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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335890
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Beatrice Schuler-Thurner, Ph.D, University Hospital Erlangen

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
Melanoma, Uveal Metastatic 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 24, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2025


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 Name: Dendritic Cell vaccine




Primary Outcome Measures :
  1. Safety of DCIKKb [ Time Frame: 1 year ]
    Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

  2. Tolerability of DCIKKb [ Time Frame: 1 year ]
    Assesment of Quality of life using Quality of life EORTC QLQ-C30, Version 2

  3. Dose-limiting toxicities (DLTs) of DCIKKb [ Time Frame: 1 year ]
    Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)

  4. Maximum tolerated dose (MTD) of DCIKKb [ Time Frame: 1 year ]
    Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)


Secondary Outcome Measures :
  1. Prolongation of median overall survival [ Time Frame: 2 years ]
    Assesment of survival

  2. Prolongation of overall survival (OS) after 1 and 2 years [ Time Frame: 2 years ]
    Assesment of survival

  3. Induction of antigen specific CD8+ T cells and / or CD4+ T cells against TAA and mutated drivers [ Time Frame: 2 years ]
    Assesment of immune responses



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335890


Contacts
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Contact: Beatrice Schuler-Thurner, MD 0049 9131 85 ext 45833 beatrice.schuler-thurner@uk-erlangen.de
Contact: Michael Erdmann, MD 0049 9131 85 ext 45833 michael.erdmann@uk-erlangen.de

Locations
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Germany
University Hospital Erlangen Dept. of Dermatology Recruiting
Erlangen, Bavaria, Germany, 91054
Contact: B Schuler-Thurner, Associate Professor    +49 9131 853 ext 5833    experimentelle-immuntherapie@uk-erlangen.de   
Contact: Michael Erdmann, MD    +49 9131 853 ext 5833    experimentelle-immuntherapie@uk-erlangen.de   
Sponsors and Collaborators
Hasumi International Research Foundation
Investigators
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Principal Investigator: Beatrice Schuler-Thurner, MD University Hospital Erlangen Germany
Publications of Results:
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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: April 7, 2020    Key Record Dates
Last Update Posted: August 4, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, University Hospital Erlangen:
local treatment not sufficient
systemic treatment indicated
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Immunologic Factors
Physiological Effects of Drugs