Expired Study
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Bethesda, Maryland 20892


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.

Study summary:

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 TCR gene-engineered cells. - Determine the ability of a 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 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 (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.


DISEASE CHARACTERISTICS: - Diagnosis of metastatic cancer - Tumor overexpresses p53 as assessed by immunohistochemistry (i.e., ≥ 5% tumor cells stain positive for p53) - Biopsy must be available to evaluate p53 expression - HLA-A*0201 positive - Progressive or recurrent disease after prior standard therapy for metastatic disease - Patients with melanoma or renal cell cancer must have previously received aldesleukin - Patients with other histologies, not including hematologic malignancies, must have previously received first-line and second-line or higher systemic standard therapy (or effective salvage chemotherapy regimens) PATIENT CHARACTERISTICS: - ECOG performance status 0 or 1 - Life expectancy > 3 months - Absolute neutrophil count > 1,000/mm^3 - WBC > 3,000/mm^3 - Platelet count > 100,000/mm^3 - Hemoglobin > 8.0 g/dL - Serum ALT/AST ≤ 2.5 times upper limit of normal - Serum creatinine ≤ 1.6 mg/dL - Total bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL in patients with Gilbert's syndrome) - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 4 months after completion of study treatment - Patients who have previously received ipilimumab or ticilimumab must have a normal colonoscopy with normal colonic biopsies - HIV antibody negative - Hepatitis B antigen and hepatitis C antibody negative (unless antigen negative) - No primary immunodeficiency (e.g., severe combined immunodeficiency disease) - No active systemic infections - No history of severe immediate hypersensitivity reaction to any of the agents used in this study - No coagulation disorders - No myocardial infarction or cardiac arrhythmias - No history of coronary revascularization - No obstructive or restrictive pulmonary disease - No contraindications for high-dose aldesleukin administration - LVEF ≥ 45% in patients meeting any of the following criteria: - History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including, but not limited to, atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block - At least 60 years of age - FEV_1 > 60% predicted in patients meeting any of the following criteria: - Prolonged history of cigarette smoking (> 20 pack/year within the past 2 years) - Symptoms of respiratory dysfunction - No other major medical illness of the cardiovascular, respiratory, or immune system PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Recovered from prior therapy - More than 4 weeks since prior and no concurrent systemic steroid therapy - More than 4 weeks since other prior systemic therapy - More than 6 weeks since prior ipilimumab



Primary Contact:

Principal Investigator
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: March 16, 2018

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