Humanized CD19-Specific CAR T Cells for the Treatment of Patients With Positive Relapsed or Refractory CD19 Positive B-Cell Acute Lymphoblastic Leukemia

Inclusion Criteria: * Documented informed consent of the participant * Agreement to allow the use of archival tissue from diagnostic tumor biopsies. * If unavailable, exceptions may be granted with study principal investigator (PI) approval * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky performance status (KPS) ≥ 70 * Histologically confirmed CD19+ relapsed/refractory ALL with at least 2 prior lines of therapy * Prior alloHCT \> 100 days prior to enrollment may be considered a prior line of therapy * Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease * Participants with central nervous system (CNS) involvement by leukemia (CNS2 and CNS3) may be considered eligible after discussions with the study team * Patients with only MRD+ disease may be eligible * Patients with isolated extramedullary disease may also be eligible * Total bilirubin ≤ 2.0 X upper limit of normal (ULN) (unless has Gilbert's disease or related to leukemia involving the liver) * Aspartate aminotransferase (AST) ≤ 2.5 x ULN (unless related to leukemia involving the liver) * Alanine aminotransferase (ALT) ≤ 2.5 x ULN (unless related to leukemia involving the liver) * Creatinine clearance of ≥ 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula * Left ventricular ejection fraction (LVEF) ≥ 45% * Note: To be performed within 28 days prior to start of protocol therapy * Cardiac function (12 lead-electrocardiogram \[ECG\]): Corrected QT interval (QTc) must be ≤ 480 msec * Oxygen (O2) saturation \> 92% on room air * Note To be performed within 28 days prior to start of protocol therapy * Seronegative for HIV quantitative polymerase chain reaction (qPCR), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\]) * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed. OR * If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. The viral load must be undetectable * Meets other institutional and federal requirements for infectious disease titer requirements * Note Infectious disease testing to be performed within 28 days prior to start of protocol therapy * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) * ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) COLLECTION FOR CAR T CELL MANUFACTURING * Research participant has signed the 'screening and leukapheresis' informed consent * Research participant must have appropriate venous access, have a central line or be willing to undergo central or temporary line placement * The last dose of systemic chemotherapy must be at least 2 weeks before the leukapheresis procedure with the following exceptions: * Steroids and vincristine are allowed up to 7 days prior to leukapheresis. * Intrathecal chemotherapy is allowed up to 3 days prior to leukapheresis. * Tyrosine kinase inhibitors are allowed up to 48 hours prior to leukapheresis. * Hydrea is allowed up to 48 hours prior to leukapheresis. * The research participant cannot be on ≥ 7.5 mg prednisone or equivalent doses of other corticosteroids at the time of leukapheresis. Note: Topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed * The last dose of prior targeted agents, immunotherapy or radiation must be at least 2 weeks before the leukapheresis procedure * If the research participant has undergone prior alloHCT, 100 days must have elapsed since allogeneic stem cell transplant to undergo PBMC collection for CAR T cell manufacturing * ELIGIBILITY TO UNDERGO LYMPHODEPLETION * Research participant's absolute leukemic blast count does not exceed 10,000 cells/uL * The last dose of chemotherapy, maintenance therapy, radiation therapy, biological therapy, and/or immunotherapy must have been 7 days prior to start of lymphodepletion * The following washout periods must be met: * Corticosteroids 3 days * Biologic agents 3 half lives * Oral chemotherapeutic agents 3 half lives * Intrathecal chemotherapy 3 days * Chemo and/or immunotherapy 2 weeks * Local radiation to sites 7 days * Non myeloablative agents 7 days * Investigational agents 2 weeks, or at least 3 half lives * Hydroxyurea no washout period * Research participant has a released cryopreserved CAR T cell product for CAR T cell infusion on approximately day 0 (performed no more than 7 days prior to start of lymphodepletion) * ECOG \< 2 / KPS ≥ 70 (performed no more than 7 days prior to start of lymphodepletion) * No ongoing post treatment ≥ grade 3 non-heme toxicities (with exception of grade 3 glucose intolerance, cholesterol, triglyceride, peripheral neuropathy, and hyperglycemia) (performed no more than 7 days prior to start of lymphodepletion) * Research participant does not require supplemental oxygen to keep saturation greater than or equal to 92% and/or does not have any radiographic abnormalities on chest x-ray that are progressive (performed no more than 7 days prior to start of lymphodepletion) * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias (performed no more than 7 days prior to start of lymphodepletion) * Research participant does not have a fever exceeding 38.5 degree Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to lymphodepletion and/or there aren't any indications of meningitis (performed no more than 7 days prior to start of lymphodepletion) * Research participant serum total bilirubin does not exceed 2.5X normal limit or transaminases do not exceed 3X normal limit unless related to underlying leukemia (to be discussed at the discretion of the PI/study team) (performed no more than 7 days prior to start of lymphodepletion) * Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible * Research participant serum creatinine ≤ 2 mg/dL (performed no more than 7 days prior to start of lymphodepletion) * Research participant does not have uncontrolled seizure activity (performed no more than 7 days prior to start of lymphodepletion) * ELIGIBILITY TO PROCEED WITH CAR T CELL INFUSION * No ongoing post treatment ≥ grade 3 non-heme toxicities (with exception of grade 3 glucose intolerance, cholesterol, triglyceride, peripheral neuropathy, and hyperglycemia) * Prednisone (or prednisone equivalent) dose of ≤ 7.5 mg/kg/day is allowed * Prohibited medications have not been administered * KPS ≥ 70 * No untreated or active systemic infection * No Class III/IV cardiovascular disability according to the NYHA Classification * Research participant does not require supplemental oxygen to keep saturation greater than or equal to 92% and/or does not have any radiographic abnormalities on chest x-ray that are progressive * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias * Research participant does not have a fever exceeding 38.5 degree C; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis * Research participant serum total bilirubin does not exceed 2.5X normal limit or transaminases do not exceed 3X normal limit unless related to underlying leukemia (to be discussed at the discretion of the PI/study team) * Research participant serum creatinine ≤ 2 mg/dL * Research participant does not have uncontrolled seizure activity * ELIGIBILITY TO PROCEED WITH OPTIONAL CAR T CELL ABLATION * Research participant has \> 1% CAR T cells in the peripheral blood * No known hypersensitivity to cetuximab * Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 92% or higher on room air * Not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension * Serum creatinine did NOT increase by more than 2.5 fold from base line (at time of screening ) * Adequate liver function defined as total bilirubin \< 3.0 mg/dl, AST \< 5 x ULN; ALT \< 5 x ULN * Research participant without clinically significant encephalopathy/new focal deficits * No clinical evidence of uncontrolled active infectious process Exclusion Criteria: * Allogeneic stem cell transplant within 100 days at the time of enrollment * Received prior CAR T therapy within 90 days of enrollment * EXCEPTION: Participants who have previously received B-cell-activating factor receptor (BAFFR)-CAR T cells will be excluded from this study * Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent(s) * History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, recent stroke, severe brain injuries, dementia, cerebellar disease or psychosis * Autoimmune disease or active graft versus host disease (GVHD) requiring systemic immunosuppressant therapy * Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification * History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 2 years * Clinically significant uncontrolled illness * Active systemic uncontrolled infection requiring antibiotics * Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection * Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded * Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after the last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core antibody (Ab) positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment * Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded * Females only: Pregnant or breastfeeding * Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of topical or inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)