Patient case: 49-year-old male with melanoma; genetic feature: extensive tumor infiltrating lymphocytes

Clinical trial: Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

Summary: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma.
  PURPOSE: Phase II trial to compare the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have metastatic melanoma that has not responded to previous therapy.

Detailed description: OBJECTIVES:
  -  Compare the efficacy of gp100:209-217(210M) peptide and MART-1:26-35(27L) peptide administered with or without high-dose interleukin-2 (IL-2) in patients with metastatic melanoma who are HLA-A0201 positive.
  -  Determine the efficacy of these peptides in patients who cannot receive IL-2.
  -  Compare the efficacy of IL-2 with or without these peptides in patients who need immediate treatment with IL-2.
  -  Determine the efficacy of MART-1:26-35(27L) peptide in patients who have received prior gp100 antigen.
  -  Compare the immunologic response experienced by patients who have received peptide, with or without IL-2, as measured by changes in T-cell precursors from before to after treatment.
  -  Compare the toxic effects of these regimens in these patients.
  OUTLINE: This is a partially randomized study.
  Patients are assigned to 1 of 4 treatment groups based on disease status and prior therapy.
  -  Group A (eligible to receive interleukin-2 (IL-2) but not in immediate need; no prior immunization with gp100 or MART-1 antigen): Patients are randomized to 1 of 2 treatment arms.
  -  Arm I: Patients receive gp100 and MART-1 peptides emulsified in Montanide ISA-51 (ISA-51) subcutaneously (SC) on day 1. (Arm I closed as of 10/30/02).
  -  Arm II: Patients receive both peptides as in arm I on day 1 and high-dose IL-2 IV over 15 minutes every 8 hours on days 2-5 (for up to 12 doses). (Arm II closed as of 10/30/02).
  -  Group B (ineligible to receive IL-2 due to other debilitating disease): Patients receive treatment as in group A, arm I.
  -  Group C (need immediate IL-2 therapy due to extensive and rapid progression of disease): Patients receive treatment as in group A, arm II. (Group C closed as of 10/30/02).
  -  Group D (prior immunization with gp100 antigen): Patients receive modified MART-1:26-35(27L) peptide emulsified in ISA-51 SC on day 1.
  Treatment in all groups repeats every 3 weeks for 4 courses. Patients who achieve a minor, mixed, or partial response may receive up to 12 additional courses. Patients who achieve complete response receive 2 additional courses.
  Patients are followed at 4-6 weeks.
  PROJECTED ACCRUAL: A total of 103 patients (15-25 for group A, arm I; 19-33 for group A, arm II; and 15 each for groups B, C, and D) will be accrued for this study within 1 year.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed metastatic melanoma that has failed standard therapy
  -  Measurable disease
  -  HLA-A0201 positive
  PATIENT CHARACTERISTICS:
  Age:
  -  16 and over
  Performance status:
  -  ECOG 0-2
  Life expectancy:
  -  More than 3 months
  Hematopoietic:
  -  WBC at least 3,000/mm^3
  -  Platelet count at least 90,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL for patients with Gilbert's syndrome)
  -  AST/ALT less than 3 times normal
  -  Hepatitis B surface antigen negative
  -  No coagulation disorder
  Renal:
  -  Creatinine no greater than 2.0 mg/dL
  Cardiovascular:
  -  No major cardiovascular disease
  -  If cardiovascular disease or other debilitating symptoms present, may receive peptide emulsified with Montanide ISA-51 only
  Pulmonary:
  -  No major respiratory disease
  Other:
  -  Not pregnant
  -  Fertile patients must use effective contraception
  -  HIV negative
  -  No active systemic infection
  -  No autoimmune disease or immunodeficiency disease
  -  No primary or secondary immunodeficiency
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  At least 3 weeks since prior biologic therapy
  -  No prior MART-1 antigen immunization
  Chemotherapy:
  -  At least 3 weeks since prior chemotherapy
  Endocrine therapy:
  -  At least 3 weeks since prior endocrine therapy
  -  No concurrent steroid therapy
  Radiotherapy:
  -  At least 3 weeks since prior radiotherapy
  Surgery:
  -  Prior surgery allowed

Relevance to patient case: not relevant