Clinical trial NCT00471497: A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Official title: A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myelogenous Leukemia, Chronic
Keywords: leukemia
bone marrow
leukemia symptoms
lukemia
cml
complete blood count
lymphocyte
blood cancer
leukocytes
chronic leukemia
bone marrow biopsy
leukemia research
leukemia cells
bone marrow disease
chronic myeloid leukemia
blood cancer symptoms
white blood cell diseases
chronic myelogenous leukemia
leukemia treatment
leukemia facts
leucemia
facts about leukemia
myelogenous leukemia
newly diagnosed CML
newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-05-10
Enrollment: 846
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.

Detailed description: Primary objectives of this study:

* Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
* Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.

The Primary objectives of Extension Phase of the study:

- Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy.

The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months.

The key secondary endpoint was to compare the rate of durable MMR between nilotinib 300 mg bid with that of imatinib, and of nilotinib 400 mg bid with that of imatinib at 24 months. This report presents the final results of efficacy and safety at the LPLV (21-Aug-2019).

The main data analysis was done at the time when all patients completed 12 cycles of treatment (or discontinued earlier). There were two primary comparisons at this time point: the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg, and the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg. Comparisons were done sequentially, i.e. the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg was to be compared first; if it was significant at 5% level, the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg was to be compared. The study had a 90% power to detect a 15% difference between the nilotinib 400 mg arm versus imatinib 400 mg arm assuming that the MMR rate of imatinib is 40% and the MMR rate of nilotinib is 55%. The study also had a 90% power to detect a 15% difference between the nilotinib 300 mg and the imatinib 400 mg arms, if the comparison between the nilotinib 400 mg and the imatinib 400 mg was significant.

The second main data analysis was done at the time when all patients completed 24 cycles of treatment (or discontinued earlier). There were two key comparisons at this time point: the rate of durable MMR at 24 months of the nilotinib 400 mg versus the imatinib 400 mg, and the rate of durable MMR at 24 months of the nilotinib 300 mg versus the imatinib 400 mg.

In order to control the overall type I error rate at or below 5%, only when the corresponding comparison on the primary efficacy endpoint(s) was (were) significant, the key secondary comparison(s) of the respective nilotinib doses (400 mg bid and/or 300 mg bid) versus imatinib 400 mg qd were tested at two-sided 5% significance level.

Patients participating after demonstrating suboptimal response/treatment failure to their assigned study treatment in the core study were offered the option to continue in the extension study and to receive imatinib 400 mg bid (option available only until protocol amendment 7) or nilotinib therapy at a dose of 400 mg bid.

Eligibility criteria: Key Inclusion criteria:

* Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis.
* Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome of (9:22) translocations

Key Exclusion criteria:

* Previously documented T315I mutation
* Treatment with a tyrosine kinase inhibitor prior to study entry is not allowed except for no more than 2 weeks in duration of imatinib
* Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
* Impaired cardiac function.
* Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
* Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
* Currently receiving treatment with any medications that have the potential to prolong the QT interval.

