Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
- Registration Number
- NCT00574873
- Lead Sponsor
- Pfizer
- Brief Summary
Two-arm, randomized, open-label trial designed to evaluate the efficacy and safety of bosutinib alone compared to imatinib alone in subjects newly diagnosed with chronic phase Chronic Myelogenous Leukemia (CML). The primary endpoint is cytogenetic response rate at one year.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 502
- Cytogenetic diagnosis of chronic phase Ph+ CML diagnosed less than 6 months.
- Diagnosis of CML chronic phase confirmed.
- Adequate hepatic and renal function.
- Able to take oral tablets.
- Exclusions include Philadelphia negative CML.
- Prior anti-leukemia treatment.
- Prior stem cell transplant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Bosutinib Bosutinib 2 imatinib Imatinib
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete Cytogenetic Response (CCyR) at Year 1 Year 1 (48 weeks) Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0 percent (%) Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or less than (\<) 1% breakpoint cluster region Abelson protooncogene (Bcr-Abl) fusion product among cells in a BM sample or peripheral blood sample when at least 200 cells were analyzed.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Major Molecular Response (MMR) at Year 1 Year 1 (48 weeks) Molecular response was assessed using Bcr-Abl transcript levels measured by reverse transcriptase polymerase chain reaction (RT-PCR) from peripheral blood. A MMR was defined as a ratio Bcr-Abl/Abl less than or equal to (≤) 0.1% on the international scale (greater than or equal to \[≥\] 3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) with at least 3000 Abl analyzed.
Kaplan-Meier Estimate of Probability of Retaining CCyR at 192 Weeks 192 weeks The Kaplan-Meier curve was generated based the time from the first date of CCyR until the first date of confirmed loss of CCyR, objectively documented, for responders only. Participants without confirmed loss of CCyR were censored at the last valid cytogenetic assessment.
CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. 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 \<1% Bcr-Abl fusion product among cells in a BM sample or peripheral blood sample when at least 200 cells were analyzed.
The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Four years rate was displayed since the majority of participants had first CCyR by Year 1.Kaplan-Meier Estimate of Probability of Retaining Complete Hematologic Response (CHR) at 192 Weeks 192 weeks The Kaplan-Meier curve was generated based on the first date of confirmed CHR until the first date of loss of CHR, objectively documented, for responders only. Participants without confirmed loss of response were censored at the last valid hematologic assessment.
CHR must have been of at least 4 weeks in duration confirmed by 2 assessments at least 4 weeks apart and was defined as follows: white blood cells ≤ institutional upper limit of normal, no peripheral blasts or promyelocytes, myelocytes + metamyelocytes \<5% in blood, absolute neutrophil count ≥1.0\*10\^9/L, platelets ≥100 but \<450\*10\^9/L unless related to therapy, \<20% basophils in blood and no extramedually involvement (including hepato- or splenomegaly).
The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Four years rate was displayed since the majority of participants had first CHR by Year 1.Kaplan-Meier Estimate of Probability of Retaining Derived MMR at 144 Weeks 144 weeks The Kaplan-Meier curve was generated based on the first date of MMR until the first date loss of MMR, objectively documented, for responders only. Participants without confirmed loss of response were censored at the last valid molecular assessment.
Molecular response was assessed using Bcr-Abl transcript levels measured by RT-PCR from peripheral blood. MMR is defined as a ratio Bcr-Abl/Abl ≤0.1% on the international scale (≥3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) with at least 3000 Abl analyzed.
The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided. Three years rate was displayed since the majority of imatinib participants had first MMR by Year 2.Cumulative Incidence of On-Treatment Transformation to Accelerated Phase (AP) or Blast Phase (BP) at 192 Weeks 192 weeks The cumulative incidence curve was generated based on the time from randomization to the first date of transformation to AP or BP while on study treatment adjusting for the competing risk of treatment discontinuation without transformation, for each participant.
Criteria for transformation to AP: 15 to 29% blasts; ≥30% blasts + promyelocytes; ≥20% basophils in blood or bone marrow; platelets \<100\*10\^9/L (not related to therapy), in blood. Criteria for transformation to BP: ≥30% blasts in blood or bone marrow and extramedullary involvement other than liver or spleen (example: chloromas).
