Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML

Chronic Myeloid Leukemia Clinical Trial

Official title:

A PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN SUBJECTS WITH NEWLY DIAGNOSED CHRONIC PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOGENOUS LEUKEMIA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00574873
• Other study ID #: 3160A4-3000
• Secondary ID: B18710082007-003
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2008
• Est. completion date: May 27, 2015

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: May 27, 2015
• Est. primary completion date: August 31, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Exclusions include Philadelphia negative CML.

• Prior anti-leukemia treatment.

• Prior stem cell transplant.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Philadelphia Chromosome

Intervention

Drug:
• Bosutinib
500 mg once daily, by mouth (tablet) with food preferably in the morning. Drug can be increased up to 600mg daily in case of lack of efficacy, and can be reduced to 300mg daily in case of toxicity. The drug will be given daily for up to 8 years until treatment failure, unacceptable toxicity, death or withdrawal of consent.
• imatinib
400 mg once daily, by mouth (tablet). Drug can be increased up to 600mg daily in case of lack of efficacy, and can be reduced to 300mg daily in case of toxicity. The drug will be given daily for up to 8 years until treatment failure, unacceptable toxicity, death or withdrawal of consent.

Locations

Country	Name	City	State
Argentina	Centro de Investigaciones Oncologicas	Bahia Blanca	Provincia Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Buenos Aires
Argentina	Hospital Privado de Cordoba	Cordoba	Prov. DE Cordoba
Argentina	Hospital Italiano de la Plata	La Plata	Buenos Aires
Belgium	Cliniques Universitaires Saint Luc	Brussels
Belgium	C.H.R.ST. - R. Fabiola (N-D)	Charleroi
Belgium	University Hospital Gent - Department of Hematology	Gent
Belgium	Centre Hospitalier de Jolimont - Lobbes	La Louviere
Belgium	CHU de Charleroi - Hopital civil Marie Curie	Lodelinsart
Belgium	H.-Hartziekenhuis Roeselare-Menen	Roeselare
Brazil	Centro De Hematologia E Hemoterapia Da Unicamp	Campinas/ SP
Canada	Hopital Maisonneuve Rosemont	Montreal	Quebec
Canada	University Health Network, Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Chile	Instituto Oncologico del Sur	Temuco
Chile	Instituto Oncologico	Vina del Mar
China	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing
China	The Chinese PLA General Hospital	Beijing
China	Ruiging Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	P.R. China
China	The Hematology Hospital of Chinese Academy of Medical Science	Tianjin
Colombia	CIOSAD Centro de Investigaciones Oncologicas	Bogota
Colombia	Fundacion Santa Fe de Bogota	Bogota	Cundinamarca
Colombia	Fundacion Cardiovascular de Colombia	Floridablanca	Santander
France	Institut Bergonie	Bordeaux
France	CHU Caen - Cote de Nacre	Caen
France	Centre Hospitalier de Versailles Hopital Andre Mignot	Le Chesnay Cedex
France	Hopital EDOUARD HERRIOT	Lyon
France	Hopital HOTEL DIEU	Nantes
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	Hopitaux Universitaires de Strasbourg - Hopital Civil	Strasbourg
Germany	Charite University Medical Center - Campus Virchow Klinikum	Berlin
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Univeristatsklinikum Hamburg-Eppendorf	Hamburg
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
Hong Kong	Prince Of Wales Hospital	Shatin N.T.
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly	Kaposvar
Hungary	Josa Andras Hospital	Nyiregyhaza
India	Birla Cancer Centre	Jaipur	Rajasthan
India	SEAROC Cancer Center, Soni Manipal Hospital	Jaipur	Rajasthan
India	Advanced Centre for Treatment, Research and Education in Cancer	Mumbai	Maharashtra
India	Tata Memorial Center, Tata Memorial Hospital	Mumbai	Maharashtra
