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Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)

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ClinicalTrials.gov Identifier: NCT01650805
Recruitment Status : Terminated (Study terminated based on evaluation of safety data.)
First Posted : July 26, 2012
Results First Posted : October 21, 2014
Last Update Posted : November 17, 2014
Sponsor:
Information provided by (Responsible Party):
Ariad Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Myeloid Leukemia
Interventions Drug: ponatinib
Drug: imatinib (Gleevec/ Glivec)
Enrollment 307

Recruitment Details  
Pre-assignment Details A total of 307 subjects were enrolled (ponatinib patients: 155; imatinib patients: 152). Patients were randomized in a 1:1 fashion to receive either ponatinib or imatinib.
Arm/Group Title Ponatinib Imatinib
Hide Arm/Group Description ponatinib: 45 mg tablet, taken orally once daily imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Period Title: Overall Study
Started 155 [1] 152
Completed 154 [2] 152
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
Started means patient has been randomized.
[2]
Completed means patient initiated and discontinued study treatment.
Arm/Group Title Ponatinib Imatinib Total
Hide Arm/Group Description ponatinib: 45 mg tablet, taken orally once daily imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily Total of all reporting groups
Overall Number of Baseline Participants 155 152 307
Hide Baseline Analysis Population Description
ITT Population
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 152 participants 307 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
119
  76.8%
116
  76.3%
235
  76.5%
>=65 years
36
  23.2%
36
  23.7%
72
  23.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 152 participants 307 participants
51.9  (15.66) 51.2  (15.19) 51.5  (15.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 152 participants 307 participants
Female
58
  37.4%
60
  39.5%
118
  38.4%
Male
97
  62.6%
92
  60.5%
189
  61.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 155 participants 152 participants 307 participants
Portugal 0 2 2
United States 48 34 82
Hong Kong 4 1 5
Taiwan 3 2 5
Finland 1 0 1
Spain 16 9 25
Italy 15 14 29
United Kingdom 6 12 18
France 14 21 35
Czech Republic 1 3 4
Canada 16 13 29
Poland 0 1 1
Belgium 3 2 5
Singapore 1 11 12
Australia 1 6 7
Netherlands 1 1 2
Germany 11 12 23
New Zealand 4 4 8
Sweden 6 2 8
Korea, Republic of 3 2 5
Switzerland 1 0 1
1.Primary Outcome
Title Major Molecular Response (MMR) Rate at 12 Months
Hide Description A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.
Time Frame 12 months after first dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients with 12 month assessment (due to early termination of the study, none of the endpoints could be evaluated as planned).
Arm/Group Title Ponatinib Imatinib
Hide Arm/Group Description:
ponatinib: 45 mg tablet, taken orally once daily
imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Overall Number of Participants Analyzed 10 13
Measure Type: Number
Unit of Measure: participants
8 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ponatinib, Imatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified Analysis by Sokal score
2.Secondary Outcome
Title MMR Rate
Hide Description To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years
Time Frame 5 years after first dose
Outcome Measure Data Not Reported
3.Secondary Outcome
Title <10% BCR-ABL^IS Rate
Hide Description To compare the proportion of patients achieving a ratio of <10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (<10% BCR-ABL^IS), in patients administered ponatinib versus those administered imatinib
Time Frame 3 months after first dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients with 3 month assessment
Arm/Group Title Ponatinib Imatinib
Hide Arm/Group Description:
ponatinib: 45 mg tablet, taken orally once daily
imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Overall Number of Participants Analyzed 109 114
Measure Type: Number
Unit of Measure: participants
103 77
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ponatinib, Imatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified Analysis by Sokal score
4.Secondary Outcome
Title Complete Cytogenetic Response (CCyR) Rate
Hide Description The percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. Responses are defined as follows: Complete (CCyR): 0% Ph+ metaphases.
