Genetically Engineered PBMC and PBSC Expressing NY-ESO-1 TCR After a Myeloablative Conditioning Regimen to Treat Patients With Advanced Cancer — NYESO SCT  

Sarcoma Clinical Trial

Official title: Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a Myeloablative Conditioning Regimen, With Administration of Interleukin-2, in Patients With Advanced Malignancies

Status Terminated

Clinical Trial Summary

This phase I clinical trial evaluates the safety and feasibility of administering NY-ESO-1 TCR (T cell receptor)engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after a myeloablative conditioning regimen to treat patients with cancer that has spread to other parts of the body. The conditioning chemotherapy makes room in the patient?s bone marrow for new blood cells (PBMC) and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR PBMC and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety of administering the combination of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) following a reduced intensity conditioning regimen, both of which have been genetically modified to express NY-ESO-1 TCR.

SECONDARY OBJECTIVES:

I. To determine the feasibility of delivering the combination of TCR transduced autologous PBMC and CD34+ PBSC to patients.

II. To determine the persistence of NY-ESO-1 TCR transduced PBMC and the progeny of TCR transduced PBSC in serial peripheral blood samples.

III. Objective response rate (ORR).

EXPLORATORY OBJECTIVE:

I. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer 9-4-[18F]fluoro-3-(hydroxymethyl)butylguanine ([18F]FHBG) with the goal of determining whether the adoptively transferred NY-ESO-1 TCR transduced PBSC home to bone marrow, differentiate into T cells and expand in secondary lymphoid organs and tumor deposits.

OUTLINE:

G-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, patients undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Patients receive G-CSF subcutaneously (SC) on mobilization days 1-8 and plerixafor SC on mobilization days 4-7, during mobilization, patients will undergo mobilized leukapheresis to obtain PBSC. Patients also undergo an unmobilized leukapheresis on day -5 before infusion of cells in order to obtain PBMC.

CHEMOTHERAPY CONDITIONING REGIMEN: Patients receive busulfan intravenously (IV) on days -4 to -2 and fludarabine IV over 30 minutes on days -3 to -2.

Patients receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and after approximately 24 hours, patients receive RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, patients receive aldesleukin (interleukin-2 (IL) or IL-2) SC twice daily (BID) for up to 7 days. Patients undergo blood collection for safety and immune monitoring on days 0, 1, 3, 5, 7, 14, 30, 60, 90, and 120. Patients receive the PET tracer 18F-FHBG IV, and after 1 hour, undergo PET/computed tomography (CT) on days 25 and 120.

After completion of study treatment, patients are followed up every 2-3 months for 2 years, every 6 months for 5 years, and annually for 15 years. ;

Related Conditions & MeSH terms

• HLA-A*0201 Positive Cells Present
• Locally Advanced Malignant Neoplasm
• Neoplasms
• NY-ESO-1 Positive
• Sarcoma
• Unresectable Malignant Neoplasm

• NCT number: NCT03240861
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: July 26, 2017
• Completion date: October 19, 2023