CP-675,206 (CTLA4-Blocking Monoclonal Antibody) Combined With Dendritic Cell Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed With Surgery

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as CP-675,206, work in different ways to stimulate the immune system and stop tumor cells from growing. Vaccines may make the body build an immune response to kill tumor cells. Combining CP-675,206 with vaccine therapy may cause a stronger immune response and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of CP-675,206 when given with vaccine therapy in treating patients with stage III or stage IV melanoma that cannot be removed with surgery.

Detailed Description
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OBJECTIVES: Primary Determine the safety and maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CTLA4-blocking monoclonal antibody; CP-675,206) administered with autologous dendritic cells pulsed with MART-1 antigen in patients with unresectable stage III or stage IV melanoma. Determine the biological activity and immune effects of this regimen in these patients. Secondary Correlate CTLA4 genotype with safety of this regimen and/or immune response in these patients. Determine, preliminarily, the efficacy of this regimen, in terms of clinical benefit rate, in these patients. OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CTLA4-blocking monoclonal antibody; CP-675,206). Patients receive CP-675,206 IV on days 0, 28, 60, and 90 and autologous dendritic cells pulsed with MART-1 antigen intradermally on days 0, 14, and 28. After day 120, patients with stable or responding disease may receive additional doses of CP-675,206 monthly in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of CP-675,206 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. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 3-21 patients will be accrued for this study within 3-10 months.

Official Title
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A Phase I, Open Label, Study To Evaluate The Safety And Immune Function Effects Of CP-675,206 In Combination With MART-1 Peptide-Pulsed Dendritic Cells In Patients With Advanced Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed cutaneous or mucosal melanoma, meeting criteria for 1 of the following: Unresectable stage III disease (locally relapsed unresectable, in-transit lesions, or unresectable draining nodes) Stage IV disease, metastatic to 1 of the following sites: Skin, subcutaneous tissues, or distant lymph nodes Lung Other visceral sites with lactic dehydrogenase ≤ 2 times upper limit of normal (unless due to liver stasis) De novo metastatic disease allowed provided patient refused any standard or approved stage-appropriate therapy for melanoma Measurable disease HLA-A2.1 positive (HLA-A*0201 by molecular subtyping) MART-1-expressing tumor by reverse transcription polymerase chain reaction or immunohistochemistry No symptomatic brain metastases and/or progression of CNS metastases within the past 4 weeks Age 18 and over Performance status ECOG 0-1 OR Karnofsky 70-100% HIV negative Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after study participation More than 30 days since prior immunotherapy for metastatic, relapsed, or primary melanoma More than 30 days since prior chemotherapy for metastatic, relapsed, or primary melanoma More than 4 weeks since prior corticosteroids More than 30 days since prior radiotherapy for metastatic, relapsed, or primary melanoma More than 30 days since prior surgery for metastatic, relapsed, or primary melanoma. More than 30 days since other prior therapy for metastatic, relapsed, or primary melanoma More than 14 days since prior anti-infective therapy More than 4 weeks since prior immune suppressive therapy (e.g., cyclosporine) Exclusion Criteria: chronic hepatitis B or C asthma inflammatory bowel disease celiac disease history of chronic colitis or other chronic gastrointestinal conditions associated with diarrhea or bleeding active chronic inflammatory or autoimmune disease, including any of the following: Psoriasis Rheumatoid arthritis Multiple sclerosis Hashimoto's thyroiditis Addison's disease Graves' disease Systemic lupus erythematosus active infection OR fever over 100° F within the past 3 days allergy to study drugs pregnant symptomatic seizures other medical problem that would preclude study participation prior melanoma immunotherapy containing MART-1 antigen prior anti-T-cell therapy prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CP-675,206) organ allografts requiring long-term immune suppressive 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTLA4-Blocking Monoclonal Antibody<br> | Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody |  | 3 months | 

 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