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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00760877
Registration number
NCT00760877
Ethics application status
Date submitted
25/09/2008
Date registered
26/09/2008
Date last updated
8/11/2016
Titles & IDs
Public title
Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)
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Scientific title
An Open Label, Randomized Study of Nilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients With Evidence of Persistent Leukemia by RQ-PCR.
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Secondary ID [1]
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2009-012616-40
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Secondary ID [2]
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CAMN107A2405
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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 MYELOGENOUS LEUKEMIA
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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 - Nilotinib
Treatment: Drugs - Imatinib
Experimental: Nilotinib - Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.
Active comparator: Imatinib - Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Treatment: Drugs: Nilotinib
Supplied in 200 mg capsules
Treatment: Drugs: Imatinib
Supplied in 100 mg and 400 mg capsules
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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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Rate of Confirmed Best Cumulative Complete Molecular Response (CMR)
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Assessment method [1]
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The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the first 12 months of treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) = 0.00001 by real-time quantitative polymerase chain reaction (RQ-PCR) where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity \>4.5 logs.
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Timepoint [1]
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12 months
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Secondary outcome [1]
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Rate of Confirmed Best Cumulative CMR
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Assessment method [1]
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The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the 24, 36 and 48 months post treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) = 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity \>4.5 logs.
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Timepoint [1]
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24 months, 36 month, 48 months
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Secondary outcome [2]
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Number of Cross-over Participants With CMR
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Assessment method [2]
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The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) = 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity \>4.5 logs.
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Timepoint [2]
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24 months, 36 months, 48 months
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Secondary outcome [3]
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Progression Free Survival (PFS)
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Assessment method [3]
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PFS was defined as the time from the date of randomization to the date of the earliest documented progression-defining event as follows: transformation to blast crisis or accelerated phase disease, or death from any cause.
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Timepoint [3]
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48 months
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Secondary outcome [4]
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Event-free Survival
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Assessment method [4]
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Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.
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Timepoint [4]
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48 months
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Secondary outcome [5]
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Overall Survival
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Assessment method [5]
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Overall survival was defined as the time from the date of randomization to the date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.
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Timepoint [5]
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48 months
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Eligibility
Key inclusion criteria
Diagnosis of chronic myeloid leukemia associated with BCR-ABL quantifiable by RQ-PCR Documented CCyR by bone marrow or BCR-ABL<1% IS in the past 12 months Persistent disease demonstrated by two PCR positive tests 3 months apart both during the past 6 months.
Treatment with imatinib for at least 2 years with 400 mg or 600 mg and a stable dose No other current or planned anti-leukemia therapies
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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
Patient has evidence of rising PCR (a confirmed >1 log increase in previous 6 months) Patient has received another investigational agent within last 6 months or tyrosine kinase inhibitors (TKIs) other than imatinib Prior allogeneic stem cell transplantation
Impaired cardiac function including any one of the following:
Inability to monitor the QT interval on electrocardiogram (ECG) Long QT syndrome or a known family history of long QT syndrome. Clinically significant resting brachycardia (<50 beats per minute) QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc Myocardial infarction within 12 months prior to starting study Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) History of or presence of clinically significant ventricular or atrial tachyarrhythmias Administration of cytokine therapy (e.g. G-CSF, GM-CSF or SCF) within 4 weeks prior to study entry
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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
1/06/2009
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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
1/07/2015
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Sample size
Target
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Accrual to date
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Final
207
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Novartis Investigative Site - St. Leonards
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Novartis Investigative Site - Westmead
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Recruitment hospital [3]
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Novartis Investigative Site - Herston
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Recruitment hospital [4]
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Novartis Investigative Site - South Brisbane
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Recruitment hospital [5]
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Novartis Investigative Site - Woolloongabba
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Recruitment hospital [6]
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Novartis Investigative Site - Adelaide
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Recruitment hospital [7]
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Novartis Investigative Site - Parkville
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Recruitment hospital [8]
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Novartis Investigative Site - Prahran
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Recruitment hospital [9]
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Novartis Investigative Site - Nedlands
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Recruitment postcode(s) [1]
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2065 - St. Leonards
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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4029 - Herston
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Recruitment postcode(s) [4]
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4101 - South Brisbane
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Recruitment postcode(s) [5]
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4102 - Woolloongabba
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Recruitment postcode(s) [6]
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5000 - Adelaide
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Recruitment postcode(s) [7]
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3050 - Parkville
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Recruitment postcode(s) [8]
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3181 - Prahran
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Recruitment postcode(s) [9]
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6009 - Nedlands
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Recruitment outside Australia
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Argentina
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State/province [1]
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Buenos Aires
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Brazil
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MG
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Brazil
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PR
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Brazil
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RJ
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Brazil
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SP
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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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France
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Bordeaux
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France
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Creteil
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France
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Lyon cedex 04
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France
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Paris
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France
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Vandoeuvre les Nancy
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Spain
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Andalucia
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Spain
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Cataluña
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Spain
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Navarra
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Spain
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Madrid
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
The primary goal of this study was to determine the rate of confirmed best cumulative complete molecular response (CMR) within the first year of study therapy with imatinib or nilotinib. The study also explored the impact and significance of the achieved CMR on patient outcomes (progression free survival (PFS), event free survival (EFS) and overall survival (OS), characterized the kinetics of CMR achieved in both treatment arms and after the cross-over.
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Trial website
https://clinicaltrials.gov/study/NCT00760877
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Trial related presentations / publications
Hughes TP, Lipton JH, Spector N, Cervantes F, Pasquini R, Clementino NC, Dorlhiac Llacer PE, Schwarer AP, Mahon FX, Rea D, Branford S, Purkayastha D, Collins L, Szczudlo T, Leber B. Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib. Blood. 2014 Jul 31;124(5):729-36. doi: 10.1182/blood-2013-12-544015. Epub 2014 Jun 19.
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Public notes
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Contacts
Principal investigator
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT00760877
Download to PDF