CML14 (ASCENDANCE): This study is assessing the efficacy of an induction phase of combination targeted therapy in people with newly diagnosed chronic phase chronic myeloid leukaemia (CP-CML) with high-risk geneticsASCiminib Evaluation in Newly diagnosed CML with Dasatinib to Augment response in Complex genomic Etiology

Exclusion

 1. Abnormal clinical laboratory results
a) Total bilirubin greater than 1.5 times Upper Limit of Normal (ULN) (in patients with Gilbert’s syndrome, total bilirubin greater than 3 times ULN, or direct bilirubin greater than 1.5 times ULN)
b) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times 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 or Lipase values greater than 1.5 times institutional ULN
2. Treatment with strong inducers of CYP3A4 or CYP3A5, CYP2C8 and CYP2C9 (Consumption of grapefruit, Seville oranges, star fruit and their juice or derivatives or products is not permitted whilst a patient is taking study medication).
3. Active, uncontrolled infection requiring systemic therapy at the time of screening
4. History of significant congenital or acquired bleeding disorder unrelated to cancer.
5. Known human immunodeficiency virus (HIV) positive (testing to exclude infection is not required in the absence of suggestive history)
6. Serious medical or psychiatric illness likely to interfere with safety and efficacy monitoring or otherwise jeopardising the participant’s health within this clinical study.
7. Corrected QT interval (QTc) of greater than 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF]).
8. 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.
9. Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections, acute or chronic renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol.
10. A history of concomitant primary malignant disease that requires active cytotoxic treatment and / or a life limiting illness expected to have a life expectancy greater than 5 years.
11. History of acute pancreatitis within 1 year of study entry, chronic pancreatitis, or any ongoing pancreatic disease.
12. Acute or chronic active liver disease. (HBV core antibody positivity is not an automatic exclusion.)
13. Subjects unable to comply with requirements for contraception as per study requirements.
14. Reproductive status
a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU per 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 Women of childbearing potential (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.
e) Azoospermic males are exempt from contraceptive requirements.
15. Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).