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)

October 23, 2020 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

846

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1221ADC
        • Novartis Investigative Site
      • La Plata, Buenos Aires, Argentina, B1902AVG
        • Novartis Investigative Site
  • Austria
      • Salzburg, Austria, 5020
        • Novartis Investigative Site
      • Wien, Austria, A-1090
        • Novartis Investigative Site
  • Belgium
      • Bruxelles, Belgium, 1000
        • Novartis Investigative Site
      • Charleroi, Belgium, 6000
        • Novartis Investigative Site
      • Gent, Belgium, 9000
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
      • Yvoir, Belgium, 5530
        • Novartis Investigative Site
  • Brazil
    • DF
      • Brasilia, DF, Brazil, 70330-150
        • Novartis Investigative Site
    • PR
      • Curitiba, PR, Brazil, 80060-900
        • Novartis Investigative Site
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20211-030
        • Novartis Investigative Site
    • SP
      • Campinas, SP, Brazil, 13083-970
        • Novartis Investigative Site
      • Jau, SP, Brazil, 17210-080
        • Novartis Investigative Site
      • Sao Paulo, SP, Brazil, 05403 000
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 01224-000
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 01401-901
        • Novartis Investigative Site
  • Canada
      • Quebec, Canada, G1R 2J6
        • Novartis Investigative Site
      • Quebec, Canada, G1J 1Z4
        • Novartis Investigative Site
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Novartis Investigative Site
      • Vancouver, British Columbia, Canada, V5Z 4E3
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • Colombia
      • Bogota, Colombia, 110001
        • Novartis Investigative Site
    • Cundinamarca
      • Bogota, Cundinamarca, Colombia, 110111
        • Novartis Investigative Site
  • Czechia
    • CZE
      • Olomouc, CZE, Czechia, 775 20
        • Novartis Investigative Site
    • Czech Republic
      • Praha 2, Czech Republic, Czechia, 128 20
        • Novartis Investigative Site
  • Denmark
      • Copenhagen, Denmark, DK-2100
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      • Vejle, Denmark, DK-7100
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  • Egypt
      • Cairo, Egypt
        • Novartis Investigative Site
  • Finland
      • HUS Helsinki, Finland, FIN-00029
        • Novartis Investigative Site
      • Turku, Finland, FIN-20521
        • Novartis Investigative Site
  • France
      • Angers Cedex 1, France, 49033
        • Novartis Investigative Site
      • Bordeaux, France, 33076
        • Novartis Investigative Site
      • Creteil, France, 94010
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      • Grenoble, France, 38043
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      • Lille, France, 59037
        • Novartis Investigative Site
      • Marseille, France, 13273
        • Novartis Investigative Site
      • Nantes, France, 44035
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      • Nice Cedex, France, 06202
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      • Pierre Benite Cedex, France, 69495
        • Novartis Investigative Site
      • Poitiers, France, 86000
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      • Rennes, France, 35019
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      • Toulouse, France, 31059
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      • Vandoeuvre les Nancy, France, 54511
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    • Cedex
      • Caen, Cedex, France, 14033
        • Novartis Investigative Site
    • Cedex 10
      • Paris Cedex 10, Cedex 10, France, 75475
        • Novartis Investigative Site
    • Loire
      • Saint Priest en Jarez, Loire, France, 42270
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Duesseldorf, Germany, 40225
        • Novartis Investigative Site
      • Eisenach, Germany, 99817
        • Novartis Investigative Site
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
      • Kiel, Germany, 24105
        • Novartis Investigative Site
      • Koeln, Germany, 50937
        • Novartis Investigative Site
      • Leipzig, Germany, 04103
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      • Muenchen, Germany, 81675
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site
    • Baden-Wuerttemberg
      • Mannheim, Baden-Wuerttemberg, Germany, 68305
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong, Hong Kong
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1097
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80131
        • Novartis Investigative Site
      • Napoli, Italy, 80132
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      • Perugia, Italy, 06129
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    • AL
      • Alessandria, AL, Italy, 15100
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    • AN
      • Ancona, AN, Italy, 60126
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    • BG
      • Bergamo, BG, Italy, 24127
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • CT
      • Catania, CT, Italy, 95123
        • Novartis Investigative Site
    • FI
      • Firenze, FI, Italy, 50134
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
    • PE
      • Pescara, PE, Italy, 65124
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Novartis Investigative Site
    • PV
      • Pavia, PV, Italy, 27100
        • Novartis Investigative Site
    • RC
      • Reggio Calabria, RC, Italy, 89124
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00144
        • Novartis Investigative Site
      • Roma, RM, Italy, 00161
        • Novartis Investigative Site
      • Roma, RM, Italy, 00133
        • Novartis Investigative Site
    • SI
      • Siena, SI, Italy, 53100
        • Novartis Investigative Site
    • UD
      • Udine, UD, Italy, 33100
        • Novartis Investigative Site
  • Japan
      • Akita, Japan, 010-8543
        • Novartis Investigative Site
      • Chiba, Japan, 260 8677
        • Novartis Investigative Site
      • Hiroshima, Japan, 734-8551
        • Novartis Investigative Site
      • Niigata, Japan, 951 8520
        • Novartis Investigative Site
      • Osaka, Japan, 545-8586
        • Novartis Investigative Site
      • Saitama, Japan, 330 8503
        • Novartis Investigative Site
    • Aichi
      • Nagoya, Aichi, Japan, 453-8511
        • Novartis Investigative Site
      • Nagoya, Aichi, Japan, 466 8560
        • Novartis Investigative Site
    • Gunma
      • Maebashi, Gunma, Japan, 371-0821
        • Novartis Investigative Site
      • Maebashi city, Gunma, Japan, 371 8511
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0006
        • Novartis Investigative Site
      • Sapporo city, Hokkaido, Japan, 060 8648
        • Novartis Investigative Site
    • Hyogo
      • Nishinomiya, Hyogo, Japan, 663 8501
        • Novartis Investigative Site
    • Ibaraki
      • Tsukuba city, Ibaraki, Japan, 305-8576
        • Novartis Investigative Site
    • Ishikawa
      • Kanazawa-city, Ishikawa, Japan, 920-8641
        • Novartis Investigative Site
    • Kumamoto
      • Kumamoto City, Kumamoto, Japan, 860-8556
        • Novartis Investigative Site
    • Mie
      • Tsu-city, Mie, Japan, 514-8507
        • Novartis Investigative Site
    • Nagasaki
      • Nagasaki-city, Nagasaki, Japan, 852-8501
        • Novartis Investigative Site
    • Osaka
      • Osaka Sayama, Osaka, Japan, 589 8511
        • Novartis Investigative Site
      • Suita city, Osaka, Japan, 565 0871
        • Novartis Investigative Site
    • Saitama
      • Hidaka-city, Saitama, Japan, 350-1298
        • Novartis Investigative Site
    • Shizuoka
      • Hamamatsu-city, Shizuoka, Japan, 431-3192
        • Novartis Investigative Site
    • Tochigi
      • Shimotsuke, Tochigi, Japan, 329-0498
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo ku, Tokyo, Japan, 113 8655
        • Novartis Investigative Site
      • Bunkyo-ku, Tokyo, Japan, 113-8519
        • Novartis Investigative Site
      • Chuo ku, Tokyo, Japan, 104 0045
        • Novartis Investigative Site
      • Shinagawa ku, Tokyo, Japan, 141 8625
        • Novartis Investigative Site
      • Shinjuku-ku, Tokyo, Japan, 160-0023
        • Novartis Investigative Site
      • Shinjuku-ku, Tokyo, Japan, 160 8582
        • Novartis Investigative Site
  • Korea, Republic of
      • 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
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
    • Seocho Gu
      • Seoul, Seocho Gu, Korea, Republic of, 06591
        • Novartis Investigative Site
  • Malaysia
      • Selangor, Malaysia, 68000
        • Novartis Investigative Site
  • Mexico
    • Distrito Federal
      • Mexico, Distrito Federal, Mexico, 06726
        • Novartis Investigative Site
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Novartis Investigative Site
  • Norway
      • Oslo, Norway, NO-0310
        • Novartis Investigative Site
      • Trondheim, Norway, 7006
        • Novartis Investigative Site
  • Poland
      • 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
        • Novartis Investigative Site
  • Russian Federation
      • Moscow, Russian Federation, 125167
        • Novartis Investigative Site
      • Novosibirsk, Russian Federation, 630051
        • Novartis Investigative Site
      • Saint Petersburg, Russian Federation, 197022
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Novartis Investigative Site
      • Singapore, Singapore, 169608
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 85107
        • Novartis Investigative Site
    • Slovak Republic
      • Bratislava, Slovak Republic, Slovakia, 833 10
        • Novartis Investigative Site
  • South Africa
      • 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, 0027
        • Novartis Investigative Site
      • Pretoria, South Africa, 0001
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28034
        • Novartis Investigative Site
      • Madrid, Spain, 28046
        • Novartis Investigative Site
      • Madrid, Spain, 28006
        • Novartis Investigative Site
      • Zaragoza, Spain, 50009
        • Novartis Investigative Site
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Novartis Investigative Site
    • Andalucia
      • Granada, Andalucia, Spain, 18014
        • Novartis Investigative Site
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Novartis Investigative Site
    • Castilla Y Leon
      • Salamanca, Castilla Y Leon, Spain, 37007
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
    • Galicia
      • La Coruna, Galicia, Spain, 15006
        • Novartis Investigative Site
      • Santiago de Compostela, Galicia, Spain, 15706
        • Novartis Investigative Site
    • Pais Vasco
      • Bilbao, Pais Vasco, Spain, 48013
        • Novartis Investigative Site
      • San Sebastian, Pais Vasco, Spain, 20080
        • Novartis Investigative Site
    • Santa Cruz De Tenerife
      • La Laguna, Santa Cruz De Tenerife, Spain, 38320
        • Novartis Investigative Site
  • Sweden
      • 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
        • Novartis Investigative Site
  • Switzerland
      • Geneve, Switzerland, 1205
        • Novartis Investigative Site
  • Taiwan
      • Kaohsiung City, Taiwan, 83301
        • Novartis Investigative Site
      • Taipei, Taiwan, 10002
        • Novartis Investigative Site
      • Taoyuan, Taiwan, 33305
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Novartis Investigative Site
      • Bangkok, Thailand, 10700
        • Novartis Investigative Site
      • Bangkok, Thailand, 10400
        • Novartis Investigative Site
  • Turkey
      • Adana, Turkey, 01330
        • Novartis Investigative Site
      • Ankara, Turkey, 06500
        • Novartis Investigative Site
      • Izmir, Turkey, 35340
        • Novartis Investigative Site
    • TUR
      • Istanbul, TUR, Turkey, 34098
        • Novartis Investigative Site
  • United Kingdom
      • 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
        • Novartis Investigative Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California at Los Angeles Dept. of Hematology Clinic
      • San Diego, California, United States, 92120
        • Kaiser Permanente - California Southern Dept of Kaiser South 3
      • Vallejo, California, United States, 94589
        • Kaiser Permanente - California Northern Vallejo Med Center/Med Offices
      • Vallejo, California, United States, 94609
        • Kaiser Permanente - California Northern Kaiser Med
    • Colorado
      • Greenwood Village, Colorado, United States
        • Rocky Mountain Cancer Centers RMCC - Colorado Springs
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists Dept. FloridaCancerSpecialists
      • Miami, Florida, United States, 33176
        • Advanced Medical Specialties Research Dept.
      • Ocoee, Florida, United States, 34761
        • Cancer Centers of Florida PA Cancer Centers of FL
      • Orlando, Florida, United States, 32804
        • Florida Retina Institute Flordia Cancer Affilates
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Section of Hematology/Oncology
    • Indiana
      • Beech Grove, Indiana, United States, 46107
        • Indiana Blood and Marrow Institute Dept. of Indiana Blood&Marrow
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics Dept.of U of Iowa Hosp&Clinics
    • Kansas
      • Overland Park, Kansas, United States, 66210
        • Kansas City Cancer Center KCCC Business Office
    • Louisiana
      • New Orleans, Louisiana, United States, 70115
        • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
    • Michigan
      • Lansing, Michigan, United States, 48824
        • Michigan State University / Breslin Cancer Center Breslin Cancer Center
    • Missouri
      • Columbia, Missouri, United States, 65201
        • Missouri Cancer Associates Dept. of Boone Hospital Center
      • Saint Louis, Missouri, United States, 63136
        • Hematology Oncology Consultants, Inc. Deptof Hem. Onc.Consunsultants
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Department of Research
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center Clinical Trials Office
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina UNC Lineberger Cancer Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences Dept. of Industry Research
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati / Barrett Cancer Center Dept.of Internal Med.
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation CCF
    • Oregon
      • Portland, Oregon, United States, 97210
        • Northwest Cancer Specialists Compass Oncology -BKM
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Cancer Centers of the Carolinas CC of C -Eastside
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology Dept. of Centennial Medical
    • Texas
      • Dallas, Texas, United States, 75230
        • Texas Cancer Center ( Medical City Dallas Hospital)
      • San Antonio, Texas, United States, 78229
        • Cancer Care Centers of South Texas HOAST CCC of So.TX- Medical Center
      • Tyler, Texas, United States, 75702
        • Tyler Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
  • Venezuela
    • Distrito Capital
      • Caracas, Distrito Capital, Venezuela, 1010
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • STI571

