CAR T Cell Receptor Immunotherapy for Patients With B-cell Lymphoma

• INCLUSION CRITERIA:
• Patient must have a cluster of differentiation 19 (CD19)-expressing B-cell lymphoma. Patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma must have measurable disease after at least two prior chemotherapy regimens one of which must have contained doxorubicin and rituximab.
• Confirmation of diagnosis of B-cell malignancy and positivity for CD19 confirmed by the Laboratory of Pathology of the National Cancer Institute (NCI). The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient. Immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood, fine needle aspirates and bone marrow samples.
• Patients must have indications for treatment for their B-cell malignancy at the time of enrollment on this trial.
• Greater than or equal to 18 years of age and less than or equal to age 70.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Life expectancy of greater than three months.
• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
• Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
• Serology:
• Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.).
• Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive. Then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
• Hematology:
• Absolute neutrophil count greater than or equal to 1000/mm^3 without the support of filgrastim.
• Platelet count greater than or equal to 50,000/mm^3.
• Hemoglobin greater than 8.0 g/dl.
• Lymphocyte count less than or equal to 4,000/ mm^3
• Chemistry:
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 5 times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl
• Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl
• More than three weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patient toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
• Normal cardiac ejection fraction and no evidence of pericardial effusion as determined by an echocardiogram.

EXCLUSION CRITERIA

• Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
• Patients that have active hemolytic anemia.
• Patients with active brain metastases, or with a history of any central nervous system (CNS) metastases or cerebrospinal fluid malignant cells.

Note: patients who are asymptomatic but are found to have malignant cells in the cerebrospinal fluid (CSF) on lumbar puncture prior to treatment will be considered eligible.

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, r