AzTrials
AzTrials

Myelogenous Leukemia, ChronicPhase 3ENESTndNCT00471497

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

A Phase 3 study testing nilotinib and imatinib in people with Myelogenous Leukemia, Chronic, run by Novartis Pharmaceuticals at 213 sites in 35 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelogenous Leukemia, Chronic
What is being tested?
nilotinib and imatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
846 participants
Where
213 sitesin 35 countries
Study dates
31 Jul 2007to 21 Aug 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

213 sites in 35 countries.

213 sites in 35 countries

United States31 sites

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

    Beech Grove, Indiana, 46107

  • University of North Carolina UNC Lineberger Cancer Center

    Chapel Hill, North Carolina, 27514

  • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

    Chattanooga, Tennessee, 37404

  • University of Chicago Section of Hematology/Oncology

    Chicago, Illinois, 60637

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

    Cincinnati, Ohio, 45219

  • Cleveland Clinic Foundation CCF

    Cleveland, Ohio, 44195

  • Missouri Cancer Associates Dept. of Boone Hospital Center

    Columbia, Missouri, 65201

  • Texas Cancer Center ( Medical City Dallas Hospital)

    Dallas, Texas, 75230

  • Florida Cancer Specialists Dept. FloridaCancerSpecialists

    Fort Myers, Florida, 33901

  • Cancer Centers of the Carolinas CC of C -Eastside

    Greenville, South Carolina, 29605

  • Rocky Mountain Cancer Centers RMCC - Colorado Springs

    Greenwood Village, Colorado

  • Hackensack University Medical Center Department of Research

    Hackensack, New Jersey, 07601

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

    Iowa City, Iowa, 52242

  • Michigan State University / Breslin Cancer Center Breslin Cancer Center

    Lansing, Michigan, 48824

  • University of California at Los Angeles Dept. of Hematology Clinic

    Los Angeles, California, 90095

  • Advanced Medical Specialties Research Dept.

