Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia (PAC326)

• ClinicalTrials.gov Identifier: NCT02055781
• Recruitment Status: Terminated
• First Posted: February 5, 2014
• Last Update Posted: October 22, 2018
• Sponsor: CTI BioPharma
• Information provided by (Responsible Party): CTI BioPharma

Study Description

Brief Summary:

The primary hypothesis of the study is that treatment with either once-daily or twice-daily pacritinib results in a greater proportion of patients with thrombocytopenia and myelofibrosis achieving ≥ 35% reduction in spleen volume from baseline to Week 24 than treatment with Best Available Therapy, and a greater proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.

Condition or disease	Intervention/treatment	Phase
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis	Drug: Pacritinib; Drug: Best Available Therapy	Phase 3

Detailed Description:

The primary objective is to compare the efficacy of two dose-schedule arms(s) of pacritinib (pooled once-daily [QD] and twice-daily [BID] dosing arms) with that of best available therapy (BAT) in patients with thrombocytopenia and primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF). The efficacy co-endpoints for this analysis are the 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) scan and the proportion of patients achieving a ≥ 50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 311 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: December 2013
• Actual Primary Completion Date: August 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pacritinib, Once Daily; Pacritinib 400 mg taken orally, once daily	Drug: Pacritinib
Experimental: Pacritinib, Twice Daily; Pacritinib 200 mg taken orally, twice daily	Drug: Pacritinib
Active Comparator: Best Available Therapy; Best Available Therapy includes any physician-selected treatment for primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis, such as approved JAK2 inhibitors, and may include any treatment received before study entry. Best Available Therapy may include ruxolitinib, other approved JAK2 inhibitors, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan, or other agents and may also include no treatment and symptom-directed treatment without myelofibrosis-specific treatment.	Drug: Best Available Therapy

Outcome Measures

Primary Outcome Measures :

1. To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
   To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy in patients with thrombocytopenia and primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis; the efficacy measure for this analysis is the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.

Secondary Outcome Measures :

1. To compare the efficacy of once-daily pacritinib with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
   To compare the efficacy of once-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the 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.
2. To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy [ Time Frame: Baseline to Week 24 ]
   To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
• Thrombocytopenia (platelet count ≤ 100,000/µL) at any time after signing informed consent
• Palpable splenomegaly ≥ 5 cm on physical examination
• Total Symptom Score ≥ 13 on the MPN-SAF TSS 2.0, not including the inactivity question
• Patients who are platelet or red blood cell transfusion-dependent are eligible
• Adequate white blood cell counts (with low blast counts), liver function, and renal function
• At least 6 months from prior splenic irradiation
• At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent
• Not pregnant, not lactating, and agree to use effective birth control
• Able and willing to undergo frequent MRI or CT assessments and complete symptom assessments using a patient-reported outcome instrument

Exclusion Criteria:

• Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
• There is no maximum cumulative prior JAK2 inhibitor treatment
• History of (or plans to undergo) spleen removal surgery or allogeneic stem cell transplant
• Ongoing gastrointestinal medical condition such as Crohn's disease, Inflammatory bowel disease, chronic diarrhea, or constipation
• Active bleeding that requires hospitalization during the screening period
• Cardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction
• Other malignancy within last 3 years other than certain limited skin, cervical, prostate, breast, or bladder cancers
• Other ongoing, uncontrolled illnesses (including HIV infection and active hepatitis A, B, or C), psychiatric disorder, or social situation that would prevent good care on this study
• Life expectancy < 6 months

Contacts and Locations

  Hide Study Locations

Locations

United States, Arizona

Mayo Clinic Arizona

Scottsdale, Arizona, United States, 85259

Arizona Clinical Research Center

Tucson, Arizona, United States, 85715

United States, California

City of Hope

Duarte, California, United States, 91010

Moores Cancer Centre

La Jolla, California, United States, 92093

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Stanford Cancer Center

Stanford, California, United States, 94305

United States, Colorado

Rocky Mountain Cancer Center

Boulder, Colorado, United States, 80303

United States, District of Columbia

George Washington University- Medical Faculty Associates

Washington, District of Columbia, United States, 20037

United States, Florida

SCRI- Florida Cancer Specialists South Region

Fort Myers, Florida, United States, 33916

SCRI - Florida Cancer Specialists North Region

Saint Petersburg, Florida, United States, 33705

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

Carle Cancer Center

Urbana, Illinois, United States, 61801

United States, Indiana

Indiana University Goshen Cancer Centre

Goshen, Indiana, United States, 46526

Investigative Clinical Research of Indiana

Indianapolis, Indiana, United States, 46260

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

Siouxland Hematology-Oncology Associates, L.L.P (SHOA)

