NCT00704938

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

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
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: National Institutes of Health Clinical Center (CC) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	aldesleukin	Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.
BIOLOGICAL	anti-p53 T-cell receptor-transduced peripheral blood lymphocytes	Intravenous (IV) anti-p53 TCR transduced PBL will be administered at a a dose of 1 x 10\^8 cells to 5 x 10\^10 cells.
BIOLOGICAL	autologous dendritic cell-adenovirus p53 vaccine	Ad-p53 DC vaccine, up to 2 x 10\^8 ad-p53 DCs per dose will be administered subcutaneously, divided into 4 injections, one into each of the 4 extremities. Ad-p53 DCs will be administered subcutaneously on day 7 (± 2 days), day 14 (between day 14 and day 18), and day 28 (between day 25 and day 42) post T cell infusion.
BIOLOGICAL	filgrastim	subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).
DRUG	cyclophosphamide	60mg/kg/day (Days-7,-6)
DRUG	fludarabine phosphate	25mg/m\^2 (Days -5, -4, -3, -2, and -1)

Timeline

• Start date: 2008-06-01
• Primary completion: 2009-08-01
• Completion: 2009-08-01
• First posted: 2008-06-25
• Last updated: 2015-10-28
• Results posted: 2012-08-14

Locations

1 site across 1 country: United States