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Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma

21. februar 2017 oppdatert av: University of Pennsylvania

Mature Dendritic Cell Vaccination Against gp100 in Patients With Advanced Melanoma

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.

Studieoversikt

Status

Fullført

Forhold

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

17

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Missouri
      • St. Louis, Missouri, Forente stater, 63110
        • Washington University School of Medicine

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Dendritic Cell Vaccine (First Group)
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.
Andre navn:
  • Cytoksan
Eksperimentell: Dendritic Cell Vaccine (Second Group)
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.
Andre navn:
  • Cytoksan
Eksperimentell: Dendritic Cell Vaccine (Third Group)
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.
Andre navn:
  • Cytoksan

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay.
Tidsramme: Through completion of treatment
  • Starting on Day 0, two tubes will be drawn weekly until Day 64. Thereafter, two tubes will be drawn every 21 days until Day 190. For patients receiving maintenance treatment, blood is drawn every month.
  • Data are presented as the percentage of CD8+ T cells positive for tetramer binding based on gating variables set using the iMASC reagent kit (Beckman Coulter).
Through completion of treatment
Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events
Tidsramme: 30 days after end of treatment
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
30 days after end of treatment

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Time to progression
Tidsramme: Through completion of treatment or until progressive disease
Through completion of treatment or until progressive disease
Regulatory T cell depletion after cyclophosphamide administration.
Tidsramme: Day -3 (72 hours prior to vaccine dose 1)
Regulatory T cells (Treg) are defined as CD4+CD25+foxP3+ (triple positive) cells. At the indicated time points, the percentage of Treg cells is determined by 3 color flow cytometry. The depletion of Treg is defined as follows [Treg baseline - Treg nadir/ Treg baseline x 100= % depletion].
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.
Tidsramme: Day 0 (prior to vaccine dose 1)
Day 0 (prior to vaccine dose 1)
Clinical response rate using RECIST criteria
Tidsramme: After third vaccine, sixth vaccine, and then every 8 weeks
After third vaccine, sixth vaccine, and then every 8 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Gerald P. Linette, M.D., Ph.D., Abramson Cancer Center of the University of Pennsylvania

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. august 2008

Primær fullføring (Faktiske)

1. juni 2016

Studiet fullført (Faktiske)

1. juni 2016

Datoer for studieregistrering

Først innsendt

19. mai 2008

Først innsendt som oppfylte QC-kriteriene

19. mai 2008

Først lagt ut (Anslag)

23. mai 2008

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

23. februar 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. februar 2017

Sist bekreftet

1. februar 2017

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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