Time to transformation was calculated as weeks = (\[date of first documented occurrence of the event - date of randomization\] + 1)/7. If transformation was not obtained, censoring was at the last hematologic assessment or death (whichever was earliest). Participants who were not treated contributed time = 1 day/7. 95% confidence interval for the cumulative incidence is from Gray's method.
Trial Locations
- Locations (162)
Pacific Cancer Medical Center Inc
🇺🇸Anaheim, California, United States
Robert A Moss, MD, FACP, Inc
🇺🇸Fountain Valley, California, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Associates In Oncology and Hematology
🇺🇸Chattanooga, Tennessee, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Advanced Centre for Treatment, Research and Education in Cancer
🇮🇳Mumbai, Maharashtra, India
Jehangir Clinical Development Centre,
🇮🇳Pune, Maharashtra, India
SEAROC Cancer Center, Soni Manipal Hospital
🇮🇳Jaipur, Rajasthan, India
Indiana Blood and Marrow Transplantation Research Franciscan St. Francis Health Center Inc.
🇺🇸Indianapolis, Indiana, United States
Indiana Blood and Marrow Transplantation Research
🇺🇸Indianapolis, Indiana, United States
Tower Cancer Research Foundation (TCRF)
🇺🇸Beverly Hills, California, United States
UCSD Medical Center-Thornton
🇺🇸La Jolla, California, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
UCSD Medical Center-Hillcrest
🇺🇸San Diego, California, United States
Stanford Hospital and Clinics Investigational Drug Services
🇺🇸Stanford, California, United States
Stanford Hospitals and Clinics
🇺🇸Stanford, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Cancer Care Centers of Florida
🇺🇸New Port Richey, Florida, United States
Orlando Health, Inc.
🇺🇸Orlando, Florida, United States
Pasco Pinellas Cancer Center
🇺🇸Tarpon Springs, Florida, United States
Northside Hospital, Inc. - GCS/Annex
🇺🇸Atlanta, Georgia, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Kentucky Cancer Clinic
🇺🇸Hazard, Kentucky, United States
Study Supplies: Regional Cancer Care Associates
🇺🇸Cherry Hill, New Jersey, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Centro De Hematologia E Hemoterapia Da Unicamp
🇧🇷Campinas/ SP, Brazil
Hopital Maisonneuve Rosemont
🇨🇦Montreal, Quebec, Canada
Instituto Oncologico del Sur
🇨🇱Temuco, Chile
Ruiging Hospital Affiliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, P.R. China, China
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
🇨🇳Beijing, China
The Chinese PLA General Hospital
🇨🇳Beijing, China
The Hematology Hospital of Chinese Academy of Medical Science
🇨🇳Tianjin, China
Institut Bergonie
🇫🇷Bordeaux, France
CIOSAD Centro de Investigaciones Oncologicas
🇨🇴Bogota, Colombia
Centre Hospitalier de Versailles Hopital Andre Mignot
🇫🇷Le Chesnay Cedex, France
Hopital HOTEL DIEU
🇫🇷Nantes, France
Hopital EDOUARD HERRIOT
🇫🇷Lyon, France
Hospital Archet 1
🇫🇷Nice Cedex 3, France
Centre d'Investigation Clinique- CIC INSERM802
🇫🇷Poitiers, France
CHU de Poitiers
🇫🇷Poitiers, France
Clinique Sainte Anne
🇫🇷Strasbourg, France
Charite University Medical Center - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Hopitaux Universitaires de Strasbourg - Hopital Civil
🇫🇷Strasbourg, France
Univeristatsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitaetsklinikum Leipzig Zentrum fur Innere Medizin
🇩🇪Leipzig, Germany
III. Medizinische Klinik, Universitaetsklinikum Mannheim gGmbH
🇩🇪Mannheim, Germany
III. Medizinischen Klinik und Poliklinik des Klinikums Rechts der Isar der TU-MUNCHEN
🇩🇪Muenchen, Germany
Azienda Ospedaliera Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-Shi, Fukuoka, Japan
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Jikei University Hospital Daisan
🇯🇵Komae-shi, Tokyo, Japan
Niigata University Medical and Dental Hospital
🇯🇵Niigata, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Tokyo Metropolitan Cancer & Infectious Disease Centre Komagome Hp
🇯🇵Tokyo, Japan
The Catholic University of Korea, Seoul St. Mary's Hospital/Division of Hematology
🇰🇷Seoul, Korea, Republic of
Riga Centre Of Haematology
🇱🇻Riga, Latvia
Hematology, Oncology & Transfusion Medicine Center
🇱🇹Vilnius, Lithuania
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Samodzielny Publiczny Szpital Kliniczny Im. A. Mieleckiego Slaskiego Uniwersytetu Medycznego
🇵🇱Katowice, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
🇵🇱Lodz, Poland
Republican Hospital na Baranov
🇷🇺Petrozavodsk, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺Saint Petersburg, Russian Federation
St-Petersburg Pavlov's State Medical University
🇷🇺St. Petersburg, Russian Federation
University Witwatersrand and Oncology
🇿🇦Johannesburg, South Africa
Singapore General Hospital
🇸🇬Singapore, Singapore
Johannesburg Hospital, Department of Medical Oncology
🇿🇦Parktown, South Africa
Clinical Haematology Unit - Department of Medicine
🇿🇦Soweto, South Africa
Department of Cardiology, Chris Hani Baragwanath Hospital
🇿🇦Soweto, South Africa
Department of Radiology, Chris Hani Baragwanath Hospital
🇿🇦Soweto, South Africa
Hospital Universitari Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital De La Princesa
🇪🇸Madrid, Spain
Hospital de Madrid Norte-Sanchinarro Centro Integral Oncologico
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia (CHUV)
🇪🇸Valencia, Spain
Complejo Hospitalario de Toledo- Servicio de Hematologia.
🇪🇸Toledo, Spain
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi
🇹🇷Ankara, Turkey
Clinical Assocation of Emergency Care
🇺🇦Dnipropetrovsk, Ukraine
Clinical Diagnostic Laboratory of Komunalnyj Zaklad
🇺🇦Dnipropetrovsk, Ukraine
Cherkaskiy oblasniy onkologichniy dispanser
🇺🇦Cherkassy, Ukraine
Komunalnyj Zaklad "Dnipropetrovska Miska Bagatoprofilna Klinichna Likarnja #4"
🇺🇦Dnipropetrovsk, Ukraine
Instytut Nevidkladnoi ta Vidnovnoi Hirurgii im. P.K. Husaka NAMN Ukrainy, Viddilennja Hematologii
🇺🇦Donetsk, Ukraine
Miska klinichna likarnja # 9
🇺🇦Kyev, Ukraine
Oleksandrovska clinical hospital cardiological rehabilitation department
🇺🇦Kiev, Ukraine
Polyclinic of 5th Municipal Hospital
🇺🇦Lviv, Ukraine
Birmingham Heartlands Hospital
🇬🇧Birmingham, WEST Midlands, United Kingdom
3rd Floor Centre for Clinical Haematology
🇬🇧Nottingham, EAST Midlands, United Kingdom
Department of Haematology - Level 3, Bexley Wing
🇬🇧Leeds, WEST Yorkshire, United Kingdom
Hammersmith Hospital Clinical Trial Units
🇬🇧Hammersmith, London, United Kingdom
Good Hope Hospital
🇬🇧Birmingham, WEST Midlands, United Kingdom
The Park Hospital
🇬🇧Nottingham, EAST Midlands, United Kingdom
Department of Haematology
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Birla Cancer Centre
🇮🇳Jaipur, Rajasthan, India
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Division of Hematology, Department of Medicine
🇹🇭Bangkoknoi, Bangkok, Thailand
Henry Ford Hospital - West Bloomfield
🇺🇸Detroit, Michigan, United States
Tata Memorial Center, Tata Memorial Hospital
🇮🇳Mumbai, Maharashtra, India
Instituto Medico Especializado Alexander Fleming
🇦🇷Buenos Aires, Argentina
C.H.R.ST. - R. Fabiola (N-D)
🇧🇪Charleroi, Belgium
Centre Hospitalier de Jolimont - Lobbes
🇧🇪La Louviere, Belgium
Prince Of Wales Hospital
🇭🇰Shatin N.T., Hong Kong
Henry Ford Medical Center- Fairlane
