A Study To Describe The Real World Use Of Bosutinib In The UK And Netherlands

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02546375
Collaborator
pH Associates (Other)
87
Enrollment
3
Locations
18.1
Actual Duration (Months)
29
Patients Per Site
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to describe the efficacy and safety of bosutinib in patients with chronic myeloid leukaemia used in a real world setting

Condition or DiseaseIntervention/TreatmentPhase

Study Design

Study Type:
Observational
Actual Enrollment :
87 participants
Observational Model:
Case-Only
Time Perspective:
Retrospective
Official Title:
A RETROSPECTIVE OBSERVATIONAL RESEARCH STUDY TO DESCRIBE THE REAL WORLD USE OF BOSUTINIB IN THE UK AND NETHERLANDS
Actual Study Start Date :
Jul 15, 2015
Actual Primary Completion Date :
Jan 16, 2017
Actual Study Completion Date :
Jan 16, 2017

Arms and Interventions

ArmIntervention/Treatment
Chronic Myeloid Leukaemia

Patients diagnosed with chronic myeloid leukaemia treated with Bosutinib

Drug: Bosutinib
Bosutinib 100mg film-coated tablets; Bosutinib 500mg film-coated tablets Dosage as prescribed at treating institution; (observational study)
Other Names:
  • Bosulif
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Cumulative Complete Haematological Response (CHR) [Baseline up to 5.5 years]

      Haematological response used blood sample of the participants to evaluate response to treatment for CML. Based on the European LeukemiaNet (ELN) 2013 definition: CHR is defined as platelet count less than (<) 450*10^9 per liter, white blood cells count <10*10^9 per liter, no immature granulocytes and <5 percent (%) basophils on differential and a non-palpable spleen.

    2. Percentage of Participants With Cumulative Partial Haematological Response (PHR) [Baseline up to 5.5 years]

      Haematological response used blood sample of the participants to evaluate response to treatment for CML.

    3. Percentage of Participants With Cumulative Complete Cytogenetic Response (CCyR) [Baseline up to 5.5 years]

      Cytogenetic response (CyR) used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by chromosome banding analysis (CBA) or fluorescence in situ hybridisation (FISH). CCyR was indicated by absence of Philadelphia chromosome positive (Ph+) cells metaphases from FISH of blood interphase cell nuclei.

    4. Percentage of Participants With Cumulative Minor Cytogenetic Response (MCyR) [Baseline up to 5.5 years]

      CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. MCyR was indicated by presence of 36-65% Ph+ cells from CBA of bone marrow metaphases.

    5. Percentage of Participants With Cumulative Minimal Cytogenetic Response (mCyR) [Baseline up to 5.5 years]

      CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. mCyR was indicated by presence of 66-95% Ph+ cells from CBA of bone marrow metaphases.

    6. Percentage of Participants With Cumulative Partial Cytogenetic Response (PCyR) [Baseline up to 5.5 years]

      CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. PCyR was indicated by presence of 1-35% Ph+ cells from CBA of bone marrow metaphases.

    7. Percentage of Participants With Cumulative Complete Molecular Response 4.0 (MR4.0) [Baseline up to 5.5 years]

      Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.0 was defined and recorded as detectable disease with <0.01% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with greater than (>) 10,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.

    8. Percentage of Participants With Cumulative Complete Molecular Response 4.5 (MR4.5) [Baseline up to 5.5 years]

      Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.5 was defined and recorded as detectable disease with <0.0032% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with >32,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.

    9. Percentage of Participants With Cumulative Major Molecular Response (MMR)/Molecular Response 3.0 (MR3.0) [Baseline up to 5.5 years]

      Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MMR was defined as a BCR-ABL1 to ABL1 less than or equal to (<=) 0.1% on the IS.

    Secondary Outcome Measures

    1. Percentage of Participants With Treatment Related Adverse Events (AEs) [Baseline up to 5.5 years]

      Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. Relatedness to Bosutinib was assessed by the investigator.

    2. Percentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3 [Baseline up to 5.5 years]

      Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.

    3. Progression-free Survival (PFS) [Year 1, 2, 3]

      PFS was defined as the duration between initiation of Bosutinib therapy and date of progression estimated by the treating physician or death of participant (all causes combined). Progression was defined as change from chronic phase of CML (CP-CML) to accelerated phase of CML (AP-CML) or to blast crisis of CML (BC-CML). CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy. Participants who were alive at the date of last assessment were censored on the date of data collection.

    4. Overall Survival (OS) [From baseline up to 1 Year, baseline up to Year 2, baseline up to Year 3]

      OS was defined as the duration from initiation of Bosutinib therapy to date of death (all causes combined). For participants who were alive or lost to follow-up (LTFU), overall survival was censored on the date of data collection or date LTFU, respectively.

