Universal Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)-Producing and CD40L Expressing Bystander Cell Line for Tumor Vaccine in Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to find out what effects (good and/or bad) this new cancer vaccine has on the patient and their cancer, whether it is safe and whether it can help get rid of their cancer (malignant melanoma). We want to check how the patient's immune system reacts, both before and after the vaccine treatment.

Detailed Description
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The vaccine will be made by mixing two kinds of cells: 1) some of the patient's own malignant melanoma cells which were removed by surgery and then processed in the Cell Therapy Laboratory, and 2) experimental bystander cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells, called GM.CD40L, are human cells that have been genetically changed. The original cells, called K562, had the genes for human GM-CSF and CD40L inserted into them. These changes are designed to help boost the patient's immune system to better fight the cancer in their body.

Official Title
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A Phase II Trial Using a Universal GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) in the Formulation of Autologous Tumor Cell-Based Vaccines for Patients With Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: Bystander-Based Autologous Tumor Cell Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage IIIC or stage IV melanoma Measurable disease Age 18 or older Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 No radiation therapy within 2 weeks prior to first vaccine administration No chemotherapy within 4 weeks prior to first vaccine administration No steroid therapy within 4 weeks prior to first vaccine administration No surgery within 10 days prior to first vaccine administration Patient's written informed consent Patient's ability to comply with the visit schedule and assessments required by the protocol Adequate organ function (measured within a week of beginning treatment): White blood count (WBC) > 3,000/mm^3 and absolute neutrophil count (ANC) >1500/mm^3 Platelets > 100,000/mm^3 Hematocrit > 25% and Hgb > 8 g/dL Bilirubin < 2.0 mg/dL Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min Exclusion Criteria: Symptomatic or untreated brain metastasis Any serious ongoing infection Current corticosteroid or other immunosuppressive therapy Any other pre-existing immunodeficiency condition (including known HIV infection) Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment) ECOG performance status of 2, 3, or 4 Any second active primary cancer

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: Vaccine Therapy<br>Treatment consisted of intradermal vaccine injections at 28-day intervals for a total of 3 immunizations. Injections were performed on Days 1, 29, and 57. | Biological: Bystander-Based Autologous Tumor Cell Vaccine<br>* The vaccine, consisting of one mL of cell suspension (GM.CD40L bystander cells admixed with an equivalent number of thawed autologous tumor cells), was administered into 8 separate injection sites, as described in treatment arm.<br>* Other names: Immunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Partial Response | Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | Average of 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAEs) Related to Study Treatment | Frequency of Study Related Toxicity. To evaluate the toxicity of the autologous tumor cell / GM.CD40L bystander cell vaccine. Toxicity was scored using the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE-3). | Average of 14 months | 
| Number of Participants With Stable Disease | Patients with stable disease by RECIST criteria after 3 vaccine injections. Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Average of 14 months | 
| Time to Progression (TTP) in Months | Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Average of 14 months | 
| Overall Survival (OS) in Months | Average overall survival time in months. | Average of 14 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