Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)
Condition: Chronic Myeloid Leukemia; Ph+ Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: Ponatinib
Intervention description: Ponatinib tablets.
Intervention MeSH terms: Ponatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 449.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CML; ALL; PH; ponatinib; Ph+ALL; T315I mutation; Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Summary:

      The purpose of this study is to determine the efficacy of ponatinib in patients with chronic
      myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or
      with philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who either are
      resistant or intolerant to either dasatinib or nilotinib, or have the
      (T)hreonine-315-(I)soleucine (T315I) mutation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL

          -  Previously treated with and developed resistance or intolerance to dasatinib or
             nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI)
             therapy

          -  ≥18 years old

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Minimum life expectancy of ≥3 months

          -  Adequate kidney function

          -  Adequate liver function

          -  Normal pancreatic function

          -  Normal QT Fridericia-corrected interval (QTcF) ≤450 ms for males and ≤470 ms for
             females

          -  Negative pregnancy test (if woman of childbearing potential)

          -  Agree to use effective form of contraception (as applicable)

          -  Ability to comply with study procedures, in the Investigator's opinion

        Exclusion Criteria:

          -  Received prior TKI treatment within 7 days prior to receiving the first dose of
             ponatinib, or have not recovered from adverse events (except alopecia) due to agents
             previously administered.

          -  Received other therapies as follows:

               1. For CML chronic phase (CP) and accelerated phase (AP) participants, received
                  hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of
                  ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first
                  dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or
                  investigational therapy within 28 days prior to receiving the first dose of
                  ponatinib.

               2. For CML blast phase (BP) participants, received chemotherapy within 14 days prior
                  to the first dose of ponatinib.

               3. For Ph+ ALL participants, received corticosteroids within 24 hours before the
                  first dose of ponatinib; or vincristine within 7 days prior to the first dose of
                  ponatinib; or received other chemotherapy within 14 days prior to the first dose
                  of ponatinib.

          -  Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib

          -  Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring
             immunosuppressive therapy

          -  Taking medications that are known to be associated with Torsades de Pointes

          -  Require concurrent treatment with immunosuppressive agents (other than corticosteroids
             prescribed for a short course of therapy)

          -  Previously treated with ponatinib

          -  CML CP participants are excluded if they are in Complete cytogenetic response (CCyR)

          -  Participants with CML AP, CML BP, or Ph+ ALL are excluded if they are in Major
             Hematologic Response (MaHR).

          -  Have active Central Nervous System (CNS) disease

          -  Have significant or active cardiovascular disease

          -  Have a significant bleeding disorder unrelated to CML or Ph+ALL

          -  Have a history of pancreatitis or alcohol abuse

          -  Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)

          -  Have malabsorption syndrome or other gastrointestinal illness that could affect
             absorption of ponatinib

          -  Diagnosed with another primary malignancy in the past 3 years

          -  Pregnant or lactating

          -  Underwent major surgery within 14 days prior to first dose of ponatinib

          -  Have ongoing or active infection

          -  Suffer from any other condition or illness that would compromise safety or interfere
             with evaluation of the drug