Dendritic Cell Vaccination in Patients With Advanced Melanoma

NCT ID: NCT03092453

Last Updated: 2024-12-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2023-03-31

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.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Mature dendritic cell (DC) vaccine

Intervention Type: BIOLOGICAL

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^2

Intervention Type: DRUG

administered prior to subject's first DC dose

Pembrolizumab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: BIOLOGICAL

Cyclophosphamide 300mg/m^2

administered prior to subject's first DC dose

Intervention Type: DRUG

Pembrolizumab

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerald P Linette, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

17616

Identifier Type: OTHER

Identifier Source: secondary_id

UPCC 17616, 826433

Identifier Type: -

Identifier Source: org_study_id