Safety And Efficacy Study Of Bosutinib In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02228382
• Collaborator: Developmental Therapeutics Consortium (Other)
• Enrollment: 163
• Locations: 48
• Arm: 1
• Actual Duration (Months): 71.2
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to fulfill the post-authorization commitment made by Pfizer to the European Medicines Agency in providing additional safety and efficacy data in approximately 150 Philadelphia Chromosome Positive Chronic Myeloid Leukemia patients with high unmet medical need, including 75 Chronic Phase, Accelerated Phase or Blast Phase patients in the fourth or later line treatment setting (i.e., after treatment with at least 3 other Tyrosine Kinase Inhibitors).

Condition or Disease	Intervention/Treatment	Phase
Previously Treated PH + CML	Drug: Bosutinib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 163 participants
• Allocation: N/A
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 4 SAFETY AND EFFICACY STUDY OF BOSUTINIB (BOSULIF (REGISTERED)) IN PATIENTS WITH PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA PREVIOUSLY TREATED WITH ONE OR MORE TYROSINE KINASE INHIBITORS
• Actual Study Start Date: Nov 7, 2014
• Actual Primary Completion Date: Oct 13, 2020
• Actual Study Completion Date: Oct 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bosutinib	Drug: Bosutinib; 100 mg and 500 mg tablets, once daily dosage up to 4 years duration; Other Names: BOSULIF

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants [Up to 1 year (52 weeks)]

   Confirmed MCyR: confirmed (complete cytogenetic response[CCyR] or partial cytogenetic response[PCyR]) by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least major molecular response(MMR) by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments >=28 days apart. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: <=0.1% BCR-ABL1 on the international scale (IS) with at least 10,000 ABL1 transcripts assessed by central laboratory.

2. Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants [Up to 1 year (52 weeks)]

   Confirmed MCyR: confirmed CCyR or PCyR by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least MMR by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments >=28 days apart. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: <=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory.

3. Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants [Up to 1 year (52 weeks)]

   Confirmed OHR was defined as complete hematological response (CHR) or return to chronic phase (RCP) by 1 year in AP and BP participants. CHR was defined as white blood cells (WBC) <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.

Secondary Outcome Measures

1. Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR) [Up to 4 years]

   CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.

2. Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) [Up to 4 years]

   Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.

3. Percentage of Participants With Cumulative Best Response [Up to 4 years]

   Hierarchy best response: %participants with best response among molecular/cytogenetic/hematologic response. Molecular response:MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio on IS corresponding to >=4.5/4/3-log reduction from standardised baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. CyR:based on prevalence of Ph+cells. CCyR: 0% Ph+cells from >=20 metaphases from conventional cytogenetics or <1%Ph+cells from >=200 cells from FISH. PCyR:1 to 35% Ph+cells. CHR:WBC <10*10^9/L, peripheral blood basophils<5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in differential, platelet count<450*10^9/L, spleen not palpable.

4. Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24 [Months 3, 6, 12, 18, and 24]

   CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.

5. Percentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24 [Months 3, 6, 9, 12, 18, and 24]

   Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.

6. Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR) [Up to 4 years]

   CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.

7. Percentage of Participants With Cumulative Major Molecular Response (MMR) [Up to 4 years]

   Molecular response: MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio respectively, on IS corresponding to >=4.5/4/3-log reduction from standardized baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. To be considered a responder, the participant must have had maintenance of baseline response while on-treatment or an improvement from baseline.

8. Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36 [At Month 36]

   Kaplan-Meier analysis. Duration of CCyR: from first date of CCyR to date of confirmed loss of CCyR/disease progression/on-treatment death or censoring, analyzed for responders only. CyR: prevalence of Ph+ cells. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >=200 cells analyzed by FISH or MMR (<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory). Confirmed loss: 2 consecutive non-response assessments >=28 days apart. Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2 weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.

9. Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36 [At Month 36]

   Kaplan-Meier analysis. Duration of MMR: from first date of MMR to confirmed loss of MMR/disease progression/on-treatment death or censoring, analyzed for responders only. MMR:<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory . Confirmed loss: 2 consecutive non-response assessments >=28 days apart with a <3-log (>0.1%) reduction in transcripts one of which corresponds to a <=2-log reduction (>=1%). Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.

10. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs [First dose of study drug up to 28 days after last dose (up to maximum of 4 years)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE: any event increasing in severity from baseline or any new event started during bosutinib therapy or within 28 days of the last dose of study drug. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly.

11. Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [First dose of study drug up to 28 days after last dose (up to maximum of 4 years)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs are reported.

12. Number of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs) [First dose of study drug up to 28 days after last dose (up to maximum of 4 years)]

    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Relatedness to drug was assessed by investigator.

13. Number of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 [First dose of study drug up to 28 days after last dose (up to maximum of 4 years)]

    Number of participants with any hematological, chemistry and coagulation abnormality of any grade were reported. Hematological: absolute neutrophil count (low), hemoglobin (low), lymphocytes (low), platelets (low) and leukocytes (low). Chemistry: alkaline phosphatase (high), alanine aminotransferase (high), amylase (high), aspartate aminotransferase (high), bilirubin (high), creatinine (high), lipase (high). Coagulation: activated partial prothrombin time (low), prothrombin time (low and high), partial prothrombin time (high).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Confirmed Philadelphia Chromosome positive Chronic Myeloid Leukemia or Confirmed BCR-ABL1 (Abelson-break point cluster) Positive if Philadelphia Chromosome negative Chronic Myeloid Leukemia (from initial diagnosis).

