Clinical trial NCT00683670: Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma
Official title: Mature Dendritic Cell Vaccination Against gp100 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: 2008-05-23
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay.
timeFrame: Through completion of treatment
measure: Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events
timeFrame: 30 days after end of treatment
Secondary outcomes:
measure: Time to progression
timeFrame: Through completion of treatment or until progressive disease
measure: Regulatory T cell depletion after cyclophosphamide administration.
timeFrame: Day -3 (72 hours prior to vaccine dose 1)
measure: Safety and side effect profile of mDC administered to patients given after a single dose of cyclophosphamide.
timeFrame: Day 0 (prior to vaccine dose 1)
measure: Clinical response rate using RECIST criteria
timeFrame: After third vaccine, sixth vaccine, and then every 8 weeks
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Gerald P. Linette, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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