High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma

• maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  will be assessed utilizing a standard 3+3 cell dose escalation to determine the maximum tolerated dose of CD19+ CAR T cells
• safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

• 2 year progression-free (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• overall survival (os) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The purpose of this study is to test the safety of delivering the patients' own immune cells, called T cells, after the high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT).

• Drug: Carmustine
• Drug: Etoposide
• Drug: Cytarabine
• Drug: Melphalan
• Biological: Pegfilgrastim
• Biological: 19-28z T CELLS
• Procedure: Autologous Stem Cell Transplantation

Transplant eligible patients will be eligible if criteria met per below.

Inclusion Criteria:

• Patients > or = to 18 years of age with aggressive B-cell non-Hodgkin lymphoma subtypes including, but not limited to, relapsed or refractory diffused large B-cell lymphoma (DLBCL), Burkitt's lymphoma or transformed indolent B-cell non-Hodgkin lymphoma (including chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) meeting at least one of the following criteria:

  • Bone marrow involvement at the time of relapse or refractory disease and not appropriate for allogeneic transplantation.
  • PET positive disease outside of one radiation port unless single-port disease treated with prior radiotherapy within the port, following > or = to 2 cycles of salvage chemotherapy, 1999 IWG criteria (section 12.2 and 12.383).
• Creatinine < or = 1.5 mg/100 ml (or measured 24 hour creatinine clearance of > or = to 50 cc/min)
• Bilirubin <2.0 mg/100 ml, AST and ALT <3x the upper-limit of normal, PT and PTT < 2x normal outside the setting of stable chronic anticoagulation therapy,
• Granulocytes >1,000/mm3, platelets >50,000/mm3, hemoglobin >8.0g/dl.
• Adequate cardiac function (LVEF>40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment.
• Adequate pulmonary function as assessed by DLCO of > or = to 45% adjusted for hemoglobin.
• Life expectancy of > 3 months.

Exclusion Criteria:

• Karnofsky performance status < or = to 70 (see appendix VI).
• Patients previously treated with allogeneic bone marrow or stem cell transplantation are ineligible.
• Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study.
• Uncontrolled bacterial, viral or fungal infection.
• Patients with HIV, active hepatitis B or hepatitis C infection.