• Prior treatment with 1 or more tyrosine kinase inhibitor drugs (imatinib, dasatinib and/or nilotinib) for Philadelphia Chromosome positive Chronic Myeloid Leukemia (CML).

• Any Chronic Myeloid Leukemia disease phase, as long as the patient is unable to receive treatment with imatinib, dasatinib and/or nilotinib for any reason.

Exclusion Criteria:

• Participation in any other clinical studies involving investigational drug(s) within 14 days or within 3 half-lives of drug levels in blood (whichever is longer) prior to the first dose of bosutinib.

• Prior treatment with bosutinib.

• Prior treatment with ponatinib.

• Known T315I or V299L mutation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck Hospital of USC	Los Angeles	California	United States	90033
2	LAC+USC Medical Center	Los Angeles	California	United States	90033
3	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Sylvester Deerfield Beach	Deerfield Beach	Florida	United States	33442
5	University of Miami Hospital & Clinics	Miami	Florida	United States	33136
6	Indiana Blood and Marrow Transplantation-Clinic	Indianapolis	Indiana	United States	46237
7	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287
8	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141-6337
9	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63129
12	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York	United States	10021
13	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
14	Medizinische Universitaet Innsbruck	Innsbruck		Austria	6020
15	Ordensklinikum Linz Gmbh Barmherzige Schwestern	Linz		Austria	4010
16	Institut Bergonie	Bordeaux Cedex 09		France	33076
17	Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- Oncology	Le Chesnay Cedex		France	78157
18	Centre Regional De Lutte Contre Le Cancer	Marseille		France	13009
19	Hopital Archet I	Nice Cedex 3		France	06202
20	Institut Universitaire du Cancer Toulouse - Oncopole	Toulouse Cedex 9		France	31059
21	CHU Brabois	Vandoeuvre-les-Nancy cedex		France	54511
22	RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und Stammzelltransplantation	Aachen		Germany	52074
23	Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)	Berlin		Germany	13353
24	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
25	Klinik fur Innere Medizin II	Jena		Germany	07747
26	Universitaetsklinikum Koeln (AoeR)	Koeln		Germany	50937
27	III. Medizinische Klinik Universitaetsmedizin Mannheim	Mannheim		Germany	D-68167
28	AOU Policlinico Consorziale di Bari - UO Ematologia con Trapianto	Bari	BA	Italy	70124
29	A.O.U. Policlinico S. Orsola-Malpighi	Bologna	BO	Italy	40138
30	Azienda Socio Sanitaria Territoriale - ASST Monza	Monza	MB	Italy	20900
31	Ospedale S. Eugenio - UOC Ematologia	Rome	RM	Italy	00144
32	AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo Ematologico	Orbassano	TO	Italy	10043
33	AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico	Catania		Italy	95123
34	SOD Ematologia	Firenze		Italy	50134
35	A.O. Ospedale Niguarda Ca Granda - SC Ematologia	Milano		Italy	20162
36	Haukeland Universitetssjukehus	Bergen		Norway	5021
37	St Olav Hospital	Trondheim		Norway	7030
38	Hospital Universitario Quiron Madrid	Pozuelo de Alarcon	Madrid	Spain	28223
39	Hospital Universitari Vall d' Hebron	Barcelona		Spain	08035
40	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
41	Hospital Clinic De Barcelona	Barcelona		Spain	08036
42	Hospital Universitario de La Princesa	Madrid		Spain	28006
43	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
44	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
45	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
46	Hospital de dia Quiron Zaragoza	Zaragoza		Spain	50012
47	Hematologiskt centrum	Stockholm		Sweden	171 76
48	Akademiska Sjukhuset	Uppsala		Sweden	751 85

Sponsors and Collaborators

• Pfizer
• Developmental Therapeutics Consortium

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Sep 7, 2017
• Statistical Analysis Plan - Nov 12, 2020

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: NCT02228382
• Other Study ID Numbers: B1871039; 2013-003250-25; BYOND
• First Posted: Aug 29, 2014
• Last Update Posted: Dec 30, 2021
• Last Verified: Dec 1, 2021

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

Study Results

Participant Flow

Recruitment Details

Participants with chronic phase (CP), accelerated phase (AP), or blast phase (BP) philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML), or breakpoint cluster region-abelson kinase (BCR-ABL1) positive and Philadelphia chromosome negative (Ph-), who failed prior treatment with commercially available tyrosine kinase inhibitors (TKIs) due to drug resistance or intolerance, or were otherwise contraindicated for treatment with commercially available TKIs were enrolled.

