Dendritic Cell Vaccination in Patients With Advanced Melanoma

University of Pennsylvania5 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma

Interventions

Mature dendritic cell (DC) vaccineBIOLOGICAL

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.

Cyclophosphamide 300mg/m^2DRUG

administered prior to subject's first DC dose

PembrolizumabDRUG

administered 7-8 weeks after subject's last DC dose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

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. 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.

Time frame: Screening through week 21

Safety and Tolerability of the Mature Dendritic Cell Vaccine (mDC3/8 Vaccines).

Safety endpoint is type and number of adverse events. Tolerability endpoint is subject's completion or withdrawal from study treatment.

Time frame: End of Study visit (10-28 days after last DC vaccine)

Secondary Outcomes

Clinical Response to the mDC3/8 Vaccine(s)

using RECIST 1.1

Time frame: At the End of Study Treatment visit (~10-28 Days after the last DC vaccine)

Time to Progression Post-mDC3/8 Vaccine Administration

based on RECIST 1.1 criteria, until occurrence of a censoring event

Time frame: Up to 30 weeks after the first mDC3/8 Vaccine

Safety and Side Effect Profile of the Dendritic Cell Vaccine (mDC3/8 Vaccines) Administered to Patients Given After a Single Dose of Cyclophosphamide.

Assessed through collection of Adverse Events.

Time frame: End of Study visit (10-28 days after last DC vaccine)

Data from ClinicalTrials.gov

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