India	Jehangir Clinical Development Centre,	Pune	Maharashtra
Italy	Ospedale Ferrarotto - Divisione di Ematologia	Catania
Italy	Azienda Ospedaliera San Gerardo	Monza	Lombardia
Italy	Azienda Ospedaliera Universitaria San Luigi Gonzaga	Orbassano	Torino
Italy	Dipartimento Di Ematologia Ospedale Santo Eugenio	Roma
Japan	Aichi Cancer Center Hospital	Aichi
Japan	Japanese Red Cross Nagoya First Hospital	Aichi
Japan	Akita University Hospital	Akita City	Akita
Japan	Chiba University Hospital	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-Shi	Fukuoka
Japan	Tokai University Hospital	Kanagawa
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	Jikei University Hospital Daisan	Komae-shi	Tokyo
Japan	Nagasaki University Hospital	Nagasaki
Japan	Niigata University Medical and Dental Hospital	Niigata
Japan	Osaka University Hospital	Osaka
Japan	Kinki University School Of Medicine	Osakasayama	Osaka
Japan	Tohoku Univesity Hospital	Sendai	Miyagi
Japan	Hamamatsu Medical University Hospital Faculty of Medicine	Shizuoka
Japan	Tokyo Metropolitan Cancer & Infectious Disease Centre Komagome Hp	Tokyo
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital/Division of Hematology	Seoul
Latvia	Riga Centre Of Haematology	Riga
Lithuania	Hematology, Oncology & Transfusion Medicine Center	Vilnius
Mexico	Centro Medico de las Americas	Merida
Poland	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	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin
Russian Federation	Regional State Budgetary Healthcare Institution "Barnaul City Hospital #8"	Barnaul
Russian Federation	Central City Hospital #7	Ekaterinburg
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Kirov Research Institute of Hematology and Blood Transfusion of	Kirov
Russian Federation	Federal State Budget Institution Hematology Scientific Center of Minzdravsotsrazvitiya of Russia	Moscow
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	Perm Territory State Budgetary Healthcare Inst	Perm
Russian Federation	Republican Hospital na Baranov	Petrozavodsk
Russian Federation	Rostov Regional Clinical Hospital	Rostov-on-Don
Russian Federation	Rostov State Medical University of the Minzdravsotsrazvitiya of Russia	Rostov-On-Don
Russian Federation	Leningrad Regional Clinical Hospital	Saint Petersburg
Russian Federation	St-Petersburg Pavlov's State Medical University	Saint Petersburg
Russian Federation	St-Petersburg State Medical University	Saint Petersburg
Russian Federation	Samara Regional Clinical Hospital M.I. Kalinin	Samara
Russian Federation	St-Petersburg Pavlov's State Medical University	St. Petersburg
Russian Federation	GUZ Komi Republican Oncology Center	Syktyvkar	KOMI Republic
Russian Federation	Yaroslavl Region State Budgetary Healthcare Institution Regional Clinical Hospital	Yaroslavl
Singapore	Singapore General Hospital	Singapore
South Africa	University Witwatersrand and Oncology	Johannesburg
South Africa	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
Spain	Hospital Universitari Clinic de Barcelona	Barcelona
Spain	Hospital De La Princesa	Madrid
Spain	Hospital de Madrid Norte-Sanchinarro Centro Integral Oncologico	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Complejo Hospitalario de Toledo- Servicio de Hematologia.	Toledo
Spain	Hospital Clinico Universitario de Valencia (CHUV)	Valencia
Taiwan	Changhua Christian Hospital	Changhua City
Taiwan	National Taiwan University Hospital	Taipei TOC
Thailand	Division of Hematology, Department of Medicine	Bangkoknoi	Bangkok
Turkey	Ankara Universitesi Tip Fakultesi Cebeci Hastanesi	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara	Sihhiye
Turkey	Gaziantep Universitesi Tip Fakultesi	Gaziantep
Ukraine	Cherkaskiy oblasniy onkologichniy dispanser	Cherkassy
Ukraine	Clinical Assocation of Emergency Care	Dnipropetrovsk
Ukraine	Clinical Diagnostic Laboratory of Komunalnyj Zaklad	Dnipropetrovsk
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	Oleksandrovska clinical hospital cardiological rehabilitation department	Kiev
Ukraine	Miska klinichna likarnja # 9	Kyev
Ukraine	Institut Klinichnoi Radiologii DU "Natsionalnyj Naukovyj Centr Radiacijnoi Medicini NAMN Ukraini"	Kyiv
Ukraine	Institut Klinichnoi Radiologii Naukovogo	Kyiv
Ukraine	Institut Klinichnoi Radiologii Naukovogo Centru Radiacijnoi Medicini NAMN Ukraini	Kyiv
Ukraine	Instutut Patologii Krovi to Transfuziynoi Medicinu AMN Ukraini	Lviv
Ukraine	Polyclinic of 5th Municipal Hospital	Lviv
Ukraine	Ultrasaund Educational and Diagnostic Center	Lviv
United Kingdom	Birmingham Heartlands Hospital	Birmingham	WEST Midlands
United Kingdom	Good Hope Hospital	Birmingham	WEST Midlands
United Kingdom	Hammersmith Hospital Clinical Trial Units	Hammersmith	London
United Kingdom	Department of Haematology - Level 3, Bexley Wing	Leeds	WEST Yorkshire
United Kingdom	Department of Haematology	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	3rd Floor Centre for Clinical Haematology	Nottingham	EAST Midlands
United Kingdom	The Park Hospital	Nottingham	EAST Midlands
United States	Pacific Cancer Medical Center Inc	Anaheim	California
United States	Northside Hospital, Inc. - GCS/Annex	Atlanta	Georgia
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Tower Cancer Research Foundation (TCRF)	Beverly Hills	California
United States	Josephine Ford Cancer - Downriver	Brownstown	Michigan
United States	Associates In Oncology and Hematology	Chattanooga	Tennessee
United States	Regional Cancer Care Associates	Cherry Hill	New Jersey
United States	Study Supplies: Regional Cancer Care Associates	Cherry Hill	New Jersey
United States	Henry Ford Medical Center- Fairlane	Dearborn	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Henry Ford Hospital - West Bloomfield	Detroit	Michigan
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Robert A Moss, MD, FACP, Inc	Fountain Valley	California
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Cancer Care Centers of Florida	Hudson	Florida
United States	Indiana Blood and Marrow Transplantation Research	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation Research Franciscan St. Francis Health Center Inc.	Indianapolis	Indiana
United States	UCSD Medical Center-Thornton	La Jolla	California
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Cancer Care Centers of Florida	New Port Richey	Florida
United States	Pasco Pinellas Cancer Center	New Port Richey	Florida
United States	Orlando Health, Inc.	Orlando	Florida
United States	Cancer Center of Kansas	Salinas	Kansas
United States	UCSD Medical Center-Hillcrest	San Diego	California
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Somerset Hematology Oncology Associates	Somerville	New Jersey
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	Pasco Pinellas Cancer Center	Tarpon Springs	Florida
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Wyeth is now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  France,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete Cytogenetic Response (CCyR) at Year 1	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.	Year 1 (48 weeks)
Secondary	Percentage of Participants With Major Molecular Response (MMR) at Year 1	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.	Year 1 (48 weeks)
Secondary	Kaplan-Meier Estimate of Probability of Retaining CCyR at 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.	192 weeks
Secondary	Kaplan-Meier Estimate of Probability of Retaining Complete Hematologic Response (CHR) at 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.	192 weeks
Secondary	Kaplan-Meier Estimate of Probability of Retaining Derived MMR at 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.	144 weeks
Secondary	Cumulative Incidence of On-Treatment Transformation to Accelerated Phase (AP) or Blast Phase (BP) at 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.	192 weeks

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