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

Sponsor
Hasumi International Research Foundation (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04335890
Collaborator
(none)
12
Enrollment
1
Location
1
Arm
43.2
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
  • Biological: Vaccination with IKKb matured Dendritic Cells
 Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 24, 2020
Anticipated Primary Completion Date :
Jan 30, 2023
Anticipated Study Completion Date :
Jan 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: DC IKKb

Vaccination with IKKb matured RNA loaded Dendritic Cells

Biological: Vaccination with IKKb matured Dendritic Cells
IKKb matured autologous monocyte derived dendritic cells loaded with RNAs; intravenous Infusion with a dose escalation starting with 7.5 mio Dendritic Cells for the first vaccination up to 30 mio cells per vaccination
Other Names:
  • Dendritic Cell vaccine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety of DCIKKb [1 year]

      Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

    2. Tolerability of DCIKKb [1 year]

      Assesment of Quality of life using Quality of life EORTC QLQ-C30, Version 2

    3. Dose-limiting toxicities (DLTs) of DCIKKb [1 year]

      Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

    4. Maximum tolerated dose (MTD) of DCIKKb [1 year]

      Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

    Secondary Outcome Measures

    1. Prolongation of median overall survival [2 years]

      Assesment of survival

    2. Prolongation of overall survival (OS) after 1 and 2 years [2 years]

      Assesment of survival

    3. Induction of antigen specific CD8+ T cells and / or CD4+ T cells against TAA and mutated drivers [2 years]

      Assesment of immune responses

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital Erlangen Dept. of Dermatology Erlangen Bavaria Germany 91054

    Sponsors and Collaborators

    • Hasumi International Research Foundation

    Investigators

    • Principal Investigator: Beatrice Schuler-Thurner, MD, University Hospital Erlangen Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Beatrice Schuler-Thurner, Ph.D, PD Dr. Beatrice Schuler-Thurner, University Hospital Erlangen
    ClinicalTrials.gov Identifier:
    NCT04335890
    Other Study ID Numbers:
    • DERMA-ER-DC 09
    First Posted:
    Apr 7, 2020
    Last Update Posted:
    Mar 17, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Beatrice Schuler-Thurner, Ph.D, PD Dr. Beatrice Schuler-Thurner, University Hospital Erlangen
    local treatment not sufficient
    systemic treatment indicated
    Additional relevant MeSH terms:
    Melanoma
    Vaccines

    Study Results

    No Results Posted as of Mar 17, 2022