RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase I trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Procedure: biological response modifier therapy  Procedure: tumor infiltrating lymphocyte therapy  Procedure: leukocyte therapy  Procedure: lymphokine-activated killer cell therapy  Vaccine: non-tumor cell derivative vaccine  Procedure: vaccine therapy  Drug: dendritic cell-MART-1 peptide vaccine  Drug: gp100 antigen  Drug: tyrosinase peptide	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the dose-limiting toxicities, maximum tolerated dose, recommended phase II dose, and rate of sensitization of T cells at each dose level in patients with melanoma receiving dendritic cell vaccine. II. Determine the overall (complete and partial) response rate, duration of response, and optimal route of administration in this patient population.

PROTOCOL OUTLINE: This is a dose escalation study. Patients are randomized to one of three treatment arms. All patients undergo leukopheresis to obtain lymphocyte and myeloid origin mononuclear cell fractions for preparation of dendritic cell (DC) vaccine. In each arm, cohorts of up to 5 patients receive escalating doses of vaccine. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 5 patients experience dose-limiting toxicity. Randomization ceases if the MTD has been reached in 2 arms, although accrual may continue. Treatment repeats every 2 weeks for a total of 4 doses. Arm I: Patients receive 3 different doses of peptide pulsed DC vaccine IV, each divided into 3 different peptide pulsed pools administered over 30 minutes. Arm II: Patients receive 3 different doses of peptide pulsed DC vaccine subcutaneously/intradermally to sites with no evidence of disease. At the lowest dose, patients receive 3 different peptide pulsed pools, each administered at a separate site. At the higher doses, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. Arm III: Patients receive peptide pulsed DC vaccine intranodally in groin or ancillary lymph nodes at the lower 2 doses of the 3 administered to arms I and II. At the lower dose, patients receive 3 different peptide pulsed pools, each administered into a different node. At the higher dose, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. Patients are followed at 2 weeks and then monthly for 3 months.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 14 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed stage IV melanoma
• Must be MHC Class I HLA-A2.1

--Prior/Concurrent Therapy--

• Biologic therapy: At least 30 days since prior immunotherapy; No concurrent immunotherapy
• Chemotherapy: At least 30 days since prior chemotherapy; No concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 30 days since prior radiotherapy; No concurrent radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: Over 18
• Performance status: ECOG 0-1
• Life expectancy: At least 2 months
• Hematopoietic: Platelet count at least 100,000/mm3; INR no greater than 1.5 mg/dL; No coagulopathies including thrombocytopenia
• Hepatic: Partial thromboplastin time no greater than 50 seconds
• Renal: Not specified
• Cardiovascular: No major cardiac illness
• Pulmonary: No major respiratory illness
• Other: No active systemic infection or other illness; No peripheral vascular disease; Not pregnant or nursing; Effective contraception required of all fertile patients during and for one month after completion of treatment

Pennsylvania
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States

Study chairs or principal investigators

Brian J. Czerniecki,  Study Chair,  University of Pennsylvania Cancer Center   

Study ID Numbers:  CDR0000066759; UPCC-4697; NCI-T98-0033
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003665
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08