Clinical trial NCT00704938
Conditions: Kidney Cancer Melanoma (Skin) Unspecified Adult Solid Tumor, Protocol Specific
Keywords: recurrent renal cell cancer stage IV renal cell cancer recurrent melanoma stage IV melanoma unspecified adult solid tumor, protocol specific
Sponsor: National Institutes of Health Clinical Center (CC)
Start date: 2008-06-01; Completion date: 2009-08-01
Enrollment: 3 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2) arm 2: Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
Interventions: intervention 1: aldesleukin intervention 2: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes intervention 3: autologous dendritic cell-adenovirus p53 vaccine intervention 4: filgrastim intervention 5: cyclophosphamide intervention 6: fludarabine phosphate
Intervention descriptions: intervention 1: Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses. intervention 2: 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. intervention 3: 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. intervention 4: subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day). intervention 5: 60mg/kg/day (Days-7,-6) intervention 6: 25mg/m\^2 (Days -5, -4, -3, -2, and -1)

Protocol documents: