Vaccine Therapy With High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response that will kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with interleukin-2 in treating patients with metastatic melanoma.

Detailed Description
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OBJECTIVES: Define the antitumor activity of gp100:209-217 (210M), a melanoma peptide derived from gp100 mixed with Montanide ISA-51, in combination with high-dose interleukin-2 (IL-2) administered by various schedules in patients with advanced melanoma. Examine the effect of the addition of gp100:209-217 (210M) peptide vaccine to high-dose IL-2 on the toxicity of the treatment in these patients. Define the induction of T-cell responses to gp100:209-217 (210M) peptide and its gp100 (parent) protein by ELISA with interferon gamma production or CTL precursor frequencies in these patients after the initial course of treatment. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (adjuvant interferon vs chemotherapy for advanced disease vs both vs none), ECOG performance status (0 vs 1), and number of organ sites involved (1 vs more than 1). Patients are randomized into 1 of 3 treatment arms. (Arm III closed to accrual as of 11/30/1998.) Arm I: Patients receive vaccination comprising gp100:209-217 (210M) peptide mixed with Montanide ISA-51 subcutaneously on days 1, 22, 43, and 64. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 2-6 and 16-20. Arm II: Patients receive vaccination as in arm I on days 1, 22, 43, and 64. Patients also receive high-dose IL-2 as in arm I on days 44-48 and 60-64. Patients who demonstrate rapid visible disease progression during the initial 4 weeks of therapy while maintaining good performance status may begin high-dose IL-2 on day 23. Arm III (closed to accrual as of 11/30/1998): Patients receive vaccination as in arm I on day 1 and then high-dose IL-2 as in arm I on day 2. Patients with nonhematologic toxicity may only receive vaccination on weeks 4, 7, and 10. Other patients may also receive IL-2 beginning on day 2 of each treatment week (4, 7, and 10) for up to 14 doses. Patients in each arm may receive up to a total of 3 courses of treatment. Patients are followed until death. PROJECTED ACCRUAL: Approximately 90 patients (25 patients for arms I and II and 40 patients for arm III [arm III closed to accrual as of 11/30/1998]) will be accrued for this study within 12-18 months.

Official Title
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A Randomized Phase II Trial of a Mutated gp100 Melanoma Peptide (g209-217(210M) With Hight Dose Interleukin-2 (IL-2) in HLA-A2.1+Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed clearly progressive metastatic or unresectable melanoma Must be HLA-A2.1 positive Measurable disease No active brain metastases, leptomeningeal disease, or seizure disorder More than 4 months since prior definitive therapy (surgery or radiotherapy) for brain metastases and must not have evidence of disease on brain CT scan or MRI No ascites or pleural effusions PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 OR Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No congestive heart failure No symptoms of coronary artery disease No serious cardiac arrhythmias No evidence of prior myocardial infarction on EKG Normal cardiac stress test required for all patients over 40 years Pulmonary: FEV_1 greater than 2.0 liters or at least 75% of predicted No chronic obstructive pulmonary disease Other: HIV negative No significant systemic infection No contraindication to use of pressor agents No history of major psychiatric illness No other major illness that would significantly increase the risk of immunotherapy No other active malignancy except surgically cured nonmelanoma skin cancer or carcinoma in situ or stage I carcinoma of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior interleukin-2 At least 4 weeks since prior vaccine therapy or other cytokine therapy Chemotherapy: One prior chemotherapy regimen allowed At least 4 weeks since prior chemotherapy (6 weeks for carmustine or lomustine) and recovered Endocrine therapy: No concurrent steroids Radiotherapy: See Disease Characteristics No prior radiotherapy to areas of measurable disease unless there has been clearly progressive disease in this site or there is measurable disease outside of areas of prior radiation At least 2 weeks since prior radiotherapy for local control or palliative therapy and recovered Surgery: See Disease Characteristics Recovered from prior major surgery No prior organ allografts Other: No antihypertensive therapy within 24 hours prior to interleukin-2

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, recurrent melanoma