Safety Study of AP24534 to Treat Chronic Myelogenous Leukemia (CML) and Other Hematological Malignancies

Inclusion Criteria:

- Male or Female ≥ 18 years old

- Diagnosed hematologic malignancy (other than lymphoma) that has relapsed or is
refractory to standard care or for which no standard care is available or acceptable

- Able to give written informed consent

- ECOG performance status ≤ 2

- BSA ≥ 1.5 m² (first cohort only)

- Minimum life expectancy of 3 months or more

- Adequate renal function defined as serum creatinine <1.5× upper limit of normal (ULN)
for institution

- Adequate hepatic function (defined as: Total bilirubin <1.5 × ULN for institution; ALT
and AST <2.5 × ULN for institution [<5 X ULN if liver involvement with leukemia];
Prothrombin time <1.5 × ULN)

- Ability to comply with study procedures in the Investigator's opinion

- Adequate cardiac function defined as ejection fraction (EF) >40% by any method of the
investigator's choice

- Normal QTcF interval on screening ECG evaluation, defined as QTcF of <450 ms.

- For females of childbearing potential, a negative pregnancy test must be documented
prior to enrollment

- Female patients who are of childbearing potential must agree to use an effective form
of contraception with their sexual partners throughout participation in this study

Exclusion Criteria:

- Have had cytotoxic chemotherapy or radiotherapy within 21 days prior to entering the
study, or those who have not recovered from adverse events due to agents administered
more than 28 days earlier with the exception of alopecia

- Received any other investigational agents or have received an investigational agent
within 14 days of starting ponatinib

- Malabsorption syndrome or other illness which could affect oral absorption

- Significant uncontrolled cardiac disease

- Patients taking medicinal products that are known to be associated with prolongation
of the QT interval on the electrocardiogram.

- Uncontrolled hypertension (Diastolic BP >100 mmHg; Systolic >150 mmHg)

- Uncontrolled intercurrent illness

- Pregnant

- Known infection with HIV

- Autologous or allogeneic stem cell transplant < 3 months prior to enrollment; any
evidence of ongoing graft versus host disease (GVHD), or GVHD requiring
immunosuppressive therapy

- Another primary malignancy within the past 3 years

- Any condition or illness which, in the opinion of the investigator, would compromise
patient safety or interfere with the evaluation of the safety of the drug

- Patients taking medicinal products that are known to be associated with prolongation
of the QT interval on the electrocardiogram

- Major surgery (with the exception of intravenous catheter placement or bone marrow
biopsy) within 14 days prior to initiating ponatinib therapy