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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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)
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.
Secondary ID [1] 0 0
2009-012616-40
Secondary ID [2] 0 0
CAMN107A2405
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CHRONIC MYELOGENOUS 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 - 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

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

Outcomes
Primary outcome [1] 0 0
Rate of Confirmed Best Cumulative Complete Molecular Response (CMR) - 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.
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Rate of Confirmed Best Cumulative CMR - 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.
Timepoint [1] 0 0
24 months, 36 month, 48 months
Secondary outcome [2] 0 0
Number of Cross-over Participants With CMR - 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.
Timepoint [2] 0 0
24 months, 36 months, 48 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS) - 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.
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
Event-free Survival - 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.
Timepoint [4] 0 0
48 months
Secondary outcome [5] 0 0
Overall Survival - 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.
Timepoint [5] 0 0
48 months

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

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,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [3] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [4] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [5] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [6] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [7] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [8] 0 0
Novartis Investigative Site - Prahran
Recruitment hospital [9] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment postcode(s) [8] 0 0
3181 - Prahran
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Brazil
State/province [2] 0 0
MG
Country [3] 0 0
Brazil
State/province [3] 0 0
PR
Country [4] 0 0
Brazil
State/province [4] 0 0
RJ
Country [5] 0 0
Brazil
State/province [5] 0 0
SP
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux
Country [10] 0 0
France
State/province [10] 0 0
Creteil
Country [11] 0 0
France
State/province [11] 0 0
Lyon cedex 04
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Vandoeuvre les Nancy
Country [14] 0 0
Spain
State/province [14] 0 0
Andalucia
Country [15] 0 0
Spain
State/province [15] 0 0
Cataluña
Country [16] 0 0
Spain
State/province [16] 0 0
Navarra
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid

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

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT00760877
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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