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

A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02130557

Enrollment

536

Registered

2014-05-05

Start date

2014-07-15

Completion date

2020-04-17

Last updated

2021-05-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive

Keywords

Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Bosutinib, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Philadelphia Chromosome, Neoplasms by Histologic Type, Bone Marrow Diseases, Hematologic Diseases, Translocation, Genetic, Pathologic Processes, Imatinib, Therapeutic Uses, Pharmacologic Actions, Molecular Mechanisms of Pharmacological Action

Brief summary

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Detailed description

The study will be open for enrollment until the planned number of approximately 500 Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+ patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All patients will be treated and/or followed for approximately 5 years (240 weeks) after randomization until the study has closed. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 5 years (240 weeks) after randomization.

Interventions

DRUGBosutinib

Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.\[1\] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.

DRUGImatinib

Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial. Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Masking description

NOTE: Value was Open Label in old format; This study has an open-label design. Although most efficacy studies have a double blind design, this is not feasible in this trial, due to the complexity of the dose reduction and dose escalation schemes with tablets of various sizes, dosage strengths, as well as the number of tablets that would be required daily. However, the opportunity for bias is mitigated by the use of objective outcome measures (MMR, CCyR, CHR). The Investigators will be instructed to ensure that laboratory/pathology personnel are blinded to treatment information. For these reasons, an open-label, randomized study is appropriate.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis). 2. Adequate hepatic, renal and pancreatic function. 3. Age ≥ 18 years.

Exclusion criteria

1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject's region. 2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia. 3. Extramedullary disease only. 4. Major surgery or radiotherapy within 14 days of randomization. 5. History of clinically significant or uncontrolled cardiac disease. 6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included. 7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy. 8. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months. 9. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Major Molecular Response (MMR) at Month 12	Month 12	MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (\<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to \[\>=\] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.

Secondary

Measure	Time frame	Description
Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48	Month 48	The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio \>0.1% in association with a \>=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.
Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12	Up to Month 12	Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.
Percentage of Participants With Major Molecular Response (MMR) Up to Month 18	Up to Month 18	MMR was defined as a ratio of BCR-ABL/ABL \<=0.1% on the international scale (\>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.
Cumulative Incidence of Event Free Survival (EFS) Events	Up to Month 60	EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to \>20.0\10\^9/L, platelet count rises to \>=600\10\^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of \<100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.
Overall Survival (OS) Rate	Up to Month 60	OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.
Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48	Month 48	The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.

Other

Measure	Time frame	Description
Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation	Baseline up to end of treatment (up to Month 60)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR) of Bosutinib	Pre-dose on Days 28, 56 and 84	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.
Number of Participants With Treatment-Emergent Adverse Events by National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.0)	Baseline up to end of treatment (up to Month 60)	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.
Summary of Trough Plasma Concentration by Major Molecular Response (MMR) of Bosutinib	Pre-dose on Days 28, 56 and 84	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.
Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs) of Bosutinib	Pre-dose on Days 28, 56 and 84	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.
Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs) of Bosutinib	Pre-dose on Days 28, 56 and 84	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.
Number of Participants With Vital Signs Abnormalities	Baseline up to end of treatment (up to Month 60)	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.
Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03	Baseline up to end of treatment (up to Month 60)	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.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Baseline up to end of treatment (up to Month 60)	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.

Countries

Australia, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Poland, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Bosutinib 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.	268
Imatinib 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.	268
Total	536

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Deceased	14	14
Overall Study	Investigator Request	0	2
Overall Study	Lost to Follow-up	6	7
Overall Study	Missing	2	1
Overall Study	Other	2	1
Overall Study	Withdrawal by Subject	12	12

Baseline characteristics

Characteristic	Bosutinib	Imatinib	Total
Age, Continuous	50.8 years STANDARD_DEVIATION 15.4	50.9 years STANDARD_DEVIATION 14.43	50.9 years STANDARD_DEVIATION 14.91
Sex: Female, Male Female	112 Participants	113 Participants	225 Participants
Sex: Female, Male Male	156 Participants	155 Participants	311 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	14 / 268	14 / 268
other Total, other adverse events	264 / 268	260 / 265
serious Total, serious adverse events	98 / 268	68 / 265

Outcome results

Primary

Percentage of Participants With Major Molecular Response (MMR) at Month 12

MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (\<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to \[\>=\] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.

Time frame: Month 12

Population: 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	Measure	Value (NUMBER)
Bosutinib	Percentage of Participants With Major Molecular Response (MMR) at Month 12	47.2 percentage of participants
Imatinib	Percentage of Participants With Major Molecular Response (MMR) at Month 12	36.9 percentage of participants

Comparison: 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).p-value: 0.0195% CI: [1.072, 2.233]Cochran-Mantel-Haenszel

Secondary

Cumulative Incidence of Event Free Survival (EFS) Events

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

Arm	Measure	Value (NUMBER)
Bosutinib	Cumulative Incidence of Event Free Survival (EFS) Events	6.9 percentage of participants
Imatinib	Cumulative Incidence of Event Free Survival (EFS) Events	10.4 percentage of participants

Comparison: 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.p-value: 0.074995% CI: [0.35, 1.17]Gray's test

Secondary

Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48

The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.

Time frame: Month 48

Population: 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	Measure	Value (NUMBER)
Bosutinib	Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48	97.4 percentage of participants
Imatinib	Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48	93.7 percentage of participants

Comparison: The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided.95% CI: [0.14, 1.13]

Secondary

Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48

The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio \>0.1% in association with a \>=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.

Time frame: Month 48

Population: 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	Measure	Value (NUMBER)
Bosutinib	Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48	92.2 percentage of participants
Imatinib	Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48	92.0 percentage of participants

Comparison: The medians have not been reached in either arm, as such, the premature estimated hazard ratio is provided.95% CI: [0.49, 2.44]

Secondary

Overall Survival (OS) Rate

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

Arm	Measure	Value (NUMBER)
Bosutinib	Overall Survival (OS) Rate	94.9 percentage of participants
Imatinib	Overall Survival (OS) Rate	94.0 percentage of participants

Secondary

Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12

Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.

Time frame: Up to Month 12

Arm	Measure	Value (NUMBER)
Bosutinib	Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12	77.2 percentage of participants
Imatinib	Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12	66.4 percentage of participants

Comparison: 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.p-value: 0.003795% CI: [1.16, 2.61]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Major Molecular Response (MMR) Up to Month 18

MMR was defined as a ratio of BCR-ABL/ABL \<=0.1% on the international scale (\>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.

Time frame: Up to Month 18

Arm	Measure	Value (NUMBER)
Bosutinib	Percentage of Participants With Major Molecular Response (MMR) Up to Month 18	61.0 percentage of participants
Imatinib	Percentage of Participants With Major Molecular Response (MMR) Up to Month 18	52.7 percentage of participants

Other Pre-specified

Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.