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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01903733
Registration number
NCT01903733
Ethics application status
Date submitted
16/07/2013
Date registered
19/07/2013
Date last updated
19/07/2022
Titles & IDs
Public title
Bosutinib Treatment Extension Study Only For Subjects With Chronic Myeloid Leukemia (CML) Who Have Previously Participated In Bosutinib Studies B1871006 Or B1871008
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Scientific title
AN OPEN-LABEL BOSUTINIB TREATMENT EXTENSION STUDY FOR SUBJECTS WITH CHRONIC MYELOID LEUKEMIA (CML) WHO HAVE PREVIOUSLY PARTICIPATED IN BOSUTINIB STUDIES B1871006 OR B1871008
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Secondary ID [1]
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2013-000691-15
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Secondary ID [2]
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B1871040
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
0
0
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0
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Leukaemia - Chronic leukaemia
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Cancer
0
0
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0
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - bosutinib
Treatment: Drugs: bosutinib
The starting bosutinib dose is 500 mg once daily, however the dose can vary from 300 mg to 600 mg.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)
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Assessment method [1]
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug.
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Timepoint [1]
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From first dose of drug up to 30 days after last dose (up to approximately 14 years)
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Primary outcome [2]
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Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)
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Assessment method [2]
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were assessed according to severity grading based on NCI CTCAE version 3.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug.
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Timepoint [2]
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From first dose of drug up to 30 days after last dose (up to approximately 14 years)
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Primary outcome [3]
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Number of Participants With Treatment-Emergent Treatment Related Adverse Events (AEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)
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Assessment method [3]
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An AE was any untoward medical occurrence in a participant who received study drug. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug. Related TEAEs were those AEs who were related to the study treatment as judged by the investigator.
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Timepoint [3]
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From first dose of drug up to 30 days after last dose (up to approximately 14 years)
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Primary outcome [4]
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Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)
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Assessment method [4]
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Laboratory parameters included Chemistry: high alkaline phosphatase; high alanine aminotransferase; high aspartate aminotransferase; high blood bilirubin; high creatinine. Hematology: absolute neutrophils count decreased; anemia; platelet count decreased; white blood cells (WBC) decreased. Abnormalities in laboratory tests were graded per NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.
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Timepoint [4]
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From first dose of drug up to 30 days after last dose (up to approximately 14 years)
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Primary outcome [5]
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Number of Participants With Adverse Events as Reason for Treatment Discontinuation
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Assessment method [5]
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
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Timepoint [5]
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From first dose of drug up to 30 days after last dose (up to approximately 14 years)
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Primary outcome [6]
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Number of Participants With Diarrhea After Switch From Bosutinib Clinical Formulation to Bosutinib Commercial Formulation
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Assessment method [6]
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The incidence of diarrhea was collected and analyzed before and after the switch from the clinical formulation of bosutinib to the commercial formulation of bosutinib.
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Timepoint [6]
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Last 6 months on clinical formulation and first 6 months on commercial formulation
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Primary outcome [7]
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Number of Participants With Breakpoint Cluster Region Abelson Protooncogene (BCR-ABL) Mutations Present at Time of Bosutinib Treatment Discontinuation
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Assessment method [7]
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BCR-ABL is a gene resulting from the 9:22 chromosomal translocation (Philadelphia chromosome). In this outcome measure, the number of participants who had emergent mutation or new BCR-ABL mutations (participants who had a post-baseline mutation which was not present at baseline) were reported.
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Timepoint [7]
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Post-baseline on Day 1 (maximum up to 14 years)
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Primary outcome [8]
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Overall Survival (OS) Rate at Year 10
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Assessment method [8]
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OS was defined as the time from randomization (B1871008) and time from first dose (B1871006) to the occurrence of death due to any cause or censoring. Kaplan-Meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.
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Timepoint [8]
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Year 10
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Primary outcome [9]
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Plasma Steady-State Trough Concentrations (Ctrough) of Bosutinib
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Assessment method [9]
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Ctrough refers to plasma concentration of bosutinib observed just before treatment administration.
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Timepoint [9]
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One pre-dose sample was collected at the first scheduled visit (after approval and implementation of protocol amendment 1) following at least 2 weeks of uninterrupted dosing at the same dose level
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Primary outcome [10]
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Kaplan-Meier Estimate of Probability of Maintaining Major Cytogenetic Response (MCyR) at Year 10: B1871006 Participants
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Assessment method [10]
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Cytogenetic response (CyR) is based on prevalence of Ph+ cells. Duration for MCyR: time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive non-responses at least 28 days apart. MCyR was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Response was achieved when there was 0% (CCyR) or 1-35% (PCyR) Ph+ cells analyzed from conventional cytogenetics based on the analysis of 20 to 100 metaphases or <1% (CCyR) or 1-35% (PCyR) Ph+ cells analyzed from fluorescence in-situ hybridization (FISH) based on analysis of at least 200 nuclei. CCyR may be imputed on a specific date if an MMR or better is achieved and denoted on the CRF on that date for B1871040 study visits. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining MCyR at Year 10.
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Timepoint [10]
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Year 10
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Primary outcome [11]
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Kaplan-Meier Estimate of Probability of Maintaining Complete Cytogenetic Response (CCyR) at Year 10: B1871006 Participants
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Assessment method [11]
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Duration for CCyR was defined as time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive assessments with >0 Ph+ metaphases or >=1% positive cells from FISH at least 28 days apart or progression or death. CCyR was achieved when there was 0% Ph+ cells analysed from conventional cytogenetics with 20 to 100 metaphases or <1% Ph+ cells analysed from FISH with at least 200 nuclei. CCyR may be imputed on a specific date if MMR or better is achieved and denoted on the CRF on that date for B1871040 study visits. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining CCyR at Year 10.
