Primary Objective: To determine the safety of the treatment of relapsed or refractory B cell
lymphomas with chimeric antigen receptor T cells targeting cluster of differentiation antigen
19 (CD19) and to find the recommended phase II dose for this cellular therapy
Secondary Objectives
- To describe the safety profile of the infusion of CAR-T cells targeting CD19.
- To describe the toxicities related to infusion of CAR-T cells targeting CD19.
- To describe the overall response rate and complete response rate of relapsed B cell
malignancies treated with CAR-T cells targeting CD19.
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 transaminase (AST or SGOT) ≤ 3 X institutional upper limit of normal
- Alanine transaminase (ALT or SGPT) ≤ 3 X institutional upper limit of normal
- Serum Creatinine ≤ 2 X the institutional upper limit of normal
- Subjects must have the following hematologic function parameters:
- 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.
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 or 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 evaluation and
contrast-enhanced 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).
- 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.
