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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00574873
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Enrollment: 502
• Locations: 166
• Arms: 2
• Actual Duration (Months): 87.7
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: Bosutinib; Drug: imatinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 502 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 5, 2008
• Actual Primary Completion Date: Aug 31, 2010
• Actual Study Completion Date: May 27, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Bosutinib	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.; Other Names: SKI 606
Active Comparator: 2 Imatinib	Drug: 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.; Other Names: Gleevec

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Cancer Medical Center Inc	Anaheim	California	United States	92801
2	Tower Cancer Research Foundation (TCRF)	Beverly Hills	California	United States	90211-1848
3	Robert A Moss, MD, FACP, Inc	Fountain Valley	California	United States	92708
4	UCSD Medical Center-Thornton	La Jolla	California	United States	92037
5	UCSD Moores Cancer Center	La Jolla	California	United States	92093
6	UCSD Medical Center-Hillcrest	San Diego	California	United States	92103
7	Stanford Hospital and Clinics Investigational Drug Services	Stanford	California	United States	94305
8	Stanford Hospitals and Clinics	Stanford	California	United States	94305
9	Stanford University Medical Center	Stanford	California	United States	94305
10	Cancer Care Centers of Florida	Hudson	Florida	United States	34667
11	Cancer Care Centers of Florida	New Port Richey	Florida	United States	34652
12	Pasco Pinellas Cancer Center	New Port Richey	Florida	United States	34652
13	Orlando Health, Inc.	Orlando	Florida	United States	32806
14	Pasco Pinellas Cancer Center	Tarpon Springs	Florida	United States	34689
15	Northside Hospital, Inc. - GCS/Annex	Atlanta	Georgia	United States	30341
16	Indiana Blood and Marrow Transplantation Research Franciscan St. Francis Health Center Inc.	Indianapolis	Indiana	United States	46237
17	Indiana Blood and Marrow Transplantation Research	Indianapolis	Indiana	United States	46237
18	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
19	Cancer Center of Kansas	Salinas	Kansas	United States	67401
20	Cancer Center of Kansas	Wichita	Kansas	United States	67214
21	Kentucky Cancer Clinic	Hazard	Kentucky	United States	41701-9466
22	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
23	Josephine Ford Cancer - Downriver	Brownstown	Michigan	United States	48183
24	Henry Ford Medical Center- Fairlane	Dearborn	Michigan	United States	48126
25	Henry Ford Hospital	Detroit	Michigan	United States	48202-2689
26	Henry Ford Hospital - West Bloomfield	Detroit	Michigan	United States	48322
27	Regional Cancer Care Associates	Cherry Hill	New Jersey	United States	08003
28	Study Supplies: Regional Cancer Care Associates	Cherry Hill	New Jersey	United States	08003
29	Somerset Hematology Oncology Associates	Somerville	New Jersey	United States	08876
30	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
31	Associates In Oncology and Hematology	Chattanooga	Tennessee	United States	37421
32	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030-4009
33	Hospital Italiano de la Plata	La Plata	Buenos Aires	Argentina	1900
34	Hospital Privado de Cordoba	Cordoba	Prov. DE Cordoba	Argentina	5000
35	Centro de Investigaciones Oncologicas	Bahia Blanca	Provincia Buenos Aires	Argentina	B8000FJI
36	Instituto Medico Especializado Alexander Fleming	Buenos Aires		Argentina	1426
37	Cliniques Universitaires Saint Luc	Brussels		Belgium	1200
38	C.H.R.ST. - R. Fabiola (N-D)	Charleroi		Belgium	6000
39	University Hospital Gent - Department of Hematology	Gent		Belgium	9000
40	Centre Hospitalier de Jolimont - Lobbes	La Louviere		Belgium	7100
41	CHU de Charleroi - Hopital civil Marie Curie	Lodelinsart		Belgium	6042
42	H.-Hartziekenhuis Roeselare-Menen	Roeselare		Belgium	8800
43	Centro De Hematologia E Hemoterapia Da Unicamp	Campinas/ SP		Brazil	6198
44	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
45	University Health Network, Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
46	Hopital Maisonneuve Rosemont	Montreal	Quebec	Canada	H1T 2M4
47	Instituto Oncologico del Sur	Temuco		Chile
48	Instituto Oncologico	Vina del Mar		Chile
49	Ruiging Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	P.R. China	China	200025
50	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing		China	100730
51	The Chinese PLA General Hospital	Beijing		China	100853
52	The Hematology Hospital of Chinese Academy of Medical Science	Tianjin		China	300020
53	Fundacion Santa Fe de Bogota	Bogota	Cundinamarca	Colombia
54	Fundacion Cardiovascular de Colombia	Floridablanca	Santander	Colombia
55	CIOSAD Centro de Investigaciones Oncologicas	Bogota		Colombia
56	Institut Bergonie	Bordeaux		France	33076
57	CHU Caen - Cote de Nacre	Caen		France	14000
58	Centre Hospitalier de Versailles Hopital Andre Mignot	Le Chesnay Cedex		France	78157
59	Hopital EDOUARD HERRIOT	Lyon		France	69437
60	Hopital HOTEL DIEU	Nantes		France	44000
61	Hospital Archet 1	Nice Cedex 3		France	06202
62	Centre d'Investigation Clinique- CIC INSERM802	Poitiers		France	86021
63	CHU de Poitiers	Poitiers		France	86021
64	Clinique Sainte Anne	Strasbourg		France	67000
65	Hopitaux Universitaires de Strasbourg - Hopital Civil	Strasbourg		France	67098
66	Charite University Medical Center - Campus Virchow Klinikum	Berlin		Germany	13353
67	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
68	Univeristatsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
69	Universitaetsklinikum Leipzig Zentrum fur Innere Medizin	Leipzig		Germany	04103
70	III. Medizinische Klinik, Universitaetsklinikum Mannheim gGmbH	Mannheim		Germany	68167
71	III. Medizinischen Klinik und Poliklinik des Klinikums Rechts der Isar der TU-MUNCHEN	Muenchen		Germany	81675
72	Prince Of Wales Hospital	Shatin N.T.		Hong Kong
73	Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet	Budapest		Hungary	1097
74	Petz Aladar Megyei Oktato Korhaz	Gyor		Hungary	9023
75	Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly	Kaposvar		Hungary	7400
76	Josa Andras Hospital	Nyiregyhaza		Hungary	4400
77	Tata Memorial Center, Tata Memorial Hospital	Mumbai	Maharashtra	India	400 012
78	Advanced Centre for Treatment, Research and Education in Cancer	Mumbai	Maharashtra	India	410 210
79	Jehangir Clinical Development Centre,	Pune	Maharashtra	India	411001
80	Birla Cancer Centre	Jaipur	Rajasthan	India	302 004
81	SEAROC Cancer Center, Soni Manipal Hospital	Jaipur	Rajasthan	India	302013
82	Azienda Ospedaliera San Gerardo	Monza	Lombardia	Italy	20900
83	Azienda Ospedaliera Universitaria San Luigi Gonzaga	Orbassano	Torino	Italy	10043
84	Ospedale Ferrarotto - Divisione di Ematologia	Catania		Italy	95124
85	Dipartimento Di Ematologia Ospedale Santo Eugenio	Roma		Italy	00144
86	Toyohashi Municipal Hospital	Toyohashi	Aichi	Japan	441-8570
87	Akita University Hospital	Akita City	Akita	Japan	010-8543
88	National Hospital Organization Kyushu Cancer Center	Fukuoka-Shi	Fukuoka	Japan	8111395
89	Kanazawa University Hospital	Kanazawa	Ishikawa	Japan	920-8641
90	Tohoku Univesity Hospital	Sendai	Miyagi	Japan	9808574
91	Kinki University School Of Medicine	Osakasayama	Osaka	Japan	589-8511
92	Jikei University Hospital Daisan	Komae-shi	Tokyo	Japan	2018601
93	Japanese Red Cross Nagoya First Hospital	Aichi		Japan	453-8511
94	Aichi Cancer Center Hospital	Aichi		Japan	464-8681
95	Chiba University Hospital	Chiba		Japan	260-8677
96	Tokai University Hospital	Kanagawa		Japan	259-1193
97	Nagasaki University Hospital	Nagasaki		Japan	852-8501
98	Niigata University Medical and Dental Hospital	Niigata		Japan	9518520
99	Osaka University Hospital	Osaka		Japan	565-0871
100	Hamamatsu Medical University Hospital Faculty of Medicine	Shizuoka		Japan	4313192
101	Tokyo Metropolitan Cancer & Infectious Disease Centre Komagome Hp	Tokyo		Japan	113-8677
102	The Catholic University of Korea, Seoul St. Mary's Hospital/Division of Hematology	Seoul		Korea, Republic of	137-701
103	Riga Centre Of Haematology	Riga		Latvia	1006
104	Hematology, Oncology & Transfusion Medicine Center	Vilnius		Lithuania	LT-08661
105	Centro Medico de las Americas	Merida		Mexico	97000
106	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
107	Samodzielny Publiczny Szpital Kliniczny Im. A. Mieleckiego Slaskiego Uniwersytetu Medycznego	Katowice		Poland	40-032
108	SP ZOZ Szpital Uniwersytecki w Krakowie	Krakow		Poland	31-501
109	Wojewodzki Szpital Specjalistyczny im. M. Kopernika	Lodz		Poland	93-510
110	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin		Poland	20-081
111	GUZ Komi Republican Oncology Center	Syktyvkar	KOMI Republic	Russian Federation	167904
112	Regional State Budgetary Healthcare Institution "Barnaul City Hospital #8"	Barnaul		Russian Federation	656010
113	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg		Russian Federation	620102
114	Central City Hospital #7	Ekaterinburg		Russian Federation	620137
115	Kirov Research Institute of Hematology and Blood Transfusion of	Kirov		Russian Federation	610027