Pre-assignment Detail

A total of 177 participants signed the ICF, 14 participants were screen failure and 163 were enrolled into the study and assigned to study treatment. Reporting arms were based on line of therapy (CP2L, CP3L, CP4L) and disease phase (CP and AP). Data collection and planned analysis on BP participants was not performed because no participants with BP were enrolled in the study.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia resistant or intolerant to imatinib, dasatinib, or nilotinib received bosutinib 500 milligram (mg), orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, death or discontinuation of study (up to maximum of 4 years). Participants who discontinued bosutinib prior to completing at least 4 years of therapy were followed for survival until they completed at least 4 years of follow-up from the time of first dose.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia resistant or intolerant to imatinib and/or dasatinib and/or nilotinib received bosutinib 500 mg, orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, death or discontinuation of study (up to maximum of 4 years). Participants who discontinued bosutinib prior to completing at least 4 years of therapy were followed for survival until they completed at least 4 years of follow-up from the time of first dose.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia resistant or intolerant to imatinib and dasatinib and nilotinib received bosutinib 500 mg, orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, death or discontinuation of study (up to maximum of 4 years). Participants who discontinued bosutinib prior to completing at least 4 years of therapy were followed for survival until they completed at least 4 years of follow-up from the time of first dose.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia resistant or intolerant to at least one tyrosine kinase inhibitor among imatinib, dasatinib, or nilotinib received bosutinib 500 mg, orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, death or discontinuation of study (up to maximum of 4 years). Participants who discontinued bosutinib prior to completing at least 4 years of therapy were followed for survival until they completed at least 4 years of follow-up from the time of first dose.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia received bosutinib 500 mg, orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, death or discontinuation of study (up to maximum of 4 years). Participants who discontinued bosutinib prior to completing at least 4 years of therapy were followed for survival until they completed at least 4 years of follow-up from the time of first dose.
Period Title: Overall Study
STARTED	46	61	49	4	3
COMPLETED	36	43	28	2	1
NOT COMPLETED	10	18	21	2	2

Baseline Characteristics

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia	Total
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.	Total of all reporting groups
Overall Participants	46	61	49	4	3	163
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.8 (15.4)	61.8 (15.0)	59.4 (15.3)	40.8 (11.0)	64.3 (7.1)	58.9 (15.4)
Sex: Female, Male (Count of Participants)
Female	23 50%	24 39.3%	28 57.1%	0 0%	0 0%	75 46%
Male	23 50%	37 60.7%	21 42.9%	4 100%	3 100%	88 54%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 1.6%	0 0%	0 0%	0 0%	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 4.3%	1 1.6%	1 2%	0 0%	0 0%	4 2.5%
White	39 84.8%	55 90.2%	44 89.8%	2 50%	3 100%	143 87.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 10.9%	4 6.6%	4 8.2%	2 50%	0 0%	15 9.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
Description	Confirmed MCyR: confirmed (complete cytogenetic response[CCyR] or partial cytogenetic response[PCyR]) by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least major molecular response(MMR) by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments >=28 days apart. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: <=0.1% BCR-ABL1 on the international scale (IS) with at least 10,000 ABL1 transcripts assessed by central laboratory.
Time Frame	Up to 1 year (52 weeks)

Outcome Measure Data

Analysis Population Description

Evaluable set for cytogenetic response: treated participants with valid baseline efficacy assessment (>=20 metaphases from baseline bone marrow or CCyR with >=200 cells from FISH or baseline MMR). Data for this outcome measure was not planned to be collected and analyzed for AP CML and Ph- participants and planned to be analyzed for 2nd line and 3rd line population.

Arm/Group Title	Bosutinib, Chronic Phase 2nd and 3rd Line Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd and 3rd line chronic myelogenous leukemia.
Measure Participants	98
Number (95% Confidence Interval) [percentage of participants]	76.5 166.3%

2. Primary Outcome

Title	Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants
Description	Confirmed MCyR: confirmed CCyR or PCyR by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least MMR by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments >=28 days apart. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: <=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory.
Time Frame	Up to 1 year (52 weeks)

Outcome Measure Data

Analysis Population Description

Evaluable set cytogenetic response: treated participants with valid baseline efficacy assessment (>= 20 metaphases from baseline bone marrow or CCyR with >=200 cells from FISH or baseline MMR). Data for this outcome measure was not planned to be collected and analyzed for AP CML and Ph-participants.

Arm/Group Title	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.
Measure Participants	45
Number (95% Confidence Interval) [percentage of participants]	62.2 135.2%

3. Primary Outcome

Title	Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants
Description	Confirmed OHR was defined as complete hematological response (CHR) or return to chronic phase (RCP) by 1 year in AP and BP participants. CHR was defined as white blood cells (WBC) <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.
Time Frame	Up to 1 year (52 weeks)

Outcome Measure Data

Analysis Population Description

Evaluable set for hematological response: treated participants with a valid baseline hematologic assessment. Data for this outcome measure was not planned to be collected and analyzed for CP2L, CP3L, CP4L and Ph- CML participants.

Arm/Group Title	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	4
Number (95% Confidence Interval) [percentage of participants]	75.0 163%

4. Secondary Outcome

Title	Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)
Description	CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Evaluable set cytogenetic response: treated participants with valid baseline efficacy assessment (>=20 metaphases from baseline bone marrow or CCyR with >=200 cells from FISH or baseline MMR). Data for this outcome measure was not planned to be collected and analyzed for Ph- participants.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	43	55	45	4
Number (95% Confidence Interval) [percentage of participants]	88.4 192.2%	85.5 140.2%	77.8 158.8%	75.0 1875%

5. Secondary Outcome

Title	Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)
Description	Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Evaluable set for hematological response: treated participants with a valid baseline hematologic assessment. Data for this outcome measure was not planned to be collected and analyzed for CP2L, CP3L, CP4L and Ph- CML participants.

