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 person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage III or stage IV melanoma.

Detailed Description
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OBJECTIVES: Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides treated with vs without ex vivo CD40-ligand, in terms of tumor-specific T-cell response, in patients with HLA-A1 and/or HLA-A2.1 positive stage III or IV melanoma. Determine the safety and tolerability of these vaccinations in these patients. Determine tumor response and recurrence rates in patients treated with these vaccinations. OUTLINE: This is an open-label non-randomized study. Phase I: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMC). PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 to generate dendritic cells (DCs) on day -9. DCs are pulsed separately with HLA-A1 and HLA-A2.1-restricted flu matrix peptides derived from melanoma-associated tumor antigens (MAGE-10.A2, Melan-A, MAGE-3, NY-ESO-1, gp100 antigen, and tyrosinase peptide). Half of the DCs are treated ex vivo with CD40-ligand. Patients receive the peptide-pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression. Patients who show tumor response (at least stable disease) at day 98 progress to phase II of the study. Phase II: Patients undergo leukapheresis as in phase I on days 102, 352, and 688. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 126, 184, 268, 356, 520, and 692. Patients are followed for 10 years. PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.

Official Title
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Vaccination Of HLA-A1 And/Or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide - Loaded Autologous Dendritic Cells That Are Generated In The Absence Or Presence Of CD40 Ligand

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: recombinant CD40-ligand
* Biological: therapeutic autologous dendritic cells


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage III or IV cutaneous malignant melanoma HLA-A1 and/or HLA-A2 expression by serologic HLA typing HLA-A2.1 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells No active CNS metastases by CT scan or MRI PATIENT CHARACTERISTICS: Age Over 18 Performance status Karnofsky 60-100% Life expectancy At least 4 months Hematopoietic WBC greater than 2,500/mm^3 Neutrophil count greater than 1,000/mm^3 Lymphocyte count greater than 700/mm^3 Platelet count greater than 75,000/mm^3 Hemoglobin greater than 9 g/dL No bleeding disorders Hepatic Bilirubin less than 2.0 mg/dL Hepatitis B surface antigen negative Hepatitis C antibody negative Renal Creatinine less than 2.5 mg/dL Cardiovascular No clinically significant heart disease Pulmonary No clinically significant respiratory disease Immunologic No active systemic infection No immunodeficiency disease No evidence of HIV-1, HIV-2, or human T-cell lymphotropic virus-1 No active autoimmune disease including (but not limited to): Lupus erythematosus Autoimmune thyroiditis or uveitis Multiple sclerosis Inflammatory bowel disease Other Stable medical condition Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 1 month after study participation No organic brain syndrome or psychiatric illness that would preclude study compliance No other concurrent active malignancy No other concurrent serious illness that would preclude study treatment No contraindication to leukapheresis PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy No other concurrent immunotherapy Chemotherapy More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas) No concurrent chemotherapy Endocrine therapy No concurrent corticosteroids Radiotherapy More than 4 weeks since prior radiotherapy No prior radiotherapy to the spleen Concurrent palliative radiotherapy allowed Surgery Recovered from prior surgery No prior splenectomy No prior organ allograft Concurrent surgery on selected metastases (e.g., because of pain or local complications such as compression) allowed Other No other concurrent investigational drugs No concurrent participation in another clinical trial

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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant CD40-ligand|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 |
| --- | --- | --- |
| Comparison of the efficacy of vaccination with vs without ex vivo CD40-ligand in terms of tumor-specific T-cell response |  |  | 
| Safety |  |  | 
| Tolerability |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  |  | 
| Recurrence rates |  |  | 

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