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Timepoint [11]
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Year 10
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Primary outcome [12]
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Kaplan-Meier Estimate of Probability of Maintaining Complete Hematologic Response (CHR) at Year 10: B1871006 Participants
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Assessment method [12]
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Duration for CHR was defined as time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive non-responses at least 14 days apart. Complete hematologic response was considered when participants met all of the following criteria: White blood cells equal to or less than (<=) institutional upper limit of normal (ULN), no blasts or promyelocytes in blood, <20% basophils in blood, no extramedullary involvement (including hepatomegaly or splenomegaly), myelocytes and metamyelocytes <5% in blood, platelets <450*10^9 per liter (/L). The following were applicable only to advanced phase: <=5% bone marrow blasts, absolute neutrophil count >=1.0*10^9/L, platelets >=100*10^9/L. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining CHR at Year 10.
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Timepoint [12]
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Year 10
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Primary outcome [13]
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Cumulative Incidence of Progression/Death Events at Year 10: B1871006 Participants
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Assessment method [13]
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Progression free survival (PFS):interval from date of first dose of bosutinib in parent study until earlier date of progression or death from any cause. Participants without events censored at last evaluation date. PD:evolution from CP (or return to CP for ADV participants) to AP or BP (on 2 consecutive assessments at least 1 week apart), evolution from AP to BP (on 2 consecutive assessments at least 1 week apart) and one of following conditions occurred after dose escalation or presence of AEs prohibiting dose escalation: for 2nd or later line, loss of MCyR (need at least 30% increase); for all lines of treatment, loss of CHR confirmed by 2 assessments >=2 weeks apart; for all lines of treatment, increasing WBC defined as doubling of WBC over a period of >=1 month with second WBC >20*10^9/L confirmed at least 1 week later. Percentage of participants with PFS/death events based on cumulative incidence method adjusting for competing event of treatment discontinuation without event.
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Timepoint [13]
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Year 10
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Primary outcome [14]
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Cumulative Incidence of Rate of Transformation to Accelerated Phase (AP) or Blast Phase (BP) at Year 10: B1871006 Participants
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Assessment method [14]
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Time to transformation was defined as the time from first dose in the parent study to the first date of confirmed transformation to AP or BP. Confirmed transformation was defined as 2 consecutive assessments at least 1 week apart or 1 assessment confirmed by progression of disease or death. For participants without transformation, censorship was at the last evaluation date. Percentage of participants with time to transformation to AP/BP was reported based on cumulative incidence method adjusting for the competing risk of treatment discontinuation without the event.
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Timepoint [14]
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Year 10
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Eligibility
Key inclusion criteria
- Only subjects previously participating in two specific studies are eligible to enroll
into this study. Enrollment is not open to subjects if not previously enrolled in
studies B1871006 or B1871008.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- All subjects are excluded unless previously participating in studies B1871006 or
B1871008.
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Study design
Purpose of the study
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Not Applicable
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/08/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
5/06/2020
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Sample size
Target
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Accrual to date
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Final
281
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Recruitment in Australia
Recruitment state(s)
QLD,SA
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Recruitment hospital [1]
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Royal Brisbane & Women's Hospital - Herston
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Recruitment hospital [2]
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Royal Adelaide Hospital - Adelaide
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Recruitment postcode(s) [1]
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4029 - Herston
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Recruitment postcode(s) [2]
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5000 - Adelaide
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Florida
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United States of America
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Georgia
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Maryland
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Texas
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Argentina
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Buenos Aires
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Argentina
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Corrientes
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Belgium
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Charleroi
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Brazil
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SP
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Chile
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V Region
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China
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Beijing
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China
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Zhejiang
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China
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Shanghai
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China
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Tianjin
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Colombia
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Cundinamarca
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Finland
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Helsinki
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France
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Caen Cedex 9
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France
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Nantes cedex 1
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France
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Poitiers Cedex
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France
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Poitiers
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France
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Strasbourg
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Hong Kong
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Chai Wan
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Hong Kong
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Shatin, New Territories
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Hungary
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Budapest
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Hungary
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Kaposvar
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India
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Tamil NADU
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Italy
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BO
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Italy
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Monza AND Brianza
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Italy
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TO
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Italy
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Roma
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Japan
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Aichi
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Japan
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Akita
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Japan
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Fukuoka
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Japan
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Ishikawa
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Tokyo
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Korea, Republic of
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Seoul
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Latvia
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Riga
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Peru
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Lima
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Poland
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Gdansk
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Poland
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Krakow
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Poland
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Lublin
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Russian Federation
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Sverdlovsk Region
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Russian Federation
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Moscow
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Saint Petersburg
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Russian Federation
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Samara
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Singapore
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Singapore
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South Africa
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Gauteng
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Toledo
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Spain
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Valencia
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Thailand
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Bangkok
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Turkey
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Sehit Kamil
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Turkey
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Ankara
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Ukraine
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Cherkasy
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Ukraine
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Dnipropetrovsk
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Ukraine
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Kyiv
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Ukraine
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Lviv
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Nottinhgam
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Pfizer
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
The objective of the study is to provide long term access to bosutinib treatment and assess
long term safety, tolerability and duration of clinical benefit, without any formal
hypothesis testing; therefore, there is no formal primary endpoint.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01903733
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Pfizer CT.gov Call Center
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Address
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Pfizer
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01903733
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