A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENESTnd)

• ClinicalTrials.gov Identifier: NCT00471497
• Recruitment Status: Completed
• First Posted: May 10, 2007
• Results First Posted: June 17, 2013
• Last Update Posted: November 18, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myelogenous Leukemia, Chronic	Drug: nilotinib; Drug: imatinib	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 846 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: July 31, 2007
• Actual Primary Completion Date: September 2, 2009
• Actual Study Completion Date: August 21, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: nilotinib 300mg bid (investigating arm)	Drug: nilotinib; Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.; Other Name: AMN107
Experimental: Nilotinb 400 mg bid (investigating arm)	Drug: nilotinib; Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.; Other Name: AMN107
Experimental: imatinib 400mg QD (control arm)	Drug: imatinib; Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).; Other Name: STI571

Outcome Measures

Primary Outcome Measures :

1. Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation [ Time Frame: Baseline, 12 months ]
   MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
2. Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation [ Time Frame: 12 months ]
   MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.

Secondary Outcome Measures :

1. Rates of Durable MMR at 24 Months Between All 3 Arms [ Time Frame: 24 months ]
   Durable MMR at 24 months is defined as having MMR both at 12 months and at 24 months, and with no documented loss of MMR between these 12 month and 24 month time points.
2. Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months [ Time Frame: 12, 24, 36, 48, 60, 72 months (M) ]
   CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Patients with no CCyR as the best response by any specific time point, all missing cytogenetic evaluations by that time point or Ph- at baseline are combined as "Nocomplete cytogenetic response".
3. Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms [ Time Frame: 12 months ]
   MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months based on 12-month cut-off interim data.
4. Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms [ Time Frame: 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
   MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 6 months and beyond up to 120 months based on final data.
5. Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib [ Time Frame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
   Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
6. Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib [ Time Frame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
   This is the molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
7. Time to First MMR [ Time Frame: up to 84 months ]
   Time to MMR is defined as time from date of randomization to the date of the first documented MMR in nilotinib treatment arms, compared to imatinib in adult patients with Ph+ CML in CP.
8. Duration of MMR [ Time Frame: approx. 11 years ]
   Duration of MMR for patients with MMR is defined as the time between date of MMR and the earliest of the following: loss of MMR, CML-related death or progression to AP/BC during study treatment The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
9. Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts [ Time Frame: up to 84 months ]
   Time to BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% is defined as: date of first BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% - date of randomization +1.
10. Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts [ Time Frame: approx. 11 years ]
    It is defined as the time from the date of first documented BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% to the earliest of the following: Loss of BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032%, respectively, CML-related death or progression to AP/BC during study treatment. The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
11. Rate of Hematologic Response [ Time Frame: 12 months, 24 months, Overall on Core study (approx. 11 years) ]
    Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
12. Time to Complete Cytogenic Response (CCyR) [ Time Frame: 24 months ]
    Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR
13. Duration of CCyR [ Time Frame: up to 72 months ]
    Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.
14. Progression-free Survival (PFS) [ Time Frame: approx. 11 years ]
    Progression-free survival is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring in the core or extension study, or during the follow-up period after discontinuation of core or extension study
15. Event-free Survival (EFS) [ Time Frame: approx. 11 years ]
    Event-free survival is defined as the time from the date of randomization to the date of first occurrence of any of the following: death due to any cause (if death is the primary reason for discontinuation), progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR
16. Overall Survival (OS) [ Time Frame: approx. 11 years ]
    OS is defined as the time from the date of randomization to the date death. Up to 10 calendar years of follow up from the date when the last patient randomized received the first dose of study drug in all active treatment arms of adult patients with Ph+ CML CP.
17. Actual Dose-intensity [ Time Frame: approx. 11 years ]
    Actual dose intensity is defined as total dose over time on treatment
18. Time to Progression to AP/BC [ Time Frame: approx. 11 years ]
    Time to progression to AP/BC is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of CML related death.
19. Pharmacokinetics: Cmax [ Time Frame: 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 ]
    Cmax is defined as the maximum serum concentration after dose
20. Pharmacokinetics: Cmin [ Time Frame: 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 ]
    Cmin is defined as the minimum serum concentration after dose
21. Pharmacokinetics: Tmax [ Time Frame: 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 ]
    Tmax is defined as the sampling time when maximum measured serum concentration occurs
22. Pharmacokinetics: AUC0-last [ Time Frame: 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 ]
    AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method
23. Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
    Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
24. Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
    Rate of CCyR is defined as the percentage of participants in complete cytogenetic response (CCyR). CcyR is defined as 0% of Ph+ metaphases in the bone marrow.
25. Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
    Rate of MMR is defined as the percentage pf participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR))
26. 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) [ Time Frame: Overall for Extension study for approx. 10 years ]
    Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
27. 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) [ Time Frame: Overall for Extension study for approx. 10 years ]
    Molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
28. Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
    This is the percentage of patients with any emergent mutation on extension treatment. The mutation comprised of T315T, less sensitive to nilotinib, unknown and sensitive to nilotinib.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

