PonAZA: This phase I/II trial is combining an oral drug (ponatinib) with 5- azacitidine for the treatment of Acute Myeloid Leukaemia (AML)A phase Ib/II clinical evaluation of Ponatinib in combination with 5-azacytidine in patients failing prior therapy for FLT3-ITD positive acute myeloid leukaemia (AML M21)

Exclusion

1. Any serious medical condition which the investigator feels may interfere with the procedures or evaluations of the study
2. More than 2 prior lines of intensive chemotherapy
3. Prior exposure to ponatinib
4. If prior exposure to other FLT3 inhibitors, the presence of FLT3-TKD mutation must not be present at screening
5. Moderate/strong CYP3A4 inhibitors within 48 hours of cycle 1, day 1
6. Active graft versus host disease post-allograft or requiring steroid doses equivalent to prednisolone 15mg per day or greater
7. Prior exposure to a hypomethylating agent
8. Major surgery within 28 days prior to initiating therapy
9. History of acute pancreatitis within 1 year of study or a history of chronic pancreatitis
10. Uncontrolled diabetes
11. History of cardiovascular or thromboembolic disease including:
a. Myocardial infarction
b. Unstable angina within 6 months prior to randomization
c. Congestive heart failure within 6 months prior to randomization
d. History of clinically significant (as determined by the treating physician) atrial arrhythmia
e. Any history of ventricular arrhythmia
f. Cerebrovascular accident or transient ischemic attack
g. Any history of peripheral arterial occlusive disease requiring revascularization
h. Any history of venous thromboembolism including deep venous thrombosis (excluding catheter associated thrombosis) or pulmonary embolism
12. History of other malignancy requiring active systemic treatment or which is likely to result in an expected survival time of less than 2 years
13. Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
14. Active infection or bleeding
15. Pregnant or breastfeeding females; women of childbearing potential may participate providing they agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following completion. For females of childbearing potential, a negative pregnancy test must be documented within 7 days prior to starting treatment with ponatinib
16. Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following the date of last dose