    Miami, Florida, 33176

  • Tennessee Oncology Dept. of Centennial Medical

    Nashville, Tennessee, 37203

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

    New Orleans, Louisiana, 70115

  • Memorial Sloan Kettering Cancer Center Clinical Trials Office

    New York, New York, 10021

  • Cancer Centers of Florida PA Cancer Centers of FL

    Ocoee, Florida, 34761

  • Florida Retina Institute Flordia Cancer Affilates

    Orlando, Florida, 32804

  • Kansas City Cancer Center KCCC Business Office

    Overland Park, Kansas, 66210

  • Northwest Cancer Specialists Compass Oncology -BKM

    Portland, Oregon, 97210

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

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

    San Antonio, Texas, 78229

  • Kaiser Permanente - California Southern Dept of Kaiser South 3

    San Diego, California, 92120

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

    St Louis, Missouri, 63136

  • Tyler Cancer Center

    Tyler, Texas, 75702

  • Kaiser Permanente - California Northern Vallejo Med Center/Med Offices

    Vallejo, California, 94589

  • Kaiser Permanente - California Northern Kaiser Med

    Vallejo, California, 94609

  • Wake Forest University Health Sciences Dept. of Industry Research

    Winston-Salem, North Carolina, 27157

Other trials in United States

Japan29 sites

  • Novartis Investigative Site

    Akita, 010-8543

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 113 8655

  • Novartis Investigative Site

    Bunkyo-ku, Tokyo, 113-8519

  • Novartis Investigative Site

    Chiba, 260 8677

  • Novartis Investigative Site

    Chuo Ku, Tokyo, 104 0045

  • Novartis Investigative Site

    Hamamatsu, Shizuoka, 431-3192

  • Novartis Investigative Site

    Hidaka, Saitama, 350-1298

  • Novartis Investigative Site

    Hiroshima, 734-8551

  • Novartis Investigative Site

    Kanazawa, Ishikawa-ken, 920-8641

  • Novartis Investigative Site

    Kumamoto, Kumamoto, 860-8556

  • Novartis Investigative Site

    Maebashi, Gunma, 371 8511

  • Novartis Investigative Site

    Maebashi, Gunma, 371-0821

  • Novartis Investigative Site

    Nagasaki, Nagasaki, 852-8501

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 453-8511

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 466 8560

  • Novartis Investigative Site

    Niigata, 951 8520

  • Novartis Investigative Site

    Nishinomiya, Hyōgo, 663 8501

  • Novartis Investigative Site

    Osaka, 545-8586

  • Novartis Investigative Site

    Ōsaka-sayama, Osaka, 589 8511

  • Novartis Investigative Site

    Saitama, 330 8503

  • Novartis Investigative Site

    Sapporo, Hokkaido, 003-0006

  • Novartis Investigative Site

    Sapporo, Hokkaido, 060 8648

  • Novartis Investigative Site

    Shimotsuke, Tochigi, 329-0498

  • Novartis Investigative Site

    Shinagawa Ku, Tokyo, 141 8625

  • Novartis Investigative Site

    Shinjuku-ku, Tokyo, 160 8582

  • Novartis Investigative Site

    Shinjuku-ku, Tokyo, 160-0023

  • Novartis Investigative Site

    Suita, Osaka, 565 0871

  • Novartis Investigative Site

    Tsu, Mie-ken, 514-8507

  • Novartis Investigative Site

    Tsukuba, Ibaraki, 305-8576

Other trials in Japan

Italy20 sites

  • Novartis Investigative Site

    Alessandria, AL, 15100

  • Novartis Investigative Site

    Ancona, AN, 60126

  • Novartis Investigative Site

    Bergamo, BG, 24127

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Catania, CT, 95123

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Naples, 80132

  • Novartis Investigative Site

    Pavia, PV, 27100

  • Novartis Investigative Site

    Perugia, 06129

  • Novartis Investigative Site

    Pescara, PE, 65124

  • Novartis Investigative Site

    Pisa, PI, 56126

  • Novartis Investigative Site

    Reggio Calabria, RC, 89124

  • Novartis Investigative Site

    Roma, RM, 00133

  • Novartis Investigative Site

    Roma, RM, 00144

  • Novartis Investigative Site

    Roma, RM, 00161

  • Novartis Investigative Site

    Siena, SI, 53100

  • Novartis Investigative Site

    Udine, UD, 33100

Other trials in Italy

Spain18 sites

  • Novartis Investigative Site

    A Coruña, Galicia, 15006

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    Bilbao, Basque Country, 48013

  • Novartis Investigative Site

    Donostia / San Sebastian, Basque Country, 20080

  • Novartis Investigative Site

    Elche, Alicante, 03203

  • Novartis Investigative Site

    Granada, Andalusia, 18014

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

  • Novartis Investigative Site

    Madrid, 28006

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28046

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    Salamanca, Castille and León, 37007

  • Novartis Investigative Site

    San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320

  • Novartis Investigative Site

    Santander, Cantabria, 39008

  • Novartis Investigative Site

    Santiago de Compostela, Galicia, 15706

  • Novartis Investigative Site

    Valencia, Valencia, 46010

  • Novartis Investigative Site

    Zaragoza, 50009

Other trials in Spain

France16 sites

  • Novartis Investigative Site

    Angers, 49033

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Caen, Cedex, 14033

  • Novartis Investigative Site

    Créteil, 94010

  • Novartis Investigative Site

    Grenoble, 38043

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Nantes, 44035

  • Novartis Investigative Site

    Nice, 06202

  • Novartis Investigative Site

    Paris, Cedex 10, 75475

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Poitiers, 86000

  • Novartis Investigative Site

    Rennes, 35019

  • Novartis Investigative Site

    Saint Priest En Jarez, Pays de la Loire Region, 42270

  • Novartis Investigative Site

    Toulouse, 31059

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Germany11 sites

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Cologne, 50937

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Eisenach, 99817

  • Novartis Investigative Site

    Frankfurt, 60590

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Mannheim, Baden-Wurttemberg, 68305

  • Novartis Investigative Site

    München, 81675

  • Novartis Investigative Site

    Ulm, 89081

Other trials in Germany

Sweden9 sites

  • Novartis Investigative Site

    Gothenburg, SE-413 45

  • Novartis Investigative Site

    Huddinge, SE-14186

  • Novartis Investigative Site

    Luleå, SE 971 80

  • Novartis Investigative Site

    Lund, SE-221 85

  • Novartis Investigative Site

    Örebro, SE-701 85

  • Novartis Investigative Site

    Stockholm, SE-171 76

  • Novartis Investigative Site

    Sundsvall, SE-851 86

  • Novartis Investigative Site

    Umeå, SE-901 85

  • Novartis Investigative Site

    Uppsala, SE-751 85

Other trials in Sweden

Brazil8 sites

  • Novartis Investigative Site

    Brasília, Federal District, 70330-150

  • Novartis Investigative Site

    Campinas, São Paulo, 13083-970

  • Novartis Investigative Site

    Curitiba, Paraná, 80060-900

  • Novartis Investigative Site

    Jaú, São Paulo, 17210-080

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 20211-030

  • Novartis Investigative Site

    São Paulo, São Paulo, 01224-000

  • Novartis Investigative Site

    São Paulo, São Paulo, 01401-901

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403 000

Other trials in Brazil

South Korea6 sites

  • Novartis Investigative Site

    Jeollanam-do, Jeollanam-do, 519763

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, Seocho Gu, 06591

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 06351

  • Novartis Investigative Site

    Taegu, 41944

Other trials in South Korea

Belgium5 sites

  • Novartis Investigative Site

    Brussels, 1000

  • Novartis Investigative Site

    Charleroi, 6000

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Yvoir, 5530

Other trials in Belgium

Canada5 sites

  • Novartis Investigative Site

    Québec, Quebec, G1J 1Z4

  • Novartis Investigative Site

    Québec, Quebec, G1R 2J6

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E3

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Poland5 sites

  • Novartis Investigative Site

    Katowice, 40032

  • Novartis Investigative Site

    Lublin, 20-081

  • Novartis Investigative Site

    Rzeszów, 35 055

  • Novartis Investigative Site

    Warsaw, 02-097

  • Novartis Investigative Site

    Wroclaw, 50-367

Other trials in Poland

South Africa5 sites

  • Novartis Investigative Site

    Bloemfontein, 9301

  • Novartis Investigative Site

    Cape Town, 7925

  • Novartis Investigative Site

    Parktown, 2193

  • Novartis Investigative Site

    Pretoria, 0001

  • Novartis Investigative Site

    Pretoria, 0027

Other trials in South Africa

United Kingdom5 sites

  • Novartis Investigative Site

    Glasgow, G12 OYN

  • Novartis Investigative Site

    Leeds, LS9 7TF

  • Novartis Investigative Site

    Liverpool, L7 8XP

  • Novartis Investigative Site

    London, W12 0HS

  • Novartis Investigative Site

    Nottingham, NG5 1PB

Other trials in United Kingdom

Turkey (Türkiye)4 sites

  • Novartis Investigative Site

    Adana, 01330

  • Novartis Investigative Site

    Ankara, 06500

  • Novartis Investigative Site

    Istanbul, TUR, 34098

  • Novartis Investigative Site

    Izmir, 35340

Other trials in Turkey (Türkiye)

Russia3 sites

  • Novartis Investigative Site

    Moscow, 125167

  • Novartis Investigative Site

    Novosibirsk, 630051

  • Novartis Investigative Site

    Saint Petersburg, 197022

Other trials in Russia

Taiwan3 sites

  • Novartis Investigative Site

    Kaohsiung City, 83301

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Thailand3 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Bangkok, 10400

  • Novartis Investigative Site

    Bangkok, 10700

Other trials in Thailand

Argentina2 sites

  • Novartis Investigative Site

    CABA, Buenos Aires, C1221ADC

  • Novartis Investigative Site

    La Plata, Buenos Aires, B1902AVG

Other trials in Argentina

Austria2 sites

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, A-1090

Other trials in Austria

Colombia2 sites

  • Novartis Investigative Site

    Bogota, Cundinamarca, 110111

  • Novartis Investigative Site

    Bogotá, 110001

Other trials in Colombia

Czechia2 sites

  • Novartis Investigative Site

    Olomouc, CZE, 775 20

  • Novartis Investigative Site

    Prague, Czech Republic, 128 20

Other trials in Czechia

Denmark2 sites

  • Novartis Investigative Site

    Copenhagen, DK-2100

  • Novartis Investigative Site

    Vejle, DK-7100

Other trials in Denmark

Finland2 sites

  • Novartis Investigative Site

    HUS Helsinki, FIN-00029

  • Novartis Investigative Site

    Turku, FIN-20521

Other trials in Finland

Mexico2 sites

  • Novartis Investigative Site

    Mexico City, Mexico City, 06726

  • Novartis Investigative Site

    Monterrey, Nuevo León, 64460

Other trials in Mexico

Norway2 sites

  • Novartis Investigative Site

    Oslo, NO-0310

  • Novartis Investigative Site

    Trondheim, 7006

Other trials in Norway

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119228

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

Slovakia2 sites

  • Novartis Investigative Site

    Bratislava, Slovak Republic, 833 10

  • Novartis Investigative Site

    Bratislava, 85107

Other trials in Slovakia

Egypt1 site

  • Novartis Investigative Site

    Cairo

Other trials in Egypt

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

Hungary1 site

  • Novartis Investigative Site

    Budapest, 1097

Other trials in Hungary

Malaysia1 site

  • Novartis Investigative Site

    Kuala Selangor, 68000

Other trials in Malaysia

Netherlands1 site

  • Novartis Investigative Site

    Amsterdam, 1081 HV

Other trials in Netherlands

Switzerland1 site

  • Novartis Investigative Site

    Geneva, 1205

Other trials in Switzerland

Venezuela1 site

  • Novartis Investigative Site

    Caracas, Distrito Federal, 1010

Other trials in Venezuela

About this study

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)

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.