🇺🇸Dearborn, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Regional Cancer Care Associates
🇺🇸Cherry Hill, New Jersey, United States
University Hospital Gent - Department of Hematology
🇧🇪Gent, Belgium
Somerset Hematology Oncology Associates
🇺🇸Somerville, New Jersey, United States
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Kinki University School Of Medicine
🇯🇵Osakasayama, Osaka, Japan
Hamamatsu Medical University Hospital Faculty of Medicine
🇯🇵Shizuoka, Japan
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Poland
GUZ Komi Republican Oncology Center
🇷🇺Syktyvkar, KOMI Republic, Russian Federation
Central City Hospital #7
🇷🇺Ekaterinburg, Russian Federation
Samara Regional Clinical Hospital M.I. Kalinin
🇷🇺Samara, Russian Federation
Yaroslavl Region State Budgetary Healthcare Institution Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
Josephine Ford Cancer - Downriver
🇺🇸Brownstown, Michigan, United States
Hospital Italiano de la Plata
🇦🇷La Plata, Buenos Aires, Argentina
Hospital Privado de Cordoba
🇦🇷Cordoba, Prov. DE Cordoba, Argentina
CHU de Charleroi - Hopital civil Marie Curie
🇧🇪Lodelinsart, Belgium
Fundacion Santa Fe de Bogota
🇨🇴Bogota, Cundinamarca, Colombia
Akita University Hospital
🇯🇵Akita City, Akita, Japan
Kirov Research Institute of Hematology and Blood Transfusion of
🇷🇺Kirov, Russian Federation
Centro de Investigaciones Oncologicas
🇦🇷Bahia Blanca, Provincia Buenos Aires, Argentina
Instituto Oncologico
🇨🇱Vina del Mar, Chile
Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly
🇭🇺Kaposvar, Hungary
Josa Andras Hospital
🇭🇺Nyiregyhaza, Hungary
Japanese Red Cross Nagoya First Hospital
🇯🇵Aichi, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Centro Medico de las Americas
🇲🇽Merida, Mexico
Regional State Budgetary Healthcare Institution "Barnaul City Hospital #8"
🇷🇺Barnaul, Russian Federation
State Novosibirsk Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
St-Petersburg State Medical University
🇷🇺Saint Petersburg, Russian Federation
Fundacion Cardiovascular de Colombia
🇨🇴Floridablanca, Santander, Colombia
H.-Hartziekenhuis Roeselare-Menen
🇧🇪Roeselare, Belgium
Petz Aladar Megyei Oktato Korhaz
🇭🇺Gyor, Hungary
Toyohashi Municipal Hospital
🇯🇵Toyohashi, Aichi, Japan
Rostov State Medical University of the Minzdravsotsrazvitiya of Russia
🇷🇺Rostov-On-Don, Russian Federation
Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet
🇭🇺Budapest, Hungary
Tohoku Univesity Hospital
🇯🇵Sendai, Miyagi, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
Perm Territory State Budgetary Healthcare Inst
🇷🇺Perm, Russian Federation
Rostov Regional Clinical Hospital
🇷🇺Rostov-on-Don, Russian Federation
Federal State Budget Institution Hematology Scientific Center of Minzdravsotsrazvitiya of Russia
🇷🇺Moscow, Russian Federation
National Taiwan University Hospital
🇨🇳Taipei TOC, Taiwan
Institut Klinichnoi Radiologii DU "Natsionalnyj Naukovyj Centr Radiacijnoi Medicini NAMN Ukraini"
🇺🇦Kyiv, Ukraine
Ultrasaund Educational and Diagnostic Center
🇺🇦Lviv, Ukraine
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Sihhiye, Turkey
Gaziantep Universitesi Tip Fakultesi
🇹🇷Gaziantep, Turkey
Institut Klinichnoi Radiologii Naukovogo
🇺🇦Kyiv, Ukraine
Instutut Patologii Krovi to Transfuziynoi Medicinu AMN Ukraini
🇺🇦Lviv, Ukraine
Institut Klinichnoi Radiologii Naukovogo Centru Radiacijnoi Medicini NAMN Ukraini
🇺🇦Kyiv, Ukraine
Dipartimento Di Ematologia Ospedale Santo Eugenio
🇮🇹Roma, Italy
Azienda Ospedaliera San Gerardo
🇮🇹Monza, Lombardia, Italy
Ospedale Ferrarotto - Divisione di Ematologia
🇮🇹Catania, Italy
CHU Caen - Cote de Nacre
🇫🇷Caen, France