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

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ClinicalTrials.gov Identifier: NCT02130557
Recruitment Status : Completed
First Posted : May 5, 2014
Results First Posted : November 14, 2018
Last Update Posted : May 18, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
Interventions Drug: Bosutinib
Drug: Imatinib
Enrollment 536
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description Participants with Philadelphia chromosome-positive chronic myeloid leukemia (CML) received bosutinib tablets at a dose of 400 milligram (mg), orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Period Title: Overall Study
Started 268 268
Treated 268 265
mITT Population 246 241
Completed 232 231
Not Completed 36 37
Reason Not Completed
Withdrawal by Subject             12             12
Investigator Request             0             2
Deceased             14             14
Lost to Follow-up             6             7
Other             2             1
Missing             2             1
Arm/Group Title Bosutinib Imatinib Total
Hide Arm/Group Description Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Total of all reporting groups
Overall Number of Baseline Participants 268 268 536
Hide Baseline Analysis Population Description
Intent-to-treat population: All randomized participants with study drug assignments designated according to initial randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 268 participants 268 participants 536 participants
50.8  (15.40) 50.9  (14.43) 50.9  (14.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 268 participants 536 participants
Female
112
  41.8%
113
  42.2%
225
  42.0%
Male
156
  58.2%
155
  57.8%
311
  58.0%
1.Primary Outcome
Title Percentage of Participants With Major Molecular Response (MMR) at Month 12
Hide Description 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.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population included all randomized participants with Philadelphia chromosome positive (Ph+) CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies greater than (>) 0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.2
(40.9 to 53.4)
36.9
(30.8 to 43.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments A total sample size of 500 Ph+ participants is required for the study to provide >= 90% power to detect at least 15% difference (assuming 25% in the imatinib vs 40% in the bosutinib arm) in the MMR rates at 12 months (48 weeks) with a 1-sided alpha of 2.5%, and 2 interim futility analyses at 33% and 66% of patients with adequate follow-up with early stopping for futility only (non-binding, O'Brien-Fleming analog beta spending function).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0100
Comments 1-sided p-value based on CMH test for general association between treatment and response with stratification by sokal risk group (low, intermediate, high) and region (1-3) at time of randomization. Statistical significance threshold: 1-sided 0.025.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.547
Confidence Interval (2-Sided) 95%
1.072 to 2.233
Estimation Comments 95% Confidence Interval (CI) for the odds ratio adjusted for sokal risk group and region are based on Mantel-Haenszel confidence limits.
2.Secondary Outcome
Title Percentage of Participants With Major Molecular Response (MMR) Up to Month 18
Hide Description 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.
Time Frame Up to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.0
(54.9 to 67.1)
52.7
(46.4 to 59.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments If the primary analysis was significant, each member of the short-term family (CCyR by Month 12, MMR by Month 18) was tested via Bonferroni's procedure at the 1-sided level of 0.0125.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0303
Comments 1-sided p-value based on CMH test for general association between treatment and response with stratification by sokal risk group (low, intermediate, high) and region (1-3) at time of randomization. Statistical significance threshold: 1-sided 0.0125.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.418
Confidence Interval (2-Sided) 95%
0.986 to 2.037
Estimation Comments 95% CI for the odds ratio adjusted for sokal risk group and region are based on Mantel-Haenszel confidence limits.
3.Secondary Outcome
Title Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48
Hide Description 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.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization and who achieved MMR (responders). Here, "Overall number of Participants Analyzed (N)" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 182 158
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.2
(86.8 to 95.4)
92.0
(85.9 to 95.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.49 to 2.44
Estimation Comments Hazard ratio (95% CIs) are based on the treatment effect (Bosutinib compared with Imatinib) in a stratified (by Sokal risk group at randomization and region) Cox proportional hazards model for the hazard of the respective event.
4.Secondary Outcome
Title Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12
Hide Description 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.
Time Frame Up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
77.2
(72.0 to 82.5)
66.4
(60.4 to 72.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments If the primary analysis was significant, each member of the short-term family (CCyR by Month 12, MMR by Month 18) was tested via Bonferroni's procedure at the 1-sided level of 0.0125.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments 1-sided p-value based on CMH test for general association between treatment and response with stratification by sokal risk group (low, intermediate, high) and region (1-3) at time of randomization. Statistical significance threshold: 1-sided 0.0125.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.740
Confidence Interval (2-Sided) 95%
1.160 to 2.610
Estimation Comments 95% CI for the odds ratio adjusted for sokal risk group and region are based on Mantel-Haenszel confidence limits.
5.Secondary Outcome
Title Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48
Hide Description 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.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization and who achieved CCyR (responders). Here, "N" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 205 185
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
97.4
(93.9 to 98.9)
93.7
(88.9 to 96.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.14 to 1.13
Estimation Comments Hazard ratio (95% CIs) are based on the treatment effect (Bosutinib compared with Imatinib) in a stratified (by Sokal risk group at randomization and region) Cox proportional hazards model for the hazard of the respective event.
6.Secondary Outcome
Title Cumulative Incidence of Event Free Survival (EFS) Events
Hide Description 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.
Time Frame Up to Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.9
(4.2 to 10.5)
10.4
(6.9 to 14.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments If each member of the short-term family (CCyR by Month 12, MMR by Month 18) was significant, EFS and OS were tested sequentially via the Holm's testing procedure at the 1-sided family wise level of 0.025. If one member of the short-term family was significant, EFS and OS were tested sequentially at 1-sided 0.0125.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0749
Comments 1-sided p-value based on Gray's test for comparing cumulative incidence function between treatment arms stratified by sokal risk group (low, intermediate, high) and region (1-3). Statistical significance threshold: 1-sided 0.0125.
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.35 to 1.17
Estimation Comments The hazard ratio (95% CIs) are based on the proportional subdistribution hazards model stratified by Sokal risk group and region.
7.Secondary Outcome
Title Overall Survival (OS) Rate
Hide Description 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.
Time Frame Up to Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Ph+ CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.9
(91.1 to 97.0)
94.0
(90.1 to 96.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments If each member of the short-term family (CCyR by Month 12, MMR by Month 18) was significant, EFS and OS were tested sequentially via the Holm's testing procedure at the 1-sided family wise level of 0.025. If one member of the short-term family was significant, EFS and OS were tested sequentially at 1-sided 0.0125.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2827
Comments 1-sided p-value based on log-rank test for comparing survival curves between treatment arms stratified by sokal risk group and region. OS was not tested as EFS was not significant.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.37 to 1.73
Estimation Comments The hazard ratio (95% CIs) are based on the treatment effect (Bosutinib compared with Imatinib) in a stratified (by Sokal risk group at randomization and region) Cox proportional hazards model for the hazard of the respective event.
8.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR) of Bosutinib
Hide Description CCyR was based on the prevalence of Ph+ metaphases among cells in metaphase on a 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. Trough plasma concentration of participants who had CCyR are presented in this outcome measure.
Time Frame Pre-dose on Days 28, 56 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here, "N" signifies number of participants evaluable for this outcome measure and "number analyzed (n)" signifies participants evaluable at specified time points only. Data for this outcome measure was not planned to be collected and analyzed for Imatinib arm as pre-specified in the protocol.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 191
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Day 28 Number Analyzed 181 participants
71.282  (46.0545)
Day 56 Number Analyzed 184 participants
73.069  (45.1349)
Day 84 Number Analyzed 184 participants
83.973  (64.3206)
9.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Major Molecular Response (MMR) of Bosutinib
Hide Description 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) by quantitative RT-qPCR. Trough plasma concentration of participants who had MMR are presented in this outcome measure.
Time Frame Pre-dose on Days 28, 56 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here, "N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only. Data for this outcome measure was not planned to be collected and analyzed for Imatinib arm as pre-specified in the protocol.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 141
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28 Number Analyzed 140 participants
75.050  (51.9551)
Day 56 Number Analyzed 140 participants
78.437  (43.6019)
Day 84 Number Analyzed 141 participants
91.081  (72.1500)
10.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs) of Bosutinib
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 1 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.
