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Dendritic Cell Vaccination in Patients With Advanced Melanoma

Primary Purpose

Melanoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mature dendritic cell (DC) vaccine
Cyclophosphamide 300mg/m^2
Pembrolizumab
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mature dendritic cell (DC) vaccine

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinical response
using RECIST 1.1
Time to progression
using RECIST 1.1
Safety and side effects of vaccine per CTCAE 4.0
per CTCAE 4.0

Full Information

First Posted
March 7, 2017
Last Updated
February 2, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT03092453
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mature dendritic cell (DC) vaccine
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Mature dendritic cell (DC) vaccine
Intervention Description
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
Drug
Intervention Name(s)
Cyclophosphamide 300mg/m^2
Intervention Description
administered prior to subject's first DC dose
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
administered 7-8 weeks after subject's last DC dose
Primary Outcome Measure Information:
Title
Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay.
Description
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.
Secondary Outcome Measure Information:
Title
Clinical response
Description
using RECIST 1.1
Time Frame
every three weeks for 18 weeks beginning after the subjects last DC vaccine
Title
Time to progression
Description
using RECIST 1.1
Time Frame
10-28 days after the third vaccine through study completion approximately 30 weeks after the first DC vaccine
Title
Safety and side effects of vaccine per CTCAE 4.0
Description
per CTCAE 4.0
Time Frame
at time of consent through 30 days after the subjects last DC vaccine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerald P Linette, MD, PhD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Dendritic Cell Vaccination in Patients With Advanced Melanoma

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