Sioux City, Iowa, United States, 51101

United States, Kentucky

Norton Cancer Institute, Suburban

Louisville, Kentucky, United States, 40207

United States, Michigan

St Joseph Mercy Hospital

Ann Arbor, Michigan, United States, 48106

University of Michigan

Ann Arbor, Michigan, United States, 48109

Henry Ford Health System

Detroit, Michigan, United States, 48202

Providence Cancer Institute

Southfield, Michigan, United States, 48075

United States, Missouri

Washington University School of Medicine Division of Oncology

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Nebraska Hematology-Oncology, P.C.

Lincoln, Nebraska, United States, 68506

United States, New Jersey

Hackensack University

Hackensack, New Jersey, United States, 07601

Hematology-Oncology Associates of Northern Jersey

Morristown, New Jersey, United States, 07962

United States, New Mexico

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States, 87106

United States, New York

Mount Sinai Medical Center

New York, New York, United States, 10029

Columbia University Medical Center

New York, New York, United States, 10032

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, Ohio

SCRI-Oncology Hematology Care

Cincinnati, Ohio, United States, 45242

Cleveland Clinic-Taussig Cancer Center

Cleveland, Ohio, United States, 44195

United States, Oklahoma

University of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Upstate Oncology Associates

Greenville, South Carolina, United States, 29601

United States, Tennessee

Sarah Cannon Research Institute (SCRI)

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Onocolgy-Baylor Sammons Cancer Center

Dallas, Texas, United States, 75246

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

UTMB Galveston

Galveston, Texas, United States, 77555

Houston Methodist

Houston, Texas, United States, 77030

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Cancer Care Centers of South Texas

San Antonio, Texas, United States, 78229

United States, Utah

Huntsman Cancer Hospital

Salt Lake City, Utah, United States, 84112

United States, Virginia

Virginia Cancer Specialists

Leesburg, Virginia, United States, 20176

United States, Washington

Providence Regional Cancer Partnership

Everett, Washington, United States, 98201

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

United States, Wisconsin

Green Bay Oncology

Green Bay, Wisconsin, United States, 54301

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Australia, New South Wales

St George Hospital

Kogarah, New South Wales, Australia, 2217

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Monash Health - Monash Medical Centre

Clayton, Victoria, Australia, 3168

Australia, Western Australia

Perth Blood Institute

Nedlands, Western Australia, Australia, 6009

Australia

Haematology and Oncology Clinics of Australia

Chermside, Australia, 4032

Prince of Wales Hospital

Randwick, Australia, 2031

Belgium

Centre Hospitalier de Jolimont-Lobbes

Haine-Saint-Paul, Hainaut, Belgium

ZNA - Stuivenberg

Antwerpen, Belgium, 2060

AZ Sint Jan Brugge-Oostende AV

Brugge, Belgium, 8000

Hopital Brugmann

Brussels, Belgium, 1020

Cliniques Universitaires St-Luc

Bruxelles, Belgium, 1200

St Augustinus

Wilrijk, Belgium, 2610

UC Louvain

Yvoir, Belgium, 5530

Canada, New Brunswick

Saint John Regional Hospital

Saint John, New Brunswick, Canada, E2L 4L2

Canada, Ontario

Princess Margaret Cancer Center

Toronto, Ontario, Canada, M5G2M9

Czechia

Fakultní nemocnice Brno

Brno, NAP, Czechia, 62500

Faculty Hospital Olomouc

Olomouc, NAP, Czechia, 775 20

Fakultní nemocnice Plzeň

Plzeň, NAP, Czechia, 30460

University Hospital Hradec Kralove

Králová, Czechia, 500 05

France

Chu d'Amiens Hopital Sud

Amiens, Cedex 1, France, 80054

Hôpital Caremeau

Nimes, Cedex 9, France, 30029

CHU Rennes

Rennes, Cedex 9, France, 35033

CHU Purpan

Toulouse, Cedex 9, France, 31059

CH de Mulhouse

Mulhouse, Cedex, France, 68070

CHU de CAEN

Caen, France, 14000

Centre Hospitalier de Lens

Lens, France, 62300

Hopital l'Archet, CHU de Nice

Nice, France, BP 30 79 06202

Saint Antoine Hospital

Paris, France, 75012

Centre Hospitalier Lyon Sud

Pierre Benite, France, 69495

CHU de Strasbourg

Strasbourg, France, 67091

Institut Gustave Roussy

Villejuif Cedex, France, 94805

Germany

Charite-Medical University

Berlin, Germany, 12203

Gemeinschaftspraxis Hämatologie/Onkologie

Dresden, Germany, 01307

University Hospital Essen

Essen, Germany, D-45122

Uniklinik Freiburg

Freiburg, Germany, 79106

Universitatsklinikum Halle (Saale)

