Brexucabtagene Autoleucel plus Dasatinib for the Treatment of Relapsed or Refractory B Acute Lymphoblastic Leukemia

Inclusion Criteria

• Relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) defined as one of the following: * Primary refractory disease (>= 5% blasts or persistent extramedullary disease following induction therapy) * First or later relapse of marrow or extramedullary disease * Persistence of minimal residual disease (MRD) defined as detectable ALL by flow cytometry, polymerase chain reaction (PCR), or next-generation sequencing on at least two tests administered at least 14 days apart * Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment * Patients with isolated, asymptomatic central nervous system (CNS) relapse will be eligible
• Greater than or equal to 18 years
• Eastern Cooperative Oncology Group (ECOG) of 0-2
• Creatinine clearance (as estimated by Cockcroft Gault) >= 60 cc/min
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 mg/dl, except in individuals with Gilbert's syndrome
• Cardiac ejection fraction >= 50%, no evidence of clinically significant pericardial effusion, and no clinically significant arrhythmias
• Baseline oxygen saturation > 92% on room air
• Corrected QT (QTc) =< 500 ms
• In individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood or extramedullary site
• Negative serum or urine beta-human chorionic gonadotropin (HCG) test in females of childbearing potential within 3 weeks of enrollment
• Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study and for six (6) months after receiving the preparative conditioning regimen
• Must be able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent

Exclusion Criteria

• History of dasatinib intolerance
• Blast count > 75% in the bone marrow
• Known sensitivity or allergy to aminoglycosides or any agents/reagents used in this study
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years
• Presence of CNS-3 disease with neurological changes
• History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage with clinical signs or symptoms
• History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond or any known bone marrow failure syndrome
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History of primary immunodeficiency
• Known infection with HIV, hepatitis B (hepatitis B surface antigen [HBsAg] positive) or untreated hepatitis C virus
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
• Salvage chemotherapy including tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome (Ph)+ ALL within 1 week prior to enrollment
• Pregnant or breast feeding
• Patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year
• Corticosteroid therapy within 7 days prior to enrollment
• Acute or chronic graft versus host disease (GVHD) requiring systemic treatment within 4 weeks prior to enrollment
• Live vaccine =< 4 weeks prior to enrollment
• Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment