A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia
Condition: Chronic Phase Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Ponatinib 30 mg QD; Ponatinib 15 mg QD; Nilotinib 400 mg BID
Intervention description: Ponatinib 30 mg, taken orally once daily.; Ponatinib 15 mg, taken orally once daily.; Nilotinib 400 mg, taken orally twice daily.
Intervention MeSH terms: Ponatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CML; CP-CML; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases

Summary:

      The purpose of this study is to compare the efficacy and safety of 2 starting doses of
      ponatinib compared to nilotinib in participants with imatinib-resistant chronic myeloid
      leukemia (CML) in chronic phase (CP).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have CP-CML and are resistant to first-line imatinib treatment.

          2. Be male or female ≥18 years old.

          3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          4. Have adequate renal function as defined by the following criterion:

             • Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution.

          5. Have adequate hepatic function as defined by all of the following criteria:

               -  Total serum bilirubin ≤1.5 × ULN, unless due to Gilbert's syndrome

               -  Alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of
                  the liver is present

               -  Aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration
                  of the liver is present.

          6. Have normal pancreatic status as defined by the following criterion:

               -  Serum lipase and amylase ≤1.5 × ULN.

        Exclusion Criteria:

          1. Have previously been treated with any approved or investigational TKIs other than
             imatinib or treated with imatinib within 14 days prior to receiving study drug.

          2. Have previously been treated with any anti-CML therapy other than hydroxyurea,
             including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy,
             radiotherapy, or investigational therapy.

          3. Underwent autologous or allogeneic stem cell transplant.

          4. Are in CCyR or MMR.

          5. Have clinically significant, uncontrolled, or active cardiovascular disease,
             specifically including, but not restricted to:

               -  Any history of myocardial infarction (MI), unstable angina, cerebrovascular
                  accident, or transient ischemic attack (TIA)

               -  Any history of peripheral vascular infarction, including visceral infarction

               -  Any history of a revascularization procedure, including vascular surgery or the
                  placement of a stent

               -  History of venous thromboembolism, including deep venous thrombosis, superficial
                  venous thrombosis, or pulmonary embolism, within 6 months prior to enrollment

               -  Congestive heart failure (New York Heart Association [NYHA] class III or IV)
                  within 6 months prior to enrollment or left ventricular ejection fraction (LVEF)
                  less than 45% or less than the institutional lower limit of normal (whichever is
                  higher) within 6 months prior to enrollment.