Patient case: 47-year-old male with melanoma; genetic feature: APC loss of function

Clinical trial: Biological Therapy in Treating Patients With Metastatic Melanoma

Summary: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Treating a person's white blood cells in the laboratory and 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 maximum tolerated dose of autologous CD4+ antigen-specific T-cells for cellular adoptive immunotherapy in patients with metastatic melanoma.
  -  Determine the safety and toxicity of this regimen in these patients.
  -  Determine the duration of in vivo persistence of adoptively transferred CD4+ antigen-specific T-cell clones in these patients.
  Secondary
  -  Determine the antitumor effects of this regimen in these patients.
  OUTLINE: This is a dose-escalation study.
  Patients undergo leukapheresis to collect peripheral blood mononuclear cells. CD4+ antigen-specific T-cell clones are generated over the next 2-3 months using immunogenic peptides MART1, tyrosinase, or gp100.
  Patients receive autologous CD4+ antigen-specific T-cells IV over 30 minutes.
  Cohorts of 3-6 patients receive escalating doses of autologous CD4+ antigen-specific T-cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
  Patients are followed on days 1 and 3 post T-cell infusion, and then once weekly for 12 weeks.
  PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed metastatic melanoma
  -  HLA type expressing one of the following class II alleles:
  -  DRB1*0401
  -  DRB1*0404
  -  DRB1*1501
  -  DPB1*0401
  -  DPB1*0402
  -  Tumor expresses tyrosinase
  -  Tumor expressing NY-ESO-1 and are HLA type DP4, DP2, or DR7 allowed
  -  No CNS metastases
  -  Prior CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after treatment
  PATIENT CHARACTERISTICS:
  Age
  -  18 to 75
  Performance status
  -  Karnofsky 70-100%
  Life expectancy
  -  More than 16 weeks
  Hematopoietic
  -  WBC greater than 4,000/mm^3
  -  Absolute neutrophil count greater than 2,000/mm^3
  -  Platelet count greater than 100,000/mm^3
  -  Hematocrit greater than 30%
  Hepatic
  -  SGOT no greater than 3 times upper limit of normal
  -  INR no greater than 1.5 due to hepatic dysfunction
  -  No significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater
  Renal
  -  Creatinine no greater than 2.0 mg/dL OR
  -  Creatinine clearance at least 60 mL/min
  -  Calcium no greater than 12 mg/dL
  Cardiovascular
  -  No significant cardiac abnormalities*, defined by any 1 of the following:
  -  Congestive heart failure
  -  Clinically significant hypotension
  -  Symptoms of coronary artery disease
  -  Cardiac arrhythmias present on EKG requiring drug therapy NOTE: *Patients with a history of cardiovascular disease or any of the above abnormalities undergo a cardiac evaluation, including a cardiac stress test and/or echocardiogram
  Pulmonary
  -  No clinically significant pulmonary dysfunction
  -  FEV1 at least 1.0 L OR
  -  FEV1 at least 60%
  -  DLCO at least 55% (corrected for hemoglobin)
  Immunologic
  -  No acquired or hereditary immunodeficiency
  -  No autoimmune disease
  -  No active infection
  -  No oral temperature greater than 38.2 degrees C within the past 72 hours
  -  No systemic infection requiring chronic maintenance or suppressive therapy
  -  HIV negative
  Other
  -  No retinitis or choroiditis
  -  No history of seizures
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception during and for 3 months after study
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  No other concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer therapy)
  Chemotherapy
  -  At least 4 weeks since prior chemotherapy (standard or experimental) and recovered
  Endocrine therapy
  -  No concurrent systemic steroids except for toxicity management
  Radiotherapy
  -  At least 4 weeks since prior radiotherapy
  Surgery
  -  Not specified
  Other
  -  At least 4 weeks since prior immunosuppressive therapy
  -  More than 4 weeks since prior experimental drugs and recovered
  -  No concurrent pentoxifylline
  -  No other concurrent investigational agents

Relevance to patient case: not relevant