Gene-Modified T Cells, Vaccine Therapy, and Ipilimumab in Treating Patients With Locally Advanced or Metastatic Malignancies

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With CTLA4 Blockade

Status Terminated

Clinical Trial Summary

This pilot phase I trial studies the side effects of taking ipilimumab after gene-modified T cells and vaccine therapy when treating patients with advanced cancer that has spread to other areas of the body and has not responded to standard therapies. This trial also will determine the best dose of Ipilimumab to use in this combination treatment. T cells are a special type of white blood cell (immune cell) that have the ability to kill cancer cells. T cells are taken from the blood and modified in the laboratory to recognize a specific protein expressed on cancer cells, called NY-ESO-1. This may allow the T cells to target and kill cancer cells that express that protein. Dendritic cells are another type of blood cell that can teach other cells in the body to look for cancer cells and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help dendritic cells teach the immune system to target cancer cells expressing that protein, and further help the T cells attack cancer. Ipilimumab is a monoclonal antibody, a type of drug manufactured in the laboratory that is similar to antibodies made in the human body that fight off infection. Ipilimumab blocks a protein that turns down the immune system, so blocking this protein may make the immune system more active. This may increase the ability of immune cells to kill cancer cells and improve the effectiveness of the T cell transplant. Giving gene-modified T-cells, a dendritic cell vaccine, and ipilimumab together may teach the immune system to recognize and kill cancer cells that have the NY-ESO-1 protein.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. The safety of NY-ESO-1 T-cell receptor (TCR) transgenic adoptive cell transfer (ACT) has been reported. The current protocol includes the addition of the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blocking monoclonal antibody ipilimumab to NY ESO TCR ACT in a dose escalation scheme in two study cohorts at 1 and 3 mg/kg of ipilimumab intravenous (i.v.) every three weeks with a maximum of 4 doses (q3wx4).

SECONDARY OBJECTIVES:

I. To determine the feasibility of delivering the TCR transgenic cell dose and CTLA blockade to patients.

II. To determine the persistence of NY-ESO-1 TCR-engineered peripheral blood mononuclear cells (PBMC) in serial peripheral blood samples and in biopsies of accessible metastatic lesions.

III. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer [18F] fluorodeoxy-glucose ([18F]FDG) with the goal of determining if the adoptively transferred NY-ESO-1 TCR-engineered PBMC when administered with ipilimumab home and expand in secondary lymphoid organs and tumor deposits.

IV. Clinical antitumor activity recording objective response rate will be an exploratory endpoint in this pilot clinical trial.

OUTLINE: This is a dose-escalation study of ipilimumab.

CONDITIONING CHEMOTHERAPY REGIMEN: Patients receive cyclophosphamide IV on days -5 and -4 and fludarabine phosphate IV over 30 minutes daily on days -4 to -1.

NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 reactive TCR retroviral vector transduced autologous T cells IV on day 0.

IPILIMUMAB ADMINISTRATION: Patients receive ipilimumab IV over 90 minutes before the NY-ESO-1 TCR PBMC infusion on day 0 or after the infusion on day 1. Treatment repeats every 3 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity.

NY-ESO-1(157-165) PEPTIDE PULSED DENDRITIC CELL (DC) ADMINISTRATION: Patients receive NY-ESO-1(157-165) peptide pulsed DC vaccine intradermally (ID) on days 1, 14, and 30.

LOW DOSE INTERLEUKIN-2 (IL-2) ADMINISTRATION: Patients receive aldesleukin (IL-2) subcutaneously (SC) twice daily (BID) on days 1-14.

After completion of study treatment, patients are followed up periodically for 90 days, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. ;

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT02070406
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: July 17, 2014
• Completion date: December 18, 2018