Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01650805
Registration number
NCT01650805
Ethics application status
Date submitted
18/07/2012
Date registered
26/07/2012
Date last updated
17/11/2014
Titles & IDs
Public title
Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
Query!
Scientific title
A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase
Query!
Secondary ID [1]
0
0
AP24534-12-301
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Leukaemia - Acute leukaemia
Query!
Cancer
0
0
0
0
Query!
Leukaemia - Chronic leukaemia
Query!
Cancer
0
0
0
0
Query!
Children's - Leukaemia & Lymphoma
Query!
Intervention/exposure
Study type
Interventional(has expanded access)
Query!
Description of intervention(s) / exposure
Treatment: Drugs - ponatinib
Treatment: Drugs - imatinib (Gleevec/ Glivec)
Experimental: ponatinib -
Active comparator: imatinib -
Treatment: Drugs: ponatinib
45 mg tablet, taken orally once daily
Treatment: Drugs: imatinib (Gleevec/ Glivec)
400 mg tablet, taken orally once daily
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Major Molecular Response (MMR) Rate at 12 Months
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
12 months after first dose
Query!
Secondary outcome [1]
0
0
MMR Rate
Query!
Assessment method [1]
0
0
To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years
Query!
Timepoint [1]
0
0
5 years after first dose
Query!
Secondary outcome [2]
0
0
<10% BCR-ABL^IS Rate
Query!
Assessment method [2]
0
0
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
Query!
Timepoint [2]
0
0
3 months after first dose
Query!
Secondary outcome [3]
0
0
Complete Cytogenetic Response (CCyR) Rate
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
12 months after first dose
Query!
Secondary outcome [4]
0
0
Progression-free Survival
Query!
Assessment method [4]
0
0
To compare, according to treatment with ponatinib versus imatinib, progression-free survival
Query!
Timepoint [4]
0
0
Up to 8 years after the last patient's first dose
Query!
Secondary outcome [5]
0
0
Overall Survival
Query!
Assessment method [5]
0
0
To compare, according to treatment with ponatinib versus imatinib, overall survival
Query!
Timepoint [5]
0
0
Up to 8 years after the last patient's first dose
Query!
Eligibility
Key inclusion criteria
1. CP CML within 6 months of diagnosis
* CP-CML will be defined by (i) <15% blasts in bone marrow; (ii) <30% blasts plus promyelocytes in bone marrow; (iii) <20% basophils in peripheral blood; (iv) =100 × 10^9/L platelets (=100,000/mm^3); (v) No evidence of extramedullary disease except hepatosplenomegaly; AND (vi) No prior diagnosis of AP-CML or BP-CML
2. Cytogenetic assessment must demonstrate the BCR-ABL fusion by presence of the t(9;22) Philadelphia chromosome
* (a)Variant translocations are only allowed provided they are assessable for cytogenetic response utilizing conventional cytogenetic techniques; (b) Conventional chromosome banding must be performed; AND (c) A minimum of 20 metaphases must be assessable at entry
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
4. Adequate hepatic function as defined by the following criteria:
(a) Total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome; (b) Alanine aminotransferase (ALT) =2.5 × ULN; AND (c) Aspartate aminotransferase (AST) =2.5 × ULN
5. Adequate renal function as defined as defined by serum creatinine <1.5 x ULN
6. Adequate pancreatic function as defined by serum lipase and amylase =1.5 × ULN
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
1. Received prior imatinib therapy
2. Received prior dasatinib therapy
3. Received prior nilotinib therapy
4. Received, for CML, any other systemic anticancer therapy, experimental therapy, or radiation therapy with the exception of anagrelide or hydroxyurea
5. Major surgery within 28 days prior to initiating therapy
6. History of bleeding disorder unrelated to CML
7. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
8. History of alcohol abuse
9. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
10. Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
1. Myocardial infarction, within 6 months prior to randomization
2. Unstable angina within 6 months prior to randomization
3. Congestive heart failure within 6 months prior to randomization
4. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
5. Any history of ventricular arrhythmia
6. Cerebrovascular accident or transient ischemic attack within 6 months prior to randomization
7. Any history of peripheral arterial occlusive disease requiring revascularization
8. Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism
11. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control
12. Taking medications that are known to be associated with Torsades de Pointes
13. Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection
14. Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history
15. Pregnant or breastfeeding
16. Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs
17. Diagnosed with or received anticancer therapy for another primary malignancy within 3 years prior to entry (except for non-melanoma skin cancer or cervical cancer in situ)
18. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Stopped early
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/06/2012
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/10/2013
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
307
Query!
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC,WA
Query!
Recruitment hospital [1]
0
0
Canberra Hospital, Site #971 - Garran
Query!
Recruitment hospital [2]
0
0
Royal North Shore Hospital, Site #941 - Sydney
Query!
Recruitment hospital [3]
0
0
Royal Adelaide Hospital, Site #951 - Adelaide
Query!
Recruitment hospital [4]
0
0
The Peter MacCallum Cancer Center, Site #950 - East Melbourne
Query!
Recruitment hospital [5]
0
0
Box Hill Hospital, Site #940 - Melbourne
Query!
Recruitment hospital [6]
0
0
Royal Perth Hospital, Site #972 - Perth
Query!
Recruitment postcode(s) [1]
0
0
2605 - Garran
Query!
Recruitment postcode(s) [2]
0
0
2065 - Sydney
Query!
Recruitment postcode(s) [3]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [4]
0
0
3002 - East Melbourne
Query!
Recruitment postcode(s) [5]
0
0
3128 - Melbourne
Query!
Recruitment postcode(s) [6]
0
0
6000 - Perth
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Colorado
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Connecticut
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Delaware
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Georgia
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Illinois
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Indiana
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Iowa
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Kansas
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Louisiana
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Maryland
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Massachusetts
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Michigan
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Minnesota
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Missouri
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Nebraska
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Nevada
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
New Jersey
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
New Mexico
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
New York
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
North Carolina
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Ohio
Query!
Country [24]
0
0
United States of America
Query!
State/province [24]
0
0
Oklahoma
Query!
Country [25]
0
0
United States of America
Query!
State/province [25]
0
0
Oregon
Query!
Country [26]
0
0
United States of America
Query!
State/province [26]
0
0
Pennsylvania
Query!
Country [27]
0
0
United States of America
Query!
State/province [27]
0
0
South Carolina
Query!
Country [28]
0
0
United States of America
Query!
State/province [28]
0
0
Tennessee
Query!
Country [29]
0
0
United States of America
Query!
State/province [29]
0
0
Texas
Query!
Country [30]
0
0
United States of America
Query!
State/province [30]
0
0
Utah
Query!
Country [31]
0
0
United States of America
Query!
State/province [31]
0
0
Virginia
Query!
Country [32]
0
0
United States of America
Query!
State/province [32]
0
0
Washington
Query!
Country [33]
0
0
United States of America
Query!
State/province [33]
0
0
West Virginia
Query!
Country [34]
0
0
United States of America
Query!
State/province [34]
0
0
Wisconsin
Query!
Country [35]
0
0
Austria
Query!
State/province [35]
0
0
Wien
Query!
Country [36]
0
0
Belgium
Query!
State/province [36]
0
0
Brussel
Query!
Country [37]
0
0
Belgium
Query!
State/province [37]
0
0
Bruxelles
Query!
Country [38]
0
0
Belgium
Query!
State/province [38]
0
0
Gent
Query!
Country [39]
0
0
Belgium
Query!
State/province [39]
0
0
Leuven
Query!
Country [40]
0
0
Canada
Query!
State/province [40]
0
0
Ontario
Query!
Country [41]
0
0
Canada
Query!
State/province [41]
0
0
Quebec
Query!
Country [42]
0
0
Czech Republic
Query!
State/province [42]
0
0
Brno
Query!
Country [43]
0
0
Czech Republic
Query!
State/province [43]
0
0
Hradec Kralove
Query!
Country [44]
0
0
Czech Republic
Query!
State/province [44]
0
0
Olomouc
Query!
Country [45]
0
0
Czech Republic
Query!
State/province [45]
0
0
Praha
Query!
Country [46]
0
0
Finland
Query!
State/province [46]
0
0
Helsinki
Query!
Country [47]
0
0
France
Query!
