Description:
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.
Title
- Brief Title: Dendritic Cell Vaccination in Patients With Advanced Melanoma
- Official Title: Mature Dendritic Cell Vaccination Against Mutated Antigens in Patients With Advanced Melanoma
Clinical Trial IDs
- ORG STUDY ID:
UPCC 17616, 826433
- SECONDARY ID:
17616
- NCT ID:
NCT03092453
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Mature dendritic cell (DC) vaccine | | Mature dendritic cell (DC) vaccine |
| Cyclophosphamide 300mg/m^2 | | Mature dendritic cell (DC) vaccine |
| Pembrolizumab | | Mature dendritic cell (DC) vaccine |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Mature dendritic cell (DC) vaccine | Experimental | 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
- Cyclophosphamide 300mg/m^2
- Pembrolizumab
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. |
| Time Frame: | day 1 through week 18. After week 18 every third week for 12 weeks. |
| Safety Issue: | |
| Description: | Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. |
Secondary Outcome Measures
| Measure: | Clinical response |
| Time Frame: | every three weeks for 18 weeks beginning after the subjects last DC vaccine |
| Safety Issue: | |
| Description: | using RECIST 1.1 |
| Measure: | Time to progression |
| Time Frame: | 10-28 days after the third vaccine through study completion approximately 30 weeks after the first DC vaccine |
| Safety Issue: | |
| Description: | using RECIST 1.1 |
| Measure: | Safety and side effects of vaccine per CTCAE 4.0 |
| Time Frame: | at time of consent through 30 days after the subjects last DC vaccine |
| Safety Issue: | |
| Description: | per CTCAE 4.0 |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | University of Pennsylvania |
Last Updated
December 17, 2020
