Overview

This trial is active, not recruiting.

Condition melanoma
Treatments cyclophosphamide, mature dendritic cell vaccine
Phase phase 1
Sponsor Abramson Cancer Center of the University of Pennsylvania
Start date August 2008
End date February 2017
Trial size 17 participants
Trial identifier NCT00683670, 07-0652 / 201103308

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
cyclophosphamide Cytoxan
mature dendritic cell vaccine
(Experimental)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
cyclophosphamide Cytoxan
mature dendritic cell vaccine
(Experimental)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 6 weeks for a total of 3 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 in order to collect PBMC for immune monitoring.
cyclophosphamide Cytoxan
mature dendritic cell vaccine

Primary Outcomes

Measure
Immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay.
time frame: Through completion of treatment
Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events
time frame: 30 days after end of treatment

Secondary Outcomes

Measure
Time to progression
time frame: Through completion of treatment or until progressive disease
Regulatory T cell depletion after cyclophosphamide administration.
time frame: Day -3 (72 hours prior to vaccine dose 1)
Safety and side effect profile of mDC administered to patients given after a single dose of cyclophosphamide.
time frame: Day 0 (prior to vaccine dose 1)
Clinical response rate using RECIST criteria
time frame: After third vaccine, sixth vaccine, and then every 8 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Unresectable stage III and stage IV M1a/M1b/M1c melanoma including patients with uveal melanoma - Age ≥ 18 years - Life expectancy ≥ 4 months - ECOG performance status 0-2 - At least 28 days from prior treatment (including adjuvant interferon) except in cases of a BRAF inhibitor (such as vemurafenib); concurrent treatment with a BRAF inhibitor +/- MEK inhibitor is permitted - Required initial laboratory values (submitted within 14 days prior to registration): - WBC >3,000/mm3 - Hg ≥ 9.0 gm/dl - Platelets >75,000/mm3 - Serum Bilirubin < 2.0 mg/dl - Serum Creatinine < 2.0 mg/dl - Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial, and sexually active men must be willing to avoid fathering a new child while receiving therapy. 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 ipilumumab, anti-PD1, and BRAF inhibitor) is permitted. - Active untreated CNS metastasis - Active infection - Prior malignancy (except non-melanoma skin cancer) within 3 years - Pregnant or nursing - Concurrent treatment with corticosteroids; local (inhaled or topical) steroids are permitted. - Inability to provide adequate informed consent - Known allergy to eggs - Prior history or uveitis or autoimmune inflammatory eye disease. - Known positivity for hepatitis BsAg, hepatitis C antibody, or HIV antibody.

Additional Information

Official title Mature Dendritic Cell Vaccination Against gp100 in Patients With Advanced Melanoma
Principal investigator Gerald P. Linette, M.D., Ph.D.
Description Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production. All patients will be given cyclophosphamide 300mg/m2 IV three days prior to vaccine dose #1 in order to deplete regulatory T cells. All patients will receive mature DC for each dose of vaccine. For each dose all patients will receive autologous dendritic cells pulsed with 2 gp100 melanoma peptides (G209-2M and G280-9V) plus up to an additional 10 unique melanoma tumor-specific peptides. All patients will receive booster doses with mature DC. The DC vaccine will be given intravenously every three weeks for a total of six vaccine doses. Peripheral blood (16 ml) will be taken weekly to monitor the immune response to each peptide by tetramer assay. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Restaging is performed after three and six vaccine doses. Patients with stable disease or better (partial response/complete response) after six doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Abramson Cancer Center of the University of Pennsylvania.
Location data was received from the National Cancer Institute and was last updated in June 2016.