NCT01697527

Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies

Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) After a Nonmyeloablative Conditioning Regimen, With Administration of NY-ESO-1157-165 Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Malignancies

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Malignant Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	aldesleukin	Given SC
DRUG	fludarabine phosphate	Given IV
DRUG	cyclophosphamide	Given IV
OTHER	laboratory biomarker analysis	Correlative studies
BIOLOGICAL	NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL	Undergo NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL
BIOLOGICAL	dendritic cell vaccine therapy	Given NY-ESO-1-157-165 peptide pulsed dendritic cell vaccine ID
RADIATION	fludeoxyglucose F 18	Undergo PET scan using \[18F\] FDG tracer
PROCEDURE	positron emission tomography	Undergo fludeoxyglucose F18 PET

Timeline

• Start date: 2012-11-02
• Primary completion: 2026-11-02
• Completion: 2027-11-02
• First posted: 2012-10-02
• Last updated: 2025-11-24

Locations

1 site across 1 country: United States