Arm/Group Title	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	4
Number (95% Confidence Interval) [percentage of participants]	75.0 163%

6. Secondary Outcome

Title	Percentage of Participants With Cumulative Best Response
Description	Hierarchy best response: %participants with best response among molecular/cytogenetic/hematologic response. Molecular response:MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio on IS corresponding to >=4.5/4/3-log reduction from standardised baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. CyR:based on prevalence of Ph+cells. CCyR: 0% Ph+cells from >=20 metaphases from conventional cytogenetics or <1%Ph+cells from >=200 cells from FISH. PCyR:1 to 35% Ph+cells. CHR:WBC <10*10^9/L, peripheral blood basophils<5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in differential, platelet count<450*10^9/L, spleen not palpable.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Evaluable set:treated participants with valid baseline molecular, cytogenetic or hematologic assessment. Data for this outcome measure (all categories including OHR) was not planned to be collected and analyzed for Ph- CML participants. Data for OHR was not planned to be collected and analyzed for CP CML participants.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	46	61	49	4
MR4.5	17.4 37.8%	14.8 24.3%	8.2 16.7%	25.0 625%
MR4	15.2 33%	11.5 18.9%	6.1 12.4%	0.0 0%
MMR	8.7 18.9%	11.5 18.9%	14.3 29.2%	25.0 625%
CCyR	2.2 4.8%	13.1 21.5%	14.3 29.2%	25.0 625%
PCyR	2.2 4.8%	1.6 2.6%	4.1 8.4%	0.0 0%
CHR	10.9 23.7%	8.2 13.4%	16.3 33.3%	0.0 0%
OHR	0.0 0%

7. Secondary Outcome

Title	Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24
Description	CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.
Time Frame	Months 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Evaluable set cytogenetic response: treated participants with valid baseline efficacy assessment (>= 20 metaphases from baseline bone marrow or CCyR with >=200 cells from FISH or baseline MMR). Data for this outcome measure was not planned to be collected and analyzed for Ph- participants.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	43	55	45	4
At 3 months	81.4 177%	80.0 131.1%	55.6 113.5%	75.0 1875%
At 6 months	69.8 151.7%	63.6 104.3%	62.2 126.9%	25.0 625%
At 12 months	69.8 151.7%	65.5 107.4%	48.9 99.8%	25.0 625%
At 18 months	67.4 146.5%	63.6 104.3%	42.2 86.1%	25.0 625%
At 24 months	67.4 146.5%	54.5 89.3%	44.4 90.6%	25.0 625%

8. Secondary Outcome

Title	Percentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24
Description	Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.
Time Frame	Months 3, 6, 9, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Evaluable set hematological response: treated participants with a valid baseline hematologic assessment. Data for this outcome measure was not planned to be collected and analyzed for CP2L, CP3L, CP4L and Ph- CML participants.

Arm/Group Title	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	4
At 3 months	75.0 163%
At 6 months	50.0 108.7%
At 9 months	75.0 163%
At 12 months	75.0 163%
At 18 months	25.0 54.3%
At 24 months	0.0 0%

9. Secondary Outcome

Title	Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)
Description	CHR was defined as WBC <10*10^9/L, peripheral blood basophils <5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count <450*10^9/L, spleen not palpable. Hematologic responses must be of >=4 weeks duration confirmed by 2 assessments >=4 weeks apart.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Evaluable set for hematological response: treated participants with a valid baseline hematologic assessment. Data for this outcome measure was not planned to be collected and analyzed for Ph- participants.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	46	61	48	4
Number (95% Confidence Interval) [percentage of participants]	91.3 198.5%	82.0 134.4%	77.1 157.3%	75.0 1875%

10. Secondary Outcome

Title	Percentage of Participants With Cumulative Major Molecular Response (MMR)
Description	Molecular response: MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio respectively, on IS corresponding to >=4.5/4/3-log reduction from standardized baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. To be considered a responder, the participant must have had maintenance of baseline response while on-treatment or an improvement from baseline.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Evaluable set for molecular response: treated participants with a valid baseline molecular assessment. Data for this outcome measure was not planned to be collected and analyzed for Ph- participants.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	46	55	48	4
MMR	82.6 179.6%	76.4 125.2%	56.3 114.9%	50.0 1250%
MR4	73.9 160.7%	63.6 104.3%	41.7 85.1%	25.0 625%
MR4.5	58.7 127.6%	50.9 83.4%	35.4 72.2%	25.0 625%

11. Secondary Outcome

Title	Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36
Description	Kaplan-Meier analysis. Duration of CCyR: from first date of CCyR to date of confirmed loss of CCyR/disease progression/on-treatment death or censoring, analyzed for responders only. CyR: prevalence of Ph+ cells. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >=200 cells analyzed by FISH or MMR (<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory). Confirmed loss: 2 consecutive non-response assessments >=28 days apart. Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2 weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.
Time Frame	At Month 36

Outcome Measure Data

Analysis Population Description

Evaluable set for cytogenetic response: treated participants with valid baseline cytogenetic assessment (>= 20 metaphases from baseline bone marrow or CCyR with >=200 cells from FISH or baseline MMR) and who achieved CCyR. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure who had CCyR.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	37	46	33	3
Number (95% Confidence Interval) [percentage of participants]	96.4 209.6%	94.4 154.8%	100.0 204.1%	100.0 2500%

12. Secondary Outcome

Title	Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36
Description	Kaplan-Meier analysis. Duration of MMR: from first date of MMR to confirmed loss of MMR/disease progression/on-treatment death or censoring, analyzed for responders only. MMR:<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory . Confirmed loss: 2 consecutive non-response assessments >=28 days apart with a <3-log (>0.1%) reduction in transcripts one of which corresponds to a <=2-log reduction (>=1%). Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.
Time Frame	At Month 36

Outcome Measure Data

Analysis Population Description

Evaluable set for molecular response: treated participants with valid baseline molecular assessment and who achieved MMR. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure who had MMR.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
Measure Participants	38	42	27	2
Number (95% Confidence Interval) [percentage of participants]	90.7 197.2%	81.5 133.6%	90.2 184.1%	100.0 2500%

13. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE: any event increasing in severity from baseline or any new event started during bosutinib therapy or within 28 days of the last dose of study drug. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	First dose of study drug up to 28 days after last dose (up to maximum of 4 years)

Outcome Measure Data

Analysis Population Description

The safety analysis set included participants who received at least 1 dose of bosutinib.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia	Bosutinib: Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.	Participants with Philadelphia chromosome positive chronic phase 2nd, 3rd and 4th line chronic myelogenous leukemia, Philadelphia chromosome positive accelerated phase chronic myelogenous leukemia and BCR-ABL1-chronic myelogenous leukemia/Philadelphia chromosome negative chronic myelogenous leukemia.
Measure Participants	46	61	49	4	3	163
TEAEs	46 100%	61 100%	48 98%	4 100%	3 100%	162 99.4%
Treatment-emergent SAEs	21 45.7%	30 49.2%	14 28.6%	1 25%	3 100%	69 42.3%

14. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs are reported.
Time Frame	First dose of study drug up to 28 days after last dose (up to maximum of 4 years)

Outcome Measure Data

Analysis Population Description

The safety analysis set included participants who received at least 1 dose of bosutinib.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia	Bosutinib: Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.	Participants with Philadelphia chromosome positive chronic phase 2nd, 3rd and 4th line chronic myelogenous leukemia, Philadelphia chromosome positive accelerated phase chronic myelogenous leukemia and BCR-ABL1-chronic myelogenous leukemia/Philadelphia chromosome negative chronic myelogenous leukemia.
Measure Participants	46	61	49	4	3	163
Count of Participants [Participants]	36 78.3%	49 80.3%	39 79.6%	2 50%	3 100%	129 79.1%

15. Secondary Outcome

Title	Number of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs)
Description	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Relatedness to drug was assessed by investigator.
Time Frame	First dose of study drug up to 28 days after last dose (up to maximum of 4 years)

Outcome Measure Data

Analysis Population Description

The safety analysis set included participants who received at least 1 dose of bosutinib.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia	Bosutinib: Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.	Participants with Philadelphia chromosome positive chronic phase 2nd, 3rd and 4th line chronic myelogenous leukemia, Philadelphia chromosome positive accelerated phase chronic myelogenous leukemia and BCR-ABL1-chronic myelogenous leukemia/Philadelphia chromosome negative chronic myelogenous leukemia.
Measure Participants	46	61	49	4	3	163
Count of Participants [Participants]	46 100%	61 100%	48 98%	4 100%	3 100%	162 99.4%

16. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Description	Number of participants with any hematological, chemistry and coagulation abnormality of any grade were reported. Hematological: absolute neutrophil count (low), hemoglobin (low), lymphocytes (low), platelets (low) and leukocytes (low). Chemistry: alkaline phosphatase (high), alanine aminotransferase (high), amylase (high), aspartate aminotransferase (high), bilirubin (high), creatinine (high), lipase (high). Coagulation: activated partial prothrombin time (low), prothrombin time (low and high), partial prothrombin time (high).
Time Frame	First dose of study drug up to 28 days after last dose (up to maximum of 4 years)

Outcome Measure Data

Analysis Population Description

The safety analysis set included participants who received at least 1 dose of bosutinib.

Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia	Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia	Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia	Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia	Bosutinib: Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.	Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.	Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.	Participants with Philadelphia chromosome positive chronic phase 2nd, 3rd and 4th line chronic myelogenous leukemia, Philadelphia chromosome positive accelerated phase chronic myelogenous leukemia and BCR-ABL1-chronic myelogenous leukemia/Philadelphia chromosome negative chronic myelogenous leukemia.
Measure Participants	46	61	49	4	3	163
Hematology	38 82.6%	56 91.8%	40 81.6%	4 100%	3 100%	141 86.5%
Chemistry	46 100%	61 100%	49 100%	4 100%	3 100%	163 100%
Coagulation	18 39.1%	25 41%	12 24.5%	2 50%	1 33.3%	58 35.6%

