A Pilot / Feasibility Study of Autologous CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine in Patients With Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma
This phase I trial studies the safety and feasibility of cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T cells in combination with the CMV-modified vaccinia Ankara (MVA) triplex vaccine following lymphodepletion in treating patients with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refectory). CAR T cells are a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added in the laboratory. The special receptor is called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Vaccines such as CMV-MVA triplex are made from gene-modified viruses and may help the body build an effective immune response to kill cancer cells. Giving CMV-specific CD19-CAR T-cells plus the CMV-MVA triplex vaccine may help prevent the cancer from coming back.
• Documented informed consent of the participant and/or legally authorized representative
⁃ Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
⁃ If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed
• Age: \>= 18 years
• Karnofsky Performance Status (KPS) \>= 70
• Life expectancy \>= 16 weeks at the time of enrollment
• Patients requiring treatment for relapsed or refractory intermediate or high-grade B cell NHL (e.g., diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\], or transformed NHL) who are not eligible for, or who refuse, or have previously received autologous hematopoietic cell transplantation (autoHCT)
⁃ Note: COH pathology review should confirm that research participant's diagnostic material is consistent with history of intermediate or high-grade CD19+ malignancy
• No known contraindications to leukapheresis, lymphodepleting chemotherapy, steroids or tocilizumab, smallpox vaccine and any other MVA-based vaccines
• Patient must be CMV seropositive
• Total serum bilirubin =\< 2.0 mg/dL
• Participants with Gilbert syndrome may be included if their total bilirubin is =\< 3.0
• Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) \< 2.5 x ULN
• Serum creatinine =\< 2.5 x ULN or estimated creatinine clearance of \>= 40 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis
• Absolute neutrophil count \>= 1000/uL (Transfusions and growth factors must not be used to meet these requirements at initial screening)
• Hemoglobin (Hb) \>= 8 g/dl (Transfusions and growth factors must not be used to meet these requirements at initial screening)
• Platelet count \>= 50,000/uL (\>= 30,000/uL if bone marrow plasma cells are \>= 50% of cellularity) (Transfusions and growth factors must not be used to meet these requirements at initial screening)
• Left ventricular ejection fraction \>= 45% within 8 weeks before enrollment
• Oxygen (O2) saturation \> 92% without requiring supplemental oxygen
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
⁃ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
⁃ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)