Genetically Engineered Cells (Obecabtagene Autoleucel) for the Treatment of B-cell Acute Lymphoblastic Leukemia in First Complete Remission without Measurable Residual Disease

Inclusion Criteria

• Diagnosis of CD19+ B-cell ALL. * Both Ph-negative and Ph-positive are allowed * Patients with extramedullary disease (EMD) must have detectable disease in the bone marrow (by flow cytometry or molecular methods) in order to follow MRD
• Patients aged ≥ 40 years at time of screening A
• Patients aged 30-39 years (at time of screening A) are allowed in the presence of high-risk comorbidities or poor tolerability of chemotherapy (e.g. history or experienced pancreatitis with therapy, body mass index [BMI] ≥ 40kg/m^2, underlying liver disease precluding safer administration of pediatric inspired regimens, any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric or pediatric-inspired standard chemotherapy regimen)
• In MRD negative CR or CR with incomplete hematologic recovery (CRi) at the time of screening. MRD will be assessed by flow cytometry and/or molecular testing such as ClonoSEQ at the minimum sensitivity of 10^-4 from the bone marrow. Patients with MRD < 10^-4 will be eligible. If a patient has MRD ≥ 10^-4 by any modality at time of screening A, they will not be eligible
• Patients may receive more than one course of upfront induction and/or consolidation, but must be in MRD- CR/CRi at time of screening, within 4 months from initiation of treatment. The 4-month window will be measured from the first day of anti-leukemic therapy initiation (excluding steroid prophase) until the screening A test for the trial. Frontline regimens include but are not limited to: * Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HyperCVAD) or mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (hyper-CVD) * Asparaginase-containing multiagent chemotherapy (e.g. CALGB10403, pediatric inspired chemotherapy [chemo]) * Inotuzumab or blinatumomab with or without chemotherapy * Tyrosine kinase inhibitor plus steroids, chemotherapy, or blinatumomab
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
• Total bilirubin ≤ 2 (or ≤ 3 if history of Gilbert's syndrome or leukemic infiltration of the liver)
• Serum creatinine < 2.0mg/dL
• Oxygen saturation (SaO2) ≥ 92% on room air
• Left ventricular ejection fraction (LVEF) ≥ 50% within 1 month of screening
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• CD19 expression is required at any time since diagnosis. CD19 expression may be detected by immunohistochemistry or by flow cytometry. Patients receiving prior blinatumomab are eligible if there is no documentation of CD19-negative disease after blinatumomab
• Central nervous system (CNS)1 status must be documented at time of screening by CSF assessment. Patients with prior CNS2 or CNS3 disease must be CNS1 at screening and have no residual CNS deficits or symptoms
• Patients will need to adhere to institutional contraception guidelines for a minimum of 1 year

Exclusion Criteria

• Concurrent active malignancy excluding non-melanoma skin cancer. Patients with a history of prior malignancy who have been treated with curative intent and have been in remission for at least 2 years are eligible
• Burkitt’s leukemia or lymphoma
• Patients with measurable extramedullary disease at screening are excluded. Patients with prior history of extramedullary disease are allowed after documentation of disease resolution by either PET/CT scan (or CT with contrast if PET cannot be performed)
• The following medications are excluded: * Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion * Systemic chemotherapy: Must be discontinued 7 days prior to leukapheresis or 7 days prior to starting lymphodepleting chemotherapy if used during bridging * Tyrosine kinase inhibitors: Must be discontinued 48 hours prior to apheresis and 48 hours prior to starting lymphodepleting chemotherapy, if used during bridging * Blinatumomab must be discontinued 5 days before apheresis * Inotuzumab must be discontinued 2 weeks before apheresis to allow T cell recovery
• Patients with uncontrolled systemic fungal, bacterial, viral or other infection at time of leukapheresis or at time of CAR T cell infusion
• Blinatumomab may not be used as bridging therapy following apheresis
• Positive test indicating the presence of active infection with the following pathogens: HIV, hepatitis B (detectable hepatitis B [Hep B] deoxyribonucleic acid [DNA] by polymerase chain reaction [PCR] or Hep B surface antigen), hepatitis C (detectable hepatitis C [Hep C] ribonucleic acid [RNA] by PCR), human T cell lymphotropic virus (HTLV), syphilis. The tests required will be agreed upon with the manufacturer to comply with manufacturer’s regulatory and manufacturing requirements