Autologous Dendritic Cell Vaccination in Mesothelioma (MESODEC)

April 24, 2025 updated by: Zwi Berneman, University Hospital, Antwerp

First-line Immunotherapy Using Wilms' Tumor Protein 1 (WT1)-Targeted Dendritic Cell Vaccinations for Malignant Pleural Mesothelioma

In this multicenter phase I/II trial, dendritic cells (DCs) loaded with the mesothelioma-associated tumor antigen WT1 will be used in conjunction with conventional chemotherapy for the frontline treatment of malignant pleural mesothelioma (MPM). The general objective is to provide the first-in-human experimental demonstration that the combination of platinum/pemetrexed-based chemotherapy with WT1-targeted DC vaccination is feasible and safe and enables the induction of both systemic and in situ mesothelioma-specific immune responses in patients with MPM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Malignant pleural mesothelioma (MPM) is a highly aggressive and in virtually all cases fatal cancer that is tightly associated with prior asbestos exposure. Despite some improvement over time, the prognosis of patient diagnosed with MPM remains dismal with a median overall survival from diagnosis of only 12 months.

In this single arm phase I/II trial the investigators want to demonstrate the feasibility and safety of WT1-targeted dendritic cell vaccination in MPM patients as frontline treatment in conjunction with first line platinum/pemetrexed-based chemotherapy and the induction of both systemic and in situ mesothelioma-specific immune responses. During three years of recruitment the investigators aim at including 20 patients diagnosed with histologically proven epithelial MPM (WHO grade 0-1) who are able to undergo leukapheresis, chemotherapy, immunotherapy and pleurectomy/decortication (P/D; in case of resectable disease). Patients who underwent prior treatment for MPM or with a history of another malignancy within the last five years will be excluded.

The intention of this study is to administer four vaccine doses in combination with standard of care of four 3-weekly cytoreductive platinum/pemetrexed-based chemotherapy cycles to each participant and prior to surgery (P/D) in the case of resectable MPM. Patients will receive four 3-weekly intradermal vaccinations with autologous WT1 messenger (m)RNA-loaded dendritic cells (V1-4), at day 14 after the start of each chemotherapy cycle (CT1-4).

The dendritic cell therapy product will be generated and administered in the Antwerp University Hospital, more specifically the Center for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed by Prof. Zwi Berneman.

The DC vaccines will be under embargo from release until the safety and quality control test results have become available and all release criteria have been met. A detailed overview of all applicable release criteria is provided in the investigational medicinal product dossier. The embargo period generally lasts 3 weeks counting from the day of cryopreservation (i.e. 8 days after leukapheresis).

Recruitment started in August 2017. Study-related follow-up of the included patients is intended to be until 90 days after final DC vaccine administration or 22 months after diagnosis, whichever occurs later. In addition to feasibility and safety of the chemoimmunotherapy schedule, the investigators will look for the time to progression (TTP), progression-free survival (PFS), overall survival (OS), systemic immunogenicity and local immunogenicity.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • AZ Middelares
      • Sint-Niklaas, Belgium, 9100
        • AZ Nikolaas
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • Antwerp University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis with histologically proven epithelial
  • Aged ≥ 18 years at the time of enrollment
  • WHO performance status 0-1 at the time of enrollment
  • Fit to undergo general anesthesia, a thoracoscopy, leukapheresis, chemotherapy, immunotherapy and P/D (in case of resectable disease)
  • No history of receiving any investigational treatment within 28 days of study enrollment
  • No history of intolerance to pemetrexed and/or cisplatin
  • Women of child bearing potential must have negative serum or urine pregnancy test at the time of screening. They should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least hundred days after the last study treatment. If pregnancy does occur within this time period, the Principal investigator must be informed as soon as possible. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until hundred days after the last study treatment
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discusses with the patient before registration in the trial. Absence of any other inability or unwillingness to comply with the requirements of the protocol as assessed by the investigator
  • Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria:

  • Unwilling or unable to comply with the study requirements
  • Prior treatment for MPM
  • History of another malignancy within the last five years (except for carcinoma in situ of the cervix, basal cell or spinocellular carcinoma of the skin or unless the investigator rationalizes otherwise)
  • Known proven metastases
  • Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo
  • Pregnant or breast-feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm
dendritic cell vaccination plus chemotherapy
Biological: dendritic cell vaccination plus chemotherapy

A. Chemoimmunotherapy:

  1. four 3-weekly cycles of platinum/pemetrexed; on day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as intravenous (IV) infusion over 10 minutes followed 30 minutes later by cisplatin 75 mg/m2 as IV over approximately 2 hours.
  2. four intradermal vaccinations with 8-10 x 10e6 autologous WT1 mRNA-loaded DCs; at day 14+/- 3 days after the start of each chemotherapy cycle.

B. Surgery: pleurectomy/decortication; in case of resectable disease, 4-6 weeks after start of the last chemotherapy cycle.

Other Names:
  • chemoimmunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of MPM patients with feasible and safe DC vaccine production
Time Frame: Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)

Production of autologous DC vaccines from newly diagnosed MPM patients will be evaluated for:

  1. Feasibility, assessed by success of leukapheresis and production of sufficient (i.e. at least 4 vaccines) and qualified (phenotypic and functional requirements) vaccines.
  2. Safety, assessed by microbiological testing (bacteria, yeast, fungi, mycoplasma, endotoxin) of the DC vaccines.
Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)
Number of patients receiving investigational DC vaccine administration combined with standard of care chemotherapy within the proposed time frame
Time Frame: After the chemoimmunotherapy treatment (+/- 15 weeks after entry to trial)

Administration of 4 autologous DC vaccines combined with four 3-weekly platinum/pemetrexed-based chemotherapy cycles will be evaluated for:

  1. Feasibility, assessed by successful administration of DC vaccines and prior to surgery in case of resectable disease.
  2. Safety, assessed by local (e.g. skin reactions at injection site) and systemic (toxicity grading according to the latest version of the CTCAE and CTC ) tolerability to the treatment.
After the chemoimmunotherapy treatment (+/- 15 weeks after entry to trial)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective clinical responses by tumor evaluation (clinical efficacy)
Time Frame: Through study completion, at least after 4 DC vaccinations, prior to surgery (in case of resectable disease) + three months after the last intervention and within every 12 months during follow-up

Objective clinical responses to the chemoimmunotherapy and, in case of resectable disease, after surgery as compared to baseline tumor evaluation prior to treatment (i.e. at diagnosis), will be evaluated with:

  1. radiographic assessments (CT imaging) of the tumor response using the modified RECIST criteria.
  2. FDG-PET assessments of the tumor response using the PERCIST criteria.

Patients will be followed for disease progression; time to progression (TTP) and progression-free survival (PFS).
Through study completion, at least after 4 DC vaccinations, prior to surgery (in case of resectable disease) + three months after the last intervention and within every 12 months during follow-up
Overall survival (clinical efficacy)
Time Frame: Through study completion, an average of 1 year
Patients will be followed for survival, from diagnosis and from start of treatment, for which the accurate date and reason of death (cancer-related or non-related) will be recorded for every patient.
Through study completion, an average of 1 year
Systemic immunogenicity
Time Frame: After the fourth DC vaccine (i.e. post chemoimmunotherapy, prior to surgery in case of resectable disease)

Systemic immunogenicity will be evaluated by:

  1. Detection of WT1-specific T cell immunity and innate immunity in peripheral blood.
  2. Response to delayed-type hypersensitivity (DTH) skin testing to the DC vaccine.
After the fourth DC vaccine (i.e. post chemoimmunotherapy, prior to surgery in case of resectable disease)
Local immunogenicity
Time Frame: Upon surgery (P/D)
Local immunogenicity will be evaluated by detection of immune profile in tumor biopsies and/or pleurectomy specimens (in case of resectable disease).
Upon surgery (P/D)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Antwerp

Collaborators

Kom Op Tegen Kanker
Stichting tegen Kanker

Investigators

  • Study Director: Zwi N Berneman, MD, PhD, Antwerp University Hospital, Division of Hematology and Center for Cell Therapy and Regenerative Medicine
  • Principal Investigator: Evelien LJ Smits, MSc, PhD, University of Antwerp, Laboratory of Experimental Hematology
  • Principal Investigator: Eva Lion, MSc, PhD, University of Antwerp, Laboratory of Experimental Hematology
  • Principal Investigator: Sébastien Anguille, MD, PhD, Antwerp University Hospital, Division of Hematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 3, 2017

Primary Completion (Actual)

March 9, 2025

Study Completion (Actual)

March 9, 2025

Study Registration Dates

First Submitted

December 7, 2015

First Submitted That Met QC Criteria

January 5, 2016

First Posted (Estimated)

January 8, 2016

Study Record Updates

Last Update Posted (Actual)

April 29, 2025

Last Update Submitted That Met QC Criteria

April 24, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCRG13-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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