CART-19 Cells in Treating Patients With Chemotherapy Relapsed or Refractory B Cell Non-Hodgkin Lymphoma

Inclusion Criteria

• Subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic stem cell transplant [SCT]) who have a limited prognosis (several months to < 2 year survival) with currently available therapies
• Follicular lymphoma, previously identified as CD19+ * At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) * Patients who progress within 2 years after second or higher line of therapy will be eligible; for instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible; patients may have progression, stable disease or responding disease at the time of enrollment * Patients with a history of large cell transformation are eligible
• Mantle cell lymphoma * Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT * Relapsed after prior autologous SCT
• Diffuse large B cell lymphoma, previously identified as CD19+ * Residual disease after primary therapy and not eligible for autologous SCT * Relapsed or persistent disease after prior autologous SCT * Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT * Patients with an antecedent history of follicular lymphoma or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are eligible
• Expected survival > 12 weeks
• Creatinine < 1.6 mg/dL
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3 x upper limit of normal
• Bilirubin < 2.0 mg/dL, unless subject has Gilbert’s Syndrome (=< 3.0 mg/dL)
• Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
• Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and: * Have experienced graft rejection (no evidence of donor cells by short tandem repeat (STR) analysis on 2 occasions separated by at least 1 month) * Have no active graft-vs-host disease (GVHD) and require no immunosuppression * Are more than 6 months from transplant
• Measurable or assessable disease according to the “Revised Response Criteria for Malignant Lymphoma” (Cheson et al., J. Clin. Onc., 1999)105; patients in complete remission with no evidence of disease are not eligible
• Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 or 1
• Written informed consent is given
• Successful T cell test expansion (first 10 subjects)

Exclusion Criteria

• Pregnant or lactating women; female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Concurrent use of systemic steroids; recent or current use of inhaled steroids is not exclusionary
• Any uncontrolled active medical disorder that would preclude participation as outlined
• Human immunodeficiency virus (HIV) infection
• Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment
• Patients in complete remission with no assessable disease