A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
- Conditions
- Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
- Interventions
- Registration Number
- NCT02130557
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 536
- Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis).
- Adequate hepatic, renal and pancreatic function.
- Age ≥ 18 years.
- 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.
- Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia.
- Extramedullary disease only.
- Major surgery or radiotherapy within 14 days of randomization.
- History of clinically significant or uncontrolled cardiac disease.
- 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.
- Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Imatinib Imatinib Imatinib, 400 mg, oral administration once a day Bosutinib Bosutinib Bosutinib, 400 mg, oral administration once a day
- Primary Outcome Measures
Name Time Method Percentage of Participants With Major Molecular Response (MMR) at Month 12 Month 12 MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (\<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to \[\>=\] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48 Month 48 The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.
Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12 Up to Month 12 Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.
Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48 Month 48 The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio \>0.1% in association with a \>=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.
Cumulative Incidence of Event Free Survival (EFS) Events Up to Month 60 EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to \>20.0\*10\^9/L, platelet count rises to \>=600\*10\^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of \<100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.
Overall Survival (OS) Rate Up to Month 60 OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.
Percentage of Participants With Major Molecular Response (MMR) Up to Month 18 Up to Month 18 MMR was defined as a ratio of BCR-ABL/ABL \<=0.1% on the international scale (\>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.
Trial Locations
- Locations (182)
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, 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
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
John H. Stroger, Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Lafayette General Medical Center
🇺🇸Lafayette, Louisiana, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
St. Joseph Mercy-Canton
🇺🇸Canton, Michigan, United States
Chelsea Community Hospital
🇺🇸Chelsea, Michigan, United States
St. John Hospital&Medical Center-Van Elslander Cancer Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Minnesota Oncology Hematology, PA
🇺🇸Edina, Minnesota, United States
Van Elslander Cancer Center, Pharmacy
🇺🇸Grosse Pointe Woods, Michigan, United States
Park Nicollet Frauenshuh Cancer center
🇺🇸Saint Louis Park, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
North Mississippi Medical Center Hematology and Oncology Clinic
🇺🇸Tupelo, Mississippi, 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
FirstHealth Moore Regional Hospital
🇺🇸Pinehurst, North Carolina, United States
FirstHealth Outpatient Cancer Center
🇺🇸Pinehurst, North Carolina, United States
MUSC University Hospital
🇺🇸Charleston, South Carolina, United States
UC Health Physicians Office South,
🇺🇸West Chester, Ohio, United States
MUSC-Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
GHS Cancer Institute
🇺🇸Spartanburg, South Carolina, United States
HSHS St. Vincent Hospital Regional Cancer Center at 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
St George Hospital - Hematology Department
🇦🇺Kogarah, New South Wales, Australia
UZ Ghent (University Hospital Ghent)
🇧🇪Ghent, Belgium
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
🇨🇦Quebec, Canada
Fakultní Nemocnice Brno
🇨🇿Brno, Czechia
Fakultní Nemocnice Hradec Králové
🇨🇿Hradec Králové, Czechia
Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Institut Bergonié
🇫🇷Bordeaux, France
Všeobecná fakultní Nemocnice v Praze
🇨🇿Prague, Czechia
Oncologie Centre de Radiotherapie
🇫🇷Strasbourg, NC, France
private Practice of Pr Philippe Rousselot
🇫🇷Le Chesnay, France
Akademiska Hospital
🇸🇪Uppsala, Sweden
private Practice of Dr. Viviane Dubruille
🇫🇷Nantes cedex 1, France
INSERM CIC 1402 - CHU Poitiers
🇫🇷Poitiers, France
Hôpital L'Archet 1-CHU Nice
🇫🇷Nice, France
Institut de Cancérologie du Gard - Hématologie Clinique
🇫🇷Nimes, France
Pr Mauricette Michallet Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite, France
Universitätsklinikum Bonn
🇩🇪Bonn, RP, Germany
Institut Universitaire du Cancer de Toulouse - Oncopole
🇫🇷Toulouse cedex 9, France
Uniklinikum Aachen
🇩🇪Aachen, Germany
Charité, CVK, Med. Klinik m.S Hämatologie und Onkologie
🇩🇪Berlin, Germany
Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum
🇩🇪Hamburg, Germany
Universitätsklinikum Freiburg, Klinik für Innere Medizin I
🇩🇪Freiburg, 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
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
Dipartimento di ematologia
🇮🇹Reggio Calabria, Italy
Policlinico S. Orsola - Malpighi,
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Istituto Scientifico San Raffaele
🇮🇹Milano, Italy
IRCCS - AOU San Martino_IST, Ematologia 1
🇮🇹Genova, Italy
A.O.U. Policlinico Università degli Studi di Napoli "Federico II"
🇮🇹Napoli, Italy
Unità di Ricerca Clinica, U.O. Ematologia Adulti
🇮🇹Monza, Italy
ASL Roma 2 - Ospedale Sant'Eugenio
🇮🇹Roma, Italy
Hallym University Sacred Heart Hospital
🇰🇷Anyang-si, Korea, Republic of
Dong A University Hospital
🇰🇷Busan, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital of the Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Hospital Angeles del Pedregal (S.A. de C.V.)
