Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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

Summary: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.
  PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV, or relapsed malignant melanoma.

Detailed description: OBJECTIVES:
  -  Determine the safety of administering MART-1 peptide-pulsed dendritic cells to patients with stage IV or relapsed malignant melanoma.
  -  Determine the immunological and clinical responses in this patient population after this therapy.
  OUTLINE: This is a dose-escalation study.
  Patients undergo leukapheresis between days -14 to -8. Mononuclear cells are isolated, used to generate dendritic cells (DC), and then pulsed with MART-1 peptide. Patients are vaccinated with MART-1 peptide-pulsed DC either IV or intradermally on days 0, 14, and 28.
  Cohorts of 3-6 patients receive escalating doses of MART-1 peptide-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
  Patients are followed until death.
  PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study.

Eligibility: Inclusion Criteria:
  -  Adults over the age of 18 with malignant melanoma.
  -  HLA-A2.1 positive and express MART-1, as assessed by either RT-PCR or by immunohistochemistry
  -  Tumor stages T3N0M0 or greater are eligible for this trial according to the following:
  1. I (<.75 to 1.5 mm or Clark level III-T1-2N0M0-)—not eligible
  2. II (1.5 to 4 mm or level IV-T3N0M0-)—eligible
  3. III (limited nodal metastasis involving one regional lymph node basin, or fewer than 5 in-transit metastasis -TxN1M0-)—eligible
  4. IV (advanced regional metastasis -TxN2M0- or any distant metastasis -TxNxM1-)—eligible
  5. Relapsed melanoma—eligible
  -  Patients previously treated with any form of therapy for either metastatic, relapsed or primary melanoma are eligible for this trial, provided that previous treatment was completed >30 days prior to enrollment
  -  Both male and females may be enrolled. Premenopausal females must have a negative pregnancy test prior to treatment
  -  Karnofsky Performance Status greater than or equal to 70 percent
  -  No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease
  -  No previous evidence of opportunistic infection
  -  A minimum of 30 days must have elapsed since the completion of prior chemotherapy, immunotherapy or radiation therapy
  -  Adequate baseline hematological function as assessed by the following laboratory values within 30 days prior to study entry (day -30 to 0):
  1. Hemoglobin >9.0 g/dl
  2. Platelets > 100000/mm3
  3. WBC > 3000/mm3
  4. Absolute Neutrophil Count > 1000/mm3
  -  Positive skin test to common antigens (tetanus and candida)
  -  Ability to give informed consent
  Exclusion Criteria:
  -  Lactating females and females of child-bearing potential must have negative serum beta-HCG pregnancy test
  -  Acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must have been completed within 14 days of prior to study treatment
  -  HIV-infected patients
  -  Acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk
  -  Patients with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in this study)
  -  Patients with organ allografts
  -  Uncontrolled CNS metastasis. Patients with CNS metastasis will be eligible if they have received CNS irradiation to control local tumor growth

Relevance to patient case: not relevant