Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma

University of Pennsylvania

Status and phase: Completed; Phase 1

Conditions: Melanoma

Treatments: Biological: Mature dendritic cell vaccine; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT00683670

07-0652 / 826850

Details and patient eligibility

About

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.

Full 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.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 3 patient groups

Dendritic Cell Vaccine (First Group)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Biological: Mature dendritic cell vaccine

Dendritic Cell Vaccine (Second Group)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Biological: Mature dendritic cell vaccine

Dendritic Cell Vaccine (Third Group)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Biological: Mature dendritic cell vaccine