🇲🇽Mexico City, DF, Mexico
Monterrey International Research Center
🇲🇽Monterrey, Nuevo LEON, Mexico
Klinische Farrnacologie en Apotheek
🇳🇱Amsterdam, Noord-holland, Netherlands
Haukeland University Hospital Department of Hematology
🇳🇴Bergen, Norway
Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Universytet Medyczny im. Piastów Śląskich we Wrocławiu Katedra i
🇵🇱Wrocław, Poland
SPSK, Klinika Hematoonkologii i Transplantacji Szpiku w Lublinie
🇵🇱Lublin, Poland
Univerzitná Nemocnica Bratislava-Nemocnica sv. Cyrila a Metoda
🇸🇰Bratislava, Slovakia
Department of Medical Oncology, University of Pretoria and Steve Biko
🇿🇦Pretoria, Gauteng, South Africa
The Medical Oncology Centre of Rosebank
🇿🇦Johannesburg, Gauteng, South Africa
Department of Haematology
🇬🇧Cardiff, United Kingdom
Groenkloof Life hospital.
🇿🇦Pretoria, Gauteng, South Africa
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 Virgen de la Salud
🇪🇸Toledo, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, 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
China Medical University Hospital
🇨🇳Taichung city, R.o.c., Taiwan
Chi-Mei Medical Center
🇨🇳Tainan City, R.o.c., Taiwan
Division of Hematology, Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital
🇹🇭Muang, Chiang MAI, Thailand
King Chulalongkorn Memorial 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
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
Kyiv City Clinical Hospital #9, Hematology department #1,
🇺🇦Kyiv, Ukraine
transplantation department of hemotology and transplantology division within Clinical Radiology
🇺🇦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
Chair of internal medicine #2.
🇺🇦Kyiv, Ukraine
Linda McCartney Centre
🇬🇧Liverpool, Merseyside, United Kingdom
Department of Clinical Haematology
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Heartlands Hospital
🇬🇧Birmingham, WEST Midlands, United Kingdom
Cancer & Haematology Centre, Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Department of Haematology The Royal Hallamshire Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
St James's Institute of Oncology
🇬🇧Leeds, WEST Yorkshire, United Kingdom
The Hope Clinical Trials Facility
🇬🇧Leicester, United Kingdom
Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
PHARMACY Department Franciscan St. Francis Health ATTN:Jill Leslie, Pharm D
🇺🇸Indianapolis, Indiana, United States
The University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Rochester
🇺🇸Rochester, New York, United States
Roskilde Hospital
🇩🇰Roskilde, Denmark
A.O. Brozu - P.O. Armando Businco
🇮🇹Cagliari, Italy
University Health Shreveport
🇺🇸Shreveport, Louisiana, United States
Saint Alphonsus Caldwell Cancer Care Center
🇺🇸Caldwell, Idaho, United States
Saint Alphonsus Medical Center Nampa
🇺🇸Nampa, Idaho, United States
LSU Health Sciences Center-Shreveport
🇺🇸Shreveport, Louisiana, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Department of Haematology at UZ Leuven (7 th Floor)
🇧🇪Leuven, Belgium
Singapore General Hospital
🇸🇬Singapore, Singapore
Cancer Center of Acadiana at Lafayette General Medical Center
🇺🇸Lafayette, Louisiana, United States
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
National University Hospital, Main Building
🇸🇬Singapore, Singapore
University of Massachusetts Memorial Medical Center, ONC/Research Pharmacy
🇺🇸Worcester, Massachusetts, United States
MUSC University of South Carolina, Investigational Drug Services
🇺🇸Charleston, South Carolina, United States
Eastern Clinical Research Unit, Level 2
🇦🇺Box Hill, Victoria, Australia
Horizon Health Network - The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Hematology Department CHR Verviers
🇧🇪Verviers, Belgium
St. Joseph Mercy-Brighton
🇺🇸Brighton, Michigan, United States
Hematology Department of CHU de Liège
🇧🇪Liège, Belgium
HSHS St. Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Samodzielny Publiczny Szpital Kliniczny im. A Mielęckiego, ŚUM w Katowicach
🇵🇱Katowice, Poland
Petz Aladár Megyei OktatóKórház, II. Belgyógyászati Osztály és Haematológiai Részleg
🇭🇺Györ, Hungary
VU University Medical Center
🇳🇱Amsterdam, Noord Holland, Netherlands
SPZOZ ZSM w Chorzowie Oddzial Hematologiczny
🇵🇱Chorzow, Poland
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
St. Olavs Hospital
🇳🇴Trondheim, Norway
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Hematologii
🇵🇱Kraków, Poland
Wojewódzki Szpital Specjalistyczny im M. Kopernika, Klinika Hematologii Uniwersytetu Medycznego
🇵🇱Łódź, Poland
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Khmelnytskyi Regional Hospital, Hematology Department
🇺🇦Khmelnytskyi, Ukraine
Hospital (Universitari(o)) Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Mackay Memorial Hospital
🇨🇳Taipei City, R.o.c., Taiwan
Phramongkutklao Hospital
🇹🇭Bangkok, Thailand
Regional Clinical Hospital in Ivano-Frankivsk, Hematology Department
🇺🇦Ivano-Frankivsk, Ukraine
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Rcca Md Llc
🇺🇸Bethesda, Maryland, United States
St. John Hospital&Medical Center
🇺🇸Detroit, Michigan, United States
Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
St. Joseph Mercy Hospital - Inpatient Pharmacy
🇺🇸Ann Arbor, Michigan, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States