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)
163
Enrollment
48
Locations
1
Arm
71.2
Actual Duration (Months)
3.4
Patients Per Site
0
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Keck Hospital of USCLos AngelesCaliforniaUnited States90033
    2LAC+USC Medical CenterLos AngelesCaliforniaUnited States90033
    3USC/Norris Comprehensive Cancer CenterLos AngelesCaliforniaUnited States90033
    4Sylvester Deerfield BeachDeerfield BeachFloridaUnited States33442
    5University of Miami Hospital & ClinicsMiamiFloridaUnited States33136
    6Indiana Blood and Marrow Transplantation-ClinicIndianapolisIndianaUnited States46237
    7Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreMarylandUnited States21287
    8Siteman Cancer Center - West CountyCreve CoeurMissouriUnited States63141-6337
    9Barnes-Jewish HospitalSaint LouisMissouriUnited States63110
    10Washington University School of MedicineSaint LouisMissouriUnited States63110
    11Siteman Cancer Center - South CountySaint LouisMissouriUnited States63129
    12Weill Cornell Medical College - New York-Presbyterian HospitalNew YorkNew YorkUnited States10021
    13Seattle Cancer Care AllianceSeattleWashingtonUnited States98109
    14Medizinische Universitaet InnsbruckInnsbruckAustria6020
    15Ordensklinikum Linz Gmbh Barmherzige SchwesternLinzAustria4010
    16Institut BergonieBordeaux Cedex 09France33076
    17Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- OncologyLe Chesnay CedexFrance78157
    18Centre Regional De Lutte Contre Le CancerMarseilleFrance13009
    19Hopital Archet INice Cedex 3France06202
    20Institut Universitaire du Cancer Toulouse - OncopoleToulouse Cedex 9France31059
    21CHU BraboisVandoeuvre-les-Nancy cedexFrance54511
    22RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und StammzelltransplantationAachenGermany52074
    23Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)BerlinGermany13353
    24Universitaetsklinikum Hamburg-EppendorfHamburgGermany20246
    25Klinik fur Innere Medizin IIJenaGermany07747
    26Universitaetsklinikum Koeln (AoeR)KoelnGermany50937
    27III. Medizinische Klinik Universitaetsmedizin MannheimMannheimGermanyD-68167
    28AOU Policlinico Consorziale di Bari - UO Ematologia con TrapiantoBariBAItaly70124
    29A.O.U. Policlinico S. Orsola-MalpighiBolognaBOItaly40138
    30Azienda Socio Sanitaria Territoriale - ASST MonzaMonzaMBItaly20900
    31Ospedale S. Eugenio - UOC EmatologiaRomeRMItaly00144
    32AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo EmatologicoOrbassanoTOItaly10043
    33AOU Policlinico Vittorio Emanuele-P.O.G. RodolicoCataniaItaly95123
    34SOD EmatologiaFirenzeItaly50134
    35A.O. Ospedale Niguarda Ca Granda - SC EmatologiaMilanoItaly20162
    36Haukeland UniversitetssjukehusBergenNorway5021
    37St Olav HospitalTrondheimNorway7030
    38Hospital Universitario Quiron MadridPozuelo de AlarconMadridSpain28223
    39Hospital Universitari Vall d' HebronBarcelonaSpain08035
    40Hospital Universitari Vall d'HebronBarcelonaSpain08035
    41Hospital Clinic De BarcelonaBarcelonaSpain08036
    42Hospital Universitario de La PrincesaMadridSpain28006
    43Hospital Universitario Ramon y CajalMadridSpain28034
    44Hospital Clinico Universitario de SalamancaSalamancaSpain37007
    45Hospital Universitari i Politecnic La Fe de ValenciaValenciaSpain46026
    46Hospital de dia Quiron ZaragozaZaragozaSpain50012
    47Hematologiskt centrumStockholmSweden171 76
    48Akademiska SjukhusetUppsalaSweden751 85

    Sponsors and Collaborators

    • Pfizer
    • Developmental Therapeutics Consortium

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants 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 DetailA 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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
    STARTED46614943
    COMPLETED36432821
    NOT COMPLETED10182122

    Baseline Characteristics

    Arm/Group TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaTotal
    Arm/Group DescriptionParticipants 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 Participants46614943163
    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
    TitlePercentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
    DescriptionConfirmed 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 FrameUp 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 TitleBosutinib, Chronic Phase 2nd and 3rd Line Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants with philadelphia chromosome positive chronic phase 2nd and 3rd line chronic myelogenous leukemia.
