Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation

Exclusion Criteria

• •Known second chronic phase of CML after previous progression to CML-AP/CML-BC.
• •Previous treatment with a hematopoietic stem-cell transplantation.
• •Cardiac or cardiac repolarization abnormality, including any of the following:
• •* History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
• •* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
• •* QT corrected for heart rate by Fridericia's cube root formula (QTcF) at screening ≥450 msec (both male and 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 (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• •Inability to determine the QTcF interval.1. Known second chronic phase of CML after previous progression to CML-AP/CML-BC.
• •Previous treatment with a hematopoietic stem-cell transplantation.
• •Cardiac or cardiac repolarization abnormality, including any of the following:
• •* History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
• •* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
• •* QT corrected for heart rate by Fridericia's cube root formula (QTcF) at screening ≥450 msec (both male and 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 (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• •Inability to determine the QTcF interval
• •Concomitant medication(s) with a "Known risk of TdP" (per www.crediblemeds.org) that cannot be discontinued or replaced 7 days prior to starting study treatment by safe alternative medication.
• •Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g., uncontrolled diabetes, active or uncontrolled infection, pulmonary hypertension).
• •History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
• •Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
• •Known presence of significant congenital or acquired bleeding disorder unrelated to cancer.
• •History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively.
• •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
• •Previous treatment with or known/suspected hypersensitivity to asciminib or any of its excipients.
• •Participants must avoid consumption of grapefruit, Seville oranges, or products containing the juice of each during the entire study and 7 days before the first dose of study treatment, due to potential CYP3A4 interaction with the study treatment. Orange juice is allowed. Participants must avoid consumption of over-the-counter medications or herbal supplements as these can interact with each other and may alter the effects of asciminib.
• •Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
• •Pregnant or breastfeeding women.
• •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception.
• •Highly effective contraception methods include:
• •Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• •Female sterilization (have had surgical bilateral oophorectomy (with or without hysterectomy) total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment). In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
• •Male sterilization (vasectomy) of the male partner(s) of the female participant at least 6 months prior to screening. The vasectomized male partner should be the sole partner for that participant.
• •Use of oral, injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example, hormone vaginal ring or transdermal hormone contraception. In the case of the use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
• •Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks before taking study treatment. In the case of oophorectomy alone, women are considered menopausal and not of childbearing potential only when the reproductive status of the woman has been confirmed by a follow-up hormone level assessment.
• •\- If a participant is presenting with symptoms suggestive of possible Coronavirus Disease (COVID-19) infection, advise ruling it out by appropriate testing recommended by health authorities.
• •Nucleic acid amplification tests for viral RNA (polymerase chain reaction), to measure current infection with SARS-CoV-2
• •Antigen tests for rapid detection of SARS-CoV-2
• •Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2.