University of California at Los Angeles Dept. of Hematology Clinic

Los Angeles, California, United States, 90095

Kaiser Permanente - California Southern Dept of Kaiser South 3

San Diego, California, United States, 92120

Kaiser Permanente - California Northern Vallejo Med Center/Med Offices

Vallejo, California, United States, 94589

Kaiser Permanente - California Northern Kaiser Med

Vallejo, California, United States, 94609

United States, Colorado

Rocky Mountain Cancer Centers RMCC - Colorado Springs

Greenwood Village, Colorado, United States

United States, Florida

Florida Cancer Specialists Dept. FloridaCancerSpecialists

Fort Myers, Florida, United States, 33901

Advanced Medical Specialties Research Dept.

Miami, Florida, United States, 33176

Cancer Centers of Florida PA Cancer Centers of FL

Ocoee, Florida, United States, 34761

Florida Retina Institute Flordia Cancer Affilates

Orlando, Florida, United States, 32804

United States, Illinois

University of Chicago Section of Hematology/Oncology

Chicago, Illinois, United States, 60637

United States, Indiana

Indiana Blood and Marrow Institute Dept. of Indiana Blood&Marrow

Beech Grove, Indiana, United States, 46107

United States, Iowa

University of Iowa Hospitals and Clinics Dept.of U of Iowa Hosp&Clinics

Iowa City, Iowa, United States, 52242

United States, Kansas

Kansas City Cancer Center KCCC Business Office

Overland Park, Kansas, United States, 66210

United States, Louisiana

LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center

New Orleans, Louisiana, United States, 70115

United States, Michigan

Michigan State University / Breslin Cancer Center Breslin Cancer Center

Lansing, Michigan, United States, 48824

United States, Missouri

Missouri Cancer Associates Dept. of Boone Hospital Center

Columbia, Missouri, United States, 65201

Hematology Oncology Consultants, Inc. Deptof Hem. Onc.Consunsultants

Saint Louis, Missouri, United States, 63136

United States, New Jersey

Hackensack University Medical Center Department of Research

Hackensack, New Jersey, United States, 07601

United States, New York

Memorial Sloan Kettering Cancer Center Clinical Trials Office

New York, New York, United States, 10021

United States, North Carolina

University of North Carolina UNC Lineberger Cancer Center

Chapel Hill, North Carolina, United States, 27514

Wake Forest University Health Sciences Dept. of Industry Research

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

University of Cincinnati / Barrett Cancer Center Dept.of Internal Med.

Cincinnati, Ohio, United States, 45219

Cleveland Clinic Foundation CCF

Cleveland, Ohio, United States, 44195

United States, Oregon

Northwest Cancer Specialists Compass Oncology -BKM

Portland, Oregon, United States, 97210

United States, South Carolina

Cancer Centers of the Carolinas CC of C -Eastside

Greenville, South Carolina, United States, 29605

United States, Tennessee

Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology Dept. of Centennial Medical

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Cancer Center ( Medical City Dallas Hospital)

Dallas, Texas, United States, 75230

Cancer Care Centers of South Texas HOAST CCC of So.TX- Medical Center

San Antonio, Texas, United States, 78229

Tyler Cancer Center

Tyler, Texas, United States, 75702

United States, Utah

Utah Cancer Specialists

Salt Lake City, Utah, United States, 84106

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Korea, Republic of

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Seoul, Korea, Korea, Republic of, 05505

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Seoul, Seocho Gu, Korea, Republic of, 06591

Novartis Investigative Site

Jeollanam-do, Korea, Republic of, 519763

Novartis Investigative Site

Seoul, Korea, Republic of, 03080

Novartis Investigative Site

Seoul, Korea, Republic of, 06351

Novartis Investigative Site

Taegu, Korea, Republic of, 41944

Malaysia

Novartis Investigative Site

Selangor, Malaysia, 68000

Mexico

Novartis Investigative Site

Mexico, Distrito Federal, Mexico, 06726

Novartis Investigative Site

Monterrey, Nuevo Leon, Mexico, 64460

Netherlands

Novartis Investigative Site

Amsterdam, Netherlands, 1081 HV

Norway

Novartis Investigative Site

Oslo, Norway, NO-0310

Novartis Investigative Site

Trondheim, Norway, 7006

Poland

Novartis Investigative Site

Katowice, Poland, 40032

Novartis Investigative Site

Lublin, Poland, 20-081

Novartis Investigative Site

Rzeszow, Poland, 35 055

Novartis Investigative Site

Warszawa, Poland, 02-097

Novartis Investigative Site

Wroclaw, Poland, 50-367

Russian Federation

Novartis Investigative Site

Moscow, Russian Federation, 125167

Novartis Investigative Site

Novosibirsk, Russian Federation, 630051

Novartis Investigative Site

Saint Petersburg, Russian Federation, 197022

Singapore

Novartis Investigative Site

Singapore, Singapore, 119228

Novartis Investigative Site

Singapore, Singapore, 169608

Slovakia

Novartis Investigative Site

Bratislava, Slovak Republic, Slovakia, 833 10

Novartis Investigative Site

Bratislava, Slovakia, 85107

South Africa

Novartis Investigative Site

Bloemfontein, South Africa, 9301

Novartis Investigative Site

Cape Town, South Africa, 7925

Novartis Investigative Site

Parktown, South Africa, 2193

Novartis Investigative Site

Pretoria, South Africa, 0001

Novartis Investigative Site

Pretoria, South Africa, 0027

Spain

Novartis Investigative Site

Elche, Alicante, Spain, 03203

Novartis Investigative Site

Granada, Andalucia, Spain, 18014

Novartis Investigative Site

Malaga, Andalucia, Spain, 29010

Novartis Investigative Site

Santander, Cantabria, Spain, 39008

Novartis Investigative Site

Salamanca, Castilla Y Leon, Spain, 37007

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08036

Novartis Investigative Site

Hospitalet de LLobregat, Catalunya, Spain, 08907

Novartis Investigative Site

Valencia, Comunidad Valenciana, Spain, 46010

Novartis Investigative Site

La Coruna, Galicia, Spain, 15006

Novartis Investigative Site

Santiago de Compostela, Galicia, Spain, 15706

Novartis Investigative Site

Bilbao, Pais Vasco, Spain, 48013

Novartis Investigative Site

San Sebastian, Pais Vasco, Spain, 20080

Novartis Investigative Site

La Laguna, Santa Cruz De Tenerife, Spain, 38320

Novartis Investigative Site

Madrid, Spain, 28006

Novartis Investigative Site

Madrid, Spain, 28034

Novartis Investigative Site

Madrid, Spain, 28046

Novartis Investigative Site

Zaragoza, Spain, 50009

Sweden

Novartis Investigative Site

Göteborg, Sweden, SE-413 45

Novartis Investigative Site

Huddinge, Sweden, SE-14186

Novartis Investigative Site

Lulea, Sweden, SE 971 80

Novartis Investigative Site

Lund, Sweden, SE-221 85

Novartis Investigative Site

Orebro, Sweden, SE-701 85

Novartis Investigative Site

Stockholm, Sweden, SE-171 76

Novartis Investigative Site

Sundsvall, Sweden, SE-851 86

Novartis Investigative Site

Umeå, Sweden, SE-901 85

Novartis Investigative Site

Uppsala, Sweden, SE-751 85

Switzerland

Novartis Investigative Site

Geneve, Switzerland, 1205

Taiwan

Novartis Investigative Site

Kaohsiung City, Taiwan, 83301

Novartis Investigative Site

Taipei, Taiwan, 10002

Novartis Investigative Site

Taoyuan, Taiwan, 33305

Thailand

Novartis Investigative Site

Bangkok, Thailand, 10330

Novartis Investigative Site

Bangkok, Thailand, 10400

Novartis Investigative Site

Bangkok, Thailand, 10700

Turkey

Novartis Investigative Site

Istanbul, TUR, Turkey, 34098

Novartis Investigative Site

Adana, Turkey, 01330

Novartis Investigative Site

Ankara, Turkey, 06500

Novartis Investigative Site

Izmir, Turkey, 35340

United Kingdom

Novartis Investigative Site

Glasgow, United Kingdom, G12 OYN

Novartis Investigative Site

Leeds, United Kingdom, LS9 7TF

Novartis Investigative Site

Liverpool, United Kingdom, L7 8XP

Novartis Investigative Site

London, United Kingdom, W12 0HS

Novartis Investigative Site

Nottingham, United Kingdom, NG5 1PB

Venezuela

Novartis Investigative Site

Caracas, Distrito Capital, Venezuela, 1010

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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. Erratum In: Lancet Oncol. 2011 Oct;12(11):989.

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.

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00471497
• Obsolete Identifiers: NCT00718263
• Other Study ID Numbers: CAMN107A2303; 2007-000208-34 ( Registry Identifier: EUDRACT )
• First Posted: May 10, 2007
• Results First Posted: June 17, 2013
• Last Update Posted: November 18, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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)

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Translocation, Genetic; Chromosome Aberrations; Imatinib Mesylate; Nilotinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents