A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia

Inclusion Criteria:

- Previously treated with and developed resistance or intolerance to dasatinib or
nilotinib, or developed the T3151 mutation after any TKI therapy including imatinib

- ≥18 years old

- ECOG performance status ≤2

- Normal pancreatic function

- QTcF interval ≤450 ms for males and ≤470 ms for females

- Adequate renal and hepatic function

- Minimum life expectancy of ≥3 months

- Provide written informed consent

- Negative pregnancy test and agree to use effective form of contraception (if
applicable)

Exclusion Criteria:

- Received prior tyrosine kinase inhibitor (TKI) treatment within 7 days prior to
receiving the first dose of ponatinib

- Received other therapies as follows:

1. For CML chronic phase (CP) and accelerated phase (AP) patients, 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 ponitinib; 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) patients, received chemotherapy within 14 days prior to
the first dose of ponatinib.

3. For Ph+ ALL patients, 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.

4. All patients are excluded if they have not recovered from adverse events except
alopecia) resulting from any prior treatments administered.

- Taking medications that are known to be associated with torsades de pointes

- Previously treated with 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

- Require concurrent treatment with immunosuppressive agents

- 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)

- Underwent major surgery within 14 days prior to first dose of ponatinib

- Have ongoing or active infection

- 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

- Suffer from any other condition or illness that would compromise safety