Dendritic Cell Vaccination in Patients With Advanced Melanoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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.]
Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay.
Secondary Outcome Measures
- Clinical response [every three weeks for 18 weeks beginning after the subjects last DC vaccine]
using RECIST 1.1
- Time to progression [10-28 days after the third vaccine through study completion approximately 30 weeks after the first DC vaccine]
using RECIST 1.1
- Safety and side effects of vaccine per CTCAE 4.0 [at time of consent through 30 days after the subjects last DC vaccine]
per CTCAE 4.0
Eligibility Criteria
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.
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Male or female patients age greater than or equal to 18 years
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ECOG (Eastern Cooperative Oncology Group) performance status 0-2
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Required initial laboratory values (performed within 14 days prior to eligibility confirmation by physician-investigator):
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WBC (white blood cells) >3,000/mm3
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Hg (hemoglobin) greater than or equal to 9.0 gm/dl
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Platelets >75,000/mm3
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Serum Bilirubin < 2.0 mg/dl
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Serum Creatinine < 2.0 mg/dl
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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.
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Provide written informed consent.
Exclusion Criteria:
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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.
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Active untreated CNS (central nervous system) metastasis
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Active infection
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Prior malignancy (except non-melanoma skin cancer) within 3 years
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Pregnant or nursing (lactating) women
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Concurrent treatment with high-dose systemic corticosteroids; local (inhaled or topical) steroids are permitted
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Known allergy to eggs
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Prior history of uveitis or autoimmune inflammatory eye disease
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Known positivity for hepatitis B antibody, hepatitis C antibody, or HIV antibody
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
- Principal Investigator: Gerald P Linette, MD, PhD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UPCC 17616, 826433
- 17616