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

This study has been terminated.
(Study terminated based on evaluation of safety data.)
Sponsor:
Information provided by (Responsible Party):
Ariad Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01650805
First received: July 18, 2012
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: ponatinib
Drug: imatinib (Gleevec/ Glivec)
Phase 3

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Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase

Resource links provided by NLM:


Further study details as provided by Ariad Pharmaceuticals:

Primary Outcome Measures:
  • Major Molecular response (MMR) rate [ Time Frame: 12 months after first dose ] [ Designated as safety issue: No ]
    To compare the efficacy of ponatinib with imatinib as measured by major molecular response (MMR) rate at 12 months (1 month or cycle = 28 days)


Secondary Outcome Measures:
  • MMR rate [ Time Frame: 5 years after first dose ] [ Designated as safety issue: No ]
    To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years

  • <10% BCR-ABL^IS rate [ Time Frame: 3 months after first dose ] [ Designated as safety issue: No ]
    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

  • Complete cytogenetic response (CCyR) rate [ Time Frame: 12 months after first dose ] [ Designated as safety issue: No ]
    To compare, according to treatment with ponatinib versus imatinib, the CCyR rate at 12 months

  • Progression-free survival [ Time Frame: Up to 8 years after the last patient's first dose ] [ Designated as safety issue: No ]
    To compare, according to treatment with ponatinib versus imatinib, progression-free survival

  • Overall survival [ Time Frame: Up to 8 years after the last patient's first dose ] [ Designated as safety issue: No ]
    To compare, according to treatment with ponatinib versus imatinib, overall survival


Enrollment: 307
Study Start Date: June 2012
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ponatinib Drug: ponatinib
45 mg tablet, taken orally once daily
Active Comparator: imatinib Drug: imatinib (Gleevec/ Glivec)
400 mg tablet, taken orally once daily

Detailed Description:

This multicenter, international, phase 3 trial will test the hypothesis that ponatinib is an effective treatment for newly diagnosed CP-CML patients when compared with standard imatinib.

Patients will be randomized in a 1:1 fashion, stratified by Sokal risk score at diagnosis (low, intermediate, high), to receive once daily oral administration of either ponatinib or imatinib. Efficacy measures include molecular, cytogenetic, and hematologic response rates at various timepoints; time to, duration of, and durability of responses; and survival follow-up. Safety measures include clinical laboratory testing, adverse event monitoring, vital signs, physical exams, ECGs, and ECHOs. Other measures include two patient-reported health outcomes questionnaires (FACT-Leu and EQ-5D-5L), determination of mutation status, and, for ponatinib only, measurement of steady-state plasma concentration. Accrual is expected to take approximately 2 years, and patients will be followed for survival for up to 8 years after the last patient's first dose; therefore, patient participation may last up to 10 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01650805

  Show 170 Study Locations
Sponsors and Collaborators
Ariad Pharmaceuticals
  More Information

No publications provided

Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01650805     History of Changes
Other Study ID Numbers: AP24534-12-301
Study First Received: July 18, 2012
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medicines and Medical Devices Safety Authority
Taiwan: National Laboratories of Foods and Drugs
Israel: Israeli Health Ministry Pharmaceutical Administration
Hong Kong: Department of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Singapore: Health Sciences Authority
South Africa: Medicines Control Council
Switzerland: Swissmedic

Keywords provided by Ariad Pharmaceuticals:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014