AntiCD19 Chimeric Antigen Receptor T-Cells and Chemotherapy in Treating Patients with Recurrent or Refractory CD19 Positive Non-Hodgkin Lymphoma

Inclusion Criteria

• Subjects must have relapsed or refractory non-Hodgkin lymphoma treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
• The patient’s lymphoma must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
• Total bilirubin =< 1.5 times the institutional upper limit of normal.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 x institutional upper limit of normal.
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal.
• Serum creatinine =< 2 x the institutional upper limit of normal.
• Absolute neutrophil count (ANC) > 1,000/uL.
• Absolute lymphocyte count > 100/uL.
• Platelets > 50,000/uL.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.
• Eligibility for Infusion of Investigational Product: * Subjects will undergo a second evaluation of eligibility on day -2 or -1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions. ** Inclusion criteria exceptions: *** Hematologic function parameters will not be included as a pre-infusion eligibility criterion (because lymphodepletive chemotherapy is expected to cause pancytopenia). *** Laboratory result abnormalities that are considered not clinically significant by the principal investigator, AND are not the result of a demonstrated active infection or an active central nervous system condition

Exclusion Criteria

• Autologous transplant within 6 weeks of planned CAR-T cell infusion.
• History of allogeneic stem cell transplant.
• Recipient of CAR-T cell therapy outside of this protocol.
• Active central nervous system or meningeal involvement by lymphoma. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration.
• Active malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
• Human immunodeficiency virus (HIV) seropositivity.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
• Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
• Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson’s disease.
• History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
• Eligibility for Infusion of Investigational Product: * Subjects will undergo a second evaluation of eligibility on day -2 or -1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions. * Exclusion criteria additions: ** Use of corticosteroids within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy). ** Neurologic symptoms suggestive of an active central nervous system condition. ** Signs or laboratory markers of active infection or systemic inflammatory response.