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

Clinical trial: Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

Summary: RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells.
  PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage III or stage IV melanoma.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the dose-limiting toxicity and the maximum tolerated dose of autologous dendritic cells pulsed with autologous tumor cell lysate in patients with stage III or IV melanoma.
  -  Determine the safety and tolerability of this therapy in these patients.
  Secondary
  -  Determine the immune response, in terms of the type and degree of T-cell proliferation and delayed-type hypersensitivity responses, in patients treated with this therapy.
  OUTLINE: This is a dose-escalation, pilot study.
  Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC) on days -9, 19, and 47. Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to sargramostim (GM-CSF), interleukin-4, and tumor necrosis factor alpha and pulsed with autologous tumor cell lysate. Patients receive autologous tumor cell lysate-pulsed DC IV over 5-10 minutes on days 0, 28, and 56.
  Cohorts of 3-6 patients receive escalating doses of autologous tumor cell lysate-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of all patients experience dose-limiting toxicity.
  Patients are followed at day 84 and then every 3 months thereafter.
  PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 3-20 months.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed melanoma
  -  Stage III (lymph node or in-transit metastases) or IV (systemic metastases) disease
  -  Patients with relapsed disease OR who failed prior immunotherapy or chemotherapy are eligible (but trial not restricted to relapsed or refractory disease)
  -  Tumor tissue available and properly stored for lysate preparation
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Performance status
  -  Karnofsky 60-100%
  Life expectancy
  -  At least 12 weeks
  Hematopoietic
  -  Absolute neutrophil count ≥ 1,000/mm^3
  -  Platelet count ≥ 75,000/mm^3
  Hepatic
  -  AST ≤ 2 times upper limit of normal (ULN) (3 times ULN for liver metastases)
  -  Bilirubin ≤ 2 times ULN
  -  Hepatitis B surface antigen negative
  -  Hepatitis C negative
  Renal
  -  Creatinine ≤ 2.0 times ULN
  Immunologic
  -  No active infection
  -  No history of autoimmune disease, including any of the following:
  -  Inflammatory bowel disease
  -  Systemic lupus erythematosus
  -  Scleroderma
  -  Rheumatoid arthritis
  -  Multiple sclerosis
  -  No allergy to aminoglycosides or streptomycin
  -  HIV negative
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  No significant comorbid illness
  -  No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  See Disease Characteristics
  -  At least 10 days since prior immunotherapy
  Chemotherapy
  -  See Disease Characteristics
  Endocrine therapy
  -  At least 6 weeks since prior steroid therapy
  -  No concurrent corticosteroids
  Radiotherapy
  -  At least 10 days since prior radiotherapy
  -  No concurrent radiotherapy
  Surgery
  -  At least 10 days since prior surgery
  -  Prior diagnostic or palliative surgery allowed provided the patient has fully recovered
  Other
  -  No concurrent immunosuppressive or potentially immunosuppressive therapy

Relevance to patient case: not relevant