    Measure Participants98
    Number (95% Confidence Interval) [percentage of participants]
    76.5
    166.3%
    2. Primary Outcome
    TitlePercentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants
    DescriptionConfirmed 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 FrameUp 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 TitleBosutinib: Chronic Phase 4th Line Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants with philadelphia chromosome positive chronic phase 4th line chronic myelogenous leukemia.
    Measure Participants45
    Number (95% Confidence Interval) [percentage of participants]
    62.2
    135.2%
    3. Primary Outcome
    TitlePercentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants
    DescriptionConfirmed 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 FrameUp 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 TitleBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
    Measure Participants4
    Number (95% Confidence Interval) [percentage of participants]
    75.0
    163%
    4. Secondary Outcome
    TitlePercentage of Participants With Cumulative Major Cytogenetic Response (MCyR)
    DescriptionCyR 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 FrameUp 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants4355454
    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
    TitlePercentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)
    DescriptionConfirmed 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 FrameUp 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 TitleBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
    Measure Participants4
    Number (95% Confidence Interval) [percentage of participants]
    75.0
    163%
    6. Secondary Outcome
    TitlePercentage of Participants With Cumulative Best Response
    DescriptionHierarchy 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 FrameUp 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants4661494
    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
    TitlePercentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24
    DescriptionCyR 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 FrameMonths 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants4355454
    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
    TitlePercentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24
    DescriptionConfirmed 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 FrameMonths 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 TitleBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants with philadelphia chromosome positive accelerated phase chronic myelogenous leukemia.
    Measure Participants4
    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
    TitlePercentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)
    DescriptionCHR 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 FrameUp 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants4661484
    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
    TitlePercentage of Participants With Cumulative Major Molecular Response (MMR)
    DescriptionMolecular 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 FrameUp 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants4655484
    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
    TitleKaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36
    DescriptionKaplan-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 FrameAt 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants3746333
    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
    TitleKaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36
    DescriptionKaplan-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 FrameAt 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants3842272
    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
    TitleNumber of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs
    DescriptionAn 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 FrameFirst 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants46614943163
    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
    TitleNumber 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
    DescriptionAn 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 FrameFirst 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants46614943163
    Count of Participants [Participants]
    36
    78.3%
    49
    80.3%
    39
    79.6%
    2
    50%
    3
    100%
    129
    79.1%
    15. Secondary Outcome
    TitleNumber of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs)
    DescriptionAn 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 FrameFirst 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants46614943163
    Count of Participants [Participants]
    46
    100%
    61
    100%
    48
    98%
    4
    100%
    3
    100%
    162
    99.4%
    16. Secondary Outcome
    TitleNumber of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
    DescriptionNumber 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 FrameFirst 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 Participants46614943163
    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 FrameFrom 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 TitleBosutinib: Chronic Phase 2nd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Arm/Group DescriptionParticipants 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 LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/46 (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 LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total21/46 (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
    Anaemia1/46 (2.2%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 3/163 (1.8%)
    Abdominal lymphadenopathy1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Lymphadenopathy1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pancytopenia0/46 (0%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 1/163 (0.6%)
    Cardiac disorders
    Cardiac failure2/46 (4.3%) 3/61 (4.9%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 6/163 (3.7%)
    Atrial fibrillation3/46 (6.5%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Pericardial effusion2/46 (4.3%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 1/3 (33.3%) 4/163 (2.5%)
    Angina pectoris1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Angina unstable1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Atrioventricular block complete0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Bundle branch block right0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Cardiac failure congestive0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Cardiogenic shock0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Cardiomyopathy1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Coronary artery occlusion0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Sinus node dysfunction1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Eye disorders
    Keratoconus1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Gastrointestinal disorders
    Abdominal pain0/46 (0%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 2/163 (1.2%)
    Appendiceal mucocoele0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Ascites0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Colitis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Gastritis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Gastrointestinal haemorrhage0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Gastrooesophageal reflux disease1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Hiatus hernia0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Ileus0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Oesophageal fistula1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pancreatitis0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Rectal polyp0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Subileus1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    General disorders
    Pyrexia1/46 (2.2%) 3/61 (4.9%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 4/163 (2.5%)
    Chest pain0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Multiple organ dysfunction syndrome1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Hepatobiliary disorders
    Cholecystitis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Cholelithiasis0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Hepatic cirrhosis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Immune system disorders
    Hypersensitivity0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Infections and infestations
    Pneumonia0/46 (0%) 2/61 (3.3%) 3/49 (6.1%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Cellulitis0/46 (0%) 0/61 (0%) 1/49 (2%) 1/4 (25%) 0/3 (0%) 2/163 (1.2%)
    Appendicitis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Bronchitis0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pneumonia pneumococcal1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pseudomembranous colitis1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Sepsis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Urinary tract infection0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Viral infection1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Injury, poisoning and procedural complications
    Arterial restenosis0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Femur fracture0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Hip fracture0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Rib fracture0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Spinal fracture0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Subdural haematoma1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Tendon rupture1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Investigations
    Blood creatinine increased0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Metabolism and nutrition disorders
    Diabetes mellitus0/46 (0%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 1/163 (0.6%)
    Diabetic ketoacidosis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Fluid retention0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Metabolic disorder1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Musculoskeletal and connective tissue disorders
    Back pain1/46 (2.2%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 3/163 (1.8%)
    Groin pain0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Musculoskeletal pain0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Neck pain1/46 (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 colon0/46 (0%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 1/163 (0.6%)