Time Frame Pre-dose on Days 28, 56 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here, "N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only. Data for this outcome measure was not planned to be collected and analyzed for Imatinib arm as pre-specified in the protocol.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 177
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28: Diarrhea Number Analyzed 177 participants
69.402  (55.5005)
Day 28: Thrombocytopenia Number Analyzed 60 participants
63.529  (40.9949)
Day 28: Rash Number Analyzed 84 participants
74.779  (60.6257)
Day 28: Nausea Number Analyzed 86 participants
66.011  (42.6437)
Day 28: Vomiting Number Analyzed 44 participants
71.684  (60.7208)
Day 56: Diarrhea Number Analyzed 172 participants
68.834  (42.6621)
Day 56: Thrombocytopenia Number Analyzed 61 participants
65.327  (43.2859)
Day 56: Rash Number Analyzed 84 participants
70.016  (38.7506)
Day 56: Nausea Number Analyzed 85 participants
61.626  (44.4007)
Day 56: Vomiting Number Analyzed 40 participants
65.980  (45.9064)
Day 84: Diarrhea Number Analyzed 165 participants
81.269  (64.6462)
Day 84: Thrombocytopenia Number Analyzed 63 participants
71.585  (33.6674)
Day 84: Rash Number Analyzed 85 participants
89.080  (69.5237)
Day 84: Nausea Number Analyzed 80 participants
77.702  (61.6179)
Day 84: Vomiting Number Analyzed 41 participants
86.949  (55.3041)
11.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs) of Bosutinib
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on NCI CTCAE version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 3 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.
Time Frame Pre-dose on Days 28, 56 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here, "N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only. Data for this outcome measure was not planned to be collected and analyzed for Imatinib arm as pre-specified in the protocol.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28: Diarrhea Number Analyzed 19 participants
87.769  (102.6181)
Day 28: Thrombocytopenia Number Analyzed 23 participants
49.220  (36.3461)
Day 28: Rash Number Analyzed 4 participants
71.150  (43.3246)
Day 28: Vomiting Number Analyzed 3 participants
14.663  (21.5799)
Day 56: Diarrhea Number Analyzed 16 participants
68.513  (45.2672)
Day 56: Thrombocytopenia Number Analyzed 24 participants
56.853  (34.3892)
Day 56: Rash Number Analyzed 4 participants
58.925  (18.8656)
Day 56: Vomiting Number Analyzed 1 participants
38.200 [1]   (NA)
Day 84: Diarrhea Number Analyzed 17 participants
76.782  (46.3006)
Day 84: Thrombocytopenia Number Analyzed 23 participants
67.623  (35.3084)
Day 84: Rash Number Analyzed 3 participants
83.967  (19.2542)
Day 84: Vomiting Number Analyzed 1 participants
12.400 [1]   (NA)
[1]
As only 1 participant was analyzed, standard deviation could not be calculated.
12.Other Pre-specified Outcome
Title Number of Participants With Vital Signs Abnormalities
Hide Description Criteria for vital signs abnormalities: systolic blood pressure <80 millimeter of mercury (mmHg), >210 mmHg; diastolic blood pressure <40 mmHg, >130 mmHg; heart rate <40 beats per minute (bpm), >150 bpm; temperature <32 degree celsius, >40 degree celsius; weight >=10% increase from baseline, >=10% decrease from baseline. The number of participants with any vital sign abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article until the last date of test article +28 days.
Time Frame Baseline up to end of treatment (up to Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received. Here, "N" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 262 263
Measure Type: Count of Participants
Unit of Measure: Participants
107
  40.8%
109
  41.4%
13.Other Pre-specified Outcome
Title Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03
Hide Description Laboratory parameters included hematological (haemoglobin, lymphocytes [absolute], neutrophils [absolute], platelets and leukocytes) and biochemistry (albumin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, amylase, bilirubin, creatinine kinase, calcium, creatinine, glucose, potassium, lipase, magnesium, phosphate, sodium, urate) parameters. Abnormalities in laboratory tests were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. The number of participants with laboratory test abnormalities were reported.
