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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02130557




Registration number
NCT02130557
Ethics application status
Date submitted
1/05/2014
Date registered
5/05/2014
Date last updated
18/05/2021

Titles & IDs
Public title
A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Scientific title
A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA
Secondary ID [1] 0 0
2013-005101-31
Secondary ID [2] 0 0
AV001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive 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 - Imatinib

Experimental: Bosutinib - Bosutinib, 400 mg, oral administration once a day

Active Comparator: Imatinib - Imatinib, 400 mg, oral administration once a day


Treatment: Drugs: Bosutinib
Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.[1] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.

Treatment: Drugs: Imatinib
Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial.
Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Major Molecular Response (MMR) at Month 12 - MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.
Timepoint [1] 0 0
Month 12
Secondary outcome [1] 0 0
Percentage of Participants With Major Molecular Response (MMR) Up to Month 18 - MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.
Timepoint [1] 0 0
Up to Month 18
Secondary outcome [2] 0 0
Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48 - The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio >0.1% in association with a >=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.
Timepoint [2] 0 0
Month 48
Secondary outcome [3] 0 0
Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12 - Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.
Timepoint [3] 0 0
Up to Month 12
Secondary outcome [4] 0 0
Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48 - The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.
Timepoint [4] 0 0
Month 48
Secondary outcome [5] 0 0
Cumulative Incidence of Event Free Survival (EFS) Events - EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to >20.0*10^9/L, platelet count rises to >=600*10^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.
Timepoint [5] 0 0
Up to Month 60
Secondary outcome [6] 0 0
Overall Survival (OS) Rate - OS was defined as the time (in months) from randomization 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 [6] 0 0
Up to Month 60

Eligibility
Key inclusion criteria
1. Molecular diagnosis of CP CML of = 6 months (from initial diagnosis).

2. Adequate hepatic, renal and pancreatic function.

3. Age = 18 years.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with
the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up
to 6 months prior to study entry (signature of ICF) if suitably approved for use in
the subject's region.

2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal
leukemia.

3. Extramedullary disease only.

4. Major surgery or radiotherapy within 14 days of randomization.

5. History of clinically significant or uncontrolled cardiac disease.

6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic
hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence
of decompensated liver disease. Patients with resolved Hepatitis B can be included.

7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative
Colitis, or prior total or partial gastrectomy.

8. History of another malignancy within 5 years with the exception of basal cell
carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered
adequately treated and currently in complete remission for at least l2 months.

9. Current, or recent (within 30 days, or 5 half-lives of investigational product)
participation in other clinical trials of investigational agents and/or containing
interventional procedures deemed contrary to the objectives and conduct of this trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St George Hospital - Hematology Department - Kogarah
Recruitment hospital [2] 0 0
Eastern Clinical Research Unit, Level 2 - Box Hill
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment outside Australia
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United States of America
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California
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Louisiana
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Maryland
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Mississippi
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Ghent
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Leuven
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Liège
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Ontario
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Saskatchewan
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Brno
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Hradec Králové
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Prague
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Lublin
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Toledo
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Valencia
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Kaohsiung City
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Thailand
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Chiang MAI
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Thailand
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Bangkok
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Ukraine
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Cherkasy
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Khmelnytskyi
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Kyiv
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Lviv
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Greater London
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Merseyside
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Nottinghamshire
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Oxfordshire
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South Yorkshire
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WEST Midlands
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WEST Yorkshire
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United Kingdom
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Cardiff
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United Kingdom
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Leicester

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

Ethics approval
Ethics application status

Summary
Brief summary
Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive
bosutinib or imatinib for the duration of the study.
Trial website
https://clinicaltrials.gov/show/NCT02130557
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
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications