Safety Study of a Melanoma Vaccine (GVAX) With or Without Cyclophosphamide in Patients With Surgically Resected Melanoma

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and feasibility of administering an allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine (melanoma GVAX), alone or in combination with low dose cyclophosphamide (CPM), for the adjuvant treatment of patients with surgically resected stage IIB-IV melanoma. Secondarily, the investigators will assess in vitro correlates of anti-melanoma immunization by melanoma GVAX, including serological and cellular immune responses in patients treated with either the vaccine alone or the vaccine given with low dose CPM.

Official Title
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A Feasibility and Toxicity Study of a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Secreting Allogeneic Melanoma Vaccine Administered Alone or in Combination With Cyclophosphamide in Subjects With Surgically Resected At-Risk Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: melanoma GVAX
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient age ≥18 years with melanoma of cutaneous or mucosal origin, and with clinicopathologic stage IIB, IIC, III or IV that has been completely resected Patients must be able to provide informed consent. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 6 months. Adequate hematologic function. Adequate renal function Adequate hepatic function Patients of both genders must agree to practice effective birth control during the study period and for at least 4 weeks after the last treatment. Exclusion Criteria: Patients whose primary site of melanoma is ocular. Are undergoing or have undergone in the past 4 weeks any systemic treatment for melanoma. Are undergoing or have undergone in the past 2 weeks any surgery or focal radiation therapy. Have active systemic infections, coagulation disorders (including therapeutic anticoagulation), or other major medical or psychiatric illnesses. Are known to be positive for hepatitis B surface antigen, anti-Hepatitis C Virus or anti-Human Immunodeficiency Virus (HIV) antibody (because of possible immune effects of these conditions). Documented history of autoimmune disease, for example, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis. Any form of primary or secondary immunodeficiency. This would include hereditary disorders such as ataxia-telangiectasia or Wiskott-Aldrich syndrome, or acquired immune deficiencies such as following bone marrow transplantation. Requirement for systemic steroid therapy or immunosuppressive therapy. Have received any type of cancer immunotherapy, including but not limited to interleukin-2, interferon alfa or melanoma vaccines. Have been diagnosed with another invasive cancer within the past 3 years. Radiographic evidence of melanoma recurrence. Pregnant or lactating women. Known or suspected hypersensitivity to GM-CSF, pentastarch, hetastarch, corn, Dimethyl sulfoxide, fetal bovine serum or trypsin (porcine origin).

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Cohort A will receive four doses of vaccine, each containing 5E7 melanoma GVAX cells. | Biological: melanoma GVAX<br>* Melanoma GVAX is given as intradermal injections every 28 days x 4 doses. Cohort A will receive 5E7 cells/dose; cohorts B and C will receive 2E8 cells/dose.<br>|
| Experimental: Cohort B<br>Cohort B will receive four doses of vaccine, each containing 2E8 melanoma GVAX cells. | Biological: melanoma GVAX<br>* Melanoma GVAX is given as intradermal injections every 28 days x 4 doses. Cohort A will receive 5E7 cells/dose; cohorts B and C will receive 2E8 cells/dose.<br>|
| Experimental: Cohort C<br>Cohort C will receive four doses of vaccine, each containing 2E8 melanoma GVAX cells. One day prior to each vaccination, patients in cohort C will receive a single, low dose of intravenous cyclophosphamide. | Biological: melanoma GVAX<br>* Melanoma GVAX is given as intradermal injections every 28 days x 4 doses. Cohort A will receive 5E7 cells/dose; cohorts B and C will receive 2E8 cells/dose.<br>Drug: Cyclophosphamide<br>* 200mg/m2 given as a single dose, intravenously, one day prior to each of the 4 vaccinations to patients in cohort C only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Administering Melanoma GVAX With and Without Cyclophosphamide | To determine the side effects and tolerability of administering an allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine (melanoma GVAX), alone or in combination with low dose cyclophosphamide, for the adjuvant treatment of patients with surgically resected stage IIB-IV melanoma. | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In vitro correlates of anti-melanoma immunization | We will assess in vitro correlates of anti-melanoma immunization by melanoma GVAX, including serological and cellular immune responses in patients treated with either the vaccine alone or the vaccine given with low dose cyclophosphamide. These investigations are exploratory in nature and will not affect clinical care. | 2.5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, vaccine, GVAX, GM-CSF