Adverse Events

Time Frame	From first dose of study drug up to 28 days after last dose (up to maximum of 4 years)
Adverse Event Reporting Description	The total number of deaths occurring during study, from first dose and up to the end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as both an AE and Serious Adverse Events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.
Arm/Group Title	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia		Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia		Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia		Bosutinib: Chronic Myelogenous Leukemia
Arm/Group Description	Participants with philadelphia chromosome positive chronic phase 2nd line chronic myelogenous leukemia.		Participants with philadelphia chromosome positive chronic Phase 3rd line chronic myelogenous leukemia.		Participants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.		Participants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.		Participants with BCR-ABL1 positive and philadelphia chromosome negative chronic myelogenous leukemia.		Participants with Philadelphia chromosome positive chronic phase 2nd, 3rd and 4th line chronic myelogenous leukemia, Philadelphia chromosome positive accelerated phase chronic myelogenous leukemia and BCR-ABL1-chronic myelogenous leukemia/Philadelphia chromosome negative chronic myelogenous leukemia.
All Cause Mortality
	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia		Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia		Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia		Bosutinib: Chronic Myelogenous Leukemia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/46 (10.9%)		7/61 (11.5%)		5/49 (10.2%)		0/4 (0%)		2/3 (66.7%)		19/163 (11.7%)
Serious Adverse Events
	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia		Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia		Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia		Bosutinib: Chronic Myelogenous Leukemia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/46 (45.7%)		30/61 (49.2%)		14/49 (28.6%)		1/4 (25%)		3/3 (100%)		69/163 (42.3%)
Blood and lymphatic system disorders
Anaemia	1/46 (2.2%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		3/163 (1.8%)
Abdominal lymphadenopathy	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Lymphadenopathy	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pancytopenia	0/46 (0%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		1/163 (0.6%)
Cardiac disorders
Cardiac failure	2/46 (4.3%)		3/61 (4.9%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		6/163 (3.7%)
Atrial fibrillation	3/46 (6.5%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Pericardial effusion	2/46 (4.3%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		1/3 (33.3%)		4/163 (2.5%)
Angina pectoris	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Angina unstable	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Atrioventricular block complete	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Bundle branch block right	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Cardiac failure congestive	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Cardiogenic shock	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Cardiomyopathy	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Coronary artery occlusion	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Sinus node dysfunction	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Eye disorders
Keratoconus	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Gastrointestinal disorders
Abdominal pain	0/46 (0%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		2/163 (1.2%)
Appendiceal mucocoele	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Ascites	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Colitis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Gastritis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Gastrointestinal haemorrhage	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Gastrooesophageal reflux disease	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Hiatus hernia	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Ileus	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Oesophageal fistula	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pancreatitis	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Rectal polyp	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Subileus	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
General disorders
Pyrexia	1/46 (2.2%)		3/61 (4.9%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		4/163 (2.5%)
Chest pain	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Multiple organ dysfunction syndrome	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Hepatobiliary disorders
Cholecystitis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Cholelithiasis	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Hepatic cirrhosis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Immune system disorders
Hypersensitivity	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Infections and infestations
Pneumonia	0/46 (0%)		2/61 (3.3%)		3/49 (6.1%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Cellulitis	0/46 (0%)		0/61 (0%)		1/49 (2%)		1/4 (25%)		0/3 (0%)		2/163 (1.2%)
Appendicitis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Bronchitis	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pneumonia pneumococcal	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pseudomembranous colitis	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Sepsis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Urinary tract infection	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Viral infection	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Injury, poisoning and procedural complications
