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

Phase 2TerminatedNCT00704938

National Institutes of Health Clinical Center (CC)3 enrolled

Overview

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.

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.

Interventions

aldesleukinBIOLOGICAL

Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.

anti-p53 T-cell receptor-transduced peripheral blood lymphocytesBIOLOGICAL

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.

autologous dendritic cell-adenovirus p53 vaccineBIOLOGICAL

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.

filgrastimBIOLOGICAL

subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).

cyclophosphamideDRUG

60mg/kg/day (Days-7,-6)

fludarabine phosphateDRUG

25mg/m\^2 (Days -5, -4, -3, -2, and -1)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 * Human leukocyte antigens 0201 (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: * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy \> 3 months * Absolute neutrophil count \> 1,000/mm\^3 * White blood cell (WBC) \> 3,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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 * Human immunodeficiency virus (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 * Left ventricular ejection fraction (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 * Forced expiratory volume 1 (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

Outcomes

Primary Outcomes

Clinical Response (Complete Response + Partial Response)

Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all lesions. Partial response is a 30% decrease in the sum of the longest diameter (LD) of target lesions.

Time frame: 5 months

Secondary Outcomes

Number of Participants With Adverse Events

Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse events module.