LMB-2 Immunotoxin and Vaccine Therapy in Treating Patients With Metastatic Melanoma That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: The LMB-2 immunotoxin can find tumor cells and kill them without harming normal cells. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving LMB-2 immunotoxin together with vaccine therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving LMB-2 immunotoxin together with vaccine therapy works in treating patients with metastatic melanoma that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine objective clinical response in patients with progressive, unresectable metastatic melanoma treated with recombinant LMB-2 immunotoxin and peptide vaccination comprising gp100:209-217 (210M) antigen, MART-1:27-35 antigen, and Montanide ISA-51. Secondary Determine changes in levels of CD4+, CD25+ regulatory T cells in peripheral blood before and after treatment in patients treated with this regimen. Determine the ability of recombinant immunotoxin LMB-2 to augment peptide vaccination in these patients. Determine the toxicity profile of this regimen in these patients. OUTLINE: Patients receive LMB-2 immunotoxin IV over 30 minutes twice on days 1-3. Patients then receive peptide vaccinations comprising gp100:209-217 (210M) antigen emulsified in Montanide ISA-51 subcutaneously (SC), and MART-1:27-35 vaccine emulsified in Montanide ISA-51 SC on days 4, 5, 6, and 24-27 (course 1). After week 8, patients achieving tumor response may receive 1 additional course in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically in the absence of disease progression. PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

Official Title
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Phase II Evaluation of Peptide Immunization and LMB-2 in Metastatic Melanoma

Conditions
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Melanoma (Skin), Non-melanomatous Skin Cancer

Intervention / Treatment
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* Biological: LMB-2 immunotoxin
* Biological: MART-1 antigen
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of metastatic melanoma Unresectable disease Progressive disease while receiving standard therapy (e.g., interleukin-2 or dacarbazine) HLA-A0201 positive Measurable disease The following are not allowed: Resectable local/regional disease Patients whose serum neutralizes LMB-2 in tissue culture, due either to antitoxin or antimouse-immunoglobulin G antibodies (> 75% of the activity of 1 ug/mL of LMB-2) Received LMB-2 on another trial PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy more than 3 months WBC ≥ 3,000/mm^3 Absolute lymphocyte count > 500/mm^3 Platelet count ≥ 90,000/mm^3 Bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with Gilbert's syndrome) AST and ALT ≤ 2.5 times normal Albumin ≥ 3.0 g/dL No hepatitis B surface antigen or hepatitis C positivity Creatinine ≤ 1.4 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection Ejection fraction ≥ 45% by echocardiogram or thallium stress test (for patients > 50 years of age OR who have a history of cardiovascular disease) LVEF ≥ 45% No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No known HIV positivity No autoimmune disease No immunodeficiency No other malignancies Must be willing to undergo leukapheresis PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 12 weeks since prior monoclonal antibody therapy More than 3 weeks since prior and no concurrent systemic therapy for cancer No concurrent chronic anticoagulant therapy No concurrent systemic steroid therapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: LMB-2 immunotoxin|nan|
|Biological: MART-1 antigen|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 |
| --- | --- | --- |
| Objective clinical response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in levels of CD4+, CD25+ regulatory T cells |  |  | 
| Ability of LMB-2 to augment peptide vaccination |  |  | 
| Toxicity |  |  | 

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