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

Clinical trial: Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With Melanoma

Summary: RATIONALE: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells.
  PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Detailed description: OBJECTIVES:
  -  Compare the immune reactivity in patients with resected stage IIB, IIC, III, or IV melanoma vaccinated with tyrosinase, gp100, and MART-1 peptides emulsified with Montanide ISA-51 with interleukin-12 and either alum adjuvant or sargramostim (GM-CSF).
  OUTLINE: This is a randomized study. Patients are stratified according to disease stage (cutaneous stage IIB, IIC, III, and IV vs ocular and mucosal stage III and IV). Patients are randomized to 1 of 3 treatment arms.
  -  Arm I: Patients receive vaccine with tyrosinase:368-376 (370D)/gp100:209-217 (210M)/MART-1:26-27 (27L) peptides emulsified with Montanide ISA-51 (ISA-51), low-dose interleukin-12 (IL-12) subcutaneously (SC), and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
  -  Arm II: Patients receive peptide vaccine emulsified with ISA-51, high-dose IL-12 SC, and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
  -  Arm III: Patients receive peptide vaccine emulsified with ISA-51 on day 1 and low-dose IL-12 SC and sargramostim (GM-CSF) SC on days 1-5 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
  Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
  PROJECTED ACCRUAL: A total of 60 patients (20 per treatment arm) will be accrued for this study within 3 years.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of stage IIB, IIC, III, or IV cutaneous melanoma OR stage III or IV ocular or mucosal melanoma
  -  Resected or rendered disease-free
  -  HLA-A2.1-positive by standard cytotoxicity assay
  -  Tumor tissue must be available for analysis of gp100 staining and tyrosinase and MART-1 expression by immunohistochemistry
  -  Must be positive for at least 1 antigen
  -  Failed, ineligible for, or refused prior interferon alfa
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  ECOG 0-1
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  WBC at least 3,000/mm^3
  -  Granulocyte count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  -  Hemoglobin at least 9.0 g/dL
  -  No bleeding disorder
  Hepatic:
  -  Bilirubin no greater than 2.0 mg/dL
  -  SGOT/SGPT no greater than 2.5 times normal
  -  No coagulation disorder
  -  Hepatitis surface antigen B negative
  -  Hepatitis C negative
  Renal:
  -  Creatinine no greater than 2.0 mg/dL
  Cardiovascular:
  -  No major cardiovascular illness
  Pulmonary:
  -  No major respiratory illness
  Immunologic:
  -  No prior uveitis
  -  No prior autoimmune inflammatory eye disease
  -  No immune hemolytic anemia
  -  No other active autoimmune disease
  Other:
  -  HIV negative
  -  No major gastrointestinal illness
  -  No other malignancy within the past 5 years except squamous cell skin cancer or carcinoma in situ of the cervix curatively treated at least 30 days ago
  -  No major systemic infection (e.g., pneumonia or sepsis)
  -  No other major medical illness
  -  No prior allergic reaction to Montanide ISA-51 or alum adjuvant
  -  No requirement for steroid therapy
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  See Disease Characteristics
  -  No prior tyrosinase:368-376 (370D), gp100:209-217 (210M), or MART-1:26-35 (27L) peptides
  Chemotherapy:
  -  At least 1 month since prior adjuvant chemotherapy for this disease
  -  No concurrent adjuvant chemotherapy
  Endocrine therapy:
  -  No concurrent steroids
  Radiotherapy:
  -  At least 1 month since prior radiotherapy for this disease
  -  No concurrent radiotherapy
  Surgery:
  -  See Disease Characteristics
  Other:
  -  At least 1 month since other prior therapy, including adjuvant therapy, for this disease
  -  No other concurrent therapy, including adjuvant therapy

Relevance to patient case: not relevant