Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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)
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)
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Rate of Confirmed Best Cumulative CMR
Timepoint [1] 0 0
24 months, 36 month, 48 months
Secondary outcome [2] 0 0
Number of Cross-over Participants With CMR
Timepoint [2] 0 0
24 months, 36 months, 48 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
Event-free Survival
Timepoint [4] 0 0
48 months
Secondary outcome [5] 0 0
Overall Survival
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
Sex
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
1/06/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2015
Sample size
Target
Accrual to date
Final
207
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/study/NCT00760877
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.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00760877