116	Federal State Budget Institution Hematology Scientific Center of Minzdravsotsrazvitiya of Russia	Moscow		Russian Federation	125167
117	State Novosibirsk Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
118	Perm Territory State Budgetary Healthcare Inst	Perm		Russian Federation	614077
119	Republican Hospital na Baranov	Petrozavodsk		Russian Federation	185019
120	Rostov Regional Clinical Hospital	Rostov-on-Don		Russian Federation	344015
121	Rostov State Medical University of the Minzdravsotsrazvitiya of Russia	Rostov-On-Don		Russian Federation	344022
122	Leningrad Regional Clinical Hospital	Saint Petersburg		Russian Federation	194291
123	St-Petersburg Pavlov's State Medical University	Saint Petersburg		Russian Federation	197022
124	St-Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
125	Samara Regional Clinical Hospital M.I. Kalinin	Samara		Russian Federation	443095
126	St-Petersburg Pavlov's State Medical University	St. Petersburg		Russian Federation	197022
127	Yaroslavl Region State Budgetary Healthcare Institution Regional Clinical Hospital	Yaroslavl		Russian Federation	150062
128	Singapore General Hospital	Singapore		Singapore	169608
129	University Witwatersrand and Oncology	Johannesburg		South Africa	2193
130	Johannesburg Hospital, Department of Medical Oncology	Parktown		South Africa	2193
131	Clinical Haematology Unit - Department of Medicine	Soweto		South Africa	2013
132	Department of Cardiology, Chris Hani Baragwanath Hospital	Soweto		South Africa	2013
133	Department of Radiology, Chris Hani Baragwanath Hospital	Soweto		South Africa	2013
134	Hospital Universitari Clinic de Barcelona	Barcelona		Spain	08036
135	Hospital De La Princesa	Madrid		Spain	28006
136	Hospital Universitario La Paz	Madrid		Spain	28046
137	Hospital de Madrid Norte-Sanchinarro Centro Integral Oncologico	Madrid		Spain	28050
138	Complejo Hospitalario de Toledo- Servicio de Hematologia.	Toledo		Spain	45004
139	Hospital Clinico Universitario de Valencia (CHUV)	Valencia		Spain	46010
140	Changhua Christian Hospital	Changhua City		Taiwan	50006
141	National Taiwan University Hospital	Taipei TOC		Taiwan	100
142	Division of Hematology, Department of Medicine	Bangkoknoi	Bangkok	Thailand	10700
143	Hacettepe Universitesi Tip Fakultesi	Ankara	Sihhiye	Turkey	06100
144	Ankara Universitesi Tip Fakultesi Cebeci Hastanesi	Ankara		Turkey	06100
145	Gaziantep Universitesi Tip Fakultesi	Gaziantep		Turkey	27310
146	Cherkaskiy oblasniy onkologichniy dispanser	Cherkassy		Ukraine	18009
147	Clinical Assocation of Emergency Care	Dnipropetrovsk		Ukraine	49006
148	Clinical Diagnostic Laboratory of Komunalnyj Zaklad	Dnipropetrovsk		Ukraine	49102
149	Komunalnyj Zaklad "Dnipropetrovska Miska Bagatoprofilna Klinichna Likarnja #4"	Dnipropetrovsk		Ukraine	49102
150	Instytut Nevidkladnoi ta Vidnovnoi Hirurgii im. P.K. Husaka NAMN Ukrainy, Viddilennja Hematologii	Donetsk		Ukraine	83045
151	Oleksandrovska clinical hospital cardiological rehabilitation department	Kiev		Ukraine	01023
152	Miska klinichna likarnja # 9	Kyev		Ukraine	04112
153	Institut Klinichnoi Radiologii DU "Natsionalnyj Naukovyj Centr Radiacijnoi Medicini NAMN Ukraini"	Kyiv		Ukraine	03115
154	Institut Klinichnoi Radiologii Naukovogo Centru Radiacijnoi Medicini NAMN Ukraini	Kyiv		Ukraine	03115
155	Institut Klinichnoi Radiologii Naukovogo	Kyiv		Ukraine	03115
156	Ultrasaund Educational and Diagnostic Center	Lviv		Ukraine	79010
157	Instutut Patologii Krovi to Transfuziynoi Medicinu AMN Ukraini	Lviv		Ukraine	79044
158	Polyclinic of 5th Municipal Hospital	Lviv		Ukraine	79044
159	3rd Floor Centre for Clinical Haematology	Nottingham	EAST Midlands	United Kingdom	NG5 1PB
160	The Park Hospital	Nottingham	EAST Midlands	United Kingdom	NG5 8RX
161	Hammersmith Hospital Clinical Trial Units	Hammersmith	London	United Kingdom	W12 0HS
162	Good Hope Hospital	Birmingham	WEST Midlands	United Kingdom	B75 7RR
163	Birmingham Heartlands Hospital	Birmingham	WEST Midlands	United Kingdom	B9 5SS
164	Department of Haematology - Level 3, Bexley Wing	Leeds	WEST Yorkshire	United Kingdom	LS9 7TF
165	Department of Haematology	London		United Kingdom	SE1 9RT
166	Hammersmith Hospital	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Pfizer
• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00574873
• Other Study ID Numbers: 3160A4-3000; B1871008; 2007-003780-50
• First Posted: Dec 17, 2007
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Bosutinib; imatinib; CML
• Additional relevant MeSH terms: Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Period Title: Overall Study
STARTED	250	252
Treated	248	251
COMPLETED	12	1
NOT COMPLETED	238	251

Baseline Characteristics

Arm/Group Title	Bosutinib	Imatinib	Total
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.	Total of all reporting groups
Overall Participants	250	252	502
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (14.39)	45.6 (14.80)	46.5 (14.61)
Sex: Female, Male (Count of Participants)
Female	101 40.4%	117 46.4%	218 43.4%
Male	149 59.6%	135 53.6%	284 56.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Cytogenetic Response (CCyR) at Year 1
Description	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.
Time Frame	Year 1 (48 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - included all participants who were randomized to test article.

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	250	252
Number (95% Confidence Interval) [Percentage of Participants]	70.0 28%	68.3 27.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.667
	Comments	p-value was based on a Cochran Mantel Haenszel test for general association between treatment and responder stratification by Sokal risk group (low, intermediate, high) and region (1 to 3) as determined at time of randomization.
	Method	Stratified Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Major Molecular Response (MMR) at Year 1
Description	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.
Time Frame	Year 1 (48 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	250	252
Number (95% Confidence Interval) [Percentage of Participants]	38.0 15.2%	25.4 10.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	p-value was based on a Cochran Mantel Haenszel test for general association between treatment and responder stratification by Sokal risk group (low, intermediate, high) and region (1 to 3) as determined at time of randomization.
	Method	Stratified Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Kaplan-Meier Estimate of Probability of Retaining CCyR at 192 Weeks
Description	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.
Time Frame	192 weeks

Outcome Measure Data

Analysis Population Description

Subgroup of participants from ITT population who had CCyR.

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	197	204
Number (95% Confidence Interval) [Percentage of Participants]	92.9 37.2%	88.9 35.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio (95% confidence interval) based on the treatment effect (bosutinib compared with imatinib) in a stratified (by Sokal risk group and region at randomization) Cox model for the hazard of the respective event.

4. Secondary Outcome

Title	Kaplan-Meier Estimate of Probability of Retaining Complete Hematologic Response (CHR) at 192 Weeks
Description	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.
Time Frame	192 weeks

Outcome Measure Data

Analysis Population Description

Subgroup of participants from ITT population who had CHR.

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	219	242
Number (95% Confidence Interval) [Percentage of Participants]	91.6 36.6%	86.0 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.32 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio (95% confidence interval) based on the treatment effect (bosutinib compared with imatinib) in a stratified (by Sokal risk group and region at randomization) Cox model for the hazard of the respective event.

5. Secondary Outcome

Title	Kaplan-Meier Estimate of Probability of Retaining Derived MMR at 144 Weeks
Description	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.
Time Frame	144 weeks

Outcome Measure Data

Analysis Population Description

Subgroup of participants from ITT population who had MMR.

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	168	170
Number (95% Confidence Interval) [Percentage of Participants]	94.7 37.9%	98.0 38.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 95%; 0.90 to 11.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio (95% confidence interval) based on the treatment effect (bosutinib compared with imatinib) in a stratified (by Sokal risk group and region at randomization) Cox model for the hazard of the respective event.

6. Secondary Outcome

Title	Cumulative Incidence of On-Treatment Transformation to Accelerated Phase (AP) or Blast Phase (BP) at 192 Weeks
Description	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.
Time Frame	192 weeks

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bosutinib	Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.	Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
Measure Participants	250	252
Number (95% Confidence Interval) [Percentage of Participants]	1.6 0.6%	4.4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bosutinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.13 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio (95% confidence interval) is obtained from a Cox model for cause-specific hazard as a function of the covariate treatment (bosutinib compared with imatinib) with stratification by region and Sokal risk group at randomization.