State/province [47]
0
0
Bordeaux
Query!
Country [48]
0
0
France
Query!
State/province [48]
0
0
Brest
Query!
Country [49]
0
0
France
Query!
State/province [49]
0
0
Creteil Cedex
Query!
Country [50]
0
0
France
Query!
State/province [50]
0
0
Le Chesnay Cedex
Query!
Country [51]
0
0
France
Query!
State/province [51]
0
0
Lille Cedex
Query!
Country [52]
0
0
France
Query!
State/province [52]
0
0
Marseille
Query!
Country [53]
0
0
France
Query!
State/province [53]
0
0
Nancy Cedex
Query!
Country [54]
0
0
France
Query!
State/province [54]
0
0
Nantes Cedex
Query!
Country [55]
0
0
France
Query!
State/province [55]
0
0
Nice Cedex
Query!
Country [56]
0
0
France
Query!
State/province [56]
0
0
Paris
Query!
Country [57]
0
0
France
Query!
State/province [57]
0
0
Pierre Benite
Query!
Country [58]
0
0
France
Query!
State/province [58]
0
0
Poitiers
Query!
Country [59]
0
0
France
Query!
State/province [59]
0
0
Toulouse Cedex
Query!
Country [60]
0
0
Germany
Query!
State/province [60]
0
0
Aachen
Query!
Country [61]
0
0
Germany
Query!
State/province [61]
0
0
Berlin
Query!
Country [62]
0
0
Germany
Query!
State/province [62]
0
0
Dresden
Query!
Country [63]
0
0
Germany
Query!
State/province [63]
0
0
Freiburg
Query!
Country [64]
0
0
Germany
Query!
State/province [64]
0
0
Hamburg
Query!
Country [65]
0
0
Germany
Query!
State/province [65]
0
0
Jena
Query!
Country [66]
0
0
Germany
Query!
State/province [66]
0
0
Koln
Query!
Country [67]
0
0
Germany
Query!
State/province [67]
0
0
Mannheim
Query!
Country [68]
0
0
Germany
Query!
State/province [68]
0
0
Munchen
Query!
Country [69]
0
0
Hong Kong
Query!
State/province [69]
0
0
Hong Kong
Query!
Country [70]
0
0
Italy
Query!
State/province [70]
0
0
Bari
Query!
Country [71]
0
0
Italy
Query!
State/province [71]
0
0
Bologna
Query!
Country [72]
0
0
Italy
Query!
State/province [72]
0
0
Catania
Query!
Country [73]
0
0
Italy
Query!
State/province [73]
0
0
Genova
Query!
Country [74]
0
0
Italy
Query!
State/province [74]
0
0
Milan
Query!
Country [75]
0
0
Italy
Query!
State/province [75]
0
0
Modena
Query!
Country [76]
0
0
Italy
Query!
State/province [76]
0
0
Monza
Query!
Country [77]
0
0
Italy
Query!
State/province [77]
0
0
Napoli
Query!
Country [78]
0
0
Italy
Query!
State/province [78]
0
0
Orbassano
Query!
Country [79]
0
0
Italy
Query!
State/province [79]
0
0
Rome
Query!
Country [80]
0
0
Korea, Republic of
Query!
State/province [80]
0
0
Seoul
Query!
Country [81]
0
0
Netherlands
Query!
State/province [81]
0
0
Amsterdam
Query!
Country [82]
0
0
New Zealand
Query!
State/province [82]
0
0
Auckland
Query!
Country [83]
0
0
New Zealand
Query!
State/province [83]
0
0
Christchurch
Query!
Country [84]
0
0
New Zealand
Query!
State/province [84]
0
0
Hamilton
Query!
Country [85]
0
0
New Zealand
Query!
State/province [85]
0
0
Takapuna
Query!
Country [86]
0
0
Poland
Query!
State/province [86]
0
0
Gdansk
Query!
Country [87]
0
0
Poland
Query!
State/province [87]
0
0
Krakow
Query!
Country [88]
0
0
Poland
Query!
State/province [88]
0
0
Lodz
Query!
Country [89]
0
0
Poland
Query!
State/province [89]
0
0
Rzeszow
Query!
Country [90]
0
0
Poland
Query!
State/province [90]
0
0
Wroclaw
Query!
Country [91]
0
0
Portugal
Query!
State/province [91]
0
0
Lisboa
Query!
Country [92]
0
0
Puerto Rico
Query!
State/province [92]
0
0
San Juan
Query!
Country [93]
0
0
Singapore
Query!
State/province [93]
0
0
Singapore
Query!
Country [94]
0
0
Slovakia
Query!
State/province [94]
0
0
Bratislava
Query!
Country [95]
0
0
Slovakia
Query!
State/province [95]
0
0
Martin
Query!
Country [96]
0
0
Spain
Query!
State/province [96]
0
0
A Coruna
Query!
Country [97]
0
0
Spain
Query!
State/province [97]
0
0
Badalona
Query!
Country [98]
0
0
Spain
Query!
State/province [98]
0
0
Barcelona
Query!
Country [99]
0
0
Spain
Query!
State/province [99]
0
0
Girona
Query!
Country [100]
0
0
Spain
Query!
State/province [100]
0
0
Islas Baleares
Query!
Country [101]
0
0
Spain
Query!
State/province [101]
0
0
Madrid
Query!
Country [102]
0
0
Spain
Query!
State/province [102]
0
0
Oviedo
Query!
Country [103]
0
0
Spain
Query!
State/province [103]
0
0
Salamanca
Query!
Country [104]
0
0
Spain
Query!
State/province [104]
0
0
Valencia
Query!
Country [105]
0
0
Sweden
Query!
State/province [105]
0
0
Lund
Query!
Country [106]
0
0
Sweden
Query!
State/province [106]
0
0
Stockholm
Query!
Country [107]
0
0
Sweden
Query!
State/province [107]
0
0
Uppsala
Query!
Country [108]
0
0
Switzerland
Query!
State/province [108]
0
0
Aarau
Query!
Country [109]
0
0
Switzerland
Query!
State/province [109]
0
0
St Gallen
Query!
Country [110]
0
0
Taiwan
Query!
State/province [110]
0
0
Kaohsiung
Query!
Country [111]
0
0
Taiwan
Query!
State/province [111]
0
0
Taiching
Query!
Country [112]
0
0
Taiwan
Query!
State/province [112]
0
0
Taipei
Query!
Country [113]
0
0
United Kingdom
Query!
State/province [113]
0
0
Edinburgh
Query!
Country [114]
0
0
United Kingdom
Query!
State/province [114]
0
0
Gillingham
Query!
Country [115]
0
0
United Kingdom
Query!
State/province [115]
0
0
Glasgow
Query!
Country [116]
0
0
United Kingdom
Query!
State/province [116]
0
0
Leeds
Query!
Country [117]
0
0
United Kingdom
Query!
State/province [117]
0
0
Liverpool
Query!
Country [118]
0
0
United Kingdom
Query!
State/province [118]
0
0
London
Query!
Country [119]
0
0
United Kingdom
Query!
State/province [119]
0
0
Newcastle
Query!
Country [120]
0
0
United Kingdom
Query!
State/province [120]
0
0
Norwich
Query!
Country [121]
0
0
United Kingdom
Query!
State/province [121]
0
0
Nottingham
Query!
Country [122]
0
0
United Kingdom
Query!
State/province [122]
0
0
Oxford
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Ariad Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this study is to compare the efficacy of ponatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase.
Query!
Trial website
https://clinicaltrials.gov/study/NCT01650805
Query!
Trial related presentations / publications
Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development. J Clin Pharmacol. 2022 Apr;62(4):555-567. doi: 10.1002/jcph.1990. Epub 2021 Dec 16. Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, Etienne G, Nicolini FE, le Coutre P, Clark RE, Stenke L, Andorsky D, Oehler V, Lustgarten S, Rivera VM, Clackson T, Haluska FG, Baccarani M, Cortes JE, Guilhot F, Hochhaus A, Hughes T, Kantarjian HM, Shah NP, Talpaz M, Deininger MW; EPIC investigators. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016 May;17(5):612-21. doi: 10.1016/S1470-2045(16)00080-2. Epub 2016 Apr 12.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01650805
Download to PDF