Clinical trial NCT03092453: Dendritic Cell Vaccination in Patients With Advanced Melanoma
Official title: Mature Dendritic Cell Vaccination Against Mutated Antigens in Patients With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2017-03-28
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Immune Response Measuring Increased Numbers of Peptide Specific T Cells as Calculated by the Tetramer Assay.
timeFrame: Screening through week 21
measure: Safety and Tolerability of the Mature Dendritic Cell Vaccine (mDC3/8 Vaccines).
timeFrame: End of Study visit (10-28 days after last DC vaccine)
Secondary outcomes:
measure: Clinical Response to the mDC3/8 Vaccine(s)
timeFrame: At the End of Study Treatment visit (~10-28 Days after the last DC vaccine)
measure: Time to Progression Post-mDC3/8 Vaccine Administration
timeFrame: Up to 30 weeks after the first mDC3/8 Vaccine
measure: Safety and Side Effect Profile of the Dendritic Cell Vaccine (mDC3/8 Vaccines) Administered to Patients Given After a Single Dose of Cyclophosphamide.
timeFrame: End of Study visit (10-28 days after last DC vaccine)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Gerald P Linette, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: