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

A RETROSPECTIVE OBSERVATIONAL RESEARCH STUDY TO DESCRIBE THE REAL WORLD USE OF BOSUTINIB IN THE UK AND NETHERLANDS

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

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukaemia
• Intervention / Treatment: Drug: Bosutinib

• Study Type: Observational
• Enrollment (Actual): 87

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Royal Liverpool Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

CML out-patient clinics

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Cumulative Complete Haematological Response (CHR)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Partial Haematological Response (PHR)	Haematological response used blood sample of the participants to evaluate response to treatment for CML.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Complete Cytogenetic Response (CCyR)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Minor Cytogenetic Response (MCyR)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Minimal Cytogenetic Response (mCyR)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Partial Cytogenetic Response (PCyR)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Complete Molecular Response 4.0 (MR4.0)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Complete Molecular Response 4.5 (MR4.5)	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.	Baseline up to 5.5 years
Percentage of Participants With Cumulative Major Molecular Response (MMR)/Molecular Response 3.0 (MR3.0)	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.	Baseline up to 5.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Related Adverse Events (AEs)	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.	Baseline up to 5.5 years
Percentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3	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.	Baseline up to 5.5 years
Progression-free Survival (PFS)	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.	Year 1, 2, 3
Overall Survival (OS)	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.	From baseline up to 1 Year, baseline up to Year 2, baseline up to Year 3
Percentage of Participants With Disease Progression	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.	Year 1, 2, 3
Percentage of Participants With Permanent Discontinuation From Bosutinib Therapy		Baseline up to 5.5 years
Cross-Intolerance Between Bosutinib and Previous Therapy	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).	Baseline up to 5.5 years
Mean Dose of Bosutinib at Initiation of Treatment		Baseline up to 5.5 years
Relative Bosutinib Dose Intensity	Relative dose intensity was defined as the percentage of daily dose received over the expected daily dose of the study drug.	Baseline up to 5.5 years
Duration of Bosutinib Therapy	The duration from initiation of Bosutinib therapy up to the end of Bosutinib therapy was reported in this outcome measure.	Baseline up to 5.5 years

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: pH Associates
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2015
• Primary Completion (Actual): January 16, 2017
• Study Completion (Actual): January 16, 2017

Study Registration Dates

• First Submitted: August 26, 2015
• First Submitted That Met QC Criteria: September 8, 2015
• First Posted (Estimated): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Bosutinib; observational; retrospective; chronic myeloid leukaemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Chronic Disease; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: B1871052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.