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'MACS1252: Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome & /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01061177
Collaborator
(none)
1,090
Enrollment
321
Locations
1
Arm
50
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the efficacy and safety of nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive/BCR-ABL positive chronic myeloid leukaemia in chronic phase. The aim of the study is to confirm the rates of complete molecular remission (CMR) of nilotinib in newly diagnosed CML chronic phase patients in a pan-European population using the EUTOS standardized laboratories.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
1090 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase IIIb, Multicentre, Open-label Study of Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome and/or BCR-ABL Positive CML in Chronic Phase
Study Start Date :
May 1, 2010
Actual Primary Completion Date :
Jul 1, 2014
Actual Study Completion Date :
Jul 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nilotinib

This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.

Drug: Nilotinib
Nilotinib was supplied by Novartis as 150 mg hard gelatin capsules in bottles. Nilotinib was dosed on a flat scale and not dosed by body weight. This form of supply was continued for all participants entered into the core study.
Other Names:
  • AMN107

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Molecular Response (MR4^0) at 18 Months [at 18 months]

      MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.

    Secondary Outcome Measures

    1. Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months [at 12 and 24 months]

      The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

    2. Rate of Event Free Survival at 12 and 24 Months [at 12 and 24 months]

      EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.

    3. Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months [12 months, 24 months]

      MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR ("breakpoint cluster region") gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.

    4. Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months [12 and 24 months]

      CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, > 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.

    5. Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months [12 and 24 months]

      Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.

    6. Percentage of Participants Free From Progression to AP/BC With MR4^0 at 12 Months [at 12 months]

      The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

    7. Percentage of Participants With Event Free Survival in Participants Achieving MR4^0 at 12 Months [at 12 months]

      EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).

    8. Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months [12 months, 24 months]

      PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.

    9. Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months [12 and 24 months]

      MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.

    10. Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months [12 and 24 months]

      MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts).

    11. Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months [12 months, 24 months]

      CHR was defined as all of the following present for ≥ 4 weeks in the peripheral blood: WBC count < 10 x 109/L, Platelet count < 450 x 109/L, No circulating peripheral blood blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood, The presence of < 5% basophils, No evidence of disease-related symptoms and extramedullary disease, including spleen and liver. Loss of CHR was defined as the appearance of any of the following after having achieved a CHR confirmed by a second determination ≥ 4 weeks later (unless associated with progression to AP/BC or death, which was considered to be a confirmed loss of CHR event on its own): WBC count that increased to > 20.0 x 109/L, Platelet count that increased to ≥ 600 x 109/L, Any palpable spleen, defined as size of spleen below costal margin > 5 cm, Appearance of > 5% myelocytes plus metamyelocytes, or any promyelocytes or blasts in the peripheral blood.

    12. Percentage of Participants With Overall Survival at 12 and 24 Months [12 months, 24 months]

      OS was defined as the time between the date of Day 1 (first treatment) and the date of death from any cause. Deaths which occurred after the 24-month time window and which were occasionally reported by some Investigators were excluded from the analysis. This is in agreement with the protocol stating that patients were to be followed for survival and progression to AP/BC up to 24 months after the participants treatment start.

    13. Rate of Molecular Response (MR4^0) by 18 Months [by 18 months]

      MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts. BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase

    14. Rate of Molecular Response (MR4^5) by 18 Months [by 18 months]

      MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts). BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase

    15. Percentage of Participants With Progression Free Survival in Participants Achieving MR4^0 at 12 Months [12 months]

      PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with diagnosis of CP-CML with cytogenetic confirmation of Philadelphia (Ph) chromosome

    • Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR are also eligible

    • WHO performance status 0-2

    • Laboratory assessments within normal limits

    • Written informed consent prior to any study procedures being performed

    Exclusion Criteria:

    • Known impaired cardiac function

    • History of acute or chronic pancreatitis

    • Impaired gastrointestinal function or disease that may alter the absorption of study drug

    • Concomitant medications with potential QT prolongation, or known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9, and CYP2C8)

    • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

    • Patients who are pregnant or breast feeding, or females of reproductive potential not employing an effective method of birth control. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Graz Austria 8036
    2 Novartis Investigative Site Innsbruck Austria A-6020
    3 Novartis Investigative Site Linz Austria 4010
    4 Novartis Investigative Site Rankweil Austria A-6830
    5 Novartis Investigative Site Salzburg Austria 5020
    6 Novartis Investigative Site Vienna Austria A-1130
    7 Novartis Investigative Site Wels Austria A-4600
    8 Novartis Investigative Site Wien Austria A-1140
    9 Novartis Investigative Site Aalst Belgium 9300
    10 Novartis Investigative Site Brugge Belgium 8000
    11 Novartis Investigative Site Brussels Belgium BE-B-1200
    12 Novartis Investigative Site Brussel Belgium 1090
    13 Novartis Investigative Site Bruxelles Belgium 1000
    14 Novartis Investigative Site Bruxelles Belgium 1070
    15 Novartis Investigative Site Charleroi Belgium 6000
    16 Novartis Investigative Site Edegem Belgium 2650
    17 Novartis Investigative Site Gent Belgium 9000
    18 Novartis Investigative Site Hasselt Belgium 3500
    19 Novartis Investigative Site Laeken Belgium 1020
    20 Novartis Investigative Site Leuven Belgium 3000
    21 Novartis Investigative Site Luxembourg Belgium 1210
    22 Novartis Investigative Site Roeselare Belgium 8800
    23 Novartis Investigative Site Verviers Belgium 4800
    24 Novartis Investigative Site Yvoir Belgium 5530
    25 Novartis Investigative Site Pleven Bulgaria 5800
    26 Novartis Investigative Site Plovdiv Bulgaria 4002
    27 Novartis Investigative Site Sofia Bulgaria 1431
    28 Novartis Investigative Site Sofia Bulgaria 1756
    29 Novartis Investigative Site Varna Bulgaria 9000
    30 Novartis Investigative Site Rijeka Croatia 51000
    31 Novartis Investigative Site Zagreb Croatia 10000
    32 Novartis Investigative Site Olomouc CZE Czech Republic 775 20
    33 Novartis Investigative Site Brno - Bohunice Czech Republic 625 00
    34 Novartis Investigative Site Hradec Kralove Czech Republic 500 05
    35 Novartis Investigative Site Praha 2 Czech Republic 128 20
    36 Novartis Investigative Site Aarhus C Denmark DK-8000
    37 Novartis Investigative Site Copenhagen Denmark DK-2100
    38 Novartis Investigative Site Odense C Denmark DK-5000
    39 Novartis Investigative Site Tartu Estonia 51006
    40 Novartis Investigative Site HUS Helsinki Finland FIN-00029
    41 Novartis Investigative Site Oulu Finland 900114
    42 Novartis Investigative Site Bayonne Bayonne cedex France 64109
    43 Novartis Investigative Site Paris Cedex 10 Cedex 10 France 75475
    44 Novartis Investigative Site Saint Denis FRANCE / La Reunion France 97405
    45 Novartis Investigative Site Monte-Carlo Principauté de Monaco France 98012
    46 Novartis Investigative Site Aix en Provence Cedex 1 France 13616
    47 Novartis Investigative Site Amiens cedex1 France 80054
    48 Novartis Investigative Site Angers Cedex 1 France 49033
    49 Novartis Investigative Site Argenteuil Cedex France 95107
    50 Novartis Investigative Site Avignon cedex 9 France 84902
    51 Novartis Investigative Site Besancon cedex France 25030
    52 Novartis Investigative Site Blois Cedex France 41016
    53 Novartis Investigative Site Bordeaux France 33076
    54 Novartis Investigative Site Brest France 29200
    55 Novartis Investigative Site Caen France 14000
    56 Novartis Investigative Site Chalon sur Saône France 71321
    57 Novartis Investigative Site Chambéry cedex France 73011
    58 Novartis Investigative Site Clermont-Ferrand cedex 1 France 63003
    59 Novartis Investigative Site Compiègne cedex France 60321
    60 Novartis Investigative Site Corbeil Essonnes France 91100
    61 Novartis Investigative Site Creteil France 94010
    62 Novartis Investigative Site Dijon France 21034
    63 Novartis Investigative Site Dunkerque France 59240
    64 Novartis Investigative Site Grenoble France 38043
    65 Novartis Investigative Site La Roche sur Yon cedex 9 France 85925
    66 Novartis Investigative Site Le Chesnay France 78157
    67 Novartis Investigative Site Le Coudray France 28630
    68 Novartis Investigative Site Le Mans Cedex 09 France 72037
    69 Novartis Investigative Site Lens Cedex France 62307
    70 Novartis Investigative Site Lille cedex France 59020
    71 Novartis Investigative Site Limoges cedex France 87042
    72 Novartis Investigative Site Marseille cedex 20 France 13915
    73 Novartis Investigative Site Marseille France 13273
    74 Novartis Investigative Site Metz Cedex 01 France 57038
    75 Novartis Investigative Site Montfermeil France 93370
    76 Novartis Investigative Site Montpellier cedex 5 France 34295
    77 Novartis Investigative Site Mulhouse cedex France 68070
    78 Novartis Investigative Site Mâcon Cedex France 71018
