CML13: This trial is evaluating an oral cancer drug (asciminib) in patients with newly diagnosed chronic phase myeloid leukaemiaAn Australasian Leukaemia and Lymphoma Group (ALLG) single arm phase II study to evaluate the efficacy of asciminib in newly diagnosed patients with chronic phase chronic myeloid leukaemia

Exclusion

1. Major surgery within 2 weeks of, or having not recovered from surgery, by the time of screening.
2. Abnormal clinical laboratory results (re-screening allowed)
a) Total bilirubin greater than 1.5x ULN (in patients with Gilbert’s syndrome, total bilirubin greater than 3x ULN, or direct bilirubin greater than 1.5x ULN)
b) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3x ULN.
c) Alkaline phosphatase greater than 2.5 times the ULN unless considered to be not of hepatic origin
d) Creatinine greater than 1.5 times ULN
e) Amylase / Lipase values greater than 1.5 times institutional ULN
3. Treatment with strong inducers of CYP3A4/5, CYP2C8 and CYP2C9 (See Appendix 1 for list of prohibited drugs). Consumption of grapefruit, Seville oranges, star fruit and their juice / derivatives / products is not permitted whilst a patient is taking study medication.
4. Active infection requiring systemic therapy at the time of screening
5. History of significant congenital or acquired bleeding disorder unrelated to cancer.
6. Known human immunodeficiency virus (HIV) positive (testing to exclude infection is not required in the absence of suggestive history)
7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
8. Corrected QT interval (QTc) of greater than 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF]).
9. Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias (e.g. ventricular arrhythmias or Torsades de Pointe, or third degree heart block without pace maker insertion); congestive heart failure, angina, or myocardial infarction within the past 3 months prior to screening.
10. Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol.
11. Cytopathologically confirmed CNS infiltration. (In the absence of suspicion of CNS involvement, lumbar puncture is not required.)
12. A history of concomitant primary malignant disease that requires active cytotoxic treatment and / or a life limiting illness expected to have a life expectancy less than 5 years.
13. History of acute pancreatitis within 1 year of study entry, chronic pancreatitis, or any ongoing pancreatic disease.
14. Acute or chronic active liver disease. HBV core antibody positivity is not an automatic exclusion.
15. Subjects unable to comply with requirements for contraception as per study requirements.
16. Prior stem cell transplantation.
17. Reproductive status
a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
b) Women must not be breastfeeding.
c) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion.
d) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion. (See appendix 4)
e) Azoospermic males are exempt from contraceptive requirements.
18. Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).