A Phase I Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19 Antigen in B-cell Malignancies

Following completion of the chemotherapy, genetically modified T cells will be given intravenously at one of 3 dose levels. After the infusion patients will be monitored clinically and with serial blood and marrow evaluations to assess toxicity, therapeutic effects, and the in-vivo survival of the genetically modified T-cells. A fixed CAR EBV-CTL dose (3x106 EBV-CTLs/kg) which has been demonstrated to be the ideal manufacturing dose allowing for multiple infusions and potential for multiple patient treatments per cell line generated will be used for all patients on this trial. Cohorts will be determined separately but cohort 3 will not begin to accrue until cohort 2 has treated three (3) patients without a DLT. Each patient is eligible for up to three (3) infusions.

Cyclophosphamide-based chemotherapy regimen will be the preferred conditioning chemotherapy prior to CAR T cell infusion for patients with CD19+ malignancy in cohort 1. Recommended chemotherapy regimen consists of single agent Cyclophosphamide at a dose of 3000 mg/m2/dose IV over 1 hour or 1500mg/m2/dose x 2 doses given daily over 1 hour given for 2 days (patients may received reduced dose of cyclophosphamide based on the clinical status of the patient at discretion of the treating physician and with written approval by the MSKCC PI of this study). Alternative cyclophosphamide or non-cyclophosphamide-based regimens based on the clinical status of the patient, disease burden, and likely-hood of response may be used at the discretion of the treating physician with written approval by MSKCC PI of the study. Conditioning chemotherapy will not be given prior to infusions # 2 and #3.