Time Frame Baseline up to end of treatment (up to Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
6
   2.2%
7
   2.6%
Grade 2
67
  25.0%
59
  22.3%
Grade 3
133
  49.6%
154
  58.1%
Grade 4
61
  22.8%
45
  17.0%
14.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Hide Description Criteria for ECG abnormalities included heart rate: increase of >15 bpm from baseline value and >=120 bpm, decrease of >15 bpm from baseline value and <=45 bpm; PR interval: change of >=20 msec from baseline value and >=220 milliseconds (msec); QRS interval >=120 msec; QTcB interval >500 msec, increase of >60 msec from baseline; >450 msec (Men) or >470 msec (Women). QT interval using Fridericia's correction (QTcF) >500 msec, increase of >60 msec from baseline, >450 msec (Men) or >470 msec (Women). The number of participants with ECG abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article up until the last date of test article +28 days.
Time Frame Baseline up to end of treatment (up to Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received. Here, "N" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 266 262
Measure Type: Count of Participants
Unit of Measure: Participants
16
   6.0%
13
   5.0%
15.Other Pre-specified Outcome
Title Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time Frame Baseline up to end of treatment (up to Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
68
  25.4%
38
  14.3%
16.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events by National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.0)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE version 4.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 60 months that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.
Time Frame Baseline up to end of treatment (up to Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
7
   2.6%
24
   9.1%
Grade 2
61
  22.8%
86
  32.5%
Grade 3
144
  53.7%
120
  45.3%
Grade 4
50
  18.7%
28
  10.6%
Grade 5
3
   1.1%
4
   1.5%
Time Frame From first dose of drug up to 28 days after last dose (up to Month 60)
Adverse Event Reporting Description All-cause mortality: The total number of deaths occurred during study (from randomization and up to month 60) are reported for all randomized participants, not only for treated participants, and included deaths which occurred after 28 days post last study drug dose. Serious AEs and other AEs: Analysis performed on safety population. The safety population included all participants, regardless of Philadelphia chromosome or transcript status, who received at least 1 dose of study medication.
 
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
All-Cause Mortality
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   14/268 (5.22%)   14/268 (5.22%) 
Hide Serious Adverse Events
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   98/268 (36.57%)   68/265 (25.66%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/268 (0.37%)  3/265 (1.13%) 
Thrombocytopenia * 1  2/268 (0.75%)  1/265 (0.38%) 
Febrile neutropenia * 1  0/268 (0.00%)  2/265 (0.75%) 
Agranulocytosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Haemolysis * 1  0/268 (0.00%)  1/265 (0.38%) 
Haemolytic anaemia * 1  0/268 (0.00%)  1/265 (0.38%) 
Cardiac disorders     
Myocardial ischaemia * 1  4/268 (1.49%)  0/265 (0.00%) 
Atrial fibrillation * 1  2/268 (0.75%)  1/265 (0.38%) 
Cardiac failure acute * 1  2/268 (0.75%)  0/265 (0.00%) 
Coronary artery disease * 1  2/268 (0.75%)  0/265 (0.00%) 
Pericarditis * 1  2/268 (0.75%)  0/265 (0.00%) 
Angina pectoris * 1  1/268 (0.37%)  0/265 (0.00%) 
Pericardial effusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Acute coronary syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Acute myocardial infarction * 1  1/268 (0.37%)  0/265 (0.00%) 
Atrial thrombosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Cardiac failure * 1  1/268 (0.37%)  0/265 (0.00%) 
Cardiac failure congestive * 1  1/268 (0.37%)  0/265 (0.00%) 
Cardio-respiratory arrest * 1  1/268 (0.37%)  0/265 (0.00%) 
Coronary artery occlusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Pleuropericarditis * 1  1/268 (0.37%)  0/265 (0.00%) 
Sinus node dysfunction * 1  1/268 (0.37%)  0/265 (0.00%) 
Supraventricular tachycardia * 1  1/268 (0.37%)  0/265 (0.00%) 
Congenital, familial and genetic disorders     
Hydrocele * 1  1/268 (0.37%)  0/265 (0.00%) 
Ear and labyrinth disorders     
Vertigo positional * 1  1/268 (0.37%)  0/265 (0.00%) 
Endocrine disorders     
Thyroid disorder * 1  0/268 (0.00%)  1/265 (0.38%) 
Eye disorders     
Eye haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Ocular hypertension * 1  1/268 (0.37%)  0/265 (0.00%) 
Retinal vein occlusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Retinopathy * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  5/268 (1.87%)  1/265 (0.38%) 
Gastritis * 1  1/268 (0.37%)  1/265 (0.38%) 
Pancreatitis acute * 1  1/268 (0.37%)  1/265 (0.38%) 
Necrotising oesophagitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Abdominal pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Abdominal pain upper * 1  0/268 (0.00%)  1/265 (0.38%) 
Abdominal wall haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Anal fissure * 1  1/268 (0.37%)  0/265 (0.00%) 
Colitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Diverticulum intestinal * 1  1/268 (0.37%)  0/265 (0.00%) 
Duodenal ulcer * 1  1/268 (0.37%)  0/265 (0.00%) 
Food poisoning * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastric ulcer * 1  0/268 (0.00%)  1/265 (0.38%) 
Gastrointestinal haemorrhage * 1  0/268 (0.00%)  1/265 (0.38%) 
Haemorrhoids * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypoaesthesia oral * 1  0/268 (0.00%)  1/265 (0.38%) 
Inguinal hernia * 1  1/268 (0.37%)  0/265 (0.00%) 
Intra-abdominal haematoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Large intestine polyp * 1  0/268 (0.00%)  1/265 (0.38%) 
Oedematous pancreatitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Pancreatitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Rectal haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Small intestinal obstruction * 1  1/268 (0.37%)  0/265 (0.00%) 
General disorders     
Pyrexia * 1  5/268 (1.87%)  1/265 (0.38%) 
General physical health deterioration * 1  0/268 (0.00%)  1/265 (0.38%) 
Hyperthermia * 1  0/268 (0.00%)  1/265 (0.38%) 
Implant site haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Non-cardiac chest pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Swelling face * 1  0/268 (0.00%)  1/265 (0.38%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  2/268 (0.75%)  0/265 (0.00%) 
Cholelithiasis * 1  0/268 (0.00%)  2/265 (0.75%) 
Hepatitis * 1  2/268 (0.75%)  0/265 (0.00%) 
Hepatotoxicity * 1  2/268 (0.75%)  0/265 (0.00%) 
Cholecystitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Portal vein thrombosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Immune system disorders     
Drug hypersensitivity * 1  1/268 (0.37%)  0/265 (0.00%) 
Infections and infestations     
Pneumonia * 1  8/268 (2.99%)  5/265 (1.89%) 
Gastroenteritis * 1  6/268 (2.24%)  1/265 (0.38%) 
Cellulitis * 1  3/268 (1.12%)  2/265 (0.75%) 
Influenza * 1  1/268 (0.37%)  2/265 (0.75%) 