    5. Percentage of Participants With Disease Progression [Year 1, 2, 3]

      Progression was defined as change from CP-CML to AP-CML or to BC-CML. CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy.

    6. Percentage of Participants With Permanent Discontinuation From Bosutinib Therapy [Baseline up to 5.5 years]

    7. Cross-Intolerance Between Bosutinib and Previous Therapy [Baseline up to 5.5 years]

      Cross-intolerance was defined as percentage of participants who permanently discontinued bosutinib due to an adverse event which also resulted in discontinuation of a previous treatment (imatinib, dasatinib, nilotinib).

    8. Mean Dose of Bosutinib at Initiation of Treatment [Baseline up to 5.5 years]

    9. Relative Bosutinib Dose Intensity [Baseline up to 5.5 years]

      Relative dose intensity was defined as the percentage of daily dose received over the expected daily dose of the study drug.

    10. Duration of Bosutinib Therapy [Baseline up to 5.5 years]

      The duration from initiation of Bosutinib therapy up to the end of Bosutinib therapy was reported in this outcome measure.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of Ph+ CML aged ≥18 years at bosutinib initiation.

    • Prescribed bosutinib (irrespective of the phase of their disease) EITHER in normal clinical practice since it received marketing authorisation (27th March 2013) by the EMA11 OR via the compassionate use programme prior to marketing authorization.

    • Where required, evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

    Exclusion Criteria:
    • Prescribed bosutinib as part of an interventional clinical trial programme.

    • Initiated on bosutinib less than 3 months prior to data collection taking place.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Royal Liverpool HospitalLiverpoolMerseysideUnited KingdomL7 8XP
    2Hammersmith HospitalLondonUnited KingdomW12 0HS
    3Nottingham University HospitalNottinghamUnited KingdomNG5 1PB

    Sponsors and Collaborators

    • Pfizer
    • pH Associates

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02546375
    Other Study ID Numbers:
    • B1871052
    First Posted:
    Sep 10, 2015
    Last Update Posted:
    Jul 15, 2019
    Last Verified:
    May 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Pfizer
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive chronic myeloid leukemia (CML) receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 milligram (mg), were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved Summary of Product Characteristics (SmPC).
    Period Title: Overall Study
    STARTED87
    COMPLETED87
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Overall Participants87
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.3
    (14.3)
    Sex/Gender, Customized (Count of Participants)
    Female
    40
    46%
    Male
    47
    54%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants With Cumulative Complete Haematological Response (CHR)
    DescriptionHaematological response used blood sample of the participants to evaluate response to treatment for CML. Based on the European LeukemiaNet (ELN) 2013 definition: CHR is defined as platelet count less than (<) 450*10^9 per liter, white blood cells count <10*10^9 per liter, no immature granulocytes and <5 percent (%) basophils on differential and a non-palpable spleen.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    93
    106.9%
    2. Primary Outcome
    TitlePercentage of Participants With Cumulative Partial Haematological Response (PHR)
    DescriptionHaematological response used blood sample of the participants to evaluate response to treatment for CML.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    94
    108%
    3. Primary Outcome
    TitlePercentage of Participants With Cumulative Complete Cytogenetic Response (CCyR)
    DescriptionCytogenetic response (CyR) used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by chromosome banding analysis (CBA) or fluorescence in situ hybridisation (FISH). CCyR was indicated by absence of Philadelphia chromosome positive (Ph+) cells metaphases from FISH of blood interphase cell nuclei.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    67
    77%
    4. Primary Outcome
    TitlePercentage of Participants With Cumulative Minor Cytogenetic Response (MCyR)
    DescriptionCyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. MCyR was indicated by presence of 36-65% Ph+ cells from CBA of bone marrow metaphases.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    77
    88.5%
    5. Primary Outcome
    TitlePercentage of Participants With Cumulative Minimal Cytogenetic Response (mCyR)
    DescriptionCyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. mCyR was indicated by presence of 66-95% Ph+ cells from CBA of bone marrow metaphases.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    80
    92%
    6. Primary Outcome
    TitlePercentage of Participants With Cumulative Partial Cytogenetic Response (PCyR)
    DescriptionCyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. PCyR was indicated by presence of 1-35% Ph+ cells from CBA of bone marrow metaphases.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    77
    88.5%
    7. Primary Outcome
    TitlePercentage of Participants With Cumulative Complete Molecular Response 4.0 (MR4.0)
    DescriptionMolecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.0 was defined and recorded as detectable disease with <0.01% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with greater than (>) 10,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    33
    37.9%
    8. Primary Outcome
    TitlePercentage of Participants With Cumulative Complete Molecular Response 4.5 (MR4.5)
    DescriptionMolecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.5 was defined and recorded as detectable disease with <0.0032% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with >32,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    27
    31%
    9. Primary Outcome
    TitlePercentage of Participants With Cumulative Major Molecular Response (MMR)/Molecular Response 3.0 (MR3.0)
    DescriptionMolecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MMR was defined as a BCR-ABL1 to ABL1 less than or equal to (<=) 0.1% on the IS.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    Number [percentage of participants]
    55
    63.2%
    10. Secondary Outcome
    TitlePercentage of Participants With Treatment Related Adverse Events (AEs)
    DescriptionTreatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. Relatedness to Bosutinib was assessed by the investigator.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Number [percentage of participants]
    94
    108%
    11. Secondary Outcome
    TitlePercentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3
    DescriptionTreatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Number [percentage of participants]
    21
    24.1%
    12. Secondary Outcome
    TitleProgression-free Survival (PFS)
    DescriptionPFS was defined as the duration between initiation of Bosutinib therapy and date of progression estimated by the treating physician or death of participant (all causes combined). Progression was defined as change from chronic phase of CML (CP-CML) to accelerated phase of CML (AP-CML) or to blast crisis of CML (BC-CML). CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy. Participants who were alive at the date of last assessment were censored on the date of data collection.
    Time FrameYear 1, 2, 3

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Median (95% Confidence Interval) [years]
    NA
    13. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was defined as the duration from initiation of Bosutinib therapy to date of death (all causes combined). For participants who were alive or lost to follow-up (LTFU), overall survival was censored on the date of data collection or date LTFU, respectively.
    Time FrameFrom baseline up to 1 Year, baseline up to Year 2, baseline up to Year 3

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Median (95% Confidence Interval) [years]
    NA
    14. Secondary Outcome
    TitlePercentage of Participants With Disease Progression
    DescriptionProgression was defined as change from CP-CML to AP-CML or to BC-CML. CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy.
    Time FrameYear 1, 2, 3

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure and number analyzed (n) signifies those participants who were evaluable at specified time points only.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants84
    1 year
    3
    3.4%
    2 year
    3
    3.4%
    3 year
    0
    0%
    15. Secondary Outcome
    TitlePercentage of Participants With Permanent Discontinuation From Bosutinib Therapy
    Description
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Adverse event
    14
    16.1%
    Loss of response
    5
    5.7%
    Treatment failure
    11
    12.6%
    Participant request
    2
    2.3%
    Death
    2
    2.3%
    Disease progression
    1
    1.1%
    Other
    2
    2.3%
    16. Secondary Outcome
    TitleCross-Intolerance Between Bosutinib and Previous Therapy
    DescriptionCross-intolerance was defined as percentage of participants who permanently discontinued bosutinib due to an adverse event which also resulted in discontinuation of a previous treatment (imatinib, dasatinib, nilotinib).
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Number [percentage of participants]
    1.1
    1.3%
    17. Secondary Outcome
    TitleMean Dose of Bosutinib at Initiation of Treatment
    Description
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Mean (Standard Deviation) [milligram per day]
    331.0
    (126.6)
    18. Secondary Outcome
    TitleRelative Bosutinib Dose Intensity
    DescriptionRelative dose intensity was defined as the percentage of daily dose received over the expected daily dose of the study drug.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Number [percentage of daily dose]
    66
    19. Secondary Outcome
    TitleDuration of Bosutinib Therapy
    DescriptionThe duration from initiation of Bosutinib therapy up to the end of Bosutinib therapy was reported in this outcome measure.
    Time FrameBaseline up to 5.5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    Measure Participants87
    Median (Full Range) [months]
    15.6

