Genetically Engineered Cells (UCD19 CAR T Cells) for the Treatment of B Acute Lymphoblastic Leukemia Patients with Minimal Residual Disease at First Complete Remission

Inclusion Criteria

• >= 18 years of age with no upper age limit
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Confirmed B-cell ALL in first complete morphologic remission
• MRD positivity as defined by: * For Philadelphia chromosome negative (Ph-) ALL: > 0.01% by fluorescence-activated cell sorting (FACS) or > 0 clonal sequences by next generation sequencing (NGS) (clonoSEQ). MRD assessment for eligibility must be at least 28 days after the start of standard of care (SOC) induction therapy. Remission-induction therapy must have consisted of multi-agent chemotherapy (>= 3 systemic anti-leukemia chemotherapy agents) * For Philadelphia chromosome positive (Ph+) ALL: > 0.01% by FACS, > 0 clonal sequences by NGS (clonoSEQ), or less than complete molecular remission (undetectable BCR-ABL1 transcripts by quantitative polymerase chain reaction [PCR] assay with sensitivity of at least 1 in 100,000). MRD assessment for eligibility must be at least 85 days after the start of SOC induction therapy. Remission-induction therapy must have consisted of a BCR-ABL1 directed tyrosine kinase inhibitor and at least one other systemic anti-leukemia chemotherapy agent
• Peripheral blood CD3 count must be > 0.15 x 10^6 cells/mL within 21 days prior to proceeding with apheresis
• Toxicities from prior therapy must be stable and recovered to =< grade 2 (exceptions include non-clinically significant toxicities such as alopecia and the organ function definitions provided)
• Absolute neutrophil count (ANC) >= 750/uL
• Platelet count >= 50,000/uL
• Either creatinine =< 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) >= 60 mL/min
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN)
• Total bilirubin =< 1.5 mg/dL, except in subjects with Gilbert's syndrome where a bilirubin < 3.0 mg/dL will be acceptable
• Ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings at the time of screening
• No clinically significant pleural effusion * Baseline oxygen saturation > 92% on room air and; * Pulmonary function test: Diffuse capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) are all >= 50% of predicted by spirometry after correcting for hemoglobin
• Females of childbearing potential must have a negative serum pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
• Subjects of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the UCD19 infusion
• Must be able to give informed consent; subjects unable to give informed consent will not be eligible for this study
• Be able to consent to long-term follow-up protocol (#20-0188)
• LYMPHODEPLETING CHEMOTHERAPY ELIGIBILITY:
• In order to proceed with lymphodepleting chemotherapy, enrolled participants must have all assessments below completed, and continue to meet all inclusion criteria within 72 hours of initiation of lymphodepletion, with the following clarifications: * Disease restaging studies will be performed as clinically indicated but must be within 14 days prior to initiation of lymphodepletion * Peripheral blood for CD3 count must be obtained within 21 days prior to apheresis and, therefore, is not applicable for determining lymphodepleting chemotherapy eligibility
• Bridging disease directed maintenance antineoplastic therapy between enrollment and before initiation of lymphodepleting chemotherapy is allowed
• UCD19 CART T CELL INFUSION ELIGIBILITY:
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * UCD19 CAR T cells must have met release criteria
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * Performance status determination (ECOG must be =< 2)
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * Participant remains clinically stable without evidence of vital sign instability
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * There is no evidence of disease progression prior to cell infusion per Investigator assessment
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * Must not have ALT/serum glutamate pyruvate transaminase (SGPT) and AST/serum glutamic-oxaloacetic transaminase (SGOT) > 10 x the ULN or bilirubin > 2 x the ULN, (unless history of Gilberts syndrome where bilirubin must not be > 3 x ULN)
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * Adequate renal function as defined in the inclusion criteria
• Participants must meet the following criteria in order for cells to be infused (based on labs obtained within 24 hours of cell infusion): * No evidence of uncontrolled infection within 48 hours prior to cell infusion as determined by the site principal investigator (PI) or sub-investigator. If these criteria are not met, measures will be taken to resolve the underlying condition(s). If successful, cells may be infused up to (and including) 7 days following the time of the planned infusion with no additional lymphodepletion. If the UCD19 CAR T cell infusion is delayed greater than 7 days, lymphodepleting chemotherapy MAY be repeated. Prior to commencing a second round of lymphodepletion, participants must meet lymphodepletion criteria described above

Exclusion Criteria

• Previous CAR T therapy
• Relapsed or refractory B-cell acute lymphoblastic leukemia, including patients who have evidence of MRD after having previously documented MRD-negative remission
• Mixed phenotype acute leukemia or Burkitt’s lymphoma
• Not in hematological remission at time of enrollment (remission is defined as < 5% blasts)
• Signs or symptoms of active central nervous system (CNS) disease or detectable evidence of CNS disease by assessment of cerebrospinal fluid at the time of screening. Subjects with leukemic involvement of the cerebrospinal fluid (CSF) at diagnosis who have no detectable leukemic cells in the CSF at screening are eligible
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years
• Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen [HBsAg] positive) or hepatitis C
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
• Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment
• History of severe immediate hypersensitivity reaction to any of the agents used in this study
• Females planning to become pregnant during the course of the study