Time Frame 12 months after first dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients with 12 month assessment
Arm/Group Title Ponatinib Imatinib
Hide Arm/Group Description:
ponatinib: 45 mg tablet, taken orally once daily
imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Overall Number of Participants Analyzed 5 7
Measure Type: Number
Unit of Measure: participants
5 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ponatinib, Imatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.317
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified Analysis by Sokal score
5.Secondary Outcome
Title Progression-free Survival
Hide Description To compare, according to treatment with ponatinib versus imatinib, progression-free survival
Time Frame Up to 8 years after the last patient’s first dose
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Overall Survival
Hide Description To compare, according to treatment with ponatinib versus imatinib, overall survival
Time Frame Up to 8 years after the last patient’s first dose
Outcome Measure Data Not Reported
Time Frame Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ponatinib 45 mg Imatinib 400 mg
Hide Arm/Group Description ponatinib: 45 mg tablet, taken orally once daily imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
All-Cause Mortality
Ponatinib 45 mg Imatinib 400 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ponatinib 45 mg Imatinib 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   49/154 (31.82%)      13/152 (8.55%)    
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION  1  2/154 (1.30%)  2 0/152 (0.00%)  0
ANGINA PECTORIS  1  2/154 (1.30%)  2 0/152 (0.00%)  0
ATRIAL FIBRILLATION  1  3/154 (1.95%)  3 0/152 (0.00%)  0
CARDIAC ARREST  1  0/154 (0.00%)  0 1/152 (0.66%)  1
CARDIAC FAILURE  1  2/154 (1.30%)  4 0/152 (0.00%)  0
CORONARY ARTERY DISEASE  1  1/154 (0.65%)  1 0/152 (0.00%)  0
MYOPERICARDITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PERICARDIAL EFFUSION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Ear and labyrinth disorders     
VERTIGO POSITIONAL  1  1/154 (0.65%)  1 1/152 (0.66%)  1
Eye disorders     
EYE PAIN  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PHOTOPHOBIA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
RETINAL VEIN THROMBOSIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Gastrointestinal disorders     
ABDOMINAL PAIN  1  2/154 (1.30%)  3 0/152 (0.00%)  0
NAUSEA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PANCREATITIS  1  5/154 (3.25%)  5 0/152 (0.00%)  0
SMALL INTESTINAL OBSTRUCTION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
VOMITING  1  1/154 (0.65%)  1 0/152 (0.00%)  0
General disorders     
NON-CARDIAC CHEST PAIN  1  1/154 (0.65%)  1 0/152 (0.00%)  0
OEDEMA PERIPHERAL  1  0/154 (0.00%)  0 1/152 (0.66%)  2
PYREXIA  1  2/154 (1.30%)  2 1/152 (0.66%)  1
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Hepatobiliary disorders     
CHOLECYSTITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
HEPATITIS  1  0/154 (0.00%)  0 1/152 (0.66%)  1
Infections and infestations     
BACTERIAL PYELONEPHRITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
CERVICITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
DISSEMINATED TUBERCULOSIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
DIVERTICULITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
HEPATITIS B  1  0/154 (0.00%)  0 1/152 (0.66%)  1
HERPES ZOSTER  1  0/154 (0.00%)  0 1/152 (0.66%)  1
LUNG INFECTION  1  0/154 (0.00%)  0 1/152 (0.66%)  1
PARAINFLUENZAE VIRUS INFECTION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PARASPINAL ABSCESS  1  0/154 (0.00%)  0 1/152 (0.66%)  1
PERICOLIC ABSCESS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PNEUMONIA  1  2/154 (1.30%)  3 1/152 (0.66%)  1
PYELONEPHRITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
RESPIRATORY TRACT INFECTION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
SEPSIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
VESTIBULAR NEURONITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  0/154 (0.00%)  0 1/152 (0.66%)  1
Injury, poisoning and procedural complications     
COMPRESSION FRACTURE  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PERIORBITAL CONTUSION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
SPLENIC RUPTURE  1  0/154 (0.00%)  0 1/152 (0.66%)  1
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  1/154 (0.65%)  1 0/152 (0.00%)  0
AMYLASE INCREASED  1  1/154 (0.65%)  1 0/152 (0.00%)  0
C-REACTIVE PROTEIN INCREASED  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PLATELET COUNT DECREASED  1  3/154 (1.95%)  3 0/152 (0.00%)  0
Metabolism and nutrition disorders     
DECREASED APPETITE  1  0/154 (0.00%)  0 1/152 (0.66%)  1
FAILURE TO THRIVE  1  1/154 (0.65%)  1 0/152 (0.00%)  0
HYPONATRAEMIA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  1/154 (0.65%)  1 0/152 (0.00%)  0
BONE PAIN  1  0/154 (0.00%)  0 1/152 (0.66%)  1
MUSCULOSKELETAL CHEST PAIN  1  0/154 (0.00%)  0 1/152 (0.66%)  1
NECK PAIN  1  1/154 (0.65%)  1 0/152 (0.00%)  0
POLYARTHRITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
SACROILIITIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ANGIOMYOLIPOMA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
BLAST CRISIS IN MYELOGENOUS LEUKAEMIA  1  0/154 (0.00%)  0 2/152 (1.32%)  2
CHLOROMA  1  0/154 (0.00%)  0 1/152 (0.66%)  1
CLEAR CELL RENAL CELL CARCINOMA  1  0/154 (0.00%)  0 1/152 (0.66%)  1
Nervous system disorders     
CEREBROVASCULAR ACCIDENT  1  1/154 (0.65%)  1 0/152 (0.00%)  0
DYSARTHRIA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
HEADACHE  1  1/154 (0.65%)  1 0/152 (0.00%)  0
HYPOXIC-ISCHAEMIC ENCEPHALOPATHY  1  0/154 (0.00%)  0 1/152 (0.66%)  1
LOSS OF CONSCIOUSNESS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
POLYNEUROPATHY  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PRESYNCOPE  1  0/154 (0.00%)  0 1/152 (0.66%)  1
RADICULITIS CERVICAL  1  1/154 (0.65%)  1 0/152 (0.00%)  0
TRANSIENT ISCHAEMIC ATTACK  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Reproductive system and breast disorders     
BENIGN PROSTATIC HYPERPLASIA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
DYSPNOEA  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PLEURAL EFFUSION  1  0/154 (0.00%)  0 2/152 (1.32%)  2
PULMONARY OEDEMA  1  0/154 (0.00%)  0 1/152 (0.66%)  1
RESPIRATORY FAILURE  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Vascular disorders     
HYPERTENSION  1  1/154 (0.65%)  1 0/152 (0.00%)  0
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  2/154 (1.30%)  2 0/152 (0.00%)  0
PERIPHERAL ARTERY THROMBOSIS  1  1/154 (0.65%)  1 0/152 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ponatinib 45 mg Imatinib 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   145/154 (94.16%)      144/152 (94.74%)    
Blood and lymphatic system disorders     
ANAEMIA  1  13/154 (8.44%)  15 12/152 (7.89%)  14
Eye disorders     
DRY EYE  1  10/154 (6.49%)  10 3/152 (1.97%)  3
EYELID OEDEMA  1  1/154 (0.65%)  1 13/152 (8.55%)  13
PERIORBITAL OEDEMA  1  1/154 (0.65%)  1 33/152 (21.71%)  37
Gastrointestinal disorders     
