Dendritic Cell Vaccination in Patients With Advanced Melanoma

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: Mature dendritic cell (DC) vaccine; Drug: Cyclophosphamide 300mg/m^2; Drug: Pembrolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: Mature dendritic cell (DC) vaccine; 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.; Drug: Cyclophosphamide 300mg/m^2; administered prior to subject's first DC dose; Drug: Pembrolizumab; administered 7-8 weeks after subject's last DC dose

What is the study measuring?

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. 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.	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.	End of Study visit (10-28 days after last DC vaccine)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response to the mDC3/8 Vaccine(s)	using RECIST 1.1	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	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.	End of Study visit (10-28 days after last DC vaccine)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Gerald P Linette, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Pembrolizumab
• Other Study ID Numbers: UPCC 17616, 826433; 17616 (Other Identifier: Abramson Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No