Frontline Asciminib Combination in Chronic Phase CML

Inclusion Criteria:

* Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of the Ph+ chromosome \[t(9;22)(q34;q11)\].
* Ph-negative cases or patients with variant translocations who are BCR-ABL1 positive in multiplex PCR 35 will be also considered eligible.
* ECOG performance status of ≤2.
* Age ≥ 18 years old (no upper age limit is given)
* Serum levels of potassium, magnesium, total calcium within the normal limits (≥LLN \[lower limit of normal\] and ≤ULN \[upper limit of normal\]). Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
* AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
* Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
* Total bilirubin ≤1.5 x ULN, except known Gilbert disease
* Serum creatinine ≤2 x ULN
* Written informed consent prior to any study procedures being performed.

Exclusion Criteria:

* Allogeneic stem cell transplantation
* Known impaired cardiac function, including any of the following:

  * Congenital long QT syndrome
  * History of or presence of clinically significant ventricular or atrial tachyarrhythmia
  * QTc \>450 msec on screening ECG
  * Myocardial infarction within 12 months prior to starting therapy
* Other clinical significant heart disease (e.g. unstable angina, congestive heart failure)
* Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores \>6), even if controlled
* Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
* Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
* Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
* Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
* Patients who are pregnant or breastfeeding or women of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study start. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of birth control throughout the study and for up to 2 weeks following discontinuation of study drug
* Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
* Known serious hypersensitivity reactions to asciminib, imatinib, nilotinib or dasatinib
* Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
* Patients unwilling or unable to comply with the protocol.