Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

Prior treatment

• Known presence of the T315I mutation at any time prior to study entry
• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a hematopoietic stem cell transplantation
• Participants planning to undergo allogeneic hematopoietic stem cell transplantation

Other illness

• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  • Other protocol-defined inclusion/exclusion criteria may apply.

Lab values

• Cardiac or cardiac repolarization abnormality, including any of the following:
  • History within 6 months prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft Clinically significant cardiac arrhythmias , complete left bundle branch block, high-grade AV block QTcF at screening ≥450 msec (male participants), ≥460 msec (female participants)
  • Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
  • Risk factors for Torsades de Pointes including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia Concomitant medication(s) with a "Known risk of Torsades de Pointes" that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
  • Inability to determine the QTcF interval

• Diagnosed as CML-CP:
• Participants must meet all of the following laboratory values at the screening visit:
  • \< 15% blasts in peripheral blood and bone marrow \< 30% blasts plus promyelocytes in peripheral blood and bone marrow \< 20% basophils in the peripheral blood
  • 50 x 10\^9/ L (≥ 50,000/mm3) platelets Transient prior therapy related thrombocytopenia (\< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Prior treatment with a minimum of 2 prior ATP-competitive TKIs.
• Failure (adapted from the 2013 European Leukemia Net (ELN) Guidelines) or intolerance to the most recent TKI therapy at the time of screening.
• Evidence of typical BCR-ABL1 transcript \[e14a2 and/or e13a2\] at the time of screening which are amenable to standardized RQ-PCR quantification