Dendritic Cell Vaccination in Patients With Advanced Melanoma

Phase 1

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Mature dendritic cell (DC) vaccine	Cyclophosphamide 300mg/m^2	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
Mature dendritic cell (DC) vaccine	Pembrolizumab	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
Mature dendritic cell (DC) vaccine	Mature dendritic cell (DC) vaccine	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

Primary Outcome Measures

Name	Time	Method
Immune Response Measuring Increased Numbers of Peptide Specific T Cells as Calculated by the Tetramer Assay.	Screening through week 21	Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. The numbers of Peptide Specific T Cells are reported as the percent of CD8+ T cells that were p/HLA multimer positive for each antigen.
Safety and Tolerability of the Mature Dendritic Cell Vaccine (mDC3/8 Vaccines).	End of Study visit (10-28 days after last DC vaccine)	Safety endpoint is type and number of adverse events. Tolerability endpoint is subject's completion or withdrawal from study treatment.

Secondary Outcome Measures

Name	Time	Method
Clinical Response to the mDC3/8 Vaccine(s)	At the End of Study Treatment visit (~10-28 Days after the last DC vaccine)	using RECIST 1.1
Time to Progression Post-mDC3/8 Vaccine Administration	Up to 30 weeks after the first mDC3/8 Vaccine	based on RECIST 1.1 criteria, until occurrence of a censoring event
Safety and Side Effect Profile of the Dendritic Cell Vaccine (mDC3/8 Vaccines) Administered to Patients Given After a Single Dose of Cyclophosphamide.	End of Study visit (10-28 days after last DC vaccine)	Assessed through collection of Adverse Events.