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, 12 months
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months
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".
12, 24, 36, 48, 60, 72 months (M)
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.
12 months
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.
6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
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)
at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
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)
at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
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.
up to 84 months
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.
approx. 11 years
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.
up to 84 months
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.
approx. 11 years
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 months, 24 months, Overall on Core study (approx. 11 years)
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
24 months
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.
up to 72 months
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
approx. 11 years
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
approx. 11 years
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.
approx. 11 years
Actual Dose-intensity
Time Frame: approx. 11 years
Actual dose intensity is defined as total dose over time on treatment
approx. 11 years
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.
approx. 11 years
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
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
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
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
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
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
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
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
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).
Overall for Extension study for approx. 10 years
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.
Overall for Extension study for approx. 10 years
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))
Overall for Extension study for approx. 10 years
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)
Overall for Extension study for approx. 10 years
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)
Overall for Extension study for approx. 10 years
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.
Overall for Extension study for approx. 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2007

Primary Completion (Actual)

September 2, 2009

Study Completion (Actual)

August 21, 2019

Study Registration Dates

First Submitted

May 7, 2007

First Submitted That Met QC Criteria

May 9, 2007

First Posted (Estimate)

May 10, 2007

Study Record Updates

Last Update Posted (Actual)

November 18, 2020

Last Update Submitted That Met QC Criteria

October 23, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAMN107A2303
  • 2007-000208-34 (Registry Identifier: EUDRACT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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