Sepsis * 1  0/268 (0.00%)  3/265 (1.13%) 
Urinary tract infection * 1  1/268 (0.37%)  2/265 (0.75%) 
Abscess * 1  1/268 (0.37%)  1/265 (0.38%) 
Abscess limb * 1  0/268 (0.00%)  2/265 (0.75%) 
Appendicitis * 1  0/268 (0.00%)  2/265 (0.75%) 
Appendicitis perforated * 1  0/268 (0.00%)  1/265 (0.38%) 
Bacteraemia * 1  1/268 (0.37%)  0/265 (0.00%) 
Bronchitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Candida pneumonia * 1  1/268 (0.37%)  0/265 (0.00%) 
Cholecystitis infective * 1  1/268 (0.37%)  0/265 (0.00%) 
Fournier's gangrene * 1  0/268 (0.00%)  1/265 (0.38%) 
Hepatitis E * 1  1/268 (0.37%)  0/265 (0.00%) 
Infected dermal cyst * 1  0/268 (0.00%)  1/265 (0.38%) 
Infective pericardial effusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Liver abscess * 1  0/268 (0.00%)  1/265 (0.38%) 
Lower respiratory tract infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Meningococcal sepsis * 1  0/268 (0.00%)  1/265 (0.38%) 
Neutropenic infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Orchitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Oropharyngitis fungal * 1  1/268 (0.37%)  0/265 (0.00%) 
Pelvic abscess * 1  1/268 (0.37%)  0/265 (0.00%) 
Periorbital cellulitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Pyelonephritis * 1  1/268 (0.37%)  0/265 (0.00%) 
Respiratory tract infection viral * 1  0/268 (0.00%)  1/265 (0.38%) 
Splenic infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Upper respiratory tract infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/268 (0.37%)  1/265 (0.38%) 
Femoral neck fracture * 1  2/268 (0.75%)  0/265 (0.00%) 
Hip fracture * 1  0/268 (0.00%)  1/265 (0.38%) 
Patella fracture * 1  0/268 (0.00%)  1/265 (0.38%) 
Post procedural haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Road traffic accident * 1  1/268 (0.37%)  0/265 (0.00%) 
Subdural haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Tendon rupture * 1  1/268 (0.37%)  0/265 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  6/268 (2.24%)  0/265 (0.00%) 
Aspartate aminotransferase increased * 1  2/268 (0.75%)  0/265 (0.00%) 
Blood creatine phosphokinase increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood sodium decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Lipase increased * 1  1/268 (0.37%)  0/265 (0.00%) 
Transaminases increased * 1  1/268 (0.37%)  0/265 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypomagnesaemia * 1  1/268 (0.37%)  0/265 (0.00%) 
Tumour lysis syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis * 1  1/268 (0.37%)  2/265 (0.75%) 
Musculoskeletal chest pain * 1  2/268 (0.75%)  0/265 (0.00%) 
Osteochondrosis * 1  1/268 (0.37%)  1/265 (0.38%) 
Arthralgia * 1  1/268 (0.37%)  0/265 (0.00%) 
Back pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Intervertebral disc protrusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Rectal cancer * 1  2/268 (0.75%)  0/265 (0.00%) 
Chronic myeloid leukaemia * 1  0/268 (0.00%)  1/265 (0.38%) 
Bladder papilloma * 1  0/268 (0.00%)  1/265 (0.38%) 
Carcinoid tumour of the caecum * 1  1/268 (0.37%)  0/265 (0.00%) 
Colon cancer * 1  1/268 (0.37%)  0/265 (0.00%) 
Colon cancer metastatic * 1  1/268 (0.37%)  0/265 (0.00%) 
Endometrial cancer metastatic * 1  1/268 (0.37%)  0/265 (0.00%) 
Fallopian tube cancer stage III * 1  1/268 (0.37%)  0/265 (0.00%) 
Fibromatosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Hepatocellular carcinoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Invasive ductal breast carcinoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Lung neoplasm malignant * 1  1/268 (0.37%)  0/265 (0.00%) 
