SJCAR19 and Combination Chemotherapy in Treating Younger Patients with CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

Inclusion Criteria

• AUTOLOGOUS APHERESIS: Age =< 21 years old
• AUTOLOGOUS APHERESIS: CD19+ ALL with any of the following: * Minimal residual disease (MRD) >= 1% at end of up-front induction therapy * Hypodiploid (< 44 chromosomes or < 0.95 deoxyribonucleic acid [DNA] index) CD19+ ALL with detectable disease at the end of up-front induction therapy * Increase in disease burden any time after the completion of up-front induction therapy * Primary refractory disease despite 2 cycles of an intensive chemotherapy regimen designed to induce remission * Refractory disease despite salvage therapy * 1st or greater relapse * Note: if patient meets CD19+ ALL disease criteria, subsequent receipt of cancer directed therapy that eradicates disease does not preclude them from proceeding with this study
• AUTOLOGOUS APHERESIS: Estimated life expectancy of > 12 weeks
• AUTOLOGOUS APHERESIS: Karnofsky or Lansky (age-dependent) performance score >= 50
• AUTOLOGOUS APHERESIS: Patients with a history of prior allogeneic hematopoietic cell transplantation (HCT) must be clinically recovered from prior HCT therapy, have no evidence of active graft versus host disease (GVHD) and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
• AUTOLOGOUS APHERESIS: For females of child bearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
• MANUFACTURING SJCAR19: CD19+ ALL with any of the following: * Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission * Refractory disease despite salvage therapy * 2nd or greater relapse * Any relapse after allogeneic hematopoietic cell transplantation * 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT * Note: if patient meets CD19+ ALL disease criteria, subsequent receipt of cancer directed therapy that eradicates disease does not preclude them from proceeding with this study
• MANUFACTURING SJCAR19: Age: =< 21 years of age
• MANUFACTURING SJCAR19: Karnofsky or Lansky (age-dependent) performance score >= 50
• MANUFACTURING SJCAR19: Estimated life expectancy of > 12 weeks
• MANUFACTURING SJCAR19: Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis
• TREATMENT WITH SJCAR19: CD19+ ALL with any of the following: * Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission * Refractory disease despite salvage therapy * 2nd or greater relapse * Any relapse after allogeneic hematopoietic cell transplantation * 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT for any of the following reasons: ** Patients that do not have an available allogeneic donor (defined as at least a 7/8 human leukocyte antigen (HLA)-matched related/unrelated donor, 5/6 HLA-matched umbilical cord donor, or 3/6 HLA-matched haploidentical donor) ** Patients with refractory leukemia, for which allogeneic transplant is known to be less effective in the B-ALL population, and ** Patients who are unable to receive myeloablative total body irradiation (TBI), which is included in standard transplant regimens for patients with B-ALL. **ALL must be confirmed to be CD19+ within 3 months prior to enrollment for treatment
• TREATMENT WITH SJCAR19: Age: =< 21 years of age
• TREATMENT WITH SJCAR19: Detectable disease
• TREATMENT WITH SJCAR19: Estimated life expectancy of > 8 weeks
• TREATMENT WITH SJCAR19: Prior to planned SJCAR19 infusion, patients with a history of prior allogeneic HCT must be at least 3 months from HCT, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned infusion
• TREATMENT WITH SJCAR19: Left ventricular ejection fraction > 40%, or shortening fraction >= 25%
• TREATMENT WITH SJCAR19: Electrocardiogram (EKG) without evidence of clinically significant arrhythmia
• TREATMENT WITH SJCAR19: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 50 ml/min/1.73 m^2 (GFR >= 40 ml/min/1.73 m^2 if < 2 years of age)
• TREATMENT WITH SJCAR19: Forced vital capacity (FVC) >= 50% of predicted value; or pulse oximetry >= 92% on room air if patient is unable to perform pulmonary function testing
• TREATMENT WITH SJCAR19: Karnofsky or Lansky (age-dependent) performance score >= 50
• TREATMENT WITH SJCAR19: Total bilirubin =< 3 times the upper limit of normal for age, except in subjects with Gilbert’s syndrome
• TREATMENT WITH SJCAR19: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 5 times the upper limit of normal for age
• TREATMENT WITH SJCAR19: Has recovered from all National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade III-IV, non-hematologic acute toxicities from prior therapy
• TREATMENT WITH SJCAR19: For females of child bearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment * If sexually active, agreement to use birth control until 6 months after T-cell infusion; male partners should use a condom

Exclusion Criteria

• AUTOLOGOUS APHERESIS: Known primary immunodeficiency
• AUTOLOGOUS APHERESIS: History of human immunodeficiency virus (HIV) infection
• AUTOLOGOUS APHERESIS: Severe intercurrent bacterial, viral or fungal infection
• AUTOLOGOUS APHERESIS: History of hypersensitivity reactions to murine protein-containing products
• TREATMENT WITH SJCAR19: Central nervous system (CNS)-3 disease with or without neurologic changes
• TREATMENT WITH SJCAR19: CNS-1/CNS-2 disease with neurologic changes
• TREATMENT WITH SJCAR19: Known primary immunodeficiency
• TREATMENT WITH SJCAR19: History of HIV infection
• TREATMENT WITH SJCAR19: Evidence of active, uncontrolled neurologic disease
• TREATMENT WITH SJCAR19: Severe, uncontrolled bacterial, viral or fungal infection
• TREATMENT WITH SJCAR19: History of hypersensitivity reactions to murine protein-containing products
• TREATMENT WITH SJCAR19: Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to CAR T-cell infusion
• TREATMENT WITH SJCAR19: Receiving systemic immunosuppressive therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the SJCAR19 product in vivo (in the opinion of the study PI[s])
• TREATMENT WITH SJCAR19: Receiving intrathecal chemotherapy in the 7 days prior to CAR T-cell infusion