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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
2013-000691-15
Secondary ID [2] 0 0
B1871040
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Primary outcome [2] 0 0
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)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Primary outcome [3] 0 0
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)
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Primary outcome [4] 0 0
Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Primary outcome [5] 0 0
Number of Participants With Adverse Events as Reason for Treatment Discontinuation
Assessment method [5] 0 0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Timepoint [5] 0 0
From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Primary outcome [6] 0 0
Number of Participants With Diarrhea After Switch From Bosutinib Clinical Formulation to Bosutinib Commercial Formulation
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Last 6 months on clinical formulation and first 6 months on commercial formulation
Primary outcome [7] 0 0
Number of Participants With Breakpoint Cluster Region Abelson Protooncogene (BCR-ABL) Mutations Present at Time of Bosutinib Treatment Discontinuation
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Post-baseline on Day 1 (maximum up to 14 years)
Primary outcome [8] 0 0
Overall Survival (OS) Rate at Year 10
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
Year 10
Primary outcome [9] 0 0
Plasma Steady-State Trough Concentrations (Ctrough) of Bosutinib
Assessment method [9] 0 0
Ctrough refers to plasma concentration of bosutinib observed just before treatment administration.
Timepoint [9] 0 0
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
Primary outcome [10] 0 0
Kaplan-Meier Estimate of Probability of Maintaining Major Cytogenetic Response (MCyR) at Year 10: B1871006 Participants
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
Year 10
Primary outcome [11] 0 0
Kaplan-Meier Estimate of Probability of Maintaining Complete Cytogenetic Response (CCyR) at Year 10: B1871006 Participants
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Year 10
Primary outcome [12] 0 0
Kaplan-Meier Estimate of Probability of Maintaining Complete Hematologic Response (CHR) at Year 10: B1871006 Participants
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
Year 10
Primary outcome [13] 0 0
Cumulative Incidence of Progression/Death Events at Year 10: B1871006 Participants
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
Year 10
Primary outcome [14] 0 0
Cumulative Incidence of Rate of Transformation to Accelerated Phase (AP) or Blast Phase (BP) at Year 10: B1871006 Participants
Assessment method [14] 0 0
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.
Timepoint [14] 0 0
Year 10

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* All subjects are excluded unless previously participating in studies B1871006 or B1871008.

Study design
Purpose of the study
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/06/2020
Sample size
Target
Accrual to date
Final
281
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Corrientes
Country [11] 0 0
Belgium
State/province [11] 0 0
Charleroi
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Chile
State/province [17] 0 0
V Region
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Zhejiang
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Tianjin
Country [22] 0 0
Colombia
State/province [22] 0 0
Cundinamarca
Country [23] 0 0
Finland
State/province [23] 0 0
Helsinki
Country [24] 0 0
France
State/province [24] 0 0
Caen Cedex 9
Country [25] 0 0
France
State/province [25] 0 0
Nantes cedex 1
Country [26] 0 0
France
State/province [26] 0 0
Poitiers Cedex
Country [27] 0 0
France
State/province [27] 0 0
Poitiers
Country [28] 0 0
France
State/province [28] 0 0
Strasbourg
Country [29] 0 0
Hong Kong
State/province [29] 0 0
Chai Wan
Country [30] 0 0
Hong Kong
State/province [30] 0 0
Shatin, New Territories
Country [31] 0 0
Hungary
State/province [31] 0 0
Budapest
Country [32] 0 0
Hungary
State/province [32] 0 0
Kaposvar
Country [33] 0 0
India
State/province [33] 0 0
Tamil NADU
Country [34] 0 0
Italy
State/province [34] 0 0
BO
Country [35] 0 0
Italy
State/province [35] 0 0
Monza AND Brianza
Country [36] 0 0
Italy
State/province [36] 0 0
TO
Country [37] 0 0
Italy
State/province [37] 0 0
Roma
Country [38] 0 0
Japan
State/province [38] 0 0
Aichi
Country [39] 0 0
Japan
State/province [39] 0 0
Akita
Country [40] 0 0
Japan
State/province [40] 0 0
Fukuoka
Country [41] 0 0
Japan
State/province [41] 0 0
Ishikawa
Country [42] 0 0
Japan
State/province [42] 0 0
Osaka
Country [43] 0 0
Japan
State/province [43] 0 0
Shizuoka
Country [44] 0 0
Japan
State/province [44] 0 0
Tokyo
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Seoul
Country [46] 0 0
Latvia
State/province [46] 0 0
Riga
Country [47] 0 0
Netherlands
State/province [47] 0 0
Amsterdam
Country [48] 0 0
Netherlands
State/province [48] 0 0
Groningen
Country [49] 0 0
Peru
State/province [49] 0 0
Lima
Country [50] 0 0
Poland
State/province [50] 0 0
Gdansk
Country [51] 0 0
Poland
State/province [51] 0 0
Krakow
Country [52] 0 0
Poland
State/province [52] 0 0
Lublin
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Sverdlovsk Region
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Moscow
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Rostov-on-Don
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Saint Petersburg
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Samara
Country [58] 0 0
Singapore
State/province [58] 0 0
Singapore
Country [59] 0 0
South Africa
State/province [59] 0 0
Gauteng
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Toledo
Country [63] 0 0
Spain
State/province [63] 0 0
Valencia
Country [64] 0 0
Thailand
State/province [64] 0 0
Bangkok
Country [65] 0 0
Turkey
State/province [65] 0 0
Sehit Kamil
Country [66] 0 0
Turkey
State/province [66] 0 0
Ankara
Country [67] 0 0
Ukraine
State/province [67] 0 0
Cherkasy
Country [68] 0 0
Ukraine
State/province [68] 0 0
Dnipropetrovsk
Country [69] 0 0
Ukraine
State/province [69] 0 0
Kyiv
Country [70] 0 0
Ukraine
State/province [70] 0 0
Lviv
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Newcastle Upon Tyne
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Nottinhgam

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01903733