Vaccine Therapy and GM-CSF in Treating Patients With Recurrent or Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may be an effective treatment for melanoma. PURPOSE: This randomized phase II trial is studying two different vaccine therapy regimens to compare how well they work when given together with GM-CSF in treating patients with recurrent or metastatic melanoma.

Detailed Description
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OBJECTIVES: Compare overall survival, progression-free survival, event-free survival, and failure-free survival of patients with metastatic melanoma treated with vaccine therapy comprising irradiated autologous tumor cells vs autologous dendritic cells loaded with irradiated autologous tumor cells in combination with sargramostim (GM-CSF). Compare the frequency of immune response based on delayed-type hypersensitivity to irradiated autologous tumor cells and serologic and cellular assays at baseline and during and after completion of autologous tumor cell-based vaccine therapy in these patients. Compare the safety of these regimens in these patients. OUTLINE: This is a randomized study. Patients are stratified according to measurable disease (yes vs no) and location of disease (distant vs regional). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irradiated autologous tumor cells subcutaneously (SC) and sargramostim (GM-CSF) SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive autologous dendritic cells loaded with irradiated autologous tumor cells SC and GM-CSF SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.

Official Title
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Randomized Phase II Trial of Autologous Vaccines Consisting of Adjuvant GM-CSF Plus Proliferating Tumor Cells Versus GM-CSF Plus Dendritic Cells Loaded With Proliferating Tumor Cells in Patients With Metastatic Melanoma (MAC-VAC)

Conditions
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Melanoma (Skin)

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of melanoma Regionally recurrent or distant metastatic disease Must have an established continuously proliferating cell line expanded to about 200 million cells that is free of stromal cells and contamination No active CNS metastases Prior treatment for brain metastases or spinal cord compression allowed No clear evidence of disease progression in the CNS No concurrent pharmacologic doses of corticosteroids PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 70-100% OR ECOG PS 0-1 Platelet count > 100,000/mm³ Hematocrit > 30% Creatinine < 2.0 mg/dL Bilirubin < 2.0 mg/dL Albumin > 3.0 mg/dL No significant hepatic or renal dysfunction No other invasive cancer within the past 5 years No active infection or other active medical condition that could be eminently life threatening, including any of the following: Active blood clotting Bleeding diathesis No ongoing transfusion requirement No underlying cardiac disease associated with known myocardial dysfunction No unstable angina related to atherosclerotic cardiovascular disease No known autoimmune disease Negative pregnancy test PRIOR CONCURRENT THERAPY: Prior surgery, radiotherapy, chemotherapy, biological therapy (including sargramostim [GM-CSF]), or vaccine therapy allowed No concurrent anticancer therapy (e.g., hormone therapy for prostate or breast cancer) No concurrent digoxin or other medications for the treatment of heart failure No concurrent immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 16 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: Randomized


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive irradiated autologous tumor cells subcutaneously (SC) and sargramostim (GM-CSF) SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity. | Biological: autologous tumor cell vaccine<br>* Given subcutaneously<br>Biological: sargramostim<br>* Given subcutaneously<br>|
| Experimental: Arm II<br>Patients receive autologous dendritic cells loaded with irradiated autologous tumor cells SC and GM-CSF SC once weekly for 3 weeks and then once monthly for up to 5 months in the absence of disease progression or unacceptable toxicity. | Biological: sargramostim<br>* Given subcutaneously<br>Biological: therapeutic autologous dendritic cells<br>* Given subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, progression-free survival, event-free survival, and failure-free survival |  |  | 
| Frequency of immune response as measured by delayed-type hypersensitivity and serologic and cellular assays at baseline and during and after completion of study treatment |  |  | 
| Safety |  |  | 

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