Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage III or stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the dose-limiting toxicity and the maximum tolerated dose of autologous dendritic cells pulsed with autologous tumor cell lysate in patients with stage III or IV melanoma. Determine the safety and tolerability of this therapy in these patients. Secondary Determine the immune response, in terms of the type and degree of T-cell proliferation and delayed-type hypersensitivity responses, in patients treated with this therapy. OUTLINE: This is a dose-escalation, pilot study. Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC) on days -9, 19, and 47. Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to sargramostim (GM-CSF), interleukin-4, and tumor necrosis factor alpha and pulsed with autologous tumor cell lysate. Patients receive autologous tumor cell lysate-pulsed DC IV over 5-10 minutes on days 0, 28, and 56. Cohorts of 3-6 patients receive escalating doses of autologous tumor cell lysate-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of all patients experience dose-limiting toxicity. Patients are followed at day 84 and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 3-20 months.

Official Title
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En Vivo Matured Dendritic Cell Therapy in Patients With Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: autologous tumor cell vaccine
* Biological: therapeutic autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed melanoma Stage III (lymph node or in-transit metastases) or IV (systemic metastases) disease Patients with relapsed disease OR who failed prior immunotherapy or chemotherapy are eligible (but trial not restricted to relapsed or refractory disease) Tumor tissue available and properly stored for lysate preparation PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hepatic AST ≤ 2 times upper limit of normal (ULN) (3 times ULN for liver metastases) Bilirubin ≤ 2 times ULN Hepatitis B surface antigen negative Hepatitis C negative Renal Creatinine ≤ 2.0 times ULN Immunologic No active infection No history of autoimmune disease, including any of the following: Inflammatory bowel disease Systemic lupus erythematosus Scleroderma Rheumatoid arthritis Multiple sclerosis No allergy to aminoglycosides or streptomycin HIV negative Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No significant comorbid illness No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 10 days since prior immunotherapy Chemotherapy See Disease Characteristics Endocrine therapy At least 6 weeks since prior steroid therapy No concurrent corticosteroids Radiotherapy At least 10 days since prior radiotherapy No concurrent radiotherapy Surgery At least 10 days since prior surgery Prior diagnostic or palliative surgery allowed provided the patient has fully recovered Other No concurrent immunosuppressive or potentially 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: autologous tumor cell vaccine|nan|
|Biological: therapeutic autologous dendritic cells|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex Vivo Matured Dendritic Cell Therapy in Patients with Melanoma |  | 2005-2006 | 

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