Phase I Study of Cellular Immunotherapy Using Central Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma
I. To assess the safety and describe the full toxicity profile of cellular immunotherapy
initializing ex vivo expanded autologous Tcm-enriched T cells that are genetically modified
using a self-activating (SIN) lentiviral vector to express a costimulatory cluster of
differentiation (CD)19-specific chimeric antigen receptors (CAR) as well as a truncated
human epidermal growth factor receptor (EGFR) (CD19R:CD28 zeta/EGFR tau +Tcm)
(CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells) in
conjunction with a standard myeloablative autologous hematopoietic stem cell transplant
(HSCT) for patients with high-risk intermediate grade B-lineage non-Hodgkin lymphoma.
II. To determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs).
I. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell
product as it relates to the number of cells infused.
II. To study the impact of this therapeutic intervention on the development of normal CD19+
B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of
transferred autologous CD19R:CD28 zeta/EGFR tau +Tcm.
OUTLINE: This is a dose-escalation study of CD19-CAR-specific/truncated EGFR lentiviral
vector-transduced autologous T cells.
Patients undergo mobilization for autologous stem cell collection with cytoreductive
chemotherapy and filgrastim and/or plerixafor per current standard operating policies. If
rituximab is not given as part of the salvage/priming chemotherapy regimen, patients receive
rituximab intravenously (IV) per standard practice within 4 weeks of the transplant.
Patients undergo myeloablative conditioning regimen per institutional standards beginning
day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive
CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2
or 3 (may be delayed up to day 45 if the patient is not yet eligible).
After completion of study treatment, patients are followed up weekly for 1 month, monthly
for 1 year, and then yearly for 15 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.
Up to 15 years
City of Hope Medical Center
United States: Federal Government
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