    79 Novartis Investigative Site Nantes France 44035
    80 Novartis Investigative Site Nice Cedex 2 France 06189
    81 Novartis Investigative Site Nimes France 32900
    82 Novartis Investigative Site Paris France 75012
    83 Novartis Investigative Site Pau France 64000
    84 Novartis Investigative Site Perpignan France 66046
    85 Novartis Investigative Site Pringy cedex France 74374
    86 Novartis Investigative Site Reims France 51092
    87 Novartis Investigative Site Rennes France 35019
    88 Novartis Investigative Site Roubaix France 59100
    89 Novartis Investigative Site Rouen Cedex 1 France 76038
    90 Novartis Investigative Site Saint Brieuc cedex 1 France 22027
    91 Novartis Investigative Site Saint Priest en Jarez Cedex France 42271
    92 Novartis Investigative Site St Quentin Cedex France 02321
    93 Novartis Investigative Site Strasbourg cedex France 67085
    94 Novartis Investigative Site Strasbourg cedex France 67091
    95 Novartis Investigative Site Toulouse Cedex 9 France 31059
    96 Novartis Investigative Site Tours Cedex 9 France 37044
    97 Novartis Investigative Site Troyes France 10003
    98 Novartis Investigative Site Koeln Nordrhein-Westfalen Germany 50937
    99 Novartis Investigative Site Aachen Germany 52074
    100 Novartis Investigative Site Aschaffenburg Germany 63739
    101 Novartis Investigative Site Augsburg Germany 86156
    102 Novartis Investigative Site Bamberg Germany 96049
    103 Novartis Investigative Site Bayreuth Germany 95445
    104 Novartis Investigative Site Berlin Germany 10707
    105 Novartis Investigative Site Berlin Germany 10709
    106 Novartis Investigative Site Berlin Germany 13353
    107 Novartis Investigative Site Berlin Germany 14195
    108 Novartis Investigative Site Bielefeld Germany 33604
    109 Novartis Investigative Site Bonn Germany 53105
    110 Novartis Investigative Site Bottrop Germany 46236
    111 Novartis Investigative Site Bremen Germany 28177
    112 Novartis Investigative Site Dresden Germany 01307
    113 Novartis Investigative Site Duesseldorf Germany 40225
    114 Novartis Investigative Site Duisburg Germany 47166
    115 Novartis Investigative Site Eisenach Germany 99817
    116 Novartis Investigative Site Eschweiler Germany 52249
    117 Novartis Investigative Site Essen Germany 45136
    118 Novartis Investigative Site Essen Germany 45147
    119 Novartis Investigative Site Frankfurt, Oder Germany 15236
    120 Novartis Investigative Site Frankfurt Germany 60590
    121 Novartis Investigative Site Frankfurt Germany 60596
    122 Novartis Investigative Site Freiburg Germany 79106
    123 Novartis Investigative Site Fulda Germany 36043
    124 Novartis Investigative Site Giessen Germany 35392
    125 Novartis Investigative Site Goslar Germany 38642
    126 Novartis Investigative Site Greifswald Germany 17475
    127 Novartis Investigative Site Hagen Germany 58097
    128 Novartis Investigative Site Hamburg Germany 20246
    129 Novartis Investigative Site Hamm Germany 59063
    130 Novartis Investigative Site Hannover Germany 30170
    131 Novartis Investigative Site Hannover Germany 30625
    132 Novartis Investigative Site Herrsching Germany 82211
    133 Novartis Investigative Site Hildesheim Germany 31134
    134 Novartis Investigative Site Jena Germany 07740
    135 Novartis Investigative Site Karlsruhe Germany 76133
    136 Novartis Investigative Site Karlsruhe Germany 76135
    137 Novartis Investigative Site Kassel Germany 34119
    138 Novartis Investigative Site Kassel Germany 34125
    139 Novartis Investigative Site Kiel Germany 24116
    140 Novartis Investigative Site Koblenz Germany 56068
    141 Novartis Investigative Site Landshut Germany 84028
    142 Novartis Investigative Site Leipzig Germany 04103
    143 Novartis Investigative Site Lemgo Germany 32657
    144 Novartis Investigative Site Luebeck Germany 23563
    145 Novartis Investigative Site Magdeburg Germany 39104
    146 Novartis Investigative Site Mainz Germany 55131
    147 Novartis Investigative Site Mannheim Germany 68169
    148 Novartis Investigative Site Marburg Germany 35039
    149 Novartis Investigative Site Moers Germany 47441
    150 Novartis Investigative Site Muelheim Germany 45468
    151 Novartis Investigative Site Muenchen Germany 80335
    152 Novartis Investigative Site Muenchen Germany 81241
    153 Novartis Investigative Site Muenchen Germany 81737
    154 Novartis Investigative Site Muenster Germany 48149
    155 Novartis Investigative Site Mutlangen Germany 73557
    156 Novartis Investigative Site Mönchengladbach Germany 41063
    157 Novartis Investigative Site München Germany 81675
    158 Novartis Investigative Site Neunkirchen Germany 66538
    159 Novartis Investigative Site Nuernberg Germany 90419
    160 Novartis Investigative Site Nuernberg Germany 90449
    161 Novartis Investigative Site Offenburg Germany 77652
    162 Novartis Investigative Site Paderborn Germany 33102
    163 Novartis Investigative Site Ravensburg Germany 88214
    164 Novartis Investigative Site Rostock Germany 18057
    165 Novartis Investigative Site Schorndorf Germany 73614
    166 Novartis Investigative Site Schwäbisch-Hall Germany 74523
    167 Novartis Investigative Site Sindelfingen Germany 71065
    168 Novartis Investigative Site Stuttgart Germany 70376
    169 Novartis Investigative Site Traunstein Germany 83278
    170 Novartis Investigative Site Triberg Germany 78098
    171 Novartis Investigative Site Ulm Germany 89081
    172 Novartis Investigative Site Velbert Germany 42551
    173 Novartis Investigative Site Viersen Germany 45468
    174 Novartis Investigative Site Weilheim Germany 82362
    175 Novartis Investigative Site Wendlingen Germany 73240
    176 Novartis Investigative Site Wuerzburg Germany 97080
    177 Novartis Investigative Site Würzburg Germany 97080
    178 Novartis Investigative Site Zella-Mehlis Germany 98544
    179 Novartis Investigative Site Alexandroupolis Evros Greece 68100
    180 Novartis Investigative Site Athens GR Greece 115 27
    181 Novartis Investigative Site Larissa GR Greece 411 10
    182 Novartis Investigative Site Thessaloniki GR Greece 546 42
    183 Novartis Investigative Site Athens Greece 11527
    184 Novartis Investigative Site Heraklion Crete Greece 711 10
    185 Novartis Investigative Site Patras Greece 265 00
    186 Novartis Investigative Site Budapest Hungary 1097
    187 Novartis Investigative Site Debrecen Hungary 4032
    188 Novartis Investigative Site Kaposvar Hungary 7400
    189 Novartis Investigative Site Pecs Hungary 7624
    190 Novartis Investigative Site Szeged Hungary H-6725
    191 Novartis Investigative Site Ancona AN Italy 60126
    192 Novartis Investigative Site Avellino AV Italy 83100
    193 Novartis Investigative Site Bari BA Italy 70124
    194 Novartis Investigative Site Bologna BO Italy 40138
    195 Novartis Investigative Site Brindisi BR Italy 72100
    196 Novartis Investigative Site Brescia BS Italy 25123
    197 Novartis Investigative Site Cagliari CA Italy 09121
    198 Novartis Investigative Site Cagliari CA Italy 09126
    199 Novartis Investigative Site Cuneo CN Italy 12100
    200 Novartis Investigative Site Rossano CS Italy 87067
    201 Novartis Investigative Site Catanzaro CZ Italy 88100
    202 Novartis Investigative Site Cona FE Italy 44100
    203 Novartis Investigative Site San Giovanni Rotondo FG Italy 71013
    204 Novartis Investigative Site Firenze FI Italy 50134
    205 Novartis Investigative Site Genova GE Italy 16132
    206 Novartis Investigative Site Roma Lazio Italy 00168
    207 Novartis Investigative Site Lecce LE Italy 73100
    208 Novartis Investigative Site Livorno LI Italy 57124
    209 Novartis Investigative Site Milano MI Italy 20122
    210 Novartis Investigative Site Milano MI Italy 20162
    211 Novartis Investigative Site Modena MO Italy 41100
    212 Novartis Investigative Site Nuoro NU Italy 08100
    213 Novartis Investigative Site Palermo PA Italy 90146
    214 Novartis Investigative Site Padova PD Italy 35128
    215 Novartis Investigative Site Pescara PE Italy 65124
    216 Novartis Investigative Site Pisa PI Italy 56126
    217 Novartis Investigative Site Pesaro PU Italy 61100
    218 Novartis Investigative Site Pavia PV Italy 27100
    219 Novartis Investigative Site Potenza PZ Italy 85100
    220 Novartis Investigative Site Ravenna RA Italy 48100
    221 Novartis Investigative Site Reggio Calabria RC Italy 89124
    222 Novartis Investigative Site Reggio Emilia RE Italy 42123
    223 Novartis Investigative Site Roma RM Italy 00144
    224 Novartis Investigative Site Roma RM Italy 00161
    225 Novartis Investigative Site Nocera Inferiore SA Italy 84014
    226 Novartis Investigative Site Siena SI Italy 53100
    227 Novartis Investigative Site Sassari SS Italy 07100
    228 Novartis Investigative Site Taranto TA Italy 74100
    229 Novartis Investigative Site Orbassano TO Italy 10043
    230 Novartis Investigative Site Torino TO Italy 10126
    231 Novartis Investigative Site Terni TR Italy 05100
    232 Novartis Investigative Site Treviso TV Italy 31100
    233 Novartis Investigative Site Ronciglione VT Italy 01100
    234 Novartis Investigative Site Napoli Italy 80131
    235 Novartis Investigative Site Napoli Italy 80132
    236 Novartis Investigative Site Novara Italy 28100
    237 Novartis Investigative Site Perugia Italy 06129
    238 Novartis Investigative Site Riga LV Latvia 1006
    239 Novartis Investigative Site Kaunas Lithuania 3007
    240 Novartis Investigative Site Klaipeda Lithuania LT-92231
    241 Novartis Investigative Site Vilnius Lithuania LT-08661
    242 Novartis Investigative Site Amsterdam Netherlands 1081 HV
    243 Novartis Investigative Site Delft Netherlands 2625 AD
