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

• Status: Terminated
• Trial end date: 2009-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Sargramostim; Vaccines

Criteria

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