Read the 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.

Being tested
nilotinib, imatinib
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
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Hematologic Neoplasms, Bone Marrow Diseases, Leukemia, Myeloid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nilotinibDrug

    Also called AMN107

    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.

  • imatinibDrug

    Also called STI571

    Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).

Study groups in NCT00471497
Study groupRoleWhat they receive
nilotinib 300mg bid (investigating arm)ExperimentalNot described
Receives: Drug: nilotinib
Nilotinb 400 mg bid (investigating arm)ExperimentalNot described
Receives: Drug: nilotinib
imatinib 400mg QD (control arm)ExperimentalNot described
Receives: Drug: imatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation

    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.

    Measured: Baseline, 12 months

  2. Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation

    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.

    Measured: 12 months

Secondary outcomes (28)

  1. Rates of Durable MMR at 24 Months Between All 3 Arms

    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.

    Measured: 24 months

  2. Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months

    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".

    Measured: 12, 24, 36, 48, 60, 72 months (M)

  3. Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms

    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.

    Measured: 12 months

  4. Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms

    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.

    Measured: 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months

  5. Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib

    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)

    Measured: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months

  6. Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib

    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)

    Measured: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months

  7. Time to First MMR

    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.

    Measured: up to 84 months

  8. Duration of MMR

    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.

    Measured: approx. 11 years

  9. Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts

    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.

    Measured: up to 84 months

  10. Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts

    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.

    Measured: approx. 11 years

  11. Rate of Hematologic Response

    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).

    Measured: 12 months, 24 months, Overall on Core study (approx. 11 years)

  12. Time to Complete Cytogenic Response (CCyR)

    Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR

    Measured: 24 months

  13. Duration of CCyR

    Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.

    Measured: up to 72 months

  14. Progression-free Survival (PFS)

    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

    Measured: approx. 11 years

  15. Event-free Survival (EFS)

    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

    Measured: approx. 11 years

  16. Overall Survival (OS)

    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.

    Measured: approx. 11 years

  17. Actual Dose-intensity

    Actual dose intensity is defined as total dose over time on treatment

    Measured: approx. 11 years

  18. Time to Progression to AP/BC

    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.

    Measured: approx. 11 years

  19. Pharmacokinetics: Cmax

    Cmax is defined as the maximum serum concentration after dose

    Measured: 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

  20. Pharmacokinetics: Cmin

    Cmin is defined as the minimum serum concentration after dose

    Measured: 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

  21. Pharmacokinetics: Tmax

    Tmax is defined as the sampling time when maximum measured serum concentration occurs

    Measured: 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

  22. Pharmacokinetics: AUC0-last

    AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method

    Measured: 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

  23. Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)

    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).

    Measured: Overall for Extension study for approx. 10 years

  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)

    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.

    Measured: Overall for Extension study for approx. 10 years

  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)

    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))

    Measured: Overall for Extension study for approx. 10 years

  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)

    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)

    Measured: Overall for Extension study for approx. 10 years

  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)

    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)

    Measured: Overall for Extension study for approx. 10 years

  28. Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension)

    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.

    Measured: Overall for Extension study for approx. 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2007 (estimated)
  2. Study start31 Jul 2007
  3. Primary completion2 Sep 2009
  4. Study completion21 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
846 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00471497
Sponsor's protocol ID
CAMN107A2303
Other IDs
2007-000208-34
Acronym
ENESTnd
Status last verified
Oct 2020
First submitted
7 May 2007
Last updated
18 Nov 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • 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.

    PubMed 24532039

  • 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.

    PubMed 24335106

  • 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.

    PubMed 23502220

  • 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.

    PubMed 23109697

  • 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.

    PubMed 22207416

  • 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.

    PubMed 21856226

  • 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.

    PubMed 21467546

  • 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.

    PubMed 20525993

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing nilotinib and imatinib in people with Myelogenous Leukemia, Chronic, run by Novartis Pharmaceuticals at 213 sites in 35 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 213 sites in United States, Japan, Italy, Spain, France and 30 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation (time frame: Baseline, 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00471497, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020.

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