    Anaplastic large-cell lymphoma0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Brain neoplasm0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Laryngeal squamous cell carcinoma1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Lung neoplasm malignant0/46 (0%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 1/163 (0.6%)
    Lymphoma0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Metastases to liver1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pancreatic carcinoma1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Prostate cancer0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Squamous cell carcinoma of lung0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Nervous system disorders
    Syncope1/46 (2.2%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 3/163 (1.8%)
    Cerebrovascular accident0/46 (0%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 2/163 (1.2%)
    Transient ischaemic attack1/46 (2.2%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 2/163 (1.2%)
    Sciatica1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Psychiatric disorders
    Anxiety0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Renal and urinary disorders
    Acute kidney injury2/46 (4.3%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 4/163 (2.5%)
    Chronic kidney disease0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Reproductive system and breast disorders
    Breast mass0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Ovarian cyst ruptured0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion2/46 (4.3%) 1/61 (1.6%) 3/49 (6.1%) 0/4 (0%) 1/3 (33.3%) 7/163 (4.3%)
    Respiratory failure1/46 (2.2%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 3/163 (1.8%)
    Dyspnoea1/46 (2.2%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 2/163 (1.2%)
    Acute respiratory failure0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Emphysema1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Haemoptysis1/46 (2.2%) 0/61 (0%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Hypoxia0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Lung disorder0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pneumonitis0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Pulmonary hypertension0/46 (0%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Skin and subcutaneous tissue disorders
    Skin ulcer0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Vascular disorders
    Peripheral arterial occlusive disease0/46 (0%) 2/61 (3.3%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 3/163 (1.8%)
    Peripheral ischaemia0/46 (0%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 2/163 (1.2%)
    Haemorrhage0/46 (0%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 1/163 (0.6%)
    Shock haemorrhagic0/46 (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 LeukemiaBosutinib: Chronic Phase 3rd Line Chronic Myelogenous LeukemiaBosutinib: Chronic Phase 4th Line Chronic Myelogenous LeukemiaBosutinib: Accelerated Phase Chronic Myelogenous LeukemiaBosutinib: Philadelphia Chromosome Negative Chronic Myelogenous LeukemiaBosutinib: Chronic Myelogenous Leukemia
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total46/46 (100%) 61/61 (100%) 48/49 (98%) 4/4 (100%) 3/3 (100%) 162/163 (99.4%)
    Blood and lymphatic system disorders
    Anaemia7/46 (15.2%) 14/61 (23%) 5/49 (10.2%) 0/4 (0%) 2/3 (66.7%) 28/163 (17.2%)
    Thrombocytopenia7/46 (15.2%) 6/61 (9.8%) 4/49 (8.2%) 1/4 (25%) 1/3 (33.3%) 19/163 (11.7%)
    Neutropenia3/46 (6.5%) 4/61 (6.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 7/163 (4.3%)
    Cardiac disorders
    Atrial fibrillation4/46 (8.7%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 6/163 (3.7%)
    Cardiac failure3/46 (6.5%) 2/61 (3.3%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 6/163 (3.7%)
    Eye disorders
    Dry eye3/46 (6.5%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Conjunctival hyperaemia3/46 (6.5%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Gastrointestinal disorders
    Diarrhoea43/46 (93.5%) 54/61 (88.5%) 42/49 (85.7%) 4/4 (100%) 2/3 (66.7%) 145/163 (89%)
    Nausea15/46 (32.6%) 29/61 (47.5%) 25/49 (51%) 1/4 (25%) 0/3 (0%) 70/163 (42.9%)
    Vomiting13/46 (28.3%) 22/61 (36.1%) 19/49 (38.8%) 0/4 (0%) 1/3 (33.3%) 55/163 (33.7%)
    Abdominal pain14/46 (30.4%) 17/61 (27.9%) 16/49 (32.7%) 2/4 (50%) 0/3 (0%) 49/163 (30.1%)
    Abdominal pain upper19/46 (41.3%) 8/61 (13.1%) 9/49 (18.4%) 0/4 (0%) 1/3 (33.3%) 37/163 (22.7%)
    Constipation13/46 (28.3%) 11/61 (18%) 7/49 (14.3%) 0/4 (0%) 1/3 (33.3%) 32/163 (19.6%)
    Dyspepsia4/46 (8.7%) 6/61 (9.8%) 3/49 (6.1%) 1/4 (25%) 0/3 (0%) 14/163 (8.6%)
    Abdominal distension3/46 (6.5%) 5/61 (8.2%) 3/49 (6.1%) 0/4 (0%) 0/3 (0%) 11/163 (6.7%)
    Gastrooesophageal reflux disease4/46 (8.7%) 3/61 (4.9%) 2/49 (4.1%) 1/4 (25%) 0/3 (0%) 10/163 (6.1%)
    Flatulence5/46 (10.9%) 3/61 (4.9%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 9/163 (5.5%)
    Abdominal discomfort3/46 (6.5%) 2/61 (3.3%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 6/163 (3.7%)
    Gastrointestinal disorder3/46 (6.5%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 4/163 (2.5%)
    General disorders
    Fatigue10/46 (21.7%) 15/61 (24.6%) 19/49 (38.8%) 1/4 (25%) 1/3 (33.3%) 46/163 (28.2%)
    Asthenia20/46 (43.5%) 9/61 (14.8%) 6/49 (12.2%) 1/4 (25%) 0/3 (0%) 36/163 (22.1%)
    Pyrexia7/46 (15.2%) 11/61 (18%) 13/49 (26.5%) 0/4 (0%) 0/3 (0%) 31/163 (19%)
    Oedema peripheral9/46 (19.6%) 11/61 (18%) 9/49 (18.4%) 0/4 (0%) 0/3 (0%) 29/163 (17.8%)
    Chest pain4/46 (8.7%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 6/163 (3.7%)
    Influenza like illness4/46 (8.7%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 6/163 (3.7%)
    Infections and infestations
    Nasopharyngitis7/46 (15.2%) 11/61 (18%) 8/49 (16.3%) 0/4 (0%) 0/3 (0%) 26/163 (16%)
    Influenza6/46 (13%) 3/61 (4.9%) 5/49 (10.2%) 0/4 (0%) 0/3 (0%) 14/163 (8.6%)
    Urinary tract infection1/46 (2.2%) 6/61 (9.8%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 9/163 (5.5%)
    Bronchitis3/46 (6.5%) 3/61 (4.9%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 8/163 (4.9%)
    Upper respiratory tract infection1/46 (2.2%) 5/61 (8.2%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 8/163 (4.9%)
    Folliculitis6/46 (13%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 7/163 (4.3%)
    Injury, poisoning and procedural complications
    Fall2/46 (4.3%) 10/61 (16.4%) 3/49 (6.1%) 0/4 (0%) 0/3 (0%) 15/163 (9.2%)
    Investigations
    Alanine aminotransferase increased10/46 (21.7%) 18/61 (29.5%) 16/49 (32.7%) 0/4 (0%) 0/3 (0%) 44/163 (27%)
    Aspartate aminotransferase increased9/46 (19.6%) 11/61 (18%) 13/49 (26.5%) 0/4 (0%) 0/3 (0%) 33/163 (20.2%)
    Blood creatinine increased8/46 (17.4%) 7/61 (11.5%) 10/49 (20.4%) 1/4 (25%) 0/3 (0%) 26/163 (16%)
    Lipase increased9/46 (19.6%) 11/61 (18%) 5/49 (10.2%) 0/4 (0%) 0/3 (0%) 25/163 (15.3%)
    Amylase increased5/46 (10.9%) 8/61 (13.1%) 3/49 (6.1%) 0/4 (0%) 0/3 (0%) 16/163 (9.8%)
    Weight decreased2/46 (4.3%) 7/61 (11.5%) 4/49 (8.2%) 0/4 (0%) 1/3 (33.3%) 14/163 (8.6%)
    Gamma-glutamyl transferase increased3/46 (6.5%) 6/61 (9.8%) 3/49 (6.1%) 0/4 (0%) 1/3 (33.3%) 13/163 (8%)
    Blood uric acid increased1/46 (2.2%) 6/61 (9.8%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 9/163 (5.5%)
    Blood folate decreased3/46 (6.5%) 2/61 (3.3%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Metabolism and nutrition disorders
    Decreased appetite4/46 (8.7%) 10/61 (16.4%) 7/49 (14.3%) 1/4 (25%) 1/3 (33.3%) 23/163 (14.1%)
    Hyperuricaemia3/46 (6.5%) 0/61 (0%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia8/46 (17.4%) 18/61 (29.5%) 10/49 (20.4%) 0/4 (0%) 1/3 (33.3%) 37/163 (22.7%)
    Myalgia7/46 (15.2%) 12/61 (19.7%) 4/49 (8.2%) 0/4 (0%) 0/3 (0%) 23/163 (14.1%)
    Pain in extremity8/46 (17.4%) 8/61 (13.1%) 5/49 (10.2%) 0/4 (0%) 1/3 (33.3%) 22/163 (13.5%)
    Bone pain5/46 (10.9%) 4/61 (6.6%) 3/49 (6.1%) 0/4 (0%) 1/3 (33.3%) 13/163 (8%)
    Neck pain4/46 (8.7%) 4/61 (6.6%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 10/163 (6.1%)
    Intervertebral disc disorder3/46 (6.5%) 1/61 (1.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Back pain7/46 (15.2%) 13/61 (21.3%) 9/49 (18.4%) 0/4 (0%) 0/3 (0%) 29/163 (17.8%)
    Muscle spasms2/46 (4.3%) 5/61 (8.2%) 2/49 (4.1%) 0/4 (0%) 2/3 (66.7%) 11/163 (6.7%)
    Nervous system disorders
    Headache14/46 (30.4%) 17/61 (27.9%) 14/49 (28.6%) 2/4 (50%) 0/3 (0%) 47/163 (28.8%)
    Paraesthesia3/46 (6.5%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 1/3 (33.3%) 5/163 (3.1%)
    Dizziness8/46 (17.4%) 9/61 (14.8%) 9/49 (18.4%) 0/4 (0%) 1/3 (33.3%) 27/163 (16.6%)
    Psychiatric disorders
    Insomnia4/46 (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
    Dyspnoea9/46 (19.6%) 17/61 (27.9%) 12/49 (24.5%) 0/4 (0%) 1/3 (33.3%) 39/163 (23.9%)
    Cough8/46 (17.4%) 18/61 (29.5%) 3/49 (6.1%) 1/4 (25%) 1/3 (33.3%) 31/163 (19%)
    Pleural effusion6/46 (13%) 13/61 (21.3%) 9/49 (18.4%) 0/4 (0%) 1/3 (33.3%) 29/163 (17.8%)
    Oropharyngeal pain10/46 (21.7%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 11/163 (6.7%)
    Productive cough0/46 (0%) 4/61 (6.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)
    Epistaxis3/46 (6.5%) 1/61 (1.6%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 4/163 (2.5%)
    Skin and subcutaneous tissue disorders
    Pruritus5/46 (10.9%) 6/61 (9.8%) 7/49 (14.3%) 0/4 (0%) 0/3 (0%) 18/163 (11%)
    Alopecia5/46 (10.9%) 5/61 (8.2%) 2/49 (4.1%) 0/4 (0%) 1/3 (33.3%) 13/163 (8%)
    Dry skin3/46 (6.5%) 3/61 (4.9%) 5/49 (10.2%) 2/4 (50%) 0/3 (0%) 13/163 (8%)
    Skin lesion4/46 (8.7%) 3/61 (4.9%) 2/49 (4.1%) 0/4 (0%) 0/3 (0%) 9/163 (5.5%)
    Erythema5/46 (10.9%) 2/61 (3.3%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 8/163 (4.9%)
    Acne3/46 (6.5%) 3/61 (4.9%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 7/163 (4.3%)
    Rash pruritic4/46 (8.7%) 3/61 (4.9%) 0/49 (0%) 0/4 (0%) 0/3 (0%) 7/163 (4.3%)
    Night sweats3/46 (6.5%) 0/61 (0%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 4/163 (2.5%)
    Rash9/46 (19.6%) 8/61 (13.1%) 8/49 (16.3%) 0/4 (0%) 0/3 (0%) 25/163 (15.3%)
    Vascular disorders
    Hypertension4/46 (8.7%) 1/61 (1.6%) 8/49 (16.3%) 1/4 (25%) 1/3 (33.3%) 15/163 (9.2%)
    Haematoma0/46 (0%) 4/61 (6.6%) 1/49 (2%) 0/4 (0%) 0/3 (0%) 5/163 (3.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/TitlePfizer ClinicalTrials.gov Call Center
    OrganizationPfizer Inc.
    Phone1-800-718-1021
    EmailClinicalTrials.gov_Inquiries@pfizer.com
    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