Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: Biological Therapy in Treating Patients With Metastatic Melanoma

Summary: RATIONALE: Biological therapies such as cellular adoptive immunotherapy use different ways to stimulate the immune system and stop cancer cells from growing. Treating a person's white blood cells in the laboratory and then reinfusing them may cause a stronger immune response and kill more tumor cells.
  PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the safety and toxicity of cellular adoptive immunotherapy comprising autologous CD8+ cytotoxic T-lymphocyte clones targeting cancer-testis antigens in patients with metastatic melanoma.
  -  Determine the duration of in vivo persistence of this therapy in these patients.
  Secondary
  -  Evaluate the antitumor effects of this therapy in these patients.
  OUTLINE: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells and then CD8+ cytotoxic T-lymphocyte (CTL) clones are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones targeting cancer testis antigens IV over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-4. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a clinical response after completion of the fourth course are eligible to receive additional T-cell infusions.
  Patients are followed for 9 months.
  PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed metastatic melanoma
  -  Stage IV disease
  -  HLA-A1, -A2, and -A3 positive
  -  MAGE-1 or -3 positive by histology
  -  Bidimensionally measurable disease by palpation on clinical examination, x-ray, or CT scan
  -  No CNS metastases
  PATIENT CHARACTERISTICS:
  Age
  -  18 to 75
  Performance status
  -  Karnofsky 80-100%
  Life expectancy
  -  More than 6 months
  Hematopoietic
  -  Not specified
  Hepatic
  -  Bilirubin ≤ 1.6 mg/dL
  -  SGOT ≤ 3 times upper limit of normal
  -  PT ≤ 1.5 times control
  Renal
  -  Creatinine ≤ 2.0 mg/dL
  -  Calcium ≤ 12 mg/dL
  Cardiovascular
  -  No congestive heart failure
  -  No clinically significant hypotension
  -  No symptoms of coronary artery disease
  -  No cardiac arrhythmias on electrocardiogram requiring drug therapy
  -  Patients with prior cardiovascular disease or the presence of any of the above abnormalities undergo a cardiac evaluation, which may include a stress test and/or echocardiogram
  Pulmonary
  -  No clinically significant pulmonary dysfunction by medical history or physical examination
  -  FEV_1 ≥ 60% of normal
  -  DLCO ≥ 55% (corrected for hemoglobin)
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  No retinitis or choroiditis
  -  No active infections or oral temperature greater than 38.2 degrees Celsius within the past 72 hours
  -  No systemic infection requiring chronic maintenance or suppressive therapy
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  No other concurrent immunotherapy (e.g., other interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy)
  Chemotherapy
  -  At least 3 weeks since prior standard or experimental chemotherapy
  -  1-2 courses of prior cytoreductive chemotherapy for bulky disease allowed
  Endocrine therapy
  -  No concurrent systemic steroids (except for toxicity management)
  Radiotherapy
  -  At least 3 weeks since prior radiotherapy
  Surgery
  -  Not specified
  Other
  -  At least 3 weeks since prior immunosuppressive therapy
  -  No concurrent pentoxifylline
  -  No other concurrent investigational agents

Relevance to patient case: not relevant