RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor. Interleukin-2 and interleukin-12 may stimulate a person's white blood cells to kill melanoma cells. Combining vaccine therapy and interleukin-12 with interleukin-2 may be a more effective treatment for metastatic melanoma.

PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy and interleukin-12 with or without interleukin-2 in treating patients who have metastatic melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: MAGE-3  Drug: Melan-A  Drug: NA17-A  Drug: autologous lymphocytes  Drug: gp100 antigen  Drug: interleukin-12  Drug: interleukin-2  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare peptide-interferon-gamma production by CD8+ T cells in patients with metastatic melanoma immunized with MAGE-3, Melan-A, gp100 antigen, and NA17-A peptide-pulsed autologous peripheral blood mononuclear cells and interleukin-12 with or without low-dose interleukin-2.
• Compare the clinical response rate (complete and partial response) in patients treated with these regimens.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive immunization comprising MAGE-3, Melan-A, gp100 antigen, and NA17-A peptide-pulsed autologous peripheral blood mononuclear cells subcutaneously (SC) on day 1 and interleukin-12 (IL-12) SC on days 1, 3, and 5.
• Arm II: Patients receive immunization and IL-12 as in arm I and low-dose interleukin-2 SC on days 7-18. Treatment in both arms repeats every 21 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving an objective response or stable disease may receive additional treatment sets of 3 courses for up to a total of 9 courses.

Patients are followed every 8 weeks until disease progression and then at least every 3 months thereafter.

PROJECTED ACCRUAL: A total of 36 patients (18 per treatment arm) will be accrued for this study within 1.25 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma
• Evidence of metastatic disease by radiological or physical examination
• In-transit metastases allowed
• HLA-A2 positive
• No untreated brain metastases
• Brain lesions successfully treated by stereotactic radiotherapy or surgery with no recurrence at 28-day follow-up are allowed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm^3

Hepatic

• SGPT no greater than 2 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN
• Lactic dehydrogenase less than 1.25 times ULN
• Hepatitis B and C negative

Renal

• Creatinine no greater than 1.5 times ULN
• Calcium no greater than 11 mg/dL

Cardiovascular

• No significant cardiovascular disease
• No cardiac arrhythmia requiring medical intervention

Immunologic

• HIV negative
• No intrinsic immunosuppression
• No serious concurrent infection, including active tuberculosis
• No prior or active autoimmune disease including:
• Rheumatoid arthritis (rheumatoid factor-positive with current or recent flare)
• Inflammatory bowel disease
• Systemic lupus erythematosus
• Clinical evidence and antibody titer at least 1:80
• Ankylosing spondylitis
• Scleroderma
• Multiple sclerosis
• Autoimmune hemolytic anemia
• Immune thrombocytopenic purpura

Other

• Not pregnant or nursing
• Negative pregnancy test
• No psychiatric illness that would preclude study compliance or giving informed consent
• No active gastrointestinal bleeding
• No uncontrolled peptic ulcer disease

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior biologic therapy
• No prior melanoma vaccine therapy containing the same MAGE-3, Melan-A, gp100 antigen, or NA17 peptides used in the study

Chemotherapy

• Prior chemotherapy allowed

Endocrine therapy

• No concurrent systemic corticosteroids except physiologic replacement doses

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Other

• No concurrent immunosuppressive drugs (e.g., cyclosporine)

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting

Study chairs or principal investigators

Thomas F. Gajewski, MD, PhD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000309519; UCCRC-11447A; NCI-1330; NCT00064168
Record last reviewed:  October 2003
Last Updated:  December 9, 2004
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00064168
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08