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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/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
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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
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Secondary ID [1]
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2013-005101-31
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Secondary ID [2]
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AV001
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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:
Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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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 - 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.
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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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Percentage of Participants With Major Molecular Response (MMR) at Month 12
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Assessment method [1]
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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.
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Timepoint [1]
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Month 12
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Secondary outcome [1]
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Percentage of Participants With Major Molecular Response (MMR) Up to Month 18
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Assessment method [1]
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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.
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Timepoint [1]
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Up to Month 18
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Secondary outcome [2]
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Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48
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Assessment method [2]
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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.
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Timepoint [2]
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Month 48
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Secondary outcome [3]
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Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12
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Assessment method [3]
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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.
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Timepoint [3]
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Up to Month 12
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Secondary outcome [4]
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Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48
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Assessment method [4]
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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.
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Timepoint [4]
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Month 48
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Secondary outcome [5]
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Cumulative Incidence of Event Free Survival (EFS) Events
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Assessment method [5]
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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.
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Timepoint [5]
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Up to Month 60
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Secondary outcome [6]
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Overall Survival (OS) Rate
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Assessment method [6]
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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.
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Timepoint [6]
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Up to Month 60
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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.
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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
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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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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
Parallel
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Other design features
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Phase
Phase 3
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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
15/07/2014
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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
17/04/2020
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Sample size
Target
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Accrual to date
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Final
536
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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St George Hospital - Hematology Department - Kogarah
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Recruitment hospital [2]
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Eastern Clinical Research Unit, Level 2 - Box Hill
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Recruitment postcode(s) [1]
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2217 - Kogarah
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Recruitment postcode(s) [2]
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3128 - Box Hill
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Recruitment outside Australia
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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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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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Greater London
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United Kingdom
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Merseyside
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United Kingdom
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Nottinghamshire
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United Kingdom
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Oxfordshire
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United Kingdom
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South Yorkshire
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United Kingdom
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WEST Midlands
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United Kingdom
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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
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Pfizer
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Ethics approval
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02130557
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Public notes
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Contacts
Principal investigator
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Pfizer CT.gov Call Center
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Pfizer
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02130557
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