ABDOMINAL DISCOMFORT  1  10/154 (6.49%)  11 5/152 (3.29%)  5
ABDOMINAL PAIN  1  54/154 (35.06%)  69 15/152 (9.87%)  15
CONSTIPATION  1  41/154 (26.62%)  48 3/152 (1.97%)  3
DIARRHOEA  1  20/154 (12.99%)  28 41/152 (26.97%)  54
DRY MOUTH  1  11/154 (7.14%)  11 5/152 (3.29%)  5
DYSPEPSIA  1  7/154 (4.55%)  7 9/152 (5.92%)  10
NAUSEA  1  34/154 (22.08%)  44 52/152 (34.21%)  58
VOMITING  1  17/154 (11.04%)  18 28/152 (18.42%)  30
General disorders     
ASTHENIA  1  6/154 (3.90%)  6 12/152 (7.89%)  14
CHILLS  1  10/154 (6.49%)  12 6/152 (3.95%)  6
FATIGUE  1  32/154 (20.78%)  37 30/152 (19.74%)  35
OEDEMA PERIPHERAL  1  14/154 (9.09%)  15 22/152 (14.47%)  24
PAIN  1  9/154 (5.84%)  10 2/152 (1.32%)  2
PYREXIA  1  26/154 (16.88%)  31 6/152 (3.95%)  8
Infections and infestations     
UPPER RESPIRATORY TRACT INFECTION  1  5/154 (3.25%)  5 13/152 (8.55%)  16
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  20/154 (12.99%)  29 2/152 (1.32%)  3
AMYLASE INCREASED  1  14/154 (9.09%)  20 1/152 (0.66%)  1
ASPARTATE AMINOTRANSFERASE INCREASED  1  18/154 (11.69%)  24 6/152 (3.95%)  7
BLOOD ALKALINE PHOSPHATASE INCREASED  1  14/154 (9.09%)  20 5/152 (3.29%)  5
LIPASE INCREASED  1  41/154 (26.62%)  68 11/152 (7.24%)  13
NEUTROPHIL COUNT DECREASED  1  8/154 (5.19%)  15 17/152 (11.18%)  34
PLATELET COUNT DECREASED  1  36/154 (23.38%)  65 21/152 (13.82%)  37
WEIGHT DECREASED  1  9/154 (5.84%)  11 2/152 (1.32%)  2
WHITE BLOOD CELL COUNT DECREASED  1  5/154 (3.25%)  5 9/152 (5.92%)  11
Metabolism and nutrition disorders     
DECREASED APPETITE  1  18/154 (11.69%)  20 7/152 (4.61%)  8
HYPERTRIGLYCERIDAEMIA  1  13/154 (8.44%)  14 7/152 (4.61%)  8
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  29/154 (18.83%)  33 23/152 (15.13%)  29
BACK PAIN  1  11/154 (7.14%)  13 6/152 (3.95%)  7
BONE PAIN  1  13/154 (8.44%)  19 12/152 (7.89%)  16
MUSCLE SPASMS  1  11/154 (7.14%)  12 52/152 (34.21%)  62
MUSCULOSKELETAL PAIN  1  10/154 (6.49%)  11 4/152 (2.63%)  4
MYALGIA  1  40/154 (25.97%)  44 27/152 (17.76%)  31
PAIN IN EXTREMITY  1  19/154 (12.34%)  19 12/152 (7.89%)  15
Nervous system disorders     
DIZZINESS  1  15/154 (9.74%)  21 9/152 (5.92%)  11
HEADACHE  1  50/154 (32.47%)  61 20/152 (13.16%)  27
LETHARGY  1  3/154 (1.95%)  3 10/152 (6.58%)  12
Psychiatric disorders     
ANXIETY  1  8/154 (5.19%)  8 5/152 (3.29%)  5
DEPRESSION  1  8/154 (5.19%)  8 5/152 (3.29%)  5
INSOMNIA  1  16/154 (10.39%)  17 4/152 (2.63%)  4
Respiratory, thoracic and mediastinal disorders     
COUGH  1  8/154 (5.19%)  9 8/152 (5.26%)  8
DYSPNOEA  1  13/154 (8.44%)  18 5/152 (3.29%)  5
OROPHARYNGEAL PAIN  1  10/154 (6.49%)  10 3/152 (1.97%)  3
Skin and subcutaneous tissue disorders     
ALOPECIA  1  17/154 (11.04%)  17 8/152 (5.26%)  8
DRY SKIN  1  27/154 (17.53%)  29 5/152 (3.29%)  5
ERYTHEMA  1  11/154 (7.14%)  12 2/152 (1.32%)  3
NIGHT SWEATS  1  7/154 (4.55%)  7 9/152 (5.92%)  10
PRURITUS  1  18/154 (11.69%)  20 11/152 (7.24%)  15
RASH  1  58/154 (37.66%)  100 25/152 (16.45%)  41
RASH PRURITIC  1  6/154 (3.90%)  8 11/152 (7.24%)  14
Vascular disorders     
HYPERTENSION  1  27/154 (17.53%)  37 3/152 (1.97%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Maureen Conlan, Senior Medical Director
Organization: ARIAD Pharmaceuticals, Inc.
Phone: 1-617-621-2316
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01650805     History of Changes
Other Study ID Numbers: AP24534-12-301
First Submitted: July 18, 2012
First Posted: July 26, 2012
Results First Submitted: October 15, 2014
Results First Posted: October 21, 2014
Last Update Posted: November 17, 2014