Vaccination of Patients With Renal Cell Cancer With Dendritic Cell Tumor Fusions and GM-CSF

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to test the safety of the dendritic cell/tumor fusion study vaccine in combination with a laboratory-made agent called Granulocyte Macrophage Colony Stimulating Factor (GM-CSF). Another purpose is to determine the type and severity of any side effects associated with this study vaccine. GM-CSF is similar to a substance in the body that stimulates the production of white blood cells. To create the study vaccine, cells will be removed from the participants tumor and fused with dendritic cells which are obtained from the participants blood. Dendritic cells are responsible for immune responses to foreign substances that enter the body. Animal studies have shown that these fused cells can stimulate powerful anti-tumor responses.

Detailed Description
-----------------
Patients are being asked to participate if they have chosen to undergo a debulking nephrectomy (surgery to remove a tumor of the kidney, but not all of the cancer cells in their body) as a standard treatment for kidney cancer or they have tumor lesions that are accessible and are being removed to treat or diagnose their cancer. Participants enrolled in this study will be assigned to receive a particular dose of the dendritic cell/tumor fusion vaccine cells. The dose will be determined by when they are enrolled in the study. There are two cohorts to this study. The first cohort will be given the vaccine alone. If the vaccine is well tolerated then we will proceed to the second cohort. The second cohort will receive GM-CSF in addition to the vaccine. Tumor cells will be collected to make the study vaccine. Based on the location of the cancer, a decision will be made as to the best approach to obtain these cells. Participants will undergo a procedure known as leukapheresis in order to obtain their dendritic cells. Prior to this procedure they will receive 1 to 2 injection of GM-CSF to help increase their white blood cell count. If sufficient numbers of cells are obtained, tumor cells and dendritic cells will be fused (mixed) together in the laboratory and divided into the appropriate doses for administration. The treatment will consist of 3 vaccinations of fused cells given by an injection under your skin at 3-week intervals. The first six participants will receive only the study vaccine. The remaining participants will receive the study vaccine combined with GM-CSF. If enough vaccine cannot be made for the participant to receive 3 doses, the participant may receive only 2 doses of the study vaccine. Approximately 3 to 4 tablespoons of blood will be collected at certain times for testing the immune system and to determine if the study vaccine has increased the immune response against the tumor cells. Weekly visits for physical exam, assessment of adverse events and safety labs will be conducted. Regular blood draws will be done for at least 6 months following the completion of the study to follow safety labs and to monitor the immune response. Monthly physical exams will be performed following the last injection of the study vaccine. At one month, three months, and six months following the date the participant received the last study vaccine, they will have a CT scan to see if the study vaccine has affected their disease.

Official Title
-----------------
Vaccination of Patients With Renal Cell Cancer With Dendritic Cell Tumor Fusions and GM-CSF

Conditions
-----------------
Renal Cancer

Intervention / Treatment
-----------------
* Biological: Dendritic Cell Tumor Fusion Vaccine
* Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with stage IV renal cancer who have not received prior chemotherapy or biological therapy Patients who are to undergo debulking nephrectomy for independent clinical indications or patients with other sites of accessible disease Tumor tissue should be at least 2.0cm in longest dimension Patients should meet prognostic criteria for intermediate or favorable risk disease as defined by Motzer criteria Measurable metastatic disease as defined by a lesion of at least 1cm outside the lesion used for vaccine generation and exclusive of bony metastases ECOG Performance Status of 0-2 with greater than six week life expectancy 18 years of age or older Lab results within range outlined in protocol Exclusion Criteria: Patients who have received prior chemotherapy Clinical evidence of CNS disease. Patients with a history of treated brain metastasis must be stable with no evidence of disease for 3 months HIV positive Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, unstable ischemic coronary disease or congestive heart failure Pregnant of lactating women History of clinically significant venous thromboembolism

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients treated with DC/RCC vaccine to evaluate for treatment-limiting toxicity | Biological: Dendritic Cell Tumor Fusion Vaccine<br>* 3 vaccinations at three week intervals<br>Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)<br>* Combined with the vaccine in the remaining subjects after the first 6 are enrolled.<br>|
| Experimental: Cohort 2<br>Patients treated with DC/RCC vaccine to evaluate response | Biological: Dendritic Cell Tumor Fusion Vaccine<br>* 3 vaccinations at three week intervals<br>Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)<br>* Combined with the vaccine in the remaining subjects after the first 6 are enrolled.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Associated With Vaccination With Mature DC/Tumor Fusion and GM-CSF |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine if Cellular and Humoral Immunity is Induced by Serial Vaccination With DC/Tumor Fusion Cells and GM-CSF |  | 5 years | 
| to Correlate Immunologic Response Following Vaccination. |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GM-CSF, vaccine, debulking nephrectomy, dendritic cells