Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Biological Therapy Following Surgery in Treating Patients With Stage III or Stage IV Melanoma

Summary: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells.
  PURPOSE: Phase II trial to study the effectiveness of biological therapy following surgery in treating patients who have stage III or stage IV melanoma.

Detailed description: OBJECTIVES:
  -  Evaluate the efficacy of immunotherapy with irradiated autologous tumor cell vaccine and sargramostim (GM-CSF) followed by monoclonal antibody OKT3- activated T lymphocytes and interleukin-2 in combination with surgery in terms of response rate in patients with stage III or IV malignant melanoma.
  -  Determine the immunogenicity of malignant melanoma in this patient population.
  OUTLINE: Patients are stratified according to extent of disease, extent of antigen specific response to vaccination, performance status (0 vs 1), prior therapy (yes vs no), and gender.
  Patients undergo surgical resection of tumor on week 1. Within 1-2 weeks of surgery, patients are vaccinated with irradiated autologous tumor cells and sargramostim (GM-CSF), then receive GM-CSF alone intradermally at vaccination sites daily for 4 days. Patients are revaccinated 2 weeks later.
  Patients undergo peripheral blood mononuclear cell collection two weeks after the second vaccination. Peripheral blood mononuclear cells are stimulated with anti-CD3 monoclonal antibody (OKT3) and interleukin-2, producing activated T lymphocytes. The activated T lymphocytes are infused IV over 1-6 hours followed by 5 doses of interleukin-2 IV every other day over 10 days. Treatment continues in the absence of disease progression or unacceptable toxicity.
  Patients may receive one additional course of immunotherapy as above.
  Patients are followed every 3 months for 2 years, then every 6 months thereafter.
  PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically proven stage III or IV malignant melanoma
  -  Resectable disease
  -  At least 50,000,000 viable cells obtained from surgical specimen for use in the immunization part of this study
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  SWOG 0 or 1
  Life expectancy:
  -  At least 6 months
  Hematopoietic:
  -  Granulocyte count at least 1,500/mm^3
  -  Platelet count at least lower limit of normal
  -  No active or recent uncontrolled bleeding
  Hepatic:
  -  Bilirubin normal
  -  SGOT no greater than 2 times upper limit of normal (ULN) (no greater than 5 times ULN if liver metastases present)
  Renal:
  -  Creatinine normal
  Other:
  -  Negative stool guaiac
  -  No impaired immunity
  -  No uncontrolled diabetes
  -  No active uncontrolled infections
  -  No other serious disease
  -  No other malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  Not specified
  Chemotherapy:
  -  No concurrent chemotherapy
  Endocrine therapy:
  -  Not specified
  Radiotherapy:
  -  Not specified
  Surgery:
  -  See Disease Characteristics
  Other:
  -  At least 2 weeks since prior therapy and recovered

Relevance to patient case: not relevant