Asciminib as Maintenance Treatment after Allogeneic Stem Cell Transplant or Chimeric Antigen Receptor T Cell Therapy to Prevent Relapse for Adults with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Inclusion Criteria

• Patients must have B-ALL with detectable Philadelphia chromosome abnormalities by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or cytogenetics at time of diagnosis. Patients harboring T315I mutations will only be allowed to enroll on dose level 1 (200mg BID)
• Patients should be in morphologic remission at time of study enrollment defined as =< 5% marrow blasts and no circulating peripheral blasts. Patients with minimal residual disease by PCR, flow cytometry or next-generation sequencing (NGS) based minimal residual disease (MRD) assay with =< 5% blasts on bone marrow biopsy will be permitted. * Patients in cohort A will be recipients of alloHCT. All stem cell sources, and conditioning regimens are allowed * Patients in cohort B will be recipients of any CD19 CAR T cell therapy
• Patient is at least 18 years of age at the time of signing the informed consent form (ICF)
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0, 1 or 2
• Patient must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Patient is willing and able to adhere to the study visit schedule and protocol requirements
• Absolute neutrophil count (ANC) > 1000/m^3
• Hemoglobin > 8gm/dL
• Platelets should be over 20,000 k/uL for three consecutive days without transfusion for at least 7 days
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Human immunodeficiency virus (HIV)-infected participants on effective anti retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. The HCV viral load must be undetectable at screening
• Participants with prior history of central nervous system (CNS) disease are eligible if they have been previously treated and remain asymptomatic
• The effects of asciminib on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration and for at least 30 days after the last dose of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria

• Active malignant relapsed disease defined as >= 5% blasts
• Acute grade II-IV graft versus host disease (GVHD) requiring systemic steroids with prednisone dose equivalent to > 0.5mg/kg of steroids (Cohort A only)
• Any of the following laboratory abnormalities: * Serum creatinine clearance < 50 ml/min (as per Cockroft-Gault Equation) * Serum amylase and lipase >= 1.5 x upper limit of normal (ULN). For serum lipase and amylase >= 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis by principal investigator (PI) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN * Alkaline phosphatase >= 2.5 x ULN * Total bilirubin >= 1.5 x ULN. Exception permitted in patients with Gilbert’s syndrome as long as total bilirubin < 3.0 x ULN
• Patient is pregnant or a breastfeeding female
• History of acute pancreatitis within 1 year of study enrollment or medical history of chronic pancreatitis
• Patient with uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4)
• QT interval as corrected by Fridericia’s formula (QTcF) >= 500 msec on screening electrocardiography (EKG)
• Patient with serious uncontrolled active infection
• Concurrent active malignancy requiring therapy. Localized skin basal cell or squamous cell carcinomas are permitted
• Patient is unable to swallow capsule
• Patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study
• Patient with participation in any study of an investigational agent within 30 days prior to start of asciminib
• Patient has any condition including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study
• Patient has any condition that confounds the ability to interpret data from the study
• Patients receiving investigational CAR T products for relapsed/refractory (r/r) B-ALL. Patients enrolled in clinical trials using commercial CAR T products will require PI approval