Dendritic Cell Vaccination in Patients With Advanced Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate a method of using dendritic cells (a kind of white blood cell) as a vaccine to stimulate your own immune system to react to your melanoma cells.

Detailed Description
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This is a single arm open label trial that will assess the safety and tolerability of mature dendritic cell (mDC3/8) vaccine (primer and booster) in subjects with stage III and stage IV melanoma, followed by treatment with pembrolizumab (anti-PD-1 therapy). Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production approximately 1 week prior to vaccine infusion. Each study subject will receive cyclophosphamide 300mg/m^2 intravenously or by mouth 3 to 4 days prior to the vaccine dose, to deplete regulatory T cells. For each vaccine dose, all subjects will receive autologous dendritic cells pulsed with melanoma tumor-specific peptides. On Day 1, the subject will receive the primer vaccine dose; this will be followed by two booster vaccine doses at 6 weeks apart. Peripheral blood will be taken weekly to monitor the immune response to each peptide by tetramer assay. Re-staging will occur after the 3rd vaccine dose, along with tumor biopsy and second apheresis. Anti PD-1 therapy (standard of care) will commence 7-8 weeks after the subject's last dendritic cell vaccine.

Official Title
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Mature Dendritic Cell Vaccination Against Mutated Antigens in Patients With Advanced Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Mature dendritic cell (DC) vaccine
* Drug: Cyclophosphamide 300mg/m^2
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage III and stage IV M1a/M1b/M1c melanoma. Measurable disease is not required for enrollment eligibility and patients with completely resected disease are permitted. Male or female patients age greater than or equal to 18 years ECOG (Eastern Cooperative Oncology Group) performance status 0-2 Required initial laboratory values (performed within 14 days prior to eligibility confirmation by physician-investigator): WBC (white blood cells) >3,000/mm3 Hg (hemoglobin) greater than or equal to 9.0 gm/dl Platelets >75,000/mm3 Serum Bilirubin < 2.0 mg/dl Serum Creatinine < 2.0 mg/dl Subjects of reproductive potential must agree to use a medically accepted birth control method during the trial and for at least two months following the trial. Provide written informed consent. Exclusion Criteria: Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment with one line of cytotoxic chemotherapy is permitted. Prior treatment with targeted therapy (such as ipilimumab, anti-PD1, or BRAF + MEK inhibitor combination) is permitted. Active untreated CNS (central nervous system) metastasis Active infection Prior malignancy (except non-melanoma skin cancer) within 3 years Pregnant or nursing (lactating) women Concurrent treatment with high-dose systemic corticosteroids; local (inhaled or topical) steroids are permitted Known allergy to eggs Prior history of uveitis or autoimmune inflammatory eye disease Known positivity for hepatitis B antibody, hepatitis C antibody, or HIV antibody

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: Mature dendritic cell (DC) vaccine<br>Mature DC 7.5-15 million/peptide given day 1, every six weeks for 2 doses followed by standard of care anti PD-1 therapy | Biological: Mature dendritic cell (DC) vaccine<br>* Mature DC 7.5-15 million/peptide followed by 2 booster every six weeks of 1-5 million/peptide followed by standard of care anti PD-1 therapy.<br>Drug: Cyclophosphamide 300mg/m^2<br>* administered prior to subject's first DC dose<br>Drug: Pembrolizumab<br>* administered 7-8 weeks after subject's last DC dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. | Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. | day 1 through week 18. After week 18 every third week for 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | using RECIST 1.1 | every three weeks for 18 weeks beginning after the subjects last DC vaccine | 
| Time to progression | using RECIST 1.1 | 10-28 days after the third vaccine through study completion approximately 30 weeks after the first DC vaccine | 
| Safety and side effects of vaccine per CTCAE 4.0 | per CTCAE 4.0 | at time of consent through 30 days after the subjects last DC vaccine |