Ph I/II Study of CAR19 Regulatory T Cells (CAR19-tTreg) for R/R CD19+ B-ALL

Inclusion Criteria: * Diagnosis of R/R CD19+ B-ALL after failure of standard of care therapies with CD19 expression on blasts confirmed by flow cytometry or immunohistochemistry and meeting one or more of the following criteria: 1. Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy/immunotherapy, or 2. First relapse with no CR after 1 cycle of induction therapy, or 3. Second or greater relapse, or 4. Ph+ ALL and failure or intolerance to three lines of tyrosine kinase inhibitors (TKI) assuming one or more of the above criteria are also met. * Karnofsky performance status (KPS) ≥70% at screening * Adequate organ function is defined as: 1. Renal: Calculated estimated glomerular filtration rate greater than or equal to50 mL/min/1.73 m2 2. Hepatic: ALT and AST less than 3x upper limit of normal (ULN), and bilirubin less than2x ULN (exception, patients with Gilbert syndrome, total less than 3 x ULN and direct less than 1.5 x ULN) 3. Cardiac: Left ventricular ejection fraction (LVEF) greater than 45% by echocardiogram 4. Pulmonary: SpO2 greater than 92% on room air * Use of antiproliferative chemotherapy more than 2 weeks prior to enrollment and blinatumomab more than 4 weeks prior to enrollment * Patients with relapsed disease after prior allogeneic transplantation may be considered. In addition to the eligibility criteria otherwise listed, this subgroup must be more than 3 months from allogeneic hematopoietic stem cell transplant (HSCT), off immune suppressive therapy (e.g., calcineurin inhibitor, glucocorticoid, sirolimus) at least 4 weeks without GVHD. * Patients who received prior CAR-T therapy are eligible if more than 2 months after CAR-T infusion and CD19 expression is confirmed at the most recent relapse and all other criteria are met * Voluntary informed consent by the patient for treatment and follow-up for 15 years after treatment. Exclusion Criteria: * Availability of a FDA approved CAR T cell therapeutic targeting CD19+ B-ALL (patients eligible for but unable to receive FDA approved CAR T cells based on insurance limitations, may be eligible for the proposed trial) * Use of pharmacological immunosuppressive agents within 2 weeks (with the exception of physiologic or stress dose glucocorticoid replacement) or anti-T cell antibodies within 2 months of study participation * Diagnosis of Burkitt lymphoma * Diagnosis of active central nervous system (CNS) leukemia * Known allergy to manufacturing components: human albumin or dimethylsulfoxide (DMSO) * History of HIV infection on anti-retroviral therapy * Positive for hepatitis B or hepatitis C * Active uncontrolled bacterial, fungal, or viral infections - all prior infections must have resolved or be improving following optimal therapy * Active autoimmune disease requiring immunosuppressive therapy * Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, or supraventricular tachyarrhythmia requiring chronic therapy) * Females who are pregnant or breastfeeding * Unstable angina, arrhythmias, evidence of acute ischemia or conduction system abnormalities by electrocardiogram (ECG) or myocardial infarction in prior to 2 months * Use of other investigational agents within 2 weeks