Clinical trial NCT00760877: 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)
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CHRONIC MYELOGENOUS LEUKEMIA
Keywords: MYELOGENOUS
LEUKEMIA
Chronic Phase
CML
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-09-26
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Rate of Confirmed Best Cumulative Complete Molecular Response (CMR)
timeFrame: 12 months
Secondary outcomes:
measure: Rate of Confirmed Best Cumulative CMR
timeFrame: 24 months, 36 month, 48 months
measure: Number of Cross-over Participants With CMR
timeFrame: 24 months, 36 months, 48 months
measure: Progression Free Survival (PFS)
timeFrame: 48 months
measure: Event-free Survival
timeFrame: 48 months
measure: Overall Survival
timeFrame: 48 months
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Prahran
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Campinas
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Québec
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Vandoeuvre les Nancy
country: France
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.