Gene-Modified Lymphocytes, High-Dose Aldesleukin, and Vaccine Therapy in Treating Patients With Progressive or Recurrent Metastatic Cancer
Condition: Kidney Cancer; Melanoma (Skin); Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Melanoma; Neoplasm Metastasis; Kidney Neoplasms
Intervention: aldesleukin; anti-p53 T-cell receptor-transduced peripheral blood lymphocytes; autologous dendritic cell-adenovirus p53 vaccine; filgrastim; cyclophosphamide; fludarabine phosphate
Intervention description: Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.; 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.; 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.; subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).; 60mg/kg/day (Days-7,-6); 25mg/m^2 (Days -5, -4, -3, -2, and -1)
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent renal cell cancer; stage IV renal cell cancer; recurrent melanoma; stage IV melanoma; unspecified adult solid tumor, protocol specific

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.
    

Eligibility 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