Trial purpose
Cancer treatment
Tumor type
Haematological
Age
18+
Clinical summary
Summary
The study is evaluating Ponatinib in combination with 5-azacytidine in patients failing prior therapy for FLT3-ITD positive acute myeloid leukaemia (AML M21). Who is it for? You may be eligible to join this study if you are aged over 18 years, have enrolled in the Australasian Leukaemia and Lymphoma Acute Myeloid Leukaemia ( ALLG AML) registry, have FLT3-ITD AML (except Acute Promyelocytic Leukaemia) failing prior chemotherapy (excluding hydroxyurea and thioguanine). This study has two parts: Phase Ib which involves finding the best dose of Azacytidine to combine with Ponatinib in terms of patient tolerability and safety. In Phase II of the study, patients will be randomly (by chance) assigned to 3 groups; one group will receive Ponatinib alone, the other will receive Azacytidine alone and the last group will receive both drugs.
Conditions
This trial is treating people with Acute Myeloid Leukaemia
Eligibility
Inclusion
1. Provision of written informed consent
2. Enrolment to the ALLG National Blood Cancer Registry (Another Australiasian Leukaemia and Lymphoma group study)
3. FLT3-ITD AML (except Acute Promyelocytic Leukaemia) failing prior chemotherapy (excluding hydroxyurea and thioguanine which is not considered chemotherapy) or who are considered unfit for frontline intensive chemotherapy.
4. Age 18+
5. Eastern Cooperative Oncology Group performance status 0-2
6. Adequate haemostatic function (activated partial thromboplastin time (APTT) within 5 sec of ULN and INR less than 1.4x ULN)
7. Adequate hepatic function as defined by bilirubin less than or equal to 1.5 x the upper limit of normal (ULN) unless due to Gilbert’s syndrome and aspartate transaminase (AST) or alanine aminotransferase (ALT) less than or equal to 3 x ULN
8. Adequate pancreatic function as defined by the following criterion: serum lipase or amylase less than or equal to 1.5 × ULN
9. Adequate renal function as defined by serum creatinine less than 1.5 ULN
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
Inclusion
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ANZCTR *. View further details about this trial on the registry via the links below:
Trial sponsor
Australasian Leukaemia and Lymphoma Group (ALLG)
Scientific Title
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)
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