This phase II trial will examine whether genetically reprogramming a patient's disease fighting white blood cells may build an immune response to kill cancer cells that express the NY-ESO-1 protein. In this study, this genetic therapy will be given during a stem cell transplant along with a vaccine therapy. The vaccine will be made using the NY-ESO-1 protein and may help to stimulate the engineered immune response to tumor cells.
PRIMARY OBJECTIVES: I. To evaluate whether we can safely administer NY-ESO-1 T cell receptor transduced autologous peripheral blood mononuclear cells (PBMCs) (up to 1x10\^9 cells) along with an NY-ESO-1 dendritic cell vaccine and low dose IL-2 to patients with advanced malignancies. II. To evaluate the feasibility of delivering two patient-specific cell therapies, the NY-ESO-1 TCR transgenic peripheral blood mononuclear cell (PBMC) and NY-ESO-1 (157-165) peptide pulsed dendritic cells (DC), within a technically challenging study design that requires other significant interventions, like a lymphodepleting conditioning regimen and post-infusion of subcutaneous low dose interleukin (IL)-2 (aldesleukin). III. To determine the rate of objective tumor responses, by Response Evaluation Criteria in Solid Tumors (RECIST) objective response criteria. SECONDARY OBJECTIVES: I. To determine the persistence of NY-ESO-1 TCR-engineered cells. This will be determined by temporally analyzing peripheral blood samples for the presence of T cells with the transduced NY-ESO-1 TCR by tetramer or dextramer analysis. II. To explore the homing and persistence of the adoptively transferred NY-ESO-1 TCR-engineered PBMC in secondary lymphoid organs and tumor deposits via positron emission tomography (PET)-based imaging using the PET tracer fluorodeoxyglucose (\[18F\]FDG). OUTLINE: CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 30 minutes on days -4 to -1. TRANSPLANT: Patients receive NY-ESO-1 TCR transduced autologous PBMC IV on day 0. Patients also receive NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy intradermally (ID) on days 1, 14, and 30 and aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Patients may receive 3 additional doses of NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy after day 90. After completion of study treatment, patients are followed up at 30, 45, 60, and 75 days; every 3 months for 2 years; every 6 months for 3 years; and annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
University of California at Los Angeles (UCLA )
Los Angeles, California, United States
Clinical response
Will be determined by RECIST 1.1 Criteria on Day +90
Time frame: Day +90
NY-ESO-1 TCR transgenic cell persistence, quantitated in PBMC samples
Time frame: Up to 6 years
NY-ESO-1 TCR transgenic cell tumor trafficking
Regional uptake of fludeoxyglucose F18 within metastatic tumor sites and secondary lymphoid organs will be quantified by standardized uptake values (SUV) normalized to the body weight of the patient. The numbers of T lymphocytes will be quantified.
Time frame: Up to 40 days
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Correlative studies
Undergo NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL
Given NY-ESO-1-157-165 peptide pulsed dendritic cell vaccine ID
Undergo PET scan using \[18F\] FDG tracer
Undergo fludeoxyglucose F18 PET