Metabolically Fit CD19 CAR T Cells With CD34 Selection Markers in Adults With CD19-Positive B-Cell Acute Lymphocytic Leukemia

An individual must meet all of the following criteria to be eligible for enrollment: 1. Age 18 years or older. 2. Willing and able to give written, informed consent to the current study. 3. ECOG performance status of 0, 1 or 2. 4. Relapsed or refractory CD19-positive B-ALL defined as one of the following: 1. Primary refractory disease (not achieving CR after two cycles of induction chemotherapy). 2. Relapse after prior complete remission. 3. Relapsed or refractory disease after allogeneic transplant provided CAR-T infusion occurs at least 2 months after the stem cell transplant. NOTE: In patients treated with blinatumomab, CD19 expression on leukemic blasts must be confirmed after blinatumomab therapy has been stopped. 5. Cohort-specific inclusion criteria: a. Cohort Ia: Relapsed/Refractory B-ALL i. Presence of ≥5% blasts in BM at screening, or with isolated extramedullary disease (EMD) (including isolated CNS disease), with or without MRD in the BM ii. Patients with Philadelphia chromosome positive ALL (Ph+ ALL) are eligible if they are intolerant to or have failed two lines of any TKI or one line of second-generation TKI, or if TKI therapy is contraindicated. b. Cohort Ib: B-ALL in remission with measurable residual disease i. MRD-positive defined as ≥10-6 and \<5% blasts in the BM at screening. ii. Patients with Philadelphia chromosome positive ALL (Ph+ ALL) are eligible if they are intolerant to or have failed two lines of any TKI or one line of second-generation TKI, or if TKI therapy is contraindicated. c. Cohort Ic: B-ALL in remission, indicated but ineligible for or unwilling to undergo allogenic transplant i. B ALL in MRD negative remission, being considered (typically for high-risk B-ALL) for, but ineligible for allogeneic stem cell transplantation due to organ dysfunction, socioeconomic factors or other extraneous reasons as determined by the transplant physician. ii. B ALL in MRD negative remission, being considered (typically for high-risk B-ALL) for, but unwilling to undergo allogeneic stem cell transplantation for patient's personal reasons. 6. For females of childbearing potential (defined as \<24 months after last menstruation or not surgically sterile), a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment. 7. For females who are not postmenopausal (\<24 months of amenorrhea) or who are not surgically sterile (absence of ovaries and/or uterus), two methods of contraception comprising of one highly effective method of contraception together with a barrier method must be used during the treatment period and for at least 12 months after the last dose of study treatment. They must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 12 months after receiving the last dose of study drug (please refer to Appendix F). 8. For males, it must be agreed that two acceptable methods of contraception are used (one by the patient - usually a barrier method, and one highly effective method by the patient's partner as defined in Appendix F) during the treatment period and for at least 12 months after the last dose of study treatment and that sperm will not be donated during the treatment period and for at least 12 months after the last dose of study treatment. 9. Adequate renal, hematologic, hepatic, pulmonary, and cardiac function defined as: 1. Serum alanine aminotransferase/aspartate aminotransferase ≤3 x ULN. 2. Creatinine clearance (as estimated by Cockcroft-Gault) ≥50 cc/minute. 3. Absolute lymphocyte count (ALC) ≥150 cells/mm3. 4. Total bilirubin ≤1.5 x ULN, except in patients with Gilbert's syndrome who must have normal direct bilirubin. 5. Baseline oxygen saturation \>92% on room air. 6. Left ventricular ejection fraction (LVEF) ≥ 45%, no evidence of clinically significant pericardial effusion as determined by an ECHO. A second CAR-T cell infusion may be considered if the following criteria are met: 1. Patient to receive subsequent cell infusion did not experience unacceptable toxicity from the first infusion. Any toxicity (regardless of causality) after the previous CD19-CD34t metabolically programmed CAR-T cell infusion must resolve such that participants meet all the initial eligibility criteria. AND one or more of the following criteria are also met: 2. Loss of B-cell aplasia past 6 months from the date of original CAR-T infusion, defined as either or both: 1. CD19+ cells ≥3% of peripheral lymphocytes and absolute CD19 count ≥50/μL. 2. Patients with CD19+ cells ≥3% of peripheral lymphocytes, but absolute CD19 count \<50 are required to have at least two sets of lymphocyte subsets drawn to confirm stable to up trending absolute CD19 counts. 3. Relapse or refractory disease, defined as either or both: 1. Emergence or persistence of CD19 expressing MRD positive disease at any time past original CAR-T infusion past 4 weeks after original infusion. 2. Frank CD19 positive relapse or refractory disease past 4 weeks after original infusion. An individual will be excluded from the study if any of the following apply: 1. Diagnosis of chronic myelogenous leukemia in lymphoid blast crisis. 2. Presence of current CNS 3 disease. Prior CNS 3 disease is allowed if they are treated with residual CNS 1/2 disease. 3. Females who are pregnant or lactating. 4. Receipt of live vaccine within 6 weeks prior to enrollment. 5. Prior CAR-T or Gene Therapy: Previous treatment with any CD19-directed CAR-T cell therapy. (Rationale: prior CAR-T could affect CD19 antigen status and immune response; also, to isolate the effect of this investigational product. However, prior CD19 CAR-T is allowed if it was more than 6 months prior to enrollment and the patient has confirmed CD19+ relapse). 6. Uncontrolled Infection: Known active infection including: 1. Positive blood cultures for bacteria or fungi with signs of systemic infection that are not controlled. 2. Active tuberculosis. 3. Opportunistic infections (e.g., Pneumocystis pneumonia, CMV viremia) that are not resolved. 4. Fever of unknown origin is a caution; prior to lymphodepletion, a complete evaluation to rule out infection should be done and the treating physician must agree that it is okay to proceed. 7. Concurrent Malignancy: Another active malignancy requiring therapy or that is expected to limit survival to \<2 years, except certain low-risk cancers (e.g., treated localized prostate cancer on surveillance, adequately treated basal cell carcinoma of skin). 8. Autoimmune Disorder: Active autoimmune disease requiring systemic immunosuppressive therapy (e.g. lupus, multiple sclerosis, etc.) especially if the disease or its treatment could be worsened by CAR-T (because steroids or immunosuppressants to control autoimmunity could interfere with CAR-T function, and autoimmunity could flare with immune activation). 9. Allogeneic Transplant History: Prior allogeneic hematopoietic stem cell transplant with active graft-versus-host disease (GVHD) of any grade. 10. Significant Co-morbid Conditions: For example: 1. Unstable angina, myocardial infarction within 6 months, or uncontrolled cardiac arrhythmia. 2. No clinically significant signs or symptoms of cardiac dysfunction defined as symptoms consistent with NYHA CHF classification III or IV. 3. Acute neurological toxicity \> Grade 1 (with the exception of peripheral sensory neuropathy). 4. Stroke or seizure disorder not controlled on medication. 5. Interstitial lung disease requiring supplemental oxygen. 6. Any condition that the investigator deems would make the patient unsuitable (e.g., severe frailty or logistic inability to comply with frequent monitoring). 11. Concurrent Therapy: Use of systemic corticosteroids above a physiologic replacement dose (equivalent to \>10 mg prednisone daily) within 7 days prior to leukapheresis or planned need for such steroids. NOTE: Patients who require steroids for disease control must be tapered off before T cell collection, since steroids can impair T cell function for manufacturing and may preclude CAR T expansion after infusion. If emergent steroid use is needed for an indication like brain metastases, patient should be deferred. 1. Similarly, any other anti-cancer therapy (chemotherapy, targeted agents, investigational drugs) must be washed out before lymphodepletion (timeframe depends on drug, typically 2 weeks or 5 half-lives, whichever is longer). 2. Radiation must have stopped ≥ 2 weeks prior to collection. 3. New requirement for oxygen therapy. A second CAR-T cell infusion will not be considered if any of the following criteria are met: 1. All above exclusion criteria apply to a second infusion. 2. Grade 3 or higher CRS/ICANS with original infusion at dose level -1.