Vaccine Plus Interleukin-2 in Treating Patients With Advanced Melanoma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2 in treating patients who have advanced melanoma. Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Melanoma vaccine plus interleukin-2 may kill more cancer cells

Detailed Description
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PRIMARY OBJECTIVES: I. Determine clinical response rates in patients with advanced melanoma treated with gp100:209-217(210M) melanoma vaccine and low-dose interleukin-2. II. Assess response duration and progression-free intervals in these patients receiving this treatment. OUTLINE: Patients receive gp100:209-217(210M) emulsified in Montanide ISA-51 subcutaneously (SC) on day 1 and interleukin-2 SC on days 1-5 and 8-13. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Patients with a complete response (CR) receive 3 additional courses after achieving CR. Patients are followed every 9 weeks for 3 years or until disease recurrence. PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 3.5 years.

Official Title
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Phase II Study of Melanoma Vaccine (NSC #683472/675756, IND #6123) and Low-Dose, Subcutaneous Interleukin-2 in Advanced Melanoma

Conditions
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Recurrent Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Biological: aldesleukin
* Biological: gp100:209-217(210M) peptide vaccine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed cutaneous melanoma with clinical evidence of distant, metastatic, unresectable regional lymphatic, or extensive in-transit recurrent disease HLA-A2*0201 positive by genotyping Measurable disease as defined by the following: At least 1 lesion accurately measured in at least 1 dimension At least 20 mm by conventional techniques At least 10 mm by spiral CT scan Lesions considered intrinsically nonmeasurable include: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Lesions situated in a previously irradiated area No ocular or mucosal melanoma No prior or concurrent liver or brain metastases Performance status - ECOG 0-1 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL LDH normal Bilirubin normal AST no greater than 2.5 times upper limit of normal Creatinine normal No congestive heart failure, angina, or symptomatic cardiac arrhythmia No myocardial infarction within the past 6 months No severe chronic pulmonary disease Not pregnant or nursing Fertile patients must use effective contraception No primary or secondary immunodeficiency or autoimmune disease No currently active second malignancy (e.g., patient has completed therapy and is considered unlikely to have recurrence within 1 year) other than nonmelanoma skin cancer At least 4 weeks since prior immunotherapy No prior interleukin-2 No prior whole cell or gp100:209-217(210M)-targeted melanoma vaccine No other concurrent cytokines or growth factors At least 4 weeks since prior chemotherapy At least 1 month since prior systemic corticosteroids No concurrent systemic, inhaled, or topical corticosteroids At least 1 month since other prior immunosuppressive medication No antihypertensive medications from 1 day prior until 2 days after first course

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (gp100:209-217, aldesleukin )<br>Patients receive gp100:209-217(210M) emulsified in Montanide ISA-51 SC on day 1 and interleukin-2 SC on days 1-5 and 8-13. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Patients with a CR receive 3 additional courses after achieving CR. | Biological: aldesleukin<br>* Given SC<br>* Other names: recombinant interleukin-2;Biological: gp100:209-217(210M) peptide vaccine<br>* Given SC<br>* Other names: gp100:209-217(210M);Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate (CR or PR) |  | From the start of treatment until disease progression/recurrence, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response duration | The Kaplan-Meier method will be used to estimate duration of response. | Up to 3 years | 
| Progression-free intervals | The Kaplan-Meier method will be used to estimate time to progression. | Up to 3 years | 
| Immunologic response rate using ELISPOT assay | Described in terms of frequency and kinetics. Agreement between clinical and immunological response will be measured using the kappa coefficient. | Up to 3 years |