A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

NCT ID: NCT02130557

Last Updated: 2021-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 536 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-15
• Study Completion Date: 2020-04-17

Brief Summary

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Detailed Description

The study will be open for enrollment until the planned number of approximately 500 Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+ patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All patients will be treated and/or followed for approximately 5 years (240 weeks) after randomization until the study has closed. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 5 years (240 weeks) after randomization.

Conditions

Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bosutinib

Bosutinib, 400 mg, oral administration once a day

Group Type: EXPERIMENTAL

Bosutinib

Intervention Type: DRUG

Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.\[1\] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.

Imatinib

Imatinib, 400 mg, oral administration once a day

Group Type: ACTIVE_COMPARATOR

Imatinib

Intervention Type: DRUG

Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial.

Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

Interventions

Bosutinib

Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.\[1\] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.

Intervention Type: DRUG

Imatinib

Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial.

Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis).

2. Adequate hepatic, renal and pancreatic function.

3. Age ≥ 18 years.

Exclusion Criteria

1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject's region.

2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia.

3. Extramedullary disease only.

4. Major surgery or radiotherapy within 14 days of randomization.

5. History of clinically significant or uncontrolled cardiac disease.

6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included.

7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.

8. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months.

9. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

Emory University Hospital

Atlanta, Georgia, United States

The Emory Clinic

Atlanta, Georgia, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Kaiser Permanente Hawaii

Honolulu, Hawaii, United States

Saint Alphonsus Regional Medical Center, Cancer Care Center

Boise, Idaho, United States

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Saint Alphonsus Caldwell Cancer Care Center

Caldwell, Idaho, United States

Saint Alphonsus Medical Center Nampa

Nampa, Idaho, United States

University of Illinois Cancer Center

Chicago, Illinois, United States

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, United States

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

PHARMACY Department Franciscan St. Francis Health ATTN:Jill Leslie, Pharm D

Indianapolis, Indiana, United States

Cancer Center of Acadiana at Lafayette General Medical Center

Lafayette, Louisiana, United States

Lafayette General Medical Center

Lafayette, Louisiana, United States

LSU Health Sciences Center-Shreveport

Shreveport, Louisiana, United States

University Health Shreveport

Shreveport, Louisiana, United States

Rcca Md Llc

Bethesda, Maryland, United States

University of Massachusetts Memorial Medical Center, ONC/Research Pharmacy

Worcester, Massachusetts, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

St. Joseph Mercy Hospital - Inpatient Pharmacy

Ann Arbor, Michigan, United States

St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

St. Joseph Mercy-Brighton

Brighton, Michigan, United States

St. Joseph Mercy-Canton

Canton, Michigan, United States

Chelsea Community Hospital

Chelsea, Michigan, United States

St. John Hospital&Medical Center

Detroit, Michigan, United States

St. John Hospital&Medical Center-Van Elslander Cancer Center

Grosse Pointe Woods, Michigan, United States

Van Elslander Cancer Center, Pharmacy

Grosse Pointe Woods, Michigan, United States

Minnesota Oncology Hematology, PA

Edina, Minnesota, United States

Park Nicollet Frauenshuh Cancer center

Saint Louis Park, Minnesota, United States

Lakeview Hospital

Stillwater, Minnesota, United States

North Mississippi Medical Center Hematology and Oncology Clinic

Tupelo, Mississippi, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

San Juan Oncology Associates

Farmington, New Mexico, United States

NYU Winthrop Hospital - Oncology / Hematology department

Mineola, New York, United States

NYU Winthrop Hospital - Pharmacy Department

Mineola, New York, United States

Beth Israel Medical Center

New York, New York, United States

University of Rochester Investigational Drug Pharmacy

Rochester, New York, United States

University of Rochester

Rochester, New York, United States

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, United States

FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

UC Health Physicians Office South,

West Chester, Ohio, United States

MUSC University Hospital

Charleston, South Carolina, United States

MUSC University of South Carolina, Investigational Drug Services

Charleston, South Carolina, United States

MUSC-Hollings Cancer Center

Charleston, South Carolina, United States

GHS Cancer Institute

Easley, South Carolina, United States

GHS Cancer Institute

Greenville, South Carolina, United States

GHS Cancer Institute

Greenville, South Carolina, United States

GHS Cancer Institute

Greer, South Carolina, United States

GHS Cancer Institute

Seneca, South Carolina, United States

GHS Cancer Institute

Spartanburg, South Carolina, United States

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Utah Cancer Specialists

Murray, Utah, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Vincent Hospital