    244 Novartis Investigative Site Enschede Netherlands 7513 ER
    245 Novartis Investigative Site Groningen Netherlands 9713 GZ
    246 Novartis Investigative Site Nijmegen Netherlands 6525 GA
    247 Novartis Investigative Site Rotterdam Netherlands 3075 EA
    248 Novartis Investigative Site Zwolle Netherlands 8025 AB
    249 Novartis Investigative Site Bergen Norway NO-5021
    250 Novartis Investigative Site Oslo Norway NO-0310
    251 Novartis Investigative Site Stavanger Norway 4068
    252 Novartis Investigative Site Tromsoe Norway NO-9038
    253 Novartis Investigative Site Trondheim Norway 7006
    254 Novartis Investigative Site Gdansk Poland 80-952
    255 Novartis Investigative Site Krakow Poland 30-510
    256 Novartis Investigative Site Lublin Poland 20-081
    257 Novartis Investigative Site Warsaw Poland 02-106
    258 Novartis Investigative Site Warszawa Poland 02-776
    259 Novartis Investigative Site Wroclaw Poland 50-367
    260 Novartis Investigative Site Lisboa Portugal 1150-314
    261 Novartis Investigative Site Porto Portugal 4200-072
    262 Novartis Investigative Site Porto Portugal 4200319
    263 Novartis Investigative Site Bucharest District 2 Romania 022328
    264 Novartis Investigative Site Iasi Jud. Iasi Romania 700111
    265 Novartis Investigative Site Bucharest Romania 030171
    266 Novartis Investigative Site Bucharest Romania 050098
    267 Novartis Investigative Site Cluj-Napoca Romania 3400
    268 Novartis Investigative Site Timisoara Romania 300 079
    269 Novartis Investigative Site Kosice Slovak Republic Slovakia 04066
    270 Novartis Investigative Site Bratislava Slovakia 851 07
    271 Novartis Investigative Site Martin Slovakia 03601
    272 Novartis Investigative Site Celje Slovenia 3000
    273 Novartis Investigative Site Ljubljana Slovenia 1000
    274 Novartis Investigative Site Elche Alicante Spain 03203
    275 Novartis Investigative Site Oviedo Asturias Spain 33006
    276 Novartis Investigative Site Santander Cantabria Spain 39008
    277 Novartis Investigative Site Toledo Castilla la Mancha Spain 45071
    278 Novartis Investigative Site Salamanca Castilla y Leon Spain 37007
    279 Novartis Investigative Site Badalona Catalunya Spain 08916
    280 Novartis Investigative Site Barcelona Catalunya Spain 08003
    281 Novartis Investigative Site Barcelona Catalunya Spain 08035
    282 Novartis Investigative Site Barcelona Catalunya Spain 08036
    283 Novartis Investigative Site Tarragona Catalunya Spain 43005
    284 Novartis Investigative Site Terrassa Catalunya Spain 08221
    285 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46010
    286 Novartis Investigative Site La Coruna Galicia Spain 15006
    287 Novartis Investigative Site Orense Galicia Spain 32005
    288 Novartis Investigative Site Las Palmas de Gran Canaria Las Palmas de G.C Spain 35010
    289 Novartis Investigative Site Majadahonda Madrid Spain 28222
    290 Novartis Investigative Site Pamplona Navarra Spain 31008
    291 Novartis Investigative Site Bilbao Pais Vasco Spain 48013
    292 Novartis Investigative Site San Sebastian Pais Vasco Spain 20080
    293 Novartis Investigative Site La Laguna Santa Cruz de Tenerife Spain 38320
    294 Novartis Investigative Site Baracaldo Vizcaya Spain 48903
    295 Novartis Investigative Site Barcelona Spain 08041
    296 Novartis Investigative Site Madrid Spain 28006
    297 Novartis Investigative Site Madrid Spain 28034
    298 Novartis Investigative Site Madrid Spain 28040
    299 Novartis Investigative Site Madrid Spain 28041
    300 Novartis Investigative Site Madrid Spain 28046
    301 Novartis Investigative Site Murcia Spain 30008
    302 Novartis Investigative Site Zaragoza Spain 50009
    303 Novartis Investigative Site Göteborg Sweden SE-413 45
    304 Novartis Investigative Site Huddinge Sweden SE-14186
    305 Novartis Investigative Site Linköping Sweden SE-581 85
    306 Novartis Investigative Site Lulea Sweden SE-971 80
    307 Novartis Investigative Site Lund Sweden SE-221 85
    308 Novartis Investigative Site Stockholm Sweden SE-171 76
    309 Novartis Investigative Site Umeå Sweden SE-901 85
    310 Novartis Investigative Site Uppsala Sweden SE-751 85
    311 Novartis Investigative Site Bern Switzerland 3010
    312 Novartis Investigative Site Chur Switzerland 7000
    313 Novartis Investigative Site Genève Switzerland 1211
    314 Novartis Investigative Site Zurich Switzerland 8091
    315 Novartis Investigative Site Uxbridge London United Kingdom UB8 3NN
    316 Novartis Investigative Site Cardiff United Kingdom CF14 4XW
    317 Novartis Investigative Site Dudley United Kingdom DY1 2HQ
    318 Novartis Investigative Site London United Kingdom SE5 9RS
    319 Novartis Investigative Site London United Kingdom W12 0HS
    320 Novartis Investigative Site Nottingham United Kingdom NG5
    321 Novartis Investigative Site Oxford United Kingdom OX3 7LJ

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01061177
    Other Study ID Numbers:
    • CAMN107EIC01
    • 2009-017775-19
    First Posted:
    Feb 2, 2010
    Last Update Posted:
    Feb 24, 2017
    Last Verified:
    Dec 1, 2016
    Keywords provided by Novartis Pharmaceuticals
    Leukemia
    myeloid
    myelogenous
    chronic BCR-ABL positive
    Nilotinib
    Philadelphia chromosome
    CML in chronic phase
    Additional relevant MeSH terms:
    Philadelphia Chromosome

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail ITT: intent to treat; b3a2 & b2a2 +ve are categories of BCR-ABL transcripts (BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia and acute lymphoblastic leukemia patients; CyR (Ph+ Patients Only) = cytogenic response for Philadelphia positive patients only.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Period Title: Overall Study
    STARTED 1089
    ITT_MR (b2a2 &/or b3a2 +ve Pts Only) 1056
    ITT_CyR (Ph+ Patients Only) 983
    COMPLETED 881
    NOT COMPLETED 208

    Baseline Characteristics

    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Overall Participants 1089
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    51.6
    (14.87)
    Gender (Count of Participants)
    Female
    447
    41%
    Male
    642
    59%
    Race/Ethnicity, Customized (Number) [Number]
    Caucacian
    1045
    96%
    Black
    6
    0.6%
    Oriental
    5
    0.5%
    Native American
    2
    0.2%
    Other
    31
    2.8%
    Weight at baseline (Kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kg]
    77.47
    (15.730)
    ECOG performance score (Number) [Number]
    No restrictions (0)
    867
    79.6%
    Only light work (1)
    199
    18.3%
    Only self care (2)
    21
    1.9%
    Limited self care (3)
    0
    0%
    Completely disabled (4)
    0
    0%
    Missing
    2
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Molecular Response (MR4^0) at 18 Months
    Description MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
    Time Frame at 18 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat_Molecular (ITT_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    Number [Percentage of Participants]
    38.3
    3.5%
    2. Secondary Outcome
    Title Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months
    Description The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
    Time Frame at 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1089
    Pts free from progression to AP/BC at 12 months
    99.4
    9.1%
    Pts free from progression to AP/BC at 24 months
    99.4
    9.1%
    3. Secondary Outcome
    Title Rate of Event Free Survival at 12 and 24 Months
    Description EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.
    Time Frame at 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1089
    Percentage of participants with EFS at 12 months
    71.7
    6.6%
    Percentage of participants with EFS at 24 months
    69.1
    6.3%
    4. Secondary Outcome
    Title Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
    Description MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR ("breakpoint cluster region") gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.
    Time Frame 12 months, 24 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat_Molecular (ITT_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    at 12 months
    56.2
    5.2%
    at 24 months
    61.1
    5.6%
    by 12 months
    68.8
    6.3%
    by 24 months
    80.3
    7.4%
    5. Secondary Outcome
    Title Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
    Description CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, > 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.
    Time Frame 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 983
    at 12 months
    72.4
    6.6%
    at 24 months
    65.6
    6%
    By Month 12
    82.5
    7.6%
    By Month 24
    89.0
    8.2%
    6. Secondary Outcome
    Title Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
    Description Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.
    Time Frame 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 983
    at 12 months
    73.8
    6.8%
    at 24 months
    66.2
    6.1%
    by 12 months
    86.7
    8%
    by 24 months
    91.4
    8.4%
    7. Secondary Outcome
    Title Percentage of Participants Free From Progression to AP/BC With MR4^0 at 12 Months
    Description The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
    Time Frame at 12 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 400
    Number [Percentage of participants]
    100.0
    9.2%
    8. Secondary Outcome
    Title Percentage of Participants With Event Free Survival in Participants Achieving MR4^0 at 12 Months
    Description EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).
    Time Frame at 12 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 400
    Number [Percentage of participants]
    87.0
    8%
    9. Secondary Outcome
    Title Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months
    Description PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
    Time Frame 12 months, 24 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1089
    at 12 months
    99.2
    9.1%
    at 24 months
    99.0
    9.1%
    10. Secondary Outcome
    Title Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
    Description MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
    Time Frame 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT_MR.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    at 12 months
    30.7
    2.8%
    at 24 months
    40.2
    3.7%
    by month 12
    36.9
    3.4%
    by month 24
    55.0
    5.1%
    11. Secondary Outcome
    Title Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
    Description MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts).
    Time Frame 12 and 24 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    at 12 months
    15.2
    1.4%
    at 24 months
    21.9
    2%
    by 12 months
    20.6
    1.9%
    by 24 months
    38.4
    3.5%
    12. Secondary Outcome
    Title Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
    Description CHR was defined as all of the following present for ≥ 4 weeks in the peripheral blood: WBC count < 10 x 109/L, Platelet count < 450 x 109/L, No circulating peripheral blood blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood, The presence of < 5% basophils, No evidence of disease-related symptoms and extramedullary disease, including spleen and liver. Loss of CHR was defined as the appearance of any of the following after having achieved a CHR confirmed by a second determination ≥ 4 weeks later (unless associated with progression to AP/BC or death, which was considered to be a confirmed loss of CHR event on its own): WBC count that increased to > 20.0 x 109/L, Platelet count that increased to ≥ 600 x 109/L, Any palpable spleen, defined as size of spleen below costal margin > 5 cm, Appearance of > 5% myelocytes plus metamyelocytes, or any promyelocytes or blasts in the peripheral blood.
    Time Frame 12 months, 24 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1089
    by Month 24
    89.1
    at 12 months
    82.7
    at 24 months
    75.5
    by Month12
    86.2
    13. Secondary Outcome
    Title Percentage of Participants With Overall Survival at 12 and 24 Months
    Description OS was defined as the time between the date of Day 1 (first treatment) and the date of death from any cause. Deaths which occurred after the 24-month time window and which were occasionally reported by some Investigators were excluded from the analysis. This is in agreement with the protocol stating that patients were to be followed for survival and progression to AP/BC up to 24 months after the participants treatment start.
    Time Frame 12 months, 24 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1089
    at 12 months
    99.6
    9.1%
    at 24 months
    98.9
    9.1%
    14. Secondary Outcome
    Title Rate of Molecular Response (MR4^0) by 18 Months
    Description MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts. BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
    Time Frame by 18 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT_MR.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    Number [Percentage of participants]
    48.5
    4.5%
    15. Secondary Outcome
    Title Rate of Molecular Response (MR4^5) by 18 Months
    Description MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts). BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
    Time Frame by 18 months

    Outcome Measure Data

    Analysis Population Description
    The ITT_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 1056
    Number [Percentage of participants]
    31.6
    2.9%
    16. Secondary Outcome
    Title Percentage of Participants With Progression Free Survival in Participants Achieving MR4^0 at 12 Months
    Description PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    Measure Participants 400
    at 12 months
    99.2
    9.1%
    at 24 months
    99.0
    9.1%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Nilotinib
    Arm/Group Description This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
    All Cause Mortality
    Nilotinib
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Nilotinib
    Affected / at Risk (%) # Events
    Total 207/1089 (19%)
    Blood and lymphatic system disorders
    Anaemia 5/1089 (0.5%)
    Haemolytic anaemia 1/1089 (0.1%)
    Haemorrhagic anaemia 1/1089 (0.1%)
    Leukopenia 1/1089 (0.1%)
    Neutropenia 2/1089 (0.2%)
    Pancytopenia 1/1089 (0.1%)
    Splenic infarction 1/1089 (0.1%)
    Thrombocytopenia 3/1089 (0.3%)
    Cardiac disorders
    Acute coronary syndrome 3/1089 (0.3%)
    Acute myocardial infarction 4/1089 (0.4%)
    Angina pectoris 6/1089 (0.6%)
    Angina unstable 2/1089 (0.2%)
    Aortic valve stenosis 1/1089 (0.1%)
    Arteriosclerosis coronary artery 2/1089 (0.2%)
    Atrial fibrillation 13/1089 (1.2%)
    Atrial flutter 2/1089 (0.2%)
    Cardiac failure 1/1089 (0.1%)
    Cardiac failure congestive 3/1089 (0.3%)
    Coronary artery disease 7/1089 (0.6%)
    Coronary artery stenosis 1/1089 (0.1%)
    Coronary artery thrombosis 1/1089 (0.1%)
    Mitral valve disease 1/1089 (0.1%)
    Mitral valve incompetence 1/1089 (0.1%)
    Myocardial infarction 4/1089 (0.4%)
    Myocardial ischaemia 3/1089 (0.3%)
    Pericardial effusion 1/1089 (0.1%)
    Pericarditis 1/1089 (0.1%)
    Prinzmetal angina 1/1089 (0.1%)
    Sick sinus syndrome 1/1089 (0.1%)
    Supraventricular tachycardia 1/1089 (0.1%)
    Congenital, familial and genetic disorders
    Atrial septal defect 1/1089 (0.1%)
    Ear and labyrinth disorders
    Deafness 1/1089 (0.1%)
    Vertigo 1/1089 (0.1%)
    Endocrine disorders
    Goitre 1/1089 (0.1%)
    Hyperthyroidism 1/1089 (0.1%)
    Inappropriate antidiuretic hormone secretion 1/1089 (0.1%)
    Thyroiditis subacute 1/1089 (0.1%)
    Eye disorders
    Conjunctival disorder 1/1089 (0.1%)
    Diabetic retinopathy 1/1089 (0.1%)
    Eye haemorrhage 1/1089 (0.1%)
    Gastrointestinal disorders
    Abdominal hernia 1/1089 (0.1%)
    Abdominal pain 4/1089 (0.4%)
    Abdominal pain lower 2/1089 (0.2%)
    Colitis 1/1089 (0.1%)
    Constipation 3/1089 (0.3%)
    Diarrhoea 2/1089 (0.2%)
    Duodenal ulcer haemorrhage 1/1089 (0.1%)
    Dysphagia 1/1089 (0.1%)
    Gastric ulcer perforation 1/1089 (0.1%)
    Gastritis 2/1089 (0.2%)
    Gastrooesophageal reflux disease 1/1089 (0.1%)
    Gastrooesophageal sphincter insufficiency 1/1089 (0.1%)
    Haemorrhoids 2/1089 (0.2%)
    Haemorrhoids thrombosed 1/1089 (0.1%)
    Ileus 1/1089 (0.1%)
    Inguinal hernia 2/1089 (0.2%)
    Intestinal obstruction 1/1089 (0.1%)
    Nausea 1/1089 (0.1%)
    Pancreatic disorder 1/1089 (0.1%)
    Pancreatitis 6/1089 (0.6%)
    Pancreatitis acute 2/1089 (0.2%)
    Small intestinal haemorrhage 1/1089 (0.1%)
    Umbilical hernia 1/1089 (0.1%)
    Vomiting 5/1089 (0.5%)
    General disorders
    Chest pain 1/1089 (0.1%)
    Device dislocation 1/1089 (0.1%)
    Drug resistance 1/1089 (0.1%)
    Fatigue 2/1089 (0.2%)
    Localised oedema 1/1089 (0.1%)
    Non-cardiac chest pain 4/1089 (0.4%)
    Oedema peripheral 1/1089 (0.1%)
    Pyrexia 6/1089 (0.6%)
    Soft tissue inflammation 1/1089 (0.1%)
    Hepatobiliary disorders
    Cholangitis 1/1089 (0.1%)
    Cholecystitis 2/1089 (0.2%)
    Cholelithiasis 1/1089 (0.1%)
    Gallbladder enlargement 1/1089 (0.1%)
    Hepatic fibrosis 1/1089 (0.1%)
    Hepatic steatosis 1/1089 (0.1%)
    Hepatotoxicity 1/1089 (0.1%)
    Jaundice 1/1089 (0.1%)
    Immune system disorders
    Drug hypersensitivity 1/1089 (0.1%)
    Infections and infestations
    Abdominal abscess 1/1089 (0.1%)
    Appendicitis 1/1089 (0.1%)
    Bronchitis 2/1089 (0.2%)
    Bronchopneumonia 1/1089 (0.1%)
    Corneal abscess 1/1089 (0.1%)
    Diverticulitis 1/1089 (0.1%)
    Epididymitis 1/1089 (0.1%)
    Gangrene 1/1089 (0.1%)
    Infection 1/1089 (0.1%)
    Lung infection 1/1089 (0.1%)
    Perirectal abscess 1/1089 (0.1%)
    Phlebitis infective 1/1089 (0.1%)
    Pneumonia 4/1089 (0.4%)
    Rectal abscess 1/1089 (0.1%)
    Respiratory tract infection 1/1089 (0.1%)
    Urinary tract infection 1/1089 (0.1%)
    Urinary tract infection bacterial 1/1089 (0.1%)
    Viral pericarditis 1/1089 (0.1%)
    Injury, poisoning and procedural complications
    Cervical vertebral fracture 1/1089 (0.1%)
    Clavicle fracture 1/1089 (0.1%)
    Coronary artery restenosis 2/1089 (0.2%)
    Exposure via father 1/1089 (0.1%)
    Femoral neck fracture 1/1089 (0.1%)
    Overdose 1/1089 (0.1%)
    Post procedural inflammation 1/1089 (0.1%)
    Rib fracture 1/1089 (0.1%)
    Road traffic accident 1/1089 (0.1%)
    Sternal injury 1/1089 (0.1%)
    Tendon rupture 1/1089 (0.1%)
    Investigations
    Amylase increased 2/1089 (0.2%)
    Blood creatine phosphokinase increased 2/1089 (0.2%)
    Blood pressure increased 1/1089 (0.1%)
    C-reactive protein increased 1/1089 (0.1%)
    Electrocardiogram QT prolonged 3/1089 (0.3%)
    Lipase increased 1/1089 (0.1%)
    Platelet count decreased 3/1089 (0.3%)
    Transaminases increased 1/1089 (0.1%)
    Metabolism and nutrition disorders
    Decreased appetite 2/1089 (0.2%)
    Diabetes mellitus 3/1089 (0.3%)
    Diabetes mellitus inadequate control 1/1089 (0.1%)
    Failure to thrive 1/1089 (0.1%)
    Hypercholesterolaemia 1/1089 (0.1%)
    Hyperglycaemia 2/1089 (0.2%)
    Hyponatraemia 1/1089 (0.1%)
    Hypophosphataemia 1/1089 (0.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/1089 (0.2%)
    Arthropathy 1/1089 (0.1%)
    Back pain 5/1089 (0.5%)
    Bone pain 1/1089 (0.1%)
    Intervertebral disc protrusion 2/1089 (0.2%)
    Muscular weakness 1/1089 (0.1%)
    Musculoskeletal pain 3/1089 (0.3%)
    Neck pain 1/1089 (0.1%)
    Pain in extremity 2/1089 (0.2%)
    Rotator cuff syndrome 1/1089 (0.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm 1/1089 (0.1%)
    Blast cell crisis 2/1089 (0.2%)
    Breast cancer 1/1089 (0.1%)
    Cervix carcinoma 1/1089 (0.1%)
    Cholangiocarcinoma 1/1089 (0.1%)
    Colon adenoma 1/1089 (0.1%)
    Colorectal cancer 1/1089 (0.1%)
    Duodenal neoplasm 1/1089 (0.1%)
    Endometrial cancer 1/1089 (0.1%)
    Non-Hodgkin's lymphoma 1/1089 (0.1%)
    Prostate cancer 2/1089 (0.2%)
    Retroperitoneal cancer 1/1089 (0.1%)
    Skin cancer 2/1089 (0.2%)
    Squamous cell carcinoma 1/1089 (0.1%)
    Urinary bladder adenoma 1/1089 (0.1%)
    Uterine leiomyoma 1/1089 (0.1%)
    Nervous system disorders
    Aphasia 1/1089 (0.1%)
    Carotid artery occlusion 1/1089 (0.1%)
    Carotid artery stenosis 1/1089 (0.1%)
    Carpal tunnel syndrome 1/1089 (0.1%)
    Cerebral haemorrhage 1/1089 (0.1%)
    Cerebral ischaemia 1/1089 (0.1%)
    Cerebrovascular accident 2/1089 (0.2%)
    Cranial nerve disorder 1/1089 (0.1%)
    Facial paresis 1/1089 (0.1%)
    Headache 5/1089 (0.5%)
    Hyperaesthesia 1/1089 (0.1%)
    Intracranial aneurysm 1/1089 (0.1%)
    Ischaemic stroke 2/1089 (0.2%)
    Lethargy 1/1089 (0.1%)
    Memory impairment 1/1089 (0.1%)
    Motor neurone disease 1/1089 (0.1%)
    Neuropathy peripheral 1/1089 (0.1%)
    Occipital neuralgia 1/1089 (0.1%)
    Sciatica 1/1089 (0.1%)
    Subarachnoid haemorrhage 1/1089 (0.1%)
    Transient ischaemic attack 2/1089 (0.2%)
    VIIth nerve paralysis 1/1089 (0.1%)
    Psychiatric disorders
    Anxiety 1/1089 (0.1%)
    Bipolar disorder 1/1089 (0.1%)
    Confusional state 1/1089 (0.1%)
    Depression 4/1089 (0.4%)
    Depression suicidal 1/1089 (0.1%)
    Suicide attempt 3/1089 (0.3%)
    Renal and urinary disorders
    Dysuria 1/1089 (0.1%)
    Haematuria 1/1089 (0.1%)
    Incontinence 1/1089 (0.1%)
    Nephrolithiasis 2/1089 (0.2%)
    Renal colic 1/1089 (0.1%)
    Renal cyst 1/1089 (0.1%)
    Renal failure 1/1089 (0.1%)
    Renal failure acute 2/1089 (0.2%)
    Renal impairment 1/1089 (0.1%)
    Urinary retention 1/1089 (0.1%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/1089 (0.1%)
    Genital pain 1/1089 (0.1%)
    Genital swelling 1/1089 (0.1%)
    Menorrhagia 1/1089 (0.1%)
    Metrorrhagia 2/1089 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 5/1089 (0.5%)
    Epistaxis 2/1089 (0.2%)
    Hyperventilation 1/1089 (0.1%)
    Pleural effusion 1/1089 (0.1%)
    Pneumonitis 1/1089 (0.1%)
    Pulmonary embolism 1/1089 (0.1%)
    Sleep apnoea syndrome 1/1089 (0.1%)
    Skin and subcutaneous tissue disorders
    Diabetic foot 1/1089 (0.1%)
    Dry gangrene 1/1089 (0.1%)
    Photosensitivity reaction 1/1089 (0.1%)
    Skin haemorrhage 1/1089 (0.1%)
    Surgical and medical procedures
    Hysterectomy 1/1089 (0.1%)
    Skin neoplasm excision 1/1089 (0.1%)
    Vascular disorders
    Aneurysm ruptured 1/1089 (0.1%)
    Aortic stenosis 2/1089 (0.2%)
    Arterial disorder 1/1089 (0.1%)
    Arterial haemorrhage 1/1089 (0.1%)
    Arterial occlusive disease 1/1089 (0.1%)
    Deep vein thrombosis 1/1089 (0.1%)
    Haemorrhage 1/1089 (0.1%)
    Hypertension 1/1089 (0.1%)
    Hypertensive crisis 1/1089 (0.1%)
    Leriche syndrome 1/1089 (0.1%)
    Peripheral arterial occlusive disease 2/1089 (0.2%)
    Peripheral artery stenosis 1/1089 (0.1%)
    Peripheral ischaemia 1/1089 (0.1%)
    Raynaud's phenomenon 1/1089 (0.1%)
    Other (Not Including Serious) Adverse Events
    Nilotinib
    Affected / at Risk (%) # Events
    Total 841/1089 (77.2%)
    Blood and lymphatic system disorders
    Anaemia 65/1089 (6%)
    Thrombocytopenia 111/1089 (10.2%)
    Gastrointestinal disorders
    Abdominal pain 79/1089 (7.3%)
    Abdominal pain upper 88/1089 (8.1%)
    Constipation 65/1089 (6%)
    Diarrhoea 93/1089 (8.5%)
    Nausea 122/1089 (11.2%)
    Vomiting 62/1089 (5.7%)
    General disorders
    Asthenia 97/1089 (8.9%)
    Fatigue 150/1089 (13.8%)
    Infections and infestations
    Nasopharyngitis 113/1089 (10.4%)
    Investigations
    Alanine aminotransferase increased 86/1089 (7.9%)
    Blood bilirubin increased 80/1089 (7.3%)
    Lipase increased 76/1089 (7%)
    Metabolism and nutrition disorders
    Hypophosphataemia 77/1089 (7.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 96/1089 (8.8%)
    Back pain 78/1089 (7.2%)
    Muscle spasms 93/1089 (8.5%)
    Myalgia 99/1089 (9.1%)
    Nervous system disorders
    Headache 163/1089 (15%)
    Psychiatric disorders
    Insomnia 55/1089 (5.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 56/1089 (5.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 115/1089 (10.6%)
    Dry skin 93/1089 (8.5%)
    Pruritus 180/1089 (16.5%)
    Rash 233/1089 (21.4%)
    Vascular disorders
    Hypertension 64/1089 (5.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email trialandresults.registry@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01061177
    Other Study ID Numbers:
    • CAMN107EIC01
    • 2009-017775-19
    First Posted:
    Feb 2, 2010
    Last Update Posted:
    Feb 24, 2017
    Last Verified:
    Dec 1, 2016