Dendritic Cell Vaccination in Patients With Advanced Melanoma

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03092453
• Other study ID #: UPCC 17616, 826433
• Secondary ID: 17616
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 1, 2017
• Est. completion date: May 2023

Study information

• Verified date: February 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Melanoma

Intervention

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

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical response	using RECIST 1.1	every three weeks for 18 weeks beginning after the subjects last DC vaccine
Secondary	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
Secondary	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