Arterial restenosis	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Femur fracture	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Hip fracture	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Rib fracture	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Spinal fracture	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Subdural haematoma	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Tendon rupture	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Investigations
Blood creatinine increased	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Metabolism and nutrition disorders
Diabetes mellitus	0/46 (0%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		1/163 (0.6%)
Diabetic ketoacidosis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Fluid retention	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Metabolic disorder	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	1/46 (2.2%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		3/163 (1.8%)
Groin pain	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Musculoskeletal pain	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Neck pain	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/46 (0%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		1/163 (0.6%)
Anaplastic large-cell lymphoma	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Brain neoplasm	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Laryngeal squamous cell carcinoma	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Lung neoplasm malignant	0/46 (0%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		1/163 (0.6%)
Lymphoma	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Metastases to liver	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pancreatic carcinoma	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Prostate cancer	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Squamous cell carcinoma of lung	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Nervous system disorders
Syncope	1/46 (2.2%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		3/163 (1.8%)
Cerebrovascular accident	0/46 (0%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		2/163 (1.2%)
Transient ischaemic attack	1/46 (2.2%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		2/163 (1.2%)
Sciatica	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Psychiatric disorders
Anxiety	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Renal and urinary disorders
Acute kidney injury	2/46 (4.3%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		4/163 (2.5%)
Chronic kidney disease	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Reproductive system and breast disorders
Breast mass	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Ovarian cyst ruptured	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/46 (4.3%)		1/61 (1.6%)		3/49 (6.1%)		0/4 (0%)		1/3 (33.3%)		7/163 (4.3%)
Respiratory failure	1/46 (2.2%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		3/163 (1.8%)
Dyspnoea	1/46 (2.2%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		2/163 (1.2%)
Acute respiratory failure	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Emphysema	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Haemoptysis	1/46 (2.2%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Hypoxia	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Lung disorder	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pneumonitis	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Pulmonary hypertension	0/46 (0%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Vascular disorders
Peripheral arterial occlusive disease	0/46 (0%)		2/61 (3.3%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		3/163 (1.8%)
Peripheral ischaemia	0/46 (0%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		2/163 (1.2%)
Haemorrhage	0/46 (0%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		1/163 (0.6%)
Shock haemorrhagic	0/46 (0%)		0/61 (0%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		1/163 (0.6%)
Other (Not Including Serious) Adverse Events
	Bosutinib: Chronic Phase 2nd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 3rd Line Chronic Myelogenous Leukemia		Bosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia		Bosutinib: Accelerated Phase Chronic Myelogenous Leukemia		Bosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia		Bosutinib: Chronic Myelogenous Leukemia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/46 (100%)		61/61 (100%)		48/49 (98%)		4/4 (100%)		3/3 (100%)		162/163 (99.4%)
Blood and lymphatic system disorders
Anaemia	7/46 (15.2%)		14/61 (23%)		5/49 (10.2%)		0/4 (0%)		2/3 (66.7%)		28/163 (17.2%)
Thrombocytopenia	7/46 (15.2%)		6/61 (9.8%)		4/49 (8.2%)		1/4 (25%)		1/3 (33.3%)		19/163 (11.7%)
Neutropenia	3/46 (6.5%)		4/61 (6.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		7/163 (4.3%)
Cardiac disorders
Atrial fibrillation	4/46 (8.7%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		6/163 (3.7%)
Cardiac failure	3/46 (6.5%)		2/61 (3.3%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		6/163 (3.7%)
Eye disorders
Dry eye	3/46 (6.5%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Conjunctival hyperaemia	3/46 (6.5%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Gastrointestinal disorders
Diarrhoea	43/46 (93.5%)		54/61 (88.5%)		42/49 (85.7%)		4/4 (100%)		2/3 (66.7%)		145/163 (89%)
Nausea	15/46 (32.6%)		29/61 (47.5%)		25/49 (51%)		1/4 (25%)		0/3 (0%)		70/163 (42.9%)
Vomiting	13/46 (28.3%)		22/61 (36.1%)		19/49 (38.8%)		0/4 (0%)		1/3 (33.3%)		55/163 (33.7%)
Abdominal pain	14/46 (30.4%)		17/61 (27.9%)		16/49 (32.7%)		2/4 (50%)		0/3 (0%)		49/163 (30.1%)
Abdominal pain upper	19/46 (41.3%)		8/61 (13.1%)		9/49 (18.4%)		0/4 (0%)		1/3 (33.3%)		37/163 (22.7%)
Constipation	13/46 (28.3%)		11/61 (18%)		7/49 (14.3%)		0/4 (0%)		1/3 (33.3%)		32/163 (19.6%)
Dyspepsia	4/46 (8.7%)		6/61 (9.8%)		3/49 (6.1%)		1/4 (25%)		0/3 (0%)		14/163 (8.6%)
Abdominal distension	3/46 (6.5%)		5/61 (8.2%)		3/49 (6.1%)		0/4 (0%)		0/3 (0%)		11/163 (6.7%)