Halle (Saale), Germany, 06120

Klinik I fur Innere Medizin, Universitat Koln

Koln, Germany, 50924

University Hospital Leipzig

Leipzig, Germany, 04103

Städtisches Klinikum München GmbH

Munchen, Germany, 81737

University of Munster

Munster, Germany, 48149

University Hospital Ulm

Ulm, Germany, 89081

Hungary

Semmelweis Egyetem AOK

Budapest, Hungary, 1083

University of Debrecen, Belgyogyaszati Intezet

Debrecen, Hungary, 4032

Bekes Megyei Pandy Kalman Korhaz

Gyula, Hungary, 5700

Kaposi Mór Oktató Kórház

Kaposvár, Hungary, 7400

SZTE II. sz Belgyogyoszati Klinika es Kardiologiai Kozpont

Szeged, Hungary, 6720

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőint

Szolnok, Hungary, 5004

Netherlands

University Hospital Maastricht

Maastricht, Netherlands, 6229 HX

Erasmus MC

Rotterdam, Netherlands, 3015 CE

New Zealand

Auckland District Health Board, Auckland City Hospital

Auckland, New Zealand, 1023

Middlemore Hospital

Auckland, New Zealand, 1640

Canterbury District Health Board

Christchurch, New Zealand, 8001

North Shore Hospital

Takapuna, New Zealand, 0740

CCDHB - Wellington Hospital

Wellington, New Zealand, 6021

Russian Federation

Bashkir State Medical University

Ufa, Republic Of Bashkortostan, Russian Federation, 450083

Saratov State Medical University

Saratov, Saratov Region, Russian Federation, 410028

National Haematology Research Center

Moscow, Russian Federation, 125167

Republican Hopsital n.a. V.A. Baranov

Petrozavodsk, Russian Federation, 185019

Ryazan Regional Clinical Hospital

Ryazan, Russian Federation, 390039

Russian Research Institute of Hematology and Transfusiology

St. Petersburg, Russian Federation, 191024

Military Medical Academy n.a. S.M. Kirov

St. Petersburg, Russian Federation, 194044

United Kingdom

Royal Liverpool University Hospital

Liverpool, Merseyside, United Kingdom, L7 8XP

Belfast Health and Social Care Trust

Belfast, N. Ireland, United Kingdom, BT9 7AB

Birmingham Heartlands Hospital

Birmingham, United Kingdom, B9 5SS

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 OYN

Leicester Royal Infirmary

Leicester, United Kingdom, LE1 5WW

Guy's Hospital

London, United Kingdom, SE1 9RT

Hammersmith Hosp - ICH NHS Trust

London, United Kingdom, W12 OHS

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Oxford University Hospitals NHS Trust

Oxford, United Kingdom, OX3 7LE

Royal Hallamshire Hospital

Sheffield, United Kingdom, S10 2JF

Sponsors and Collaborators

CTI BioPharma

Investigators

• Study Director: Mary Campbell, MD; CTI BioPharma

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):652-659. doi: 10.1001/jamaoncol.2017.5818.

• Responsible Party: CTI BioPharma
• ClinicalTrials.gov Identifier: NCT02055781 History of Changes
• Other Study ID Numbers: PERSIST-2 (PAC326)
• First Posted: February 5, 2014
• Last Update Posted: October 22, 2018
• Last Verified: October 2018

Keywords provided by CTI BioPharma:

Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis; Primary Myelofibrosis; Polycythemia; Polycythemia Vera; Thrombocythemia, Essential; Thrombocythemia; Myeloproliferative Disorders; Bone Marrow Disease; Hematologic Diseases; Blood Platelet Disorders; Hemorrhagic Disorders; Splenomegaly; Pacritinib; MPN-SAF; MPN-SAF TSS; Anemia; Myeloproliferative; Myeloproliferative Neoplasm; Spleen; Spleen volume; Thrombocytopenia; SB1518

Additional relevant MeSH terms:

Polycythemia Vera; Thrombocytopenia; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Blood Platelet Disorders; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Coagulation Disorders; Hemorrhagic Disorders