Myelodysplastic syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Prostate cancer * 1  0/268 (0.00%)  1/265 (0.38%) 
Prostatic adenoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Squamous cell carcinoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Transitional cell carcinoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Nervous system disorders     
Haemorrhagic stroke * 1  1/268 (0.37%)  1/265 (0.38%) 
Cerebral haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Cerebrovascular accident * 1  0/268 (0.00%)  1/265 (0.38%) 
Headache * 1  1/268 (0.37%)  0/265 (0.00%) 
Syncope * 1  0/268 (0.00%)  1/265 (0.38%) 
Pregnancy, puerperium and perinatal conditions     
Unintended pregnancy * 1  2/268 (0.75%)  0/265 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  4/268 (1.49%)  0/265 (0.00%) 
Chronic kidney disease * 1  2/268 (0.75%)  0/265 (0.00%) 
Haematuria * 1  2/268 (0.75%)  0/265 (0.00%) 
Renal failure * 1  1/268 (0.37%)  0/265 (0.00%) 
Calculus bladder * 1  0/268 (0.00%)  1/265 (0.38%) 
Nephrotic syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Ureterolithiasis * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary incontinence * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary retention * 1  0/268 (0.00%)  1/265 (0.38%) 
Reproductive system and breast disorders     
Ovarian cyst * 1  0/268 (0.00%)  1/265 (0.38%) 
Prostatic dysplasia * 1  0/268 (0.00%)  1/265 (0.38%) 
Uterine haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Vaginal haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pleural effusion * 1  4/268 (1.49%)  1/265 (0.38%) 
Dyspnoea * 1  2/268 (0.75%)  2/265 (0.75%) 
Chronic obstructive pulmonary disease * 1  1/268 (0.37%)  1/265 (0.38%) 
Respiratory failure * 1  2/268 (0.75%)  0/265 (0.00%) 
Pneumothorax * 1  1/268 (0.37%)  0/265 (0.00%) 
Acute respiratory failure * 1  0/268 (0.00%)  1/265 (0.38%) 
Pulmonary hypertension * 1  1/268 (0.37%)  0/265 (0.00%) 
Pulmonary oedema * 1  1/268 (0.37%)  0/265 (0.00%) 
Pulmonary toxicity * 1  0/268 (0.00%)  1/265 (0.38%) 
Respiratory disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  0/268 (0.00%)  2/265 (0.75%) 
Dermatitis allergic * 1  1/268 (0.37%)  0/265 (0.00%) 
Lichen planus * 1  0/268 (0.00%)  1/265 (0.38%) 
Rash * 1  1/268 (0.37%)  0/265 (0.00%) 
Rash maculo-papular * 1  1/268 (0.37%)  0/265 (0.00%) 
Social circumstances     
Pregnancy of partner * 1  2/268 (0.75%)  1/265 (0.38%) 
Vascular disorders     
Embolism * 1  1/268 (0.37%)  1/265 (0.38%) 
Hypertensive crisis * 1  2/268 (0.75%)  0/265 (0.00%) 
Deep vein thrombosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypotension * 1  0/268 (0.00%)  1/265 (0.38%) 
Hypovolaemic shock * 1  1/268 (0.37%)  0/265 (0.00%) 
1
Term from vocabulary, MedDRA v23.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   264/268 (98.51%)   260/265 (98.11%) 
Blood and lymphatic system disorders     
Thrombocytopenia * 1  96/268 (35.82%)  53/265 (20.00%) 
Anaemia * 1  59/268 (22.01%)  59/265 (22.26%) 
Neutropenia * 1  33/268 (12.31%)  61/265 (23.02%) 
Leukopenia * 1  18/268 (6.72%)  34/265 (12.83%) 
Lymphopenia * 1  15/268 (5.60%)  8/265 (3.02%) 
Eye disorders     
Periorbital oedema * 1  4/268 (1.49%)  44/265 (16.60%) 
Eyelid oedema * 1  3/268 (1.12%)  24/265 (9.06%) 
Conjunctival haemorrhage * 1  2/268 (0.75%)  18/265 (6.79%) 
Dry eye * 1  4/268 (1.49%)  16/265 (6.04%) 
Lacrimation increased * 1  1/268 (0.37%)  18/265 (6.79%) 
Vision blurred * 1  5/268 (1.87%)  14/265 (5.28%) 
Gastrointestinal disorders     
Diarrhoea * 1  201/268 (75.00%)  106/265 (40.00%) 
Nausea * 1  100/268 (37.31%)  112/265 (42.26%) 
Vomiting * 1  55/268 (20.52%)  54/265 (20.38%) 
Abdominal pain * 1  61/268 (22.76%)  25/265 (9.43%) 
Abdominal pain upper * 1  28/268 (10.45%)  26/265 (9.81%) 
Constipation * 1  36/268 (13.43%)  17/265 (6.42%) 
Dyspepsia * 1  26/268 (9.70%)  24/265 (9.06%) 
Abdominal distension * 1  14/268 (5.22%)  8/265 (3.02%) 
Gastrooesophageal reflux disease * 1  8/268 (2.99%)  14/265 (5.28%) 
Toothache * 1  14/268 (5.22%)  7/265 (2.64%) 
General disorders     
Fatigue * 1  57/268 (21.27%)  54/265 (20.38%) 
Pyrexia * 1  44/268 (16.42%)  29/265 (10.94%) 
Oedema peripheral * 1  20/268 (7.46%)  43/265 (16.23%) 
Asthenia * 1  34/268 (12.69%)  24/265 (9.06%) 
Face oedema * 1  7/268 (2.61%)  17/265 (6.42%) 
Influenza like illness * 1  16/268 (5.97%)  6/265 (2.26%) 
Infections and infestations     
Upper respiratory tract infection * 1  36/268 (13.43%)  33/265 (12.45%) 
Nasopharyngitis * 1  36/268 (13.43%)  30/265 (11.32%) 
Urinary tract infection * 1  26/268 (9.70%)  18/265 (6.79%) 
Influenza * 1  24/268 (8.96%)  14/265 (5.28%) 
Gastroenteritis * 1  12/268 (4.48%)  17/265 (6.42%) 
Bronchitis * 1  19/268 (7.09%)  6/265 (2.26%) 
Sinusitis * 1  15/268 (5.60%)  8/265 (3.02%) 
Investigations     
Alanine aminotransferase increased * 1  90/268 (33.58%)  16/265 (6.04%) 
Aspartate aminotransferase increased * 1  69/268 (25.75%)  18/265 (6.79%) 
Lipase increased * 1  56/268 (20.90%)  30/265 (11.32%) 
Blood creatine phosphokinase increased * 1  14/268 (5.22%)  33/265 (12.45%) 
Blood creatinine increased * 1  18/268 (6.72%)  22/265 (8.30%) 
Amylase increased * 1  25/268 (9.33%)  10/265 (3.77%) 
Weight increased * 1  8/268 (2.99%)  20/265 (7.55%) 
Blood alkaline phosphatase increased * 1  17/268 (6.34%)  7/265 (2.64%) 
Blood bilirubin increased * 1  17/268 (6.34%)  7/265 (2.64%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  29/268 (10.82%)  17/265 (6.42%) 
Hypokalaemia * 1  6/268 (2.24%)  23/265 (8.68%) 
Hypophosphataemia * 1  7/268 (2.61%)  19/265 (7.17%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  48/268 (17.91%)  49/265 (18.49%) 
Muscle spasms * 1  10/268 (3.73%)  81/265 (30.57%) 
Pain in extremity * 1  26/268 (9.70%)  39/265 (14.72%) 
Myalgia * 1  13/268 (4.85%)  48/265 (18.11%) 
Back pain * 1  32/268 (11.94%)  25/265 (9.43%) 
Bone pain * 1  8/268 (2.99%)  19/265 (7.17%) 
Nervous system disorders     
Headache * 1  58/268 (21.64%)  41/265 (15.47%) 
Dizziness * 1  25/268 (9.33%)  23/265 (8.68%) 
Psychiatric disorders     
Insomnia * 1  18/268 (6.72%)  19/265 (7.17%) 
Anxiety * 1  15/268 (5.60%)  15/265 (5.66%) 
Depression * 1  9/268 (3.36%)  14/265 (5.28%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  30/268 (11.19%)  26/265 (9.81%) 
Dyspnoea * 1  29/268 (10.82%)  14/265 (5.28%) 
Oropharyngeal pain * 1  17/268 (6.34%)  10/265 (3.77%) 
Skin and subcutaneous tissue disorders     
Rash * 1  61/268 (22.76%)  39/265 (14.72%) 
Pruritus * 1  30/268 (11.19%)  10/265 (3.77%) 
Dry skin * 1  20/268 (7.46%)  14/265 (5.28%) 
Alopecia * 1  15/268 (5.60%)  14/265 (5.28%) 
Rash maculo-papular * 1  13/268 (4.85%)  16/265 (6.04%) 
Night sweats * 1  5/268 (1.87%)  14/265 (5.28%) 
Vascular disorders     
Hypertension * 1  26/268 (9.70%)  29/265 (10.94%) 
1
Term from vocabulary, MedDRA v23.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02130557    
Other Study ID Numbers: AV001
2013-005101-31 ( EudraCT Number )
B1871053 ( Other Identifier: Alias Study Number )
First Submitted: May 1, 2014
First Posted: May 5, 2014
Results First Submitted: July 13, 2018
Results First Posted: November 14, 2018
Last Update Posted: May 18, 2021