    Adverse Events

    Time FrameBaseline up to 5.5 years
    Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
    Arm/Group TitleBosutinib
    Arm/Group DescriptionParticipants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
    All Cause Mortality
    Bosutinib
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Bosutinib
    Affected / at Risk (%)# Events
    Total17/87 (19.5%)
    Blood and lymphatic system disorders
    Anaemia0/87 (0%)
    Creatinine increased0/87 (0%)
    Neutropenia0/87 (0%)
    Thrombocytopenia1/87 (1.1%)
    Cardiac disorders
    Atrial fibrillation0/87 (0%)
    Cardiac failure2/87 (2.3%)
    Hypertension0/87 (0%)
    Eye disorders
    Diseases of the eye1/87 (1.1%)
    Gastrointestinal disorders
    Abdominal Distension0/87 (0%)
    Abdominal pain0/87 (0%)
    Constipation0/87 (0%)
    Diarrhoea1/87 (1.1%)
    Dyspepsia0/87 (0%)
    Nausea0/87 (0%)
    Vomiting1/87 (1.1%)
    General disorders
    Alopecia0/87 (0%)
    Asthenia0/87 (0%)
    Chest pain1/87 (1.1%)
    Fatigue0/87 (0%)
    Oedema0/87 (0%)
    Pain0/87 (0%)
    Pyrexia0/87 (0%)
    Other1/87 (1.1%)
    Lack of efficacy4/87 (4.6%)
    Haematological - not determined1/87 (1.1%)
    Hepatobiliary disorders
    Alanine aminotransferase increased1/87 (1.1%)
    Hepatotoxicity0/87 (0%)
    Infections and infestations
    Pneumonia1/87 (1.1%)
    Respiratory tract infection0/87 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain0/87 (0%)
    Bone pain0/87 (0%)
    Muscle cramps0/87 (0%)
    Myalgia0/87 (0%)
    Pain in extremity0/87 (0%)
    Nervous system disorders
    Dizziness0/87 (0%)
    Headache0/87 (0%)
    Renal and urinary disorders
    Pyelonephritis1/87 (1.1%)
    Reproductive system and breast disorders
    Pregnancy1/87 (1.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough0/87 (0%)
    Dyspnoea0/87 (0%)
    Pleural effusion1/87 (1.1%)
    Skin and subcutaneous tissue disorders
    Acne0/87 (0%)
    Dry skin0/87 (0%)
    Rash0/87 (0%)
    Other (Not Including Serious) Adverse Events
    Bosutinib
    Affected / at Risk (%)# Events
    Total81/87 (93.1%)
    Blood and lymphatic system disorders
    Anaemia3/87 (3.4%)
    Creatinine increased5/87 (5.7%)
    Neutropenia1/87 (1.1%)
    Thrombocytopenia6/87 (6.9%)
    Cardiac disorders
    Atrial fibrillation3/87 (3.4%)
    Cardiac failure0/87 (0%)
    Hypertension1/87 (1.1%)
    Cardiac disorder1/87 (1.1%)
    Eye disorders
    Diseases of the eye1/87 (1.1%)
    Gastrointestinal disorders
    Abdominal Distension1/87 (1.1%)
    Abdominal pain8/87 (9.2%)
    Constipation1/87 (1.1%)
    Diarrhoea45/87 (51.7%)
    Dyspepsia4/87 (4.6%)
    Nausea18/87 (20.7%)
    Vomiting4/87 (4.6%)
    Mucositis1/87 (1.1%)
    Unusual taste in mouth1/87 (1.1%)
    General disorders
    Alopecia3/87 (3.4%)
    Asthenia1/87 (1.1%)
    Chest pain7/87 (8%)
    Fatigue16/87 (18.4%)
    Oedema1/87 (1.1%)
    Pain5/87 (5.7%)
    Pyrexia1/87 (1.1%)
    Other0/87 (0%)
    Lack of efficacy10/87 (11.5%)
    Haematological - not determined4/87 (4.6%)
    Fever1/87 (1.1%)
    Medication error1/87 (1.1%)
    Rigors associates with extreme tiredness and thirst1/87 (1.1%)
    1/87 (1.1%)
    Weight gain1/87 (1.1%)
    Hepatobiliary disorders
    Alanine aminotransferase increased15/87 (17.2%)
    Hepatotoxicity1/87 (1.1%)
    Infections and infestations
    Pneumonia0/87 (0%)
    Respiratory tract infection1/87 (1.1%)
    Flu like symptoms1/87 (1.1%)
    Musculoskeletal and connective tissue disorders
    Back pain1/87 (1.1%)
    Bone pain4/87 (4.6%)
    Muscle cramps1/87 (1.1%)
    Myalgia4/87 (4.6%)
    Pain in extremity6/87 (6.9%)
    Vitamin D deficiency1/87 (1.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Exostosis - benign growths of bone1/87 (1.1%)
    Nervous system disorders
    Dizziness2/87 (2.3%)
    Headache8/87 (9.2%)
    Depression2/87 (2.3%)
    Sleep disturbance1/87 (1.1%)
    Renal and urinary disorders
    Urinary tract infection2/87 (2.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough1/87 (1.1%)
    Dyspnoea3/87 (3.4%)
    Pleural effusion3/87 (3.4%)
    Skin and subcutaneous tissue disorders
    Acne1/87 (1.1%)
    Dry skin2/87 (2.3%)
    Rash15/87 (17.2%)
    Altered skin sensation1/87 (1.1%)
    Breaking nails1/87 (1.1%)
    Skin lesion1/87 (1.1%)

    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:
    NCT02546375
    Other Study ID Numbers:
    • B1871052
    First Posted:
    Sep 10, 2015
    Last Update Posted:
    Jul 15, 2019
    Last Verified:
    May 1, 2019