Patients with relapsed or refractory leukemia or lymphoma are often refractory to further chemotherapy. In this study, the investigators will attempt to use T cells obtained directly from the patient, which can be genetically engineered to express a fully human chimeric antigen receptor (CAR). The CAR used in this study can recognize CD19, a protein expressed on the surface of leukemia and lymphoma cells. The fully human CAR used in this study may help protect against rejection of the CAR T cells, which in turn could lead to lasting protection against return of the leukemia or lymphoma. The phase 1 part of this study will determine the safety of these CAR T cells, and the phase 2 part of the study will determine how effective this CAR T cell therapy is. Both patients who have never had prior CAR T cell therapy and those who have had prior CAR T cell therapy may be eligible to participate in this study.

Inclusion Criteria:

• Male and female subjects age ≥ 1 and ≤ 30 years

• First 2 enrolled subjects: age ≥ 18 and ≤ 30 years

• Disease requirements:

  • Phase 1: Evidence of refractory or recurrent CD19+ leukemia or lymphoma following previous CAR T cell immunotherapy
  • Phase 2: Evidence of refractory or recurrent CD19+ leukemia or lymphoma

• Able to tolerate apheresis, or has sufficient existing apheresis product or T cells for manufacturing investigational product

• Life expectancy ≥ 8 weeks

• Lansky or Karnofsky, as applicable, score ≥ 50

• Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy, if the subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of CAR T cells

• ≥ 7 days post last chemotherapy and biologic therapy, with the exception of intrathecal chemotherapy and maintenance chemotherapy

• No prior virotherapy

• ≥ 7 days post last corticosteroid therapy

• ≥ 3 days post Tyrosine Kinase Inhibitor (TKI) use

• ≥ 1 day post hydroxyurea

• 30 days post most recent CAR T cell infusion

• Adequate organ function

• Adequate laboratory values, including absolute lymphocyte count ≥ 100 cells/uL

• Subjects of childbearing or child-fathering potential must agree to use highly effective contraception from consent through 12 months following infusion of investigational product on trial

• Subject and/or legally authorized representative has signed the informed consent form for this study

Exclusion Criteria:

• Presence of active malignancy other than disease under study
• History of symptomatic CNS pathology or ongoing symptomatic CNS pathology
• CNS involvement of leukemia or lymphoma that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and CAR T cell infusion
• Presence of active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
• Presence of active severe infection
• Presence of primary immunodeficiency syndrome
• Subject has received prior virotherapy
• Pregnant or breastfeeding
• Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow up period, required if CAR T cell therapy is administered
• Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol