Genetically Engineered Cells (huCART19) for the Treatment of Pediatric B Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Inclusion Criteria

• Signed informed consent form must be obtained prior to any study procedure. Labs, marrows or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required window
• Subjects with documented CD19+ acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (Lly): * Cohort A: Subjects with relapsed or refractory ALL or Lly ** 2nd or greater relapse (marrow or extramedullary) OR ** Any relapse after allogeneic hematopoietic stem cell transplant (HSCT) and ≥ 4 months from HSCT at enrollment OR ** Refractory disease defined as having not achieved an MRD-negative and cerebrospinal fluid (CSF)-negative complete remission (CR) after ≥ 2 chemotherapy regimens/cycles of frontline therapy, or 1 cycle of reinduction therapy for subjects in first relapse OR ** Ineligible for allogeneic HSCT because of at least one of the following: *** Comorbid disease *** Other contraindications to HSCT conditioning regimen *** Lack of suitable donor *** Prior HSCT *** Declines HSCT as the therapeutic option after documented discussion, with expected outcomes, and the role of HSCT with a bone marrow transplant (BMT) physician not a part of the study team * Cohort B: Subjects with poor response to prior B cell directed engineered cell therapy, defined as any one of the following: ** Partial response or no response to prior cell therapy ** CD19+ relapse after prior cell therapy ** Demonstrated early (≤ 6 months from infusion) B cell recovery suggesting loss of engineered cells
• Subjects with prior or current history of central nervous system (CNS)3 disease will be eligible if CNS disease is responsive to therapy
• Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue. If the subject has received CD19-directed therapy, documentation should be obtained after this therapy to demonstrate CD19 expression
• Age 0-29 years
• Serum creatinine based on age/gender as follows: * Age: Sex (Maximum Serum Creatinine [mg/dL]) ** 0 to < 2 years: Male (0.6); Female (0.6) ** 2 to < 6 years: Male (0.8); Female (0.8) ** 6 to < 10 years: Male (1.0); Female (1.0) ** 10 to < 13 years: Male (1.2); Female (1.2) ** 13 to < 16 years: Male (1.5); Female (1.4) ** >= 16 years: Male (1.7); Female (1.4)
• Alanine aminotransferase (ALT) within 5x upper limit of normal (ULN) in the absence of ALL infiltration of the liver * ALT results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver
• Bilirubin ≤ 3x the upper limit of normal * Bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the investigator
• Left ventricular shortening fraction (LVSF) ≥ 28% or ejection fraction (LVEF) ≥ 45% confirmed by echocardiogram or another scan. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice
• Adequate performance status defined as Lansky or Karnofsky performance score ≥ 50
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Active hepatitis B or active hepatitis C
• Human immunodeficiency virus (HIV) infection
• Active acute or chronic graft versus host disease (GVHD) requiring systemic therapy
• Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well
• CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
• Pregnant or nursing (lactating) women
• Uncontrolled active infection