Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

Prior treatment

• History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond or any known bone marrow failure syndrome
• Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
• Corticosteroid therapy within 7 days prior to enrollment
• Acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
• Live vaccine ≤ 4 weeks prior to enrollment

Other illness

• History of dasatinib intolerance
• 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 myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• Known infection with HIV, hepatitis B (HBsAg positive) or untreated hepatitis C virus
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
• Patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year
• Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment

Lab values

• Blast count \> 75% in the bone marrow.

Other

• Primary immunodeficiency
• Pregnant or breast feeding

• Relapsed or refractory B-precursor 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 MRD defined as detectable ALL by flow cytometry, PCR, or next-generation sequencing
  • Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment
  • Patients with isolated, asymptomatic CNS relapse will be eligible
  • Age \>=18 years
  • Eastern cooperative oncology group (ECOG) performance status of 0-2
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:
  • 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
  • QTc ≤ 500ms
  • In individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood by flow cytometry or extramedullary site by IHC or flow cytometry
  • Negative serum or urine beta-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 Page 10 of 83 Version 1.0 dated 27-April-2023 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.