Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
Condition: Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: ponatinib; imatinib (Gleevec/ Glivec)
Intervention description: 45 mg tablet, taken orally once daily; 400 mg tablet, taken orally once daily
Intervention MeSH terms: Imatinib Mesylate; Ponatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility 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