Gastrooesophageal reflux disease	4/46 (8.7%)		3/61 (4.9%)		2/49 (4.1%)		1/4 (25%)		0/3 (0%)		10/163 (6.1%)
Flatulence	5/46 (10.9%)		3/61 (4.9%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		9/163 (5.5%)
Abdominal discomfort	3/46 (6.5%)		2/61 (3.3%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		6/163 (3.7%)
Gastrointestinal disorder	3/46 (6.5%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		4/163 (2.5%)
General disorders
Fatigue	10/46 (21.7%)		15/61 (24.6%)		19/49 (38.8%)		1/4 (25%)		1/3 (33.3%)		46/163 (28.2%)
Asthenia	20/46 (43.5%)		9/61 (14.8%)		6/49 (12.2%)		1/4 (25%)		0/3 (0%)		36/163 (22.1%)
Pyrexia	7/46 (15.2%)		11/61 (18%)		13/49 (26.5%)		0/4 (0%)		0/3 (0%)		31/163 (19%)
Oedema peripheral	9/46 (19.6%)		11/61 (18%)		9/49 (18.4%)		0/4 (0%)		0/3 (0%)		29/163 (17.8%)
Chest pain	4/46 (8.7%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		6/163 (3.7%)
Influenza like illness	4/46 (8.7%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		6/163 (3.7%)
Infections and infestations
Nasopharyngitis	7/46 (15.2%)		11/61 (18%)		8/49 (16.3%)		0/4 (0%)		0/3 (0%)		26/163 (16%)
Influenza	6/46 (13%)		3/61 (4.9%)		5/49 (10.2%)		0/4 (0%)		0/3 (0%)		14/163 (8.6%)
Urinary tract infection	1/46 (2.2%)		6/61 (9.8%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		9/163 (5.5%)
Bronchitis	3/46 (6.5%)		3/61 (4.9%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		8/163 (4.9%)
Upper respiratory tract infection	1/46 (2.2%)		5/61 (8.2%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		8/163 (4.9%)
Folliculitis	6/46 (13%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		7/163 (4.3%)
Injury, poisoning and procedural complications
Fall	2/46 (4.3%)		10/61 (16.4%)		3/49 (6.1%)		0/4 (0%)		0/3 (0%)		15/163 (9.2%)
Investigations
Alanine aminotransferase increased	10/46 (21.7%)		18/61 (29.5%)		16/49 (32.7%)		0/4 (0%)		0/3 (0%)		44/163 (27%)
Aspartate aminotransferase increased	9/46 (19.6%)		11/61 (18%)		13/49 (26.5%)		0/4 (0%)		0/3 (0%)		33/163 (20.2%)
Blood creatinine increased	8/46 (17.4%)		7/61 (11.5%)		10/49 (20.4%)		1/4 (25%)		0/3 (0%)		26/163 (16%)
Lipase increased	9/46 (19.6%)		11/61 (18%)		5/49 (10.2%)		0/4 (0%)		0/3 (0%)		25/163 (15.3%)
Amylase increased	5/46 (10.9%)		8/61 (13.1%)		3/49 (6.1%)		0/4 (0%)		0/3 (0%)		16/163 (9.8%)
Weight decreased	2/46 (4.3%)		7/61 (11.5%)		4/49 (8.2%)		0/4 (0%)		1/3 (33.3%)		14/163 (8.6%)
Gamma-glutamyl transferase increased	3/46 (6.5%)		6/61 (9.8%)		3/49 (6.1%)		0/4 (0%)		1/3 (33.3%)		13/163 (8%)
Blood uric acid increased	1/46 (2.2%)		6/61 (9.8%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		9/163 (5.5%)
Blood folate decreased	3/46 (6.5%)		2/61 (3.3%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Metabolism and nutrition disorders
Decreased appetite	4/46 (8.7%)		10/61 (16.4%)		7/49 (14.3%)		1/4 (25%)		1/3 (33.3%)		23/163 (14.1%)
Hyperuricaemia	3/46 (6.5%)		0/61 (0%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/46 (17.4%)		18/61 (29.5%)		10/49 (20.4%)		0/4 (0%)		1/3 (33.3%)		37/163 (22.7%)
Myalgia	7/46 (15.2%)		12/61 (19.7%)		4/49 (8.2%)		0/4 (0%)		0/3 (0%)		23/163 (14.1%)
Pain in extremity	8/46 (17.4%)		8/61 (13.1%)		5/49 (10.2%)		0/4 (0%)		1/3 (33.3%)		22/163 (13.5%)
Bone pain	5/46 (10.9%)		4/61 (6.6%)		3/49 (6.1%)		0/4 (0%)		1/3 (33.3%)		13/163 (8%)
Neck pain	4/46 (8.7%)		4/61 (6.6%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		10/163 (6.1%)
Intervertebral disc disorder	3/46 (6.5%)		1/61 (1.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Back pain	7/46 (15.2%)		13/61 (21.3%)		9/49 (18.4%)		0/4 (0%)		0/3 (0%)		29/163 (17.8%)
Muscle spasms	2/46 (4.3%)		5/61 (8.2%)		2/49 (4.1%)		0/4 (0%)		2/3 (66.7%)		11/163 (6.7%)
Nervous system disorders
Headache	14/46 (30.4%)		17/61 (27.9%)		14/49 (28.6%)		2/4 (50%)		0/3 (0%)		47/163 (28.8%)
Paraesthesia	3/46 (6.5%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		1/3 (33.3%)		5/163 (3.1%)
Dizziness	8/46 (17.4%)		9/61 (14.8%)		9/49 (18.4%)		0/4 (0%)		1/3 (33.3%)		27/163 (16.6%)
Psychiatric disorders
Insomnia	4/46 (8.7%)		2/61 (3.3%)		4/49 (8.2%)		0/4 (0%)		1/3 (33.3%)		11/163 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/46 (19.6%)		17/61 (27.9%)		12/49 (24.5%)		0/4 (0%)		1/3 (33.3%)		39/163 (23.9%)
Cough	8/46 (17.4%)		18/61 (29.5%)		3/49 (6.1%)		1/4 (25%)		1/3 (33.3%)		31/163 (19%)
Pleural effusion	6/46 (13%)		13/61 (21.3%)		9/49 (18.4%)		0/4 (0%)		1/3 (33.3%)		29/163 (17.8%)
Oropharyngeal pain	10/46 (21.7%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		11/163 (6.7%)
Productive cough	0/46 (0%)		4/61 (6.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)
Epistaxis	3/46 (6.5%)		1/61 (1.6%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		4/163 (2.5%)
Skin and subcutaneous tissue disorders
Pruritus	5/46 (10.9%)		6/61 (9.8%)		7/49 (14.3%)		0/4 (0%)		0/3 (0%)		18/163 (11%)
Alopecia	5/46 (10.9%)		5/61 (8.2%)		2/49 (4.1%)		0/4 (0%)		1/3 (33.3%)		13/163 (8%)
Dry skin	3/46 (6.5%)		3/61 (4.9%)		5/49 (10.2%)		2/4 (50%)		0/3 (0%)		13/163 (8%)
Skin lesion	4/46 (8.7%)		3/61 (4.9%)		2/49 (4.1%)		0/4 (0%)		0/3 (0%)		9/163 (5.5%)
Erythema	5/46 (10.9%)		2/61 (3.3%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		8/163 (4.9%)
Acne	3/46 (6.5%)		3/61 (4.9%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		7/163 (4.3%)
Rash pruritic	4/46 (8.7%)		3/61 (4.9%)		0/49 (0%)		0/4 (0%)		0/3 (0%)		7/163 (4.3%)
Night sweats	3/46 (6.5%)		0/61 (0%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		4/163 (2.5%)
Rash	9/46 (19.6%)		8/61 (13.1%)		8/49 (16.3%)		0/4 (0%)		0/3 (0%)		25/163 (15.3%)
Vascular disorders
Hypertension	4/46 (8.7%)		1/61 (1.6%)		8/49 (16.3%)		1/4 (25%)		1/3 (33.3%)		15/163 (9.2%)
Haematoma	0/46 (0%)		4/61 (6.6%)		1/49 (2%)		0/4 (0%)		0/3 (0%)		5/163 (3.1%)

Limitations/Caveats

[Not Specified]

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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.