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

Completed
Conditions
Chronic Myeloid Leukaemia
Interventions
Registration Number
NCT02546375
Lead Sponsor
Pfizer
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
87
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Chronic Myeloid LeukaemiaBosutinibPatients diagnosed with chronic myeloid leukaemia treated with Bosutinib
Primary Outcome Measures
NameTimeMethod
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.

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.

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures
NameTimeMethod
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.

Percentage of Participants With Disease ProgressionYear 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.

Percentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3Baseline 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.

Percentage of Participants With Permanent Discontinuation From Bosutinib TherapyBaseline up to 5.5 years
Cross-Intolerance Between Bosutinib and Previous TherapyBaseline 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).

Mean Dose of Bosutinib at Initiation of TreatmentBaseline up to 5.5 years
Relative Bosutinib Dose IntensityBaseline 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.

Duration of Bosutinib TherapyBaseline 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.

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.

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.

Trial Locations

Locations (3)

Hammersmith Hospital

🇬🇧

London, United Kingdom

Nottingham University Hospital

🇬🇧

Nottingham, United Kingdom

Royal Liverpool Hospital

🇬🇧

Liverpool, Merseyside, United Kingdom

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