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Bosutinib		Imatinib
Arm/Group Description	Bosutinib 500 milligram (mg) tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to bosutinib 600 mg tablet orally once daily or a reduction to bosutinib 300 mg tablet orally once daily.		Imatinib 400 mg tablet orally once daily up to 5 years or until treatment failure, unacceptable toxicity, death, withdrawal of consent. Dose adjustments, if needed, included an escalation to imatinib 600 mg tablet orally once daily or a reduction to imatinib 300 mg tablet orally once daily.
All Cause Mortality
	Bosutinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bosutinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/248 (36.3%)		57/251 (22.7%)
Blood and lymphatic system disorders
Thrombocytopenia	5/248 (2%)		7/251 (2.8%)
Anaemia	6/248 (2.4%)		8/251 (3.2%)
Neutropenia	2/248 (0.8%)		5/251 (2%)
Iron deficiency anaemia	1/248 (0.4%)		0/251 (0%)
Leukocytosis	1/248 (0.4%)		0/251 (0%)
Leukopenia	0/248 (0%)		1/251 (0.4%)
Cardiac disorders
Coronary artery disease	3/248 (1.2%)		0/251 (0%)
Arteriosclerosis coronary artery	1/248 (0.4%)		1/251 (0.4%)
Pericardial effusion	5/248 (2%)		0/251 (0%)
Angina pectoris	0/248 (0%)		1/251 (0.4%)
Atrial fibrillation	1/248 (0.4%)		0/251 (0%)
Atrioventricular block complete	0/248 (0%)		1/251 (0.4%)
Bundle branch block right	1/248 (0.4%)		0/251 (0%)
Cardiac failure	0/248 (0%)		1/251 (0.4%)
Cardiac failure congestive	2/248 (0.8%)		0/251 (0%)
Pericarditis	2/248 (0.8%)		0/251 (0%)
Ear and labyrinth disorders
Deafness unilateral	1/248 (0.4%)		0/251 (0%)
Vertigo	0/248 (0%)		1/251 (0.4%)
Endocrine disorders
Goitre	0/248 (0%)		1/251 (0.4%)
Eye disorders
Vitreous haemorrhage	0/248 (0%)		1/251 (0.4%)
Visual impairment	1/248 (0.4%)		1/251 (0.4%)
Cataract	1/248 (0.4%)		1/251 (0.4%)
Glaucoma	1/248 (0.4%)		0/251 (0%)
Retinopathy	1/248 (0.4%)		0/251 (0%)
Gastrointestinal disorders
Diarrhoea	9/248 (3.6%)		0/251 (0%)
Pancreatitis	1/248 (0.4%)		3/251 (1.2%)
Vomiting	3/248 (1.2%)		2/251 (0.8%)
Gastritis	2/248 (0.8%)		0/251 (0%)
Abdominal pain lower	0/248 (0%)		1/251 (0.4%)
Anal fistula	1/248 (0.4%)		0/251 (0%)
Enteritis	1/248 (0.4%)		0/251 (0%)
Gastric haemorrhage	1/248 (0.4%)		0/251 (0%)
Gastric ulcer	2/248 (0.8%)		0/251 (0%)
Gastrointestinal disorder	1/248 (0.4%)		0/251 (0%)
Gastrointestinal necrosis	1/248 (0.4%)		0/251 (0%)
Mesenteric artery embolism	1/248 (0.4%)		0/251 (0%)
Nausea	1/248 (0.4%)		2/251 (0.8%)
Pancreatitis acute	1/248 (0.4%)		0/251 (0%)
Peritoneal haemorrhage	0/248 (0%)		1/251 (0.4%)
Rectal haemorrhage	0/248 (0%)		1/251 (0.4%)
Small intestinal obstruction	1/248 (0.4%)		1/251 (0.4%)
Upper gastrointestinal haemorrhage	0/248 (0%)		1/251 (0.4%)
Alcoholic pancreatitis	0/248 (0%)		1/251 (0.4%)
Faecaloma	1/248 (0.4%)		0/251 (0%)
Proctitis	0/248 (0%)		1/251 (0.4%)
Rectal polyp	1/248 (0.4%)		0/251 (0%)
Umbilical hernia	1/248 (0.4%)		0/251 (0%)
Gastritis haemorrhagic	1/248 (0.4%)		0/251 (0%)
Abdominal pain	3/248 (1.2%)		1/251 (0.4%)
General disorders
Pyrexia	7/248 (2.8%)		2/251 (0.8%)
Generalised oedema	0/248 (0%)		1/251 (0.4%)
Oedema	0/248 (0%)		1/251 (0.4%)
Pain	1/248 (0.4%)		0/251 (0%)
