Clinical Trials /

IKKb-matured, RNA-loaded Dendritic Cells for Metastasised Uveal Melanoma

NCT04335890

Description:

A Phase I vaccination trial in patients suffering from recently diagnosed metastatic uveal melanoma not cureable with local therapy and needing systemic therapy. IKKb-matured Dendritic Cells loaded with autologous tumor-RNA + RNA coding for defined antigens and driver mutations will be added to a standard therapy chosen by the tumor board (either checkpoint blockade or chemotherapy).

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: IKKb-matured, RNA-loaded Dendritic Cells for Metastasised Uveal Melanoma
  • Official Title: Phase I Vaccination Trial in Metastatic Uveal Melanoma Using IKKb-matured Dendritic Cells Loaded With Autologous Tumor-RNA + RNA Coding for Defined Antigens and Driver Mutations

Clinical Trial IDs

  • ORG STUDY ID: DERMA-ER-DC 09
  • NCT ID: NCT04335890

Conditions

  • Melanoma, Uveal Metastatic

Interventions

DrugSynonymsArms
Vaccination with IKKb matured Dendritic CellsDendritic Cell vaccineDC IKKb

Purpose

A Phase I vaccination trial in patients suffering from recently diagnosed metastatic uveal melanoma not cureable with local therapy and needing systemic therapy. IKKb-matured Dendritic Cells loaded with autologous tumor-RNA + RNA coding for defined antigens and driver mutations will be added to a standard therapy chosen by the tumor board (either checkpoint blockade or chemotherapy).

Detailed Description

      Intravenous infusion of 7.5 to 30 mio DCIKKb at 9 vaccination time points (week 1, 3, 7, 13,
      19, 25, 31, 37 and 42) and in intervals of 2, 4, and 6 intervals of 6 weeks) is scheduled;
      the first 4 patients will receive reduced doses for the first 4 vaccinations, namely 7.5 mio
      (1st and 2nd vaccination) and 15 mio (3rd and 4th vaccination) DC followed by the full dose
      of 30 mio for subsequent vaccinations. Patients number 5 to 8 will receive initially reduced
      doses of 15 mio (1st and 2nd vaccination) DC for the first 2 vaccinations, and the full dose
      of 30 mio for subsequent vaccinations. Patients number 8 to 12 will receive the full dose of
      30 mio cells from vaccination 1 onwards provided that no major side effects occurred.
      Patients will be vaccinated in a staggered approach by selectively decelerating release of
      the vaccine.

      DCIKKb = autologous, monocyte-derived DC that are matured with the standard cocktail
      (TNF-alpha, IL-1 beta, IL-6 and PGE2) and IKKb-RNA loaded by electroporation with 1)
      autologous PCR-amplified total tumor mRNA, 2) RNA coding for defined tumor associated
      antigens (TAA) namely gp100, tyrosinase, PRAME, MAGE-A3, IDO) and 3) RNA coding for driver
      mutations (GNAQ/GNA11Q209 or R183, or the less frequently occurring SF3B1R625, CYSLTR2L129Q
      or PLCB4D630) by electroporation; RNAs for selected TAAs are in stock and will be transfected
      into the DCs only if expressed in the individual tumor of a patient (shown by RNA sequencing
      of the tumor); RNAs for selected driver mutations are in stock and will be loaded into the
      DCs only if the respective mutation is found (proven by exome and RNA sequencing) in the
      individual tumor.
    

Trial Arms

NameTypeDescriptionInterventions
DC IKKbExperimentalVaccination with IKKb matured RNA loaded Dendritic Cells
  • Vaccination with IKKb matured Dendritic Cells

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed unresectable stage IV metastatic uveal melanoma as per AJCC
             staging system 2014, 7th edition (updated 2018) not curable with local therapy
             modalities

          -  WHO performance status of 0, 1 or 2

          -  age from 18 and ≤ 75 years

          -  negative pregnancy test

          -  signed informed consent

        Exclusion Criteria:

          -  Major serious illness

          -  evidence for HIV-1, HIV-2, HTLV-1, HBV or HCV infection

          -  active autoimmune disease requiring immunosuppressive therapy

          -  splenectomy or radiation therapy of the spleen

          -  organ allografts

          -  pregnancy

          -  lactation

          -  psychiatric disorders

          -  severe organic brain syndrome
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of DCIKKb
Time Frame:1 year
Safety Issue:
Description:Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

Secondary Outcome Measures

Measure:Prolongation of median overall survival
Time Frame:2 years
Safety Issue:
Description:Assesment of survival
Measure:Prolongation of overall survival (OS) after 1 and 2 years
Time Frame:2 years
Safety Issue:
Description:Assesment of survival
Measure:Induction of antigen specific CD8+ T cells and / or CD4+ T cells against TAA and mutated drivers
Time Frame:2 years
Safety Issue:
Description:Assesment of immune responses

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hasumi International Research Foundation

Trial Keywords

  • local treatment not sufficient
  • systemic treatment indicated

Last Updated

April 22, 2020