Primary outcomes:
measure: Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation
timeFrame: Baseline, 12 months
measure: Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation
timeFrame: 12 months
Secondary outcomes:
measure: Rates of Durable MMR at 24 Months Between All 3 Arms
timeFrame: 24 months
measure: Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months
timeFrame: 12, 24, 36, 48, 60, 72 months (M)
measure: Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms
timeFrame: 12 months
measure: Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms
timeFrame: 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
measure: Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
timeFrame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
measure: Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
timeFrame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
measure: Time to First MMR
timeFrame: up to 84 months
measure: Duration of MMR
timeFrame: approx. 11 years
measure: Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
timeFrame: up to 84 months
measure: Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
timeFrame: approx. 11 years
measure: Rate of Hematologic Response
timeFrame: 12 months, 24 months, Overall on Core study (approx. 11 years)
measure: Time to Complete Cytogenic Response (CCyR)
timeFrame: 24 months
measure: Duration of CCyR
timeFrame: up to 72 months
measure: Progression-free Survival (PFS)
timeFrame: approx. 11 years
measure: Event-free Survival (EFS)
timeFrame: approx. 11 years
measure: Overall Survival (OS)
timeFrame: approx. 11 years
measure: Actual Dose-intensity
timeFrame: approx. 11 years
measure: Time to Progression to AP/BC
timeFrame: approx. 11 years
measure: Pharmacokinetics: Cmax
timeFrame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
measure: Pharmacokinetics: Cmin
timeFrame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
measure: Pharmacokinetics: Tmax
timeFrame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
measure: Pharmacokinetics: AUC0-last
timeFrame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
measure: Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
timeFrame: Overall for Extension study for approx. 10 years
measure: Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
timeFrame: Overall for Extension study for approx. 10 years
measure: Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
timeFrame: Overall for Extension study for approx. 10 years
measure: Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
timeFrame: Overall for Extension study for approx. 10 years
measure: Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
timeFrame: Overall for Extension study for approx. 10 years
measure: Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension)
timeFrame: Overall for Extension study for approx. 10 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles Dept. of Hematology Clinic
state: California
city: San Diego
country: United States
facility: Kaiser Permanente - California Southern Dept of Kaiser South 3
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente - California Northern Vallejo Med Center/Med Offices
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente - California Northern Kaiser Med
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC - Colorado Springs
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Dept. FloridaCancerSpecialists
state: Florida
city: Miami
country: United States
facility: Advanced Medical Specialties Research Dept.
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida PA Cancer Centers of FL
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute Flordia Cancer Affilates
state: Florida
city: Chicago
country: United States
facility: University of Chicago Section of Hematology/Oncology
state: Illinois
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Institute Dept. of Indiana Blood&Marrow
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics Dept.of U of Iowa Hosp&Clinics
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Cancer Center KCCC Business Office
state: Kansas
city: New Orleans
country: United States
facility: LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
state: Louisiana
city: Lansing
country: United States
facility: Michigan State University / Breslin Cancer Center Breslin Cancer Center
state: Michigan
city: Columbia
country: United States
facility: Missouri Cancer Associates Dept. of Boone Hospital Center
state: Missouri
city: Saint Louis
country: United States
facility: Hematology Oncology Consultants, Inc. Deptof Hem. Onc.Consunsultants
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center Department of Research
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Clinical Trials Office
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina UNC Lineberger Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences Dept. of Industry Research
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati / Barrett Cancer Center Dept.of Internal Med.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation CCF
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists Compass Oncology -BKM
state: Oregon
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas CC of C -Eastside
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Dept. of Centennial Medical
state: Tennessee
city: Dallas
country: United States
facility: Texas Cancer Center ( Medical City Dallas Hospital)
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas HOAST CCC of So.TX- Medical Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Yvoir
country: Belgium
facility: Novartis Investigative Site
city: Brasilia
country: Brazil
facility: Novartis Investigative Site
state: DF
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: Jau
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: HUS Helsinki
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Paris Cedex 10
country: France
facility: Novartis Investigative Site
state: Cedex 10
city: Caen
country: France
facility: Novartis Investigative Site
state: Cedex
city: Saint Priest en Jarez
country: France
facility: Novartis Investigative Site
state: Loire
city: Angers Cedex 1
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Nice Cedex
country: France
facility: Novartis Investigative Site
city: Pierre Benite Cedex
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Rennes
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Vandoeuvre les Nancy
country: France
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Eisenach
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Alessandria
country: Italy
facility: Novartis Investigative Site
state: AL
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pescara
country: Italy
facility: Novartis Investigative Site
state: PE
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
state: RC
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Perugia
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Maebashi city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Maebashi
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Tsukuba city
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kanazawa-city
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Nagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Osaka Sayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Hidaka-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Hamamatsu-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Akita
country: Japan
facility: Novartis Investigative Site
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Saitama
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Jeollanam-do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Taegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Selangor
country: Malaysia
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Trondheim
country: Norway
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bloemfontein
country: South Africa
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Parktown
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Elche
country: Spain
facility: Novartis Investigative Site
state: Alicante
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bilbao
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Göteborg
country: Sweden
facility: Novartis Investigative Site
city: Huddinge
country: Sweden
facility: Novartis Investigative Site
city: Lulea
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Orebro
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Sundsvall
country: Sweden
facility: Novartis Investigative Site
city: Umeå
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Caracas
country: Venezuela
facility: Novartis Investigative Site
state: Distrito Capital
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hughes TP, Hochhaus A, Kantarjian HM, Cervantes F, Guilhot F, Niederwieser D, le Coutre PD, Rosti G, Ossenkoppele G, Lobo C, Shibayama H, Fan X, Menssen HD, Kemp C, Larson RA, Saglio G. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily. Haematologica. 2014 Jul;99(7):1204-11. doi: 10.3324/haematol.2013.091272. Epub 2014 Feb 14.
citation: Hughes TP, Saglio G, Kantarjian HM, Guilhot F, Niederwieser D, Rosti G, Nakaseko C, De Souza CA, Kalaycio ME, Meier S, Fan X, Menssen HD, Larson RA, Hochhaus A. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014 Feb 27;123(9):1353-60. doi: 10.1182/blood-2013-06-510396. Epub 2013 Dec 11.
citation: Hochhaus A, Saglio G, Larson RA, Kim DW, Etienne G, Rosti G, De Souza C, Kurokawa M, Kalaycio ME, Hoenekopp A, Fan X, Shou Y, Kantarjian HM, Hughes TP. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2013 May 2;121(18):3703-8. doi: 10.1182/blood-2012-04-423418. Epub 2013 Mar 15.
citation: Branford S, Kim DW, Soverini S, Haque A, Shou Y, Woodman RC, Kantarjian HM, Martinelli G, Radich JP, Saglio G, Hochhaus A, Hughes TP, Muller MC. Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. J Clin Oncol. 2012 Dec 10;30(35):4323-9. doi: 10.1200/JCO.2011.40.5217. Epub 2012 Oct 29.
citation: Larson RA, Yin OQ, Hochhaus A, Saglio G, Clark RE, Nakamae H, Gallagher NJ, Demirhan E, Hughes TP, Kantarjian HM, le Coutre PD. Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012 May;68(5):723-33. doi: 10.1007/s00228-011-1200-7. Epub 2011 Dec 30.
citation: Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, Goh YT, Rosti G, Nakamae H, Gallagher NJ, Hoenekopp A, Blakesley RE, Larson RA, Hughes TP. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011 Sep;12(9):841-51. doi: 10.1016/S1470-2045(11)70201-7. Epub 2011 Aug 17.
citation: Cortes JE, Hochhaus A, le Coutre PD, Rosti G, Pinilla-Ibarz J, Jabbour E, Gillis K, Woodman RC, Blakesley RE, Giles FJ, Kantarjian HM, Baccarani M. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib. Blood. 2011 May 26;117(21):5600-6. doi: 10.1182/blood-2010-11-318949. Epub 2011 Apr 5.
citation: Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010 Jun 17;362(24):2251-9. doi: 10.1056/NEJMoa0912614. Epub 2010 Jun 5.