Gene-Modified Lymphocytes, High-Dose Aldesleukin, and Vaccine Therapy in Treating Patients With Progressive or Recurrent Metastatic Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: Phase II Study of Metastatic Cancer That Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes and Dendritic Cell Vaccination

Status Terminated

Clinical Trial Summary

RATIONALE: Gene-modified lymphocytes may stimulate the immune system in different ways and stop tumor cells from growing. High-dose aldesleukin may stimulate lymphocytes to kill tumor cells. Vaccines made from a gene modified virus and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. Giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy works in treating patients with progressive or recurrent metastatic cancer.

Clinical Trial Description

OBJECTIVES:

Primary

• Determine if the administration of anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes, high-dose aldesleukin, and adenovirus p53 dendritic cell (DC) vaccine after a nonmyeloablative, but lymphoid-depleting, preparative regimen will result in clinical tumor regression in patients with metastatic cancer that overexpresses p53.

Secondary

• Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

• Determine the ability of a dendritic cell (DC) vaccine to restimulate TCR gene-engineered cells in vivo.

• Determine the toxicity profile of this treatment regimen.

OUTLINE: Patients are stratified according to type of metastatic cancer (melanoma or renal cell cancer vs all other cancers).

• Peripheral blood mononuclear cell (PBMC) collection: Patients undergo PBMC collection via leukapheresis for the generation of the adenovirus p53 dendritic cell vaccine as well as anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes.

• Nonmyeloablative lymphocyte-depleting preparative regimen: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.

• Peripheral blood lymphocyte infusion: Patients receive anti-p53 TCR gene-engineered peripheral blood lymphocytes IV over 20-30 minutes on day 0. Patients receive filgrastim (growth colony stimulating factor (G-CSF)) subcutaneously (SC) once daily beginning on day 1 or 2 and continuing until blood counts recover.

• High-dose aldesleukin: Patients receive high-dose aldesleukin IV over 15 minutes three times daily on days 0-4 for up to 15 doses.

• Dendritic cell vaccine: Patients receive adenovirus p53 dendritic cell vaccine SC on days 0, 7, 14, and 28.

Patients may receive one re-treatment course as above (nonmyeloablative preparative regimen, peripheral blood lymphocyte infusion, high-dose aldesleukin, and dendritic cell vaccinations) beginning 6-8 weeks after the last dose of high-dose aldesleukin.

After completion of study treatment, patients are followed periodically for up to 15 years. ;

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Cancer
• Melanoma (Skin)
• Neoplasm Metastasis
• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT00704938
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: June 2008
• Completion date: August 2009