Disease progression	0/248 (0%)		1/251 (0.4%)
Sudden death	1/248 (0.4%)		0/251 (0%)
Hepatobiliary disorders
Drug-induced liver injury	1/248 (0.4%)		0/251 (0%)
Cholecystitis chronic	1/248 (0.4%)		0/251 (0%)
Cholelithiasis	1/248 (0.4%)		1/251 (0.4%)
Allergic hepatitis	0/248 (0%)		1/251 (0.4%)
Cholecystitis	0/248 (0%)		1/251 (0.4%)
Gallbladder polyp	1/248 (0.4%)		0/251 (0%)
Immune system disorders
Anaphylactic shock	2/248 (0.8%)		0/251 (0%)
Drug hypersensitivity	1/248 (0.4%)		0/251 (0%)
Infections and infestations
Pneumonia	8/248 (3.2%)		1/251 (0.4%)
Bronchitis	2/248 (0.8%)		1/251 (0.4%)
Gastroenteritis	3/248 (1.2%)		1/251 (0.4%)
Infected dermal cyst	1/248 (0.4%)		1/251 (0.4%)
Appendicitis perforated	1/248 (0.4%)		0/251 (0%)
Atypical pneumonia	1/248 (0.4%)		0/251 (0%)
Bronchiolitis	1/248 (0.4%)		0/251 (0%)
Cellulitis	2/248 (0.8%)		0/251 (0%)
Clostridium difficile infection	1/248 (0.4%)		0/251 (0%)
Dengue fever	0/248 (0%)		1/251 (0.4%)
Enterocolitis infectious	1/248 (0.4%)		0/251 (0%)
Infection	1/248 (0.4%)		0/251 (0%)
Lobar pneumonia	1/248 (0.4%)		0/251 (0%)
Pharyngitis	1/248 (0.4%)		0/251 (0%)
Salmonella bacteraemia	1/248 (0.4%)		0/251 (0%)
Salpingo-oophoritis	1/248 (0.4%)		0/251 (0%)
Tooth abscess	1/248 (0.4%)		0/251 (0%)
Tooth infection	1/248 (0.4%)		0/251 (0%)
Arthritis bacterial	1/248 (0.4%)		0/251 (0%)
Cellulitis of male external genital organ	1/248 (0.4%)		0/251 (0%)
Dermatitis infected	1/248 (0.4%)		0/251 (0%)
Eczema infected	1/248 (0.4%)		0/251 (0%)
Gastroenteritis rotavirus	0/248 (0%)		1/251 (0.4%)
Gastrointestinal infection	1/248 (0.4%)		0/251 (0%)
Hepatitis A	1/248 (0.4%)		0/251 (0%)
Hepatitis B	0/248 (0%)		1/251 (0.4%)
Hepatitis E	0/248 (0%)		1/251 (0.4%)
Infectious colitis	1/248 (0.4%)		0/251 (0%)
Intrauterine infection	0/248 (0%)		1/251 (0.4%)
Malaria	1/248 (0.4%)		0/251 (0%)
Parotitis	0/248 (0%)		1/251 (0.4%)
Pharyngotonsillitis	1/248 (0.4%)		0/251 (0%)
Salmonellosis	1/248 (0.4%)		0/251 (0%)
Subcutaneous abscess	0/248 (0%)		1/251 (0.4%)
Urinary tract infection	1/248 (0.4%)		0/251 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/248 (0%)		1/251 (0.4%)
Concussion	0/248 (0%)		1/251 (0.4%)
Contusion	1/248 (0.4%)		1/251 (0.4%)
Exposure via father	0/248 (0%)		1/251 (0.4%)
Facial bones fracture	1/248 (0.4%)		0/251 (0%)
Gun shot wound	0/248 (0%)		1/251 (0.4%)
Laceration	0/248 (0%)		1/251 (0.4%)
Limb injury	0/248 (0%)		1/251 (0.4%)
Lower limb fracture	1/248 (0.4%)		0/251 (0%)
Investigations
Alanine aminotransferase increased	7/248 (2.8%)		0/251 (0%)
Aspartate aminotransferase increased	4/248 (1.6%)		0/251 (0%)
Blood creatinine increased	1/248 (0.4%)		0/251 (0%)
Blood lactate dehydrogenase increased	1/248 (0.4%)		0/251 (0%)
Platelet count decreased	1/248 (0.4%)		0/251 (0%)
Blood creatine phosphokinase increased	0/248 (0%)		1/251 (0.4%)
Hepatitis C antibody positive	0/248 (0%)		1/251 (0.4%)
Lipase increased	1/248 (0.4%)		0/251 (0%)
Metabolism and nutrition disorders
Dehydration	2/248 (0.8%)		0/251 (0%)
Hypokalaemia	0/248 (0%)		1/251 (0.4%)
Cell death	0/248 (0%)		1/251 (0.4%)
Fluid overload	0/248 (0%)		1/251 (0.4%)
Gout	1/248 (0.4%)		0/251 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/248 (0%)		1/251 (0.4%)
Myalgia	0/248 (0%)		1/251 (0.4%)
Back pain	2/248 (0.8%)		2/251 (0.8%)
Intervertebral disc disorder	2/248 (0.8%)		0/251 (0%)
Osteoarthritis	0/248 (0%)		1/251 (0.4%)
Pain in extremity	0/248 (0%)		1/251 (0.4%)
Spinal osteoarthritis	1/248 (0.4%)		0/251 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast cell crisis	1/248 (0.4%)		1/251 (0.4%)
Chronic myeloid leukaemia transformation	0/248 (0%)		1/251 (0.4%)
Malignant melanoma	1/248 (0.4%)		0/251 (0%)
Metastases to bone	0/248 (0%)		1/251 (0.4%)
Adenocarcinoma gastric	2/248 (0.8%)		0/251 (0%)
Basal cell carcinoma	1/248 (0.4%)		1/251 (0.4%)
Bladder squamous cell carcinoma stage unspecified	1/248 (0.4%)		0/251 (0%)
Blast crisis in myelogenous leukaemia	0/248 (0%)		1/251 (0.4%)
Chronic lymphocytic leukaemia	0/248 (0%)		1/251 (0.4%)
Invasive ductal breast carcinoma	1/248 (0.4%)		0/251 (0%)
Rectal cancer recurrent	0/248 (0%)		1/251 (0.4%)
Renal cancer	0/248 (0%)		1/251 (0.4%)
Nervous system disorders
Cerebral haemorrhage	1/248 (0.4%)		0/251 (0%)
Cerebrovascular accident	0/248 (0%)		1/251 (0.4%)
Carotid artery aneurysm	0/248 (0%)		1/251 (0.4%)
Carpal tunnel syndrome	1/248 (0.4%)		0/251 (0%)
Headache	1/248 (0.4%)		0/251 (0%)
Lumbar radiculopathy	0/248 (0%)		1/251 (0.4%)
Central nervous system haemorrhage	0/248 (0%)		1/251 (0.4%)
Dizziness	1/248 (0.4%)		0/251 (0%)
Seizure	2/248 (0.8%)		0/251 (0%)
Syncope	1/248 (0.4%)		1/251 (0.4%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	2/248 (0.8%)		1/251 (0.4%)
Psychiatric disorders
Depression	1/248 (0.4%)		1/251 (0.4%)
Dissociative disorder	1/248 (0.4%)		0/251 (0%)
Anxiety	1/248 (0.4%)		0/251 (0%)
Disorientation	1/248 (0.4%)		0/251 (0%)
Hallucination	1/248 (0.4%)		0/251 (0%)
Renal and urinary disorders
Urinary retention	0/248 (0%)		1/251 (0.4%)
Renal failure	1/248 (0.4%)		0/251 (0%)
Acute kidney injury	5/248 (2%)		0/251 (0%)
Calculus bladder	0/248 (0%)		1/251 (0.4%)
Calculus urinary	1/248 (0.4%)		0/251 (0%)
Haematuria	1/248 (0.4%)		0/251 (0%)
Nephrotic syndrome	0/248 (0%)		1/251 (0.4%)
Reproductive system and breast disorders
Menstruation irregular	0/248 (0%)		1/251 (0.4%)
Metrorrhagia	1/248 (0.4%)		0/251 (0%)
Ovarian cyst	1/248 (0.4%)		0/251 (0%)
Vaginal haemorrhage	0/248 (0%)		1/251 (0.4%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	2/248 (0.8%)		0/251 (0%)
Pleural effusion	11/248 (4.4%)		0/251 (0%)
Acute pulmonary oedema	2/248 (0.8%)		0/251 (0%)
Bronchiectasis	1/248 (0.4%)		0/251 (0%)
Bronchitis chronic	1/248 (0.4%)		0/251 (0%)
Chronic obstructive pulmonary disease	1/248 (0.4%)		0/251 (0%)
Lung disorder	1/248 (0.4%)		0/251 (0%)
Pleuritic pain	1/248 (0.4%)		0/251 (0%)
Vocal cord polyp	1/248 (0.4%)		0/251 (0%)
Pneumonitis	1/248 (0.4%)		0/251 (0%)
Pulmonary hypertension	2/248 (0.8%)		0/251 (0%)
Skin and subcutaneous tissue disorders
Rash	1/248 (0.4%)		0/251 (0%)
Rash maculo-papular	1/248 (0.4%)		0/251 (0%)
Social circumstances
Pregnancy of partner	1/248 (0.4%)		0/251 (0%)
Surgical and medical procedures
Cyst removal	1/248 (0.4%)		0/251 (0%)
Vascular disorders
Haemorrhage	1/248 (0.4%)		0/251 (0%)
Hypertension	1/248 (0.4%)		0/251 (0%)
Other (Not Including Serious) Adverse Events
	Bosutinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	235/248 (94.8%)		238/251 (94.8%)
Blood and lymphatic system disorders
Thrombocytopenia	70/248 (28.2%)		72/251 (28.7%)
Anaemia	63/248 (25.4%)		58/251 (23.1%)
Neutropenia	35/248 (14.1%)		78/251 (31.1%)
Leukopenia	24/248 (9.7%)		57/251 (22.7%)
Lymphopenia	8/248 (3.2%)		16/251 (6.4%)
Eye disorders
Eyelid oedema	3/248 (1.2%)		20/251 (8%)
Periorbital oedema	4/248 (1.6%)		38/251 (15.1%)
Gastrointestinal disorders
Diarrhoea	174/248 (70.2%)		69/251 (27.5%)
Nausea	87/248 (35.1%)		93/251 (37.1%)
Vomiting	86/248 (34.7%)		42/251 (16.7%)
Abdominal pain upper	38/248 (15.3%)		21/251 (8.4%)
Abdominal pain	34/248 (13.7%)		19/251 (7.6%)
Dyspepsia	22/248 (8.9%)		17/251 (6.8%)
Abdominal distension	8/248 (3.2%)		13/251 (5.2%)
Constipation	13/248 (5.2%)		12/251 (4.8%)
Toothache	13/248 (5.2%)		4/251 (1.6%)
General disorders
Fatigue	38/248 (15.3%)		33/251 (13.1%)
Pyrexia	44/248 (17.7%)		34/251 (13.5%)
Oedema peripheral	14/248 (5.6%)		32/251 (12.7%)
Asthenia	23/248 (9.3%)		23/251 (9.2%)
Oedema	14/248 (5.6%)		16/251 (6.4%)
Face oedema	5/248 (2%)		15/251 (6%)
Infections and infestations
Upper respiratory tract infection	33/248 (13.3%)		24/251 (9.6%)
Nasopharyngitis	26/248 (10.5%)		28/251 (11.2%)
Bronchitis	14/248 (5.6%)		14/251 (5.6%)
Influenza	23/248 (9.3%)		11/251 (4.4%)
Pharyngitis	13/248 (5.2%)		4/251 (1.6%)
Investigations
Alanine aminotransferase increased	85/248 (34.3%)		27/251 (10.8%)
Aspartate aminotransferase increased	70/248 (28.2%)		28/251 (11.2%)
Lipase increased	47/248 (19%)		29/251 (11.6%)
Blood creatine phosphokinase increased	23/248 (9.3%)		58/251 (23.1%)
Blood alkaline phosphatase increased	18/248 (7.3%)		11/251 (4.4%)
Blood creatinine increased	14/248 (5.6%)		16/251 (6.4%)
Weight increased	6/248 (2.4%)		24/251 (9.6%)
Gamma-glutamyltransferase increased	16/248 (6.5%)		5/251 (2%)
Amylase increased	27/248 (10.9%)		16/251 (6.4%)
Haemoglobin decreased	5/248 (2%)		14/251 (5.6%)
Weight decreased	16/248 (6.5%)		3/251 (1.2%)
Metabolism and nutrition disorders
Hypophosphataemia	26/248 (10.5%)		55/251 (21.9%)
Decreased appetite	22/248 (8.9%)		8/251 (3.2%)
Hypokalaemia	8/248 (3.2%)		22/251 (8.8%)
Hyperglycaemia	6/248 (2.4%)		16/251 (6.4%)
Hypocalcaemia	11/248 (4.4%)		17/251 (6.8%)
Hypomagnesaemia	5/248 (2%)		16/251 (6.4%)
Musculoskeletal and connective tissue disorders
Muscle spasms	13/248 (5.2%)		61/251 (24.3%)
Arthralgia	24/248 (9.7%)		34/251 (13.5%)
Bone pain	10/248 (4%)		25/251 (10%)
Myalgia	16/248 (6.5%)		31/251 (12.4%)
Pain in extremity	18/248 (7.3%)		24/251 (9.6%)
Back pain	20/248 (8.1%)		21/251 (8.4%)
Nervous system disorders
Headache	33/248 (13.3%)		34/251 (13.5%)
Dizziness	23/248 (9.3%)		28/251 (11.2%)
Psychiatric disorders
Insomnia	10/248 (4%)		13/251 (5.2%)
Respiratory, thoracic and mediastinal disorders
Cough	30/248 (12.1%)		31/251 (12.4%)
Dyspnoea	24/248 (9.7%)		9/251 (3.6%)
Oropharyngeal pain	12/248 (4.8%)		15/251 (6%)
Pleural effusion	14/248 (5.6%)		1/251 (0.4%)
Skin and subcutaneous tissue disorders
Rash	64/248 (25.8%)		49/251 (19.5%)
Pruritus	16/248 (6.5%)		16/251 (6.4%)
Alopecia	13/248 (5.2%)		9/251 (3.6%)
Vascular disorders
Hypertension	20/248 (8.1%)		14/251 (5.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.