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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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)
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
Secondary ID [1] 0 0
AP24534-12-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Molecular Response (MMR) Rate at 12 Months
Timepoint [1] 0 0
12 months after first dose
Secondary outcome [1] 0 0
MMR Rate
Timepoint [1] 0 0
5 years after first dose
Secondary outcome [2] 0 0
<10% BCR-ABL^IS Rate
Timepoint [2] 0 0
3 months after first dose
Secondary outcome [3] 0 0
Complete Cytogenetic Response (CCyR) Rate
Timepoint [3] 0 0
12 months after first dose
Secondary outcome [4] 0 0
Progression-free Survival
Timepoint [4] 0 0
Up to 8 years after the last patient's first dose
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
Up to 8 years after the last patient's first dose

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2013
Sample size
Target
Accrual to date
Final
307
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital, Site #971 - Garran
Recruitment hospital [2] 0 0
Royal North Shore Hospital, Site #941 - Sydney
Recruitment hospital [3] 0 0
Royal Adelaide Hospital, Site #951 - Adelaide
Recruitment hospital [4] 0 0
The Peter MacCallum Cancer Center, Site #950 - East Melbourne
Recruitment hospital [5] 0 0
Box Hill Hospital, Site #940 - Melbourne
Recruitment hospital [6] 0 0
Royal Perth Hospital, Site #972 - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2065 - Sydney
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3128 - Melbourne
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
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Gillingham
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ariad Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01650805
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01650805