federation
        • Active, not recruiting
        • Research Institute of Hematology and Transfusiology
      • Saint Petersburg, Russian Federation
        • Active, not recruiting
        • S.M. Kirov Military Medical Academy, Department and Clinic for Intermediate-Level Training in Internal Medicine, Hematology Division
      • Saint Petersburg, Russian Federation
        • Active, not recruiting
        • V.A. Almazov North-West Federal Medical Research Center, Institute of Oncology and Hematology, Scientific Department of Clinical Oncology
      • Samara, Russian Federation
        • Withdrawn
        • V.D. Seredavin Samara Regional Clinical Hospital, Department of Hematology
      • Ufa, Russian Federation
        • Completed
        • Bashkiria State Medical University, Department of Internal Medicine
      • Volgograd, Russian Federation
        • Completed
        • Volgograd Regional Clinical Oncology Center
  • Serbia
      • Belgrade, Serbia
        • Recruiting
        • Clinical Center of Serbia, Clinic of Hematology
      • Novi Sad, Serbia
        • Recruiting
        • Clinical Center of Vojvodina, Clinic of Hematology
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Clínic de Barcelona
      • Barcelona, Spain
        • Recruiting
        • University Hospital Vall d'Hebron
      • Barcelona,, Spain
        • Recruiting
        • Hospital del Mar
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Recruiting
        • University Hospital 12 de Octubre, Department of Hematology
      • Murcia, Spain
        • Recruiting
        • Morales Meseguer University General Hospital, Department of Hematology and Hemotherapy
      • Pamplona, Spain
        • Withdrawn
        • Clinica Universidad de Navarra
      • Salamanca, Spain
        • Recruiting
        • University Clinical Hospital of Salamanca, Department of Hematology
      • Seville, Spain
        • Recruiting
        • University Hospital Virgen del Rocio (HUVR)
      • Valencia, Spain
        • Recruiting
        • University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
  • Ukraine
      • Cherkasy, Ukraine
        • Active, not recruiting
        • Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council, Regional Treatment and Diagnostic Hematology Center, Department of Hematology
      • Dnipro, Ukraine
        • Active, not recruiting
        • City Clinical Hospital #4" under Dnipro City Council
      • Ivano-Frankivs'k, Ukraine
        • Withdrawn
        • Regional Clinical Hospital, Department of Hematology,
      • Kharkiv, Ukraine
        • Active, not recruiting
        • Communal Non-profit enterprise "Regional Center of Oncology", Department of Hematology
      • Kyiv, Ukraine
        • Active, not recruiting
        • Kyiv City Clinical Hospital #9, Hematology Department #1
      • Kyiv, Ukraine
        • Active, not recruiting
        • Limited Liability Company "City Doctor"
      • Kyiv, Ukraine
        • Completed
        • Kyiv Regional Oncology Center, Department of Hematology,
      • Lviv, Ukraine
        • Active, not recruiting
        • Institute of Blood Pathology and Transfusion Medicine, Department of Hematology
      • Poltava, Ukraine
        • Active, not recruiting
        • Poltava M.V. Sklifosovskyi Regional Clinical Hospital under Poltava Regional Council, Department of Hematology
  • United Kingdom
      • Glasgow, United Kingdom, G12 0ZD
        • Recruiting
        • Beatson West of Scotland Cancer Centre
      • Gloucester, United Kingdom
        • Recruiting
        • Gloucestershire Royal Hospital
      • London, United Kingdom, E1 2ES
        • Recruiting
        • Barts Health NHS Trust - The Royal London Hospital
      • London, United Kingdom
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
      • London, United Kingdom
        • Recruiting
        • Imperial College Healthcare NHS Trust - Hammersmith Hospital
      • Manchester, United Kingdom
        • Withdrawn
        • The Christie NHS Foundation Trust
      • Oxford, United Kingdom
        • Recruiting
        • Oxford University Hospitals NHS Trust - Churchill Hospital
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom
        • Recruiting
        • Royal Hallamshire Hospital, Department of Hematology
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Active, not recruiting
        • University of Alabama at Birmingham, (UAB) Hospital, Comprehensive Cancer Center
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Completed
        • Mayo Clinic Hospital
    • California
      • Duarte, California, United States, 91010
        • Active, not recruiting
        • City of Hope
      • Los Angeles, California, United States, 90033
        • Completed
        • USC Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90095
        • Completed
        • UCLA david geffen school of medicine
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Completed
        • University of Colorado Cancer Center
      • Boulder, Colorado, United States, 80303
        • Completed
        • Rocky Mountain Cancer Centers (US Oncology/McKesson)
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Completed
        • Yale School of Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Completed
        • Georgetown University Hospital
      • Washington, District of Columbia, United States, 20037
        • Completed
        • George Washington University-Medical Faculty Associates
    • Florida
      • Weston, Florida, United States, 33331
        • Completed
        • Cleveland Clinic Florida
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Completed
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Completed
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • Completed
        • The University of Chicago Medical Center
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Completed
        • University of Kansas Cancer Center and Medical Pavilion
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Completed
        • Ochsner Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21229
        • Active, not recruiting
        • Saint Agnes Hospital
      • Baltimore, Maryland, United States, 21287
        • Completed
        • Johns Hopkins University
      • Bethesda, Maryland, United States, 20817
        • Completed
        • American Oncology Partners of Maryland, PA
      • Bethesda, Maryland, United States, 20817
        • Withdrawn
        • Regional Cancer Care Associates LLC - CCBD Division
      • Columbia, Maryland, United States, 21044
        • Completed
        • Maryland Oncology Hematology, PA- Columbia
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Withdrawn
        • Dana Farber Cancer Institute, Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Completed
        • Michigan Medicine Hematology Clinic-Rogel Cancer Center
      • Grand Rapids, Michigan, United States, 49546
        • Completed
        • Cancer and Hematology Centers of Western Michigan
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Completed
        • Washington University School of Medicine-Siteman Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Active, not recruiting
        • Comprehensive Cancer Centers of Nevada- Twain Office
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Active, not recruiting
        • Hackensack University Medical Center
    • New York
      • Commack, New York, United States, 11725
        • Active, not recruiting
        • Memorial Sloan-Kettering Cancer Center- Commack
      • New York, New York, United States, 10029
        • Active, not recruiting
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, United States, 10021
        • Active, not recruiting
        • Weill Cornell Medical College
      • New York, New York, United States, 10065
        • Active, not recruiting
        • Memorial Sloan -Kettering Cancer Center
      • New York, New York, United States, 10017
        • Completed
        • Columbia University Medical Center
      • Rochester, New York, United States, 14642
        • Completed
        • University of Rochester
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Completed
        • Duke University Hospital
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Completed
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • Active, not recruiting
        • Ohio State University Comprehensive Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Active, not recruiting
        • Oregon Health and Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Completed
        • UPMC Hillman Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Completed
        • The Sarah Cannon Research Institute-Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • Completed
        • The University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Completed
        • Mays Cancer Center
      • San Antonio, Texas, United States, 78240
        • Completed
        • Texas Oncology- San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Completed
        • University of Utah - Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98109
        • Completed
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Diagnosis and Inclusion Criteria

  1. Primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF (as defined by Tefferi and Vardiman 2008
  2. Platelet count of <50,000/μL at Screening (Day -35 to Day -3)
  3. Dynamic International Prognostic Scoring System Intermediate-1, Intermediate-2, or High-Risk (Passamonti et al 2010
  4. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination
  5. 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.
  6. Age ≥18 years
  7. Eastern Cooperative Oncology Group performance status 0 to 2
  8. Peripheral blast count of <10% throughout the Screening period prior to randomization
  9. Absolute neutrophil count of ≥500/µL
  10. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition scan
  11. 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
  12. Adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
  13. If fertile, willing to use effective birth control methods during the study
  14. Willing to undergo and able to tolerate frequent MRI or CT scan assessments during the study
  15. Able to understand and willing to complete symptom assessments using a patient-reported outcome instrument
  16. Provision of signed informed consent

Exclusion Criteria

  1. Life expectancy <6 months
  2. Completed allogeneic stem cell transplant (allo-SCT) or are eligible for and willing to complete other approved available therapy including allogeneic stem cell
  3. History of splenectomy or planning to undergo splenectomy
  4. Splenic irradiation within the last 6 months
  5. Previously treated with pacritinib
  6. Treatment with any MF-directed therapy within 14 days prior to treatment Day 1
  7. Prior treatment with more than one JAK2 inhibitor

  8. Prior treatment with with ruxolitinib, if BOTH of the following conditions are met:

    i. exposure to higher-dose ruxolitinib (>10 mg daily) within 120 days prior to treatment Day 1 AND ii. total duration of treatment with higher-dose ruxolitinib (>10 mg daily) was >90 days, from first to last exposure (i.e., this 90-day period starts on the date of first administration of ruxolitinib at a total daily dose of >10 mg and continues for 90 calendar days, regardless of whether higher-dose ruxolitinib is administered continuously or intermittently).

  9. 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.
  10. Treatment with an experimental therapy within 28 days prior to treatment Day 1
  11. Systemic treatment with a strong cytochrome P450 3A4 inhibitor or a strong cytochrome P450 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
  12. 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 (eg, surgery, trauma, or injury)
  13. 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-VEGF) agents, and daily use of cyclooxygenase-1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1
  14. 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
  15. 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.
  16. 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.
  17. 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).
  18. New York Heart Association Class II, III, or IV congestive heart failure
  19. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
  20. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation
  21. 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.
  22. 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
  23. Known seropositivity for human immunodeficiency (HIV) virus. For patients in France, Czech Republic, and Italy only: testing for HIV is required during Screening.
  24. Known active hepatitis A, B, or C virus infection. For patients in France, Czech Republic and Italy only: testing for hepatitis B and C is required during Screening.
  25. Women who are pregnant or lactating
  26. Concurrent enrollment in another interventional trial
  27. Severe thrombocytopenia due to vitamin B12 deficiency, folate deficiency, or viral infection in the opinion of the investigator
  28. 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
  29. Persons deprived of their liberty by a judicial or administrative decision
  30. Persons subject to legal protection measures or unable to express their consent
  31. Temporarily incapacitated persons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pacritinib 200 mg BID
To receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food
Drug: Pacritinib
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
Active Comparator: Physician's Choice (P/C) therapy
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.
Drug: Physician's Choice medications
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.
Other Names:
  • corticosteroids
  • hydroxyurea
  • danazol
  • low-dose ruxolitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spleen volume
Time Frame: 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
From baseline at 24 weeks
Total Symptom Score (TSS) (excluding tiredness)
Time Frame: 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)
From baseline at Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 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
until 2.5 years after the date of randomization
Patient Global Impression of Change (PGIC) assessed at Week 24
Time Frame: 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
End of Week 12 to 2 years following Week 24 visit
To compare the safety of pacritinib versus P/C therapy
Time Frame: 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.
Randomization through 30 after last treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVR of ≥35%
Time Frame: Up to 24 Weeks
Time to achievement of SVR of ≥35%
Up to 24 Weeks
Best response in SVR
Time Frame: At 24 Weeks
Best response in SVR by MRI or CT scan
At 24 Weeks
>25% SVR
Time Frame: From baseline and at Week 24
Proportion of patients achieving >25% SVR
From baseline and at Week 24
Red blood cell (RBC)
Time Frame: Baseline to End of Treatment
Achievement of red blood cell (RBC) transfusion independence at Weeks 12 and 24
Baseline to End of Treatment
hemoglobin level
Time Frame: Weeks 12 and 24
Improvement in hemoglobin level without transfusion at Weeks 12 and 24
Weeks 12 and 24
platelet count
Time Frame: Weeks 12 and 24
Improvement in platelet count at Weeks 12 and 24
Weeks 12 and 24
platelet transfusions
Time Frame: Weeks 12 and 24
Frequency of platelet transfusions at Weeks 12 and 24
Weeks 12 and 24
PROMIS
Time Frame: Baseline to Week 24
Improvement in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) v.1.0 - Fatigue from Baseline through Week 24
Baseline to Week 24
Leukemia-free survival (LFS)
Time Frame: Baseline to Week 24
Leukemia-free survival (LFS) of patients treated with pacritinib versus P/C therapy
Baseline to Week 24
The percentage of red blood cell transfusion-independent patients achieving a 1 g/dL and a 2 g/dL increase in hemoglobin
Time Frame: Baseline to 24 weeks
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
Baseline to 24 weeks
The percentage of platelet transfusion-independent patients with improvement in grade of thrombocytopenia
Time Frame: Baseline to 24 weeks
The percentage of platelet transfusion-independent patients at baseline with improvement in grade of thrombocytopenia at week 24
Baseline to 24 weeks
The percentage of transfusion-dependent patients achieving transfusion independence and achieving 50% reduction in transfusion rate
Time Frame: Baseline to 24 weeks
The percentage of transfusion-dependent patients at baseline achieving transfusion independence and achieving 50% reduction in transfusion rate at week 24
Baseline to 24 weeks
Hemaglobin A1c
Time Frame: Baseline to Week 24
Changes in hemoglobin A1c
Baseline to Week 24
mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers
Time Frame: Baseline to up to 24 Weeks
Changes in mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers
Baseline to up to 24 Weeks
The proportion of patients who experience a major adverse cardiac event (MACE)
Time Frame: Baseline to up to 24 Weeks

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
Baseline to up to 24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CTI BioPharma

Collaborators

PSI CRO

Investigators

  • Study Director: Simran Bedi Singh, CTI BioPharma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 26, 2017

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 17, 2017

First Submitted That Met QC Criteria

May 23, 2017

First Posted (Actual)

May 24, 2017

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PAC203/PAC303
  • PAC303 (Other Identifier: CTI BioPharma)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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