Asciminib-Based Induction Therapy for the Treatment of Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

• Newly diagnosed Ph+ or BCR-ABL1-positive ALL, as defined by the 2025 National Comprehensive Cancer Network (NCCN) guidelines

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)

• Aspartate aminotransferase (AST) ≤ 3.0 x ULN

• Alanine aminotransferase (ALT) ≤ 3.0 x ULN

• Serum creatinine < 1.5 mg/dL

• Left ventricular ejection fraction (LVEF) ≥ 50%

  • Note: To be performed within 28 days prior to day 1 of protocol therapy

• Normal QT interval corrected per Fridericia method (QTcF) on screening electrocardiogram, defined as QTcF of ≤ 480 msec

• Oxygen (O2) saturation > 90% on room air

• Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative)

  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• Meets other institutional and federal requirements for infectious disease titer requirements

  • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to use a highly effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Prior treatment failure with asciminib

• Prior/current treatment with any systemic anticancer therapy (including but not limited to any TKI) and/or radiotherapy for ALL, with the exception of an optional prephase therapy or chemotherapy induction (no more than one cycle), which should be discussed with the principal investigator (PI). Patients who have received no more than two weeks of chemotherapy (not including steroids) with or without other TKIs are considered minimally pretreated and still eligible

• Currently taking drugs that are known to have a risk of causing prolonged corrected QT interval (QTc) or torsades depointes (TdP) (unless these can be changed to acceptable alternatives or discontinued)

• Taking any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 within at least 14 days before the first dose of study drug

• Cardiac or cardiac repolarization abnormality, including any of the following:

  • History within 6 months prior to starting study treatment of myocardial infarction (MI), or 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)

• A history of cerebrovascular events such as stroke or transient ischemic attack

• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome. Treatment with any investigational products within 30 days before enrollment or 6 half-lives of the agent, whichever is shorter

• History of pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis

• Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)

• Clinically significant uncontrolled illness

• Active infection not responding to treatment at the time of starting therapy

• Autoimmune disease with potential central nervous system (CNS) involvement

• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)