Interleukin-7 and Vaccine Therapy in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Interleukin-7 may stimulate a person's white blood cells to kill tumor cells. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Combining interleukin-7 with vaccine therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 when given with vaccine therapy in treating patients with metastatic melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of interleukin-7 (IL-7) when administered with melanoma peptide vaccine emulsified in Montanide ISA-51 in patients with metastatic melanoma. Determine the safety of this regimen in these patients. Secondary Determine the biological effects of this regimen on T-cell function and phenotype at various doses and at the optimal biological dose in these patients. Determine the pharmacokinetic and pharmacodynamic characteristics of IL-7 in patients treated with this regimen. Determine the antitumor effects of IL-7, in terms of a dose-escalation strategy, in these patients. OUTLINE: This is a dose-escalation study of interleukin-7 (IL-7). Patients receive IL-7 subcutaneously (SC) on days 0, 3, 6, 9, 12, 15, 18, and 21. Patients also receive melanoma peptide vaccine comprising gp100 antigen and MART-1 antigen emulsified in Montanide ISA-51 SC on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of IL-7 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, an additional 13 patients are treated at that dose level. Patients are followed at 1, 2, and 5 weeks, at 3 and 6 months, and then at 1 year. PROJECTED ACCRUAL: A total of 3-37 patients will be accrued for this study within 1-12.3 months.

Official Title
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A Study of Subcutaneous CYT 99 007 (Interleukin-7) in Conjunction With Peptide Immunization in Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: MART-1 antigen
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: recombinant interleukin-7


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed melanoma Metastatic disease Measurable or evaluable disease Disease progression during or after prior interleukin-2 (IL-2) OR ineligible to receive high-dose IL-2* OR has disease burden for which IL-2 is not indicated* NOTE: *If patient did not receive prior IL-2, must have progressed after prior standard first-line therapy (e.g., metastasectomy for single lesions or dacarbazine) HLA-A*0201-positive disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count > 1,000/mm^3* Absolute lymphocyte count ≥ 200/mm^3* Platelet count > 100,000/mm^3 No proliferative hematologic disease NOTE: *For 2 consecutive readings performed on 2 different days Hepatic AST and ALT < 3 times upper limit of normal (ULN) PT/PTT ≤ 1.5 times ULN Hepatitis B negative Positive hepatitis B serology indicative of prior immunization (i.e., positive for antibody against hepatitis B surface antigen AND negative for antibody against hepatitis B core antigen) allowed Hepatitis C negative Renal Creatinine ≤ 1.4 mg/dL Cardiovascular Ejection fraction > 45% by MUGA for patients ≥ 50 years of age OR with a history of cardiac disease No resting blood pressure > 140/90 mm Hg with standard antihypertensive therapy Pulmonary DLCO/VA and FEV_1 > 50% of predicted on pulmonary function test for smokers OR for patients with clinical evidence of compromised pulmonary function No history of severe asthma Immunologic HIV negative No history of autoimmune disease No splenomegaly Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other medical or psychiatric disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics More than 4 weeks since prior cytokines No prior allogeneic hematopoietic stem cell transplantation No concurrent growth factors No concurrent monoclonal antibodies No other concurrent immunotherapy No other concurrent cytokines No other concurrent biologic agents Chemotherapy See Disease Characteristics No prior intensive myeloablative chemotherapy No concurrent chemotherapy Endocrine therapy More than 2 weeks since prior systemic corticosteroids for more than 72 hours in duration No concurrent systemic steroids Radiotherapy Not specified Surgery See Disease Characteristics No prior splenectomy No prior solid organ transplantation Other More than 4 weeks since prior cytotoxic therapy No other concurrent cytotoxic therapy No concurrent chronic anticoagulation therapy (e.g., high-dose warfarin, heparin, or aspirin) Concurrent low-dose warfarin (1-2 mg) allowed No concurrent chronic medication for asthma No concurrent immunosuppressive 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MART-1 antigen|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: recombinant interleukin-7|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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recurrent melanoma, stage IV melanoma