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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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00471497
First received: May 7, 2007
Last updated: April 18, 2016
Last verified: April 2016
Results First Received: April 10, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Myelogenous Leukemia, Chronic
Interventions: Drug: nilotinib
Drug: imatinib

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Not Completed Study means that the patient discontinued from the study by study day 294 (data cut-off).

Reporting Groups
  Description
Imatinib 400 mg QD Patients randomized to this arm were to receive 400 mg imatinib once a day (QD). If the patient required a dose escalation from 400 mg/day, the patient was to receive 400 mg imatinib twice daily orally. Imatinib was taken with food and a large glass of water. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits during the study. In cases of vomiting doses were not to be repeated.
Nilotinb 300 mg BID Patients who were randomized to this arm were to receive nilotinib 300 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.
Nilotinib 400 mg BID Patients who were randomized to this arm were to receive nilotinib 400 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.

Participant Flow:   Overall Study
    Imatinib 400 mg QD   Nilotinb 300 mg BID   Nilotinib 400 mg BID
STARTED   283   282   281 
SAFETY ANALYSIS SET   280 [1]   279 [1]   277 [1] 
COMPLETED   237 [2]   247 [2]   241 [2] 
NOT COMPLETED   46   35   40 
Adverse Event                19                11                22 
Abnormal Laboratory Value                3                6                4 
Abnormal Test Procedure                1                0                1 
Condition no longer requires study drug                0                1                0 
Withdrawal by Subject                3                5                5 
Lost to Follow-up                1                2                1 
Death                0                2                0 
Disease Progression                8                2                2 
Protocol Violation                3                3                5 
Sub optimal response or treat. failure                8                3                0 
[1] Safety set contained patients who received at least one dose of study medication.
[2] Completed means patient is on treatment in core phase of the study (ongoing) by data cut-off.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the Full Analysis Set (FAS) were analyzed according to the treatment they were randomized to regardless of actual treatment received.

Reporting Groups
  Description
Imatinib 400 mg QD Patients randomized to this arm were to receive 400 mg imatinib once a day (QD). If the patient required a dose escalation from 400 mg/day, the patient was to receive 400 mg imatinib twice daily orally. Imatinib was taken with food and a large glass of water. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits during the study. In cases of vomiting doses were not to be repeated.
Nilotinb 300 mg BID Patients who were randomized to this arm were to receive nilotinib 300 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.
Nilotinib 400 mg BID Patients who were randomized to this arm were to receive nilotinib 400 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.
Total Total of all reporting groups

Baseline Measures
   Imatinib 400 mg QD   Nilotinb 300 mg BID   Nilotinib 400 mg BID   Total 
Overall Participants Analyzed 
[Units: Participants]
 283   282   281   846 
Age, Customized 
[Units: Participants]
       
<35 years   63   67   65   195 
>= 35 - <45 years   67   50   59   176 
>=45 - <55 years   63   72   65   200 
>=55 - < 65 years   55   57   64   176 
>=65 years   35   36   28   99 
Gender 
[Units: Participants]
       
Female   125   124   106   355 
Male   158   158   175   491 


  Outcome Measures

1.  Primary:   Molecular Response Rate (MMR) at 12 Months   [ Time Frame: Baseline, 12 months ]

2.  Secondary:   Rate of Durable MMR at 24 Months.   [ Time Frame: Baseline, 24 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   Rate Reduction in BCR-ABL Transcript Levels in Nilotinib Treatment Arms With Imatinib at 12 Months   [ Time Frame: Baseline, 12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months   [ Time Frame: Baseline, 12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description Safety set contained patients who received at least one dose of study medication. Patients were summarized according to the safety treatment allocation (the treatment they actually received first).

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Imatinib 400 mg QD Patients randomized to this arm were to receive 400 mg imatinib once a day (QD). If the patient required a dose escalation from 400 mg/day, the patient was to receive 400 mg imatinib twice daily orally. Imatinib was taken with food and a large glass of water. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits during the study. In cases of vomiting doses were not to be repeated.
Nilotinib 300 mg BID Patients who were randomized to this arm were to receive nilotinib 300 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.
Nilotinib 400 mg BID Patients who were randomized to this arm were to receive nilotinib 400 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.

Other Adverse Events
    Imatinib 400 mg QD   Nilotinib 300 mg BID   Nilotinib 400 mg BID
Total, other (not including serious) adverse events       
# participants affected / at risk   270/280 (96.43%)   275/279 (98.57%)   272/277 (98.19%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   55/280 (19.64%)   34/279 (12.19%)   36/277 (13.00%) 
Leukopenia † 1       
# participants affected / at risk   44/280 (15.71%)   23/279 (8.24%)   22/277 (7.94%) 
Neutropenia † 1       
# participants affected / at risk   58/280 (20.71%)   43/279 (15.41%)   30/277 (10.83%) 
Thrombocytopenia † 1       
# participants affected / at risk   53/280 (18.93%)   51/279 (18.28%)   56/277 (20.22%) 
Cardiac disorders       
Palpitations † 1       
# participants affected / at risk   8/280 (2.86%)   14/279 (5.02%)   13/277 (4.69%) 
Eye disorders       
Conjunctival haemorrhage † 1       
# participants affected / at risk   20/280 (7.14%)   3/279 (1.08%)   5/277 (1.81%) 
Conjunctivitis † 1       
# participants affected / at risk   17/280 (6.07%)   18/279 (6.45%)   17/277 (6.14%) 
Dry eye † 1       
# participants affected / at risk   17/280 (6.07%)   17/279 (6.09%)   17/277 (6.14%) 
Eyelid oedema † 1       
# participants affected / at risk   50/280 (17.86%)   4/279 (1.43%)   5/277 (1.81%) 
Periorbital oedema † 1       
# participants affected / at risk   42/280 (15.00%)   1/279 (0.36%)   4/277 (1.44%) 
Gastrointestinal disorders       
Abdominal pain † 1       
# participants affected / at risk   31/280 (11.07%)   40/279 (14.34%)   35/277 (12.64%) 
Abdominal pain upper † 1       
# participants affected / at risk   36/280 (12.86%)   48/279 (17.20%)   45/277 (16.25%) 
Constipation † 1       
# participants affected / at risk   22/280 (7.86%)   52/279 (18.64%)   45/277 (16.25%) 
Diarrhoea † 1       
# participants affected / at risk   126/280 (45.00%)   50/279 (17.92%)   63/277 (22.74%) 
Dyspepsia † 1       
# participants affected / at risk   33/280 (11.79%)   26/279 (9.32%)   30/277 (10.83%) 
Flatulence † 1       
# participants affected / at risk   9/280 (3.21%)   10/279 (3.58%)   14/277 (5.05%) 
Gastritis † 1       
# participants affected / at risk   6/280 (2.14%)   7/279 (2.51%)   14/277 (5.05%) 
Gastrooesophageal reflux disease † 1       
# participants affected / at risk   14/280 (5.00%)   8/279 (2.87%)   14/277 (5.05%) 
Haemorrhoids † 1       
# participants affected / at risk   15/280 (5.36%)   8/279 (2.87%)   14/277 (5.05%) 
Nausea † 1       
# participants affected / at risk   114/280 (40.71%)   61/279 (21.86%)   81/277 (29.24%) 
Toothache † 1       
# participants affected / at risk   14/280 (5.00%)   11/279 (3.94%)   9/277 (3.25%) 
Vomiting † 1       
# participants affected / at risk   73/280 (26.07%)   39/279 (13.98%)   54/277 (19.49%) 
General disorders       
Asthenia † 1       
# participants affected / at risk   33/280 (11.79%)   37/279 (13.26%)   29/277 (10.47%) 
Face oedema † 1       
# participants affected / at risk   38/280 (13.57%)   2/279 (0.72%)   7/277 (2.53%) 
Fatigue † 1       
# participants affected / at risk   54/280 (19.29%)   63/279 (22.58%)   52/277 (18.77%) 
Non-cardiac chest pain † 1       
# participants affected / at risk   11/280 (3.93%)   13/279 (4.66%)   15/277 (5.42%) 
Oedema peripheral † 1       
# participants affected / at risk   58/280 (20.71%)   26/279 (9.32%)   36/277 (13.00%) 
Pyrexia † 1       
# participants affected / at risk   35/280 (12.50%)   35/279 (12.54%)   44/277 (15.88%) 
Hepatobiliary disorders       
Hyperbilirubinaemia † 1       
# participants affected / at risk   4/280 (1.43%)   49/279 (17.56%)   47/277 (16.97%) 
Infections and infestations       
Bronchitis † 1       
# participants affected / at risk   19/280 (6.79%)   17/279 (6.09%)   11/277 (3.97%) 
Folliculitis † 1       
# participants affected / at risk   2/280 (0.71%)   14/279 (5.02%)   12/277 (4.33%) 
Gastroenteritis † 1       
# participants affected / at risk   20/280 (7.14%)   15/279 (5.38%)   14/277 (5.05%) 
Influenza † 1       
# participants affected / at risk   25/280 (8.93%)   33/279 (11.83%)   40/277 (14.44%) 
Nasopharyngitis † 1       
# participants affected / at risk   58/280 (20.71%)   70/279 (25.09%)   59/277 (21.30%) 
Sinusitis † 1       
# participants affected / at risk   15/280 (5.36%)   18/279 (6.45%)   22/277 (7.94%) 
Upper respiratory tract infection † 1       
# participants affected / at risk   39/280 (13.93%)   44/279 (15.77%)   54/277 (19.49%) 
Urinary tract infection † 1       
# participants affected / at risk   8/280 (2.86%)   15/279 (5.38%)   18/277 (6.50%) 
Investigations       
Alanine aminotransferase increased † 1       
# participants affected / at risk   23/280 (8.21%)   70/279 (25.09%)   84/277 (30.32%) 
Amylase increased † 1       
# participants affected / at risk   9/280 (3.21%)   19/279 (6.81%)   21/277 (7.58%) 
Aspartate aminotransferase increased † 1       
# participants affected / at risk   15/280 (5.36%)   39/279 (13.98%)   42/277 (15.16%) 
Blood alkaline phosphatase increased † 1       
# participants affected / at risk   12/280 (4.29%)   7/279 (2.51%)   14/277 (5.05%) 
Blood bilirubin increased † 1       
# participants affected / at risk   3/280 (1.07%)   30/279 (10.75%)   35/277 (12.64%) 
Haemoglobin decreased † 1       
# participants affected / at risk   12/280 (4.29%)   6/279 (2.15%)   16/277 (5.78%) 
Lipase increased † 1       
# participants affected / at risk   13/280 (4.64%)   31/279 (11.11%)   30/277 (10.83%) 
Weight increased † 1       
# participants affected / at risk   25/280 (8.93%)   20/279 (7.17%)   19/277 (6.86%) 
Metabolism and nutrition disorders       
Decreased appetite † 1       
# participants affected / at risk   12/280 (4.29%)   26/279 (9.32%)   22/277 (7.94%) 
Hypercholesterolaemia † 1       
# participants affected / at risk   2/280 (0.71%)   17/279 (6.09%)   27/277 (9.75%) 
Hyperglycaemia † 1       
# participants affected / at risk   6/280 (2.14%)   18/279 (6.45%)   21/277 (7.58%) 
Hypokalaemia † 1       
# participants affected / at risk   14/280 (5.00%)   15/279 (5.38%)   9/277 (3.25%) 
Hypophosphataemia † 1       
# participants affected / at risk   46/280 (16.43%)   37/279 (13.26%)   44/277 (15.88%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1       
# participants affected / at risk   45/280 (16.07%)   56/279 (20.07%)   53/277 (19.13%) 
Back pain † 1       
# participants affected / at risk   45/280 (16.07%)   48/279 (17.20%)   46/277 (16.61%) 
Bone pain † 1       
# participants affected / at risk   15/280 (5.36%)   17/279 (6.09%)   25/277 (9.03%) 
Muscle spasms † 1       
# participants affected / at risk   94/280 (33.57%)   33/279 (11.83%)   31/277 (11.19%) 
Musculoskeletal pain † 1       
# participants affected / at risk   21/280 (7.50%)   20/279 (7.17%)   28/277 (10.11%) 
Myalgia † 1       
# participants affected / at risk   52/280 (18.57%)   53/279 (19.00%)   44/277 (15.88%) 
Neck pain † 1       
# participants affected / at risk   5/280 (1.79%)   15/279 (5.38%)   5/277 (1.81%) 
Pain in extremity † 1       
# participants affected / at risk   43/280 (15.36%)   35/279 (12.54%)   38/277 (13.72%) 
Nervous system disorders       
Dizziness † 1       
# participants affected / at risk   28/280 (10.00%)   30/279 (10.75%)   25/277 (9.03%) 
Headache † 1       
# participants affected / at risk   63/280 (22.50%)   89/279 (31.90%)   96/277 (34.66%) 
Psychiatric disorders       
Anxiety † 1       
# participants affected / at risk   19/280 (6.79%)   17/279 (6.09%)   18/277 (6.50%) 
Depression † 1       
# participants affected / at risk   15/280 (5.36%)   15/279 (5.38%)   18/277 (6.50%) 
Insomnia † 1       
# participants affected / at risk   24/280 (8.57%)   30/279 (10.75%)   31/277 (11.19%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1       
# participants affected / at risk   35/280 (12.50%)   47/279 (16.85%)   52/277 (18.77%) 
Dyspnoea † 1       
# participants affected / at risk   16/280 (5.71%)   26/279 (9.32%)   23/277 (8.30%) 
Oropharyngeal pain † 1       
# participants affected / at risk   17/280 (6.07%)   30/279 (10.75%)   21/277 (7.58%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1       
# participants affected / at risk   19/280 (6.79%)   36/279 (12.90%)   50/277 (18.05%) 
Dry skin † 1       
# participants affected / at risk   17/280 (6.07%)   33/279 (11.83%)   37/277 (13.36%) 
Erythema † 1       
# participants affected / at risk   9/280 (3.21%)   13/279 (4.66%)   16/277 (5.78%) 
Night sweats † 1       
# participants affected / at risk   6/280 (2.14%)   10/279 (3.58%)   16/277 (5.78%) 
Pruritus † 1       
# participants affected / at risk   20/280 (7.14%)   59/279 (21.15%)   49/277 (17.69%) 
Rash † 1       
# participants affected / at risk   50/280 (17.86%)   107/279 (38.35%)   122/277 (44.04%) 
Vascular disorders       
Hypertension † 1       
# participants affected / at risk   9/280 (3.21%)   23/279 (8.24%)   18/277 (6.50%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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