Green Bay, Wisconsin, United States

HSHS St. Vincent Hospital

Green Bay, Wisconsin, United States

HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Mary's Hospital Medical Center

Green Bay, Wisconsin, United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

St George Hospital - Hematology Department

Kogarah, New South Wales, Australia

Eastern Clinical Research Unit, Level 2

Box Hill, Victoria, Australia

UZ Ghent (University Hospital Ghent)

Ghent, , Belgium

Department of Haematology at UZ Leuven (7 th Floor)

Leuven, , Belgium

Hematology Department of CHU de Liège

Liège, , Belgium

Hematology Department CHR Verviers

Verviers, , Belgium

Horizon Health Network - The Moncton Hospital

Moncton, New Brunswick, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Lakeridge Health

Oshawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

CHU de Québec - Université Laval

Québec, , Canada

Fakultní Nemocnice Brno

Brno, , Czechia

Fakultní Nemocnice Hradec Králové

Hradec Králové, , Czechia

Fakultní nemocnice Olomouc

Olomouc, , Czechia

Všeobecná fakultní Nemocnice v Praze

Prague, , Czechia

Aalborg University Hospital

Aalborg, , Denmark

Aarhus University Hospital

Aarhus, , Denmark

Roskilde Hospital

Roskilde, , Denmark

Helsinki University Central Hospital

Helsinki, , Finland

Oncologie Centre de Radiotherapie

Strasbourg, NC, France

Institut Bergonié

Bordeaux, , France

private Practice of Pr Philippe Rousselot

Le Chesnay, , France

private Practice of Dr. Viviane Dubruille

Nantes, , France

Hôpital L'Archet 1-CHU Nice

Nice, , France

Institut de Cancérologie du Gard - Hématologie Clinique

Nîmes, , France

Pr Mauricette Michallet Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

INSERM CIC 1402 - CHU Poitiers

Poitiers, , France

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, , France

Universitätsklinikum Bonn

Bonn, Rhineland-Palatinate, Germany

Uniklinikum Aachen

Aachen, , Germany

Charité, CVK, Med. Klinik m.S Hämatologie und Onkologie

Berlin, , Germany

Universitätsklinikum Freiburg, Klinik für Innere Medizin I

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum

Hamburg, , Germany

Universitätsklinikum Jena, Klinik für Innere Medizin II

Jena Lobeda-Ost, , Germany

Schwerpunktpraxis für Hämatologie und Onkologie

Magdeburg, , Germany

Semmelweis Egyetem I. Belgyógyászat

Budapest, , Hungary

Debreceni Egyetem Klinikai Központ, Belgyógyászati Inézet Hematológiai Tanszék

Debrecen, , Hungary

Petz Aladár Megyei OktatóKórház, II. Belgyógyászati Osztály és Haematológiai Részleg

Győr, , Hungary

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, , Hungary

Szegedi Tudományegyetem, AOK, Szent-Györgyi Albert Klinikai Központ, II. sz.

Szeged, , Hungary

Jász-Nagykun-Szolnok Megyei Hetényi, Géza Kórház-Rendelőintézet

Szolnok, , Hungary

Hematology Department, Rambam Medical Centre

Haifa, , Israel

Hematology Div. Davidoff Cancer Center, Rabin Medical Center

Petah Tikva, , Israel

Azienda Ospedaliero-Universitaria "Policlinico - Vittorio Emanuele" - P.O. G. Rodolico

Catania, CT, Italy

USC Ematologia, A. O. Papa Giovanni XXIII

Bergamo, , Italy

Policlinico S. Orsola - Malpighi,

Bologna, , Italy

A.O. Brozu - P.O. Armando Businco

Cagliari, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

IRCCS - AOU San Martino_IST, Ematologia 1

Genova, , Italy

Istituto Scientifico San Raffaele

Milan, , Italy

Unità di Ricerca Clinica, U.O. Ematologia Adulti

Monza, , Italy

A.O.U. Policlinico Università degli Studi di Napoli "Federico II"

Napoli, , Italy

Dipartimento di ematologia

Reggio Calabria, , Italy

ASL Roma 2 - Ospedale Sant'Eugenio

Roma, , Italy

Hospital Angeles del Pedregal (S.A. de C.V.)

Mexico City, Mexico City, Mexico

Monterrey International Research Center

Monterrey, Nuevo León, Mexico

Klinische Farrnacologie en Apotheek

Amsterdam, North Holland, Netherlands

VU University Medical Center

Amsterdam, North Holland, Netherlands

Haukeland University Hospital Department of Hematology

Bergen, , Norway

St. Olavs Hospital

Trondheim, , Norway

Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

SPZOZ ZSM w Chorzowie Oddzial Hematologiczny

Chorzów, , Poland

Samodzielny Publiczny Szpital Kliniczny im. A Mielęckiego, ŚUM w Katowicach

Katowice, , Poland

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Hematologii

Krakow, , Poland

Wojewódzki Szpital Specjalistyczny im M. Kopernika, Klinika Hematologii Uniwersytetu Medycznego

Lodz, , Poland

SPSK, Klinika Hematoonkologii i Transplantacji Szpiku w Lublinie

Lublin, , Poland

Universytet Medyczny im. Piastów Śląskich we Wrocławiu Katedra i

Wroclaw, , Poland

National University Hospital, Main Building

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Tan Tock Seng Hospital

Singapore, , Singapore

Univerzitná Nemocnica Bratislava-Nemocnica sv. Cyrila a Metoda

Bratislava, , Slovakia

The Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, South Africa

Department of Medical Oncology, University of Pretoria and Steve Biko

Pretoria, Gauteng, South Africa

Groenkloof Life hospital.

Pretoria, Gauteng, South Africa

Department of Haematology

Cape Town, Western Cape, South Africa

Hallym University Sacred Heart Hospital

Anyang-si, , South Korea

Dong A University Hospital

Busan, , South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Chonbuk National University Hospital

Jeonju, , South Korea

Kangbuk Samsung Hospital

Seoul, , South Korea

Seoul St. Mary's Hospital of the Catholic University of Korea

Seoul, , South Korea

Hospital (Universitari(o)) Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario La Princesa

Madrid, Málaga, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic

Barcelona, , Spain

Hospital Universitario Gregorio Marañón

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Linköping University Hospital

Linköping, , Sweden

Skåne University Hospital

Lund, , Sweden

Karolinska University Hospital Solna

Stockholm, , Sweden

Norrlands University Hospital

Umeå, , Sweden

Akademiska Hospital

Uppsala, , Sweden

China Medical University Hospital

Taichung, R.o.c., Taiwan

Chi-Mei Medical Center

Tainan City, R.o.c., Taiwan

Mackay Memorial Hospital

Taipei, R.o.c., Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Division of Hematology, Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital

Muang, Chiang Mai, Thailand

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Phramongkutklao Hospital

Bangkok, , Thailand

Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital

Bangkok, , Thailand

MI "Cherkasy Regional Oncological Dispensary " of Cherkasy Regional Council

Cherkasy, , Ukraine

Regional Clinical Hospital in Ivano-Frankivsk, Hematology Department

Ivano-Frankivsk, , Ukraine

Khmelnytskyi Regional Hospital, Hematology Department

Khmelnytskyi, , Ukraine

State Institution "National research center for radiation medicine of NAMS of Ukraine",

Kyiv, , Ukraine

State Institution "National research center for radiation medicine of NAMS of Ukraine"

Kyiv, , Ukraine

transplantation department of hemotology and transplantology division within Clinical Radiology

Kyiv, , Ukraine

Chair of internal medicine #2.

Kyiv, , Ukraine

Kyiv City Clinical Hospital #9, Hematology department #1,

Kyiv, , Ukraine

State Institution "Institute of Blood Pathology and Transfusion Medicine NAMS of Ukraine"

Lviv, , Ukraine

Catherine Lewis Centre, Hammersmith Hospital

London, Greater London, United Kingdom

Linda McCartney Centre

Liverpool, Merseyside, United Kingdom

Department of Clinical Haematology

Nottingham, Nottinghamshire, United Kingdom

Cancer & Haematology Centre, Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Department of Haematology The Royal Hallamshire Hospital

Sheffield, South Yorkshire, United Kingdom

Heartlands Hospital

Birmingham, WEST Midlands, United Kingdom

St James's Institute of Oncology

Leeds, WEST Yorkshire, United Kingdom

Department of Haematology

Cardiff, , United Kingdom

The Hope Clinical Trials Facility

Leicester, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Czechia; Denmark; Finland; France; Germany; Hungary; Israel; Italy; Mexico; Netherlands; Norway; Poland; Singapore; Slovakia; South Africa; South Korea; Spain; Sweden; Taiwan; Thailand; Ukraine; United Kingdom

References

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Other Identifiers

2013-005101-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B1871053

Identifier Type: OTHER

Identifier Source: secondary_id

AV001

Identifier Type: -

Identifier Source: org_study_id