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Malignant Pleural MesotheliomaPhase 1/2MESODECNCT02649829

Autologous Dendritic Cell Vaccination in Mesothelioma

A Phase 1/2 study testing dendritic cell vaccination plus chemotherapy in people with Malignant Pleural Mesothelioma, run by University Hospital, Antwerp at 3 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Pleural Mesothelioma
What is being tested?
dendritic cell vaccination plus chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
3 sitesBelgium
Study dates
3 Oct 2017to 9 Mar 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country.

Belgium3 sites

  • Antwerp University Hospital

    Edegem, Antwerp, 2650

  • AZ Middelares

    Ghent, 9000

  • AZ Nikolaas

    Sint-Niklaas, 9100

Other trials in Belgium

About this study

Official title: 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.

Read the 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.

Being tested
dendritic cell vaccination plus chemotherapy
Keywords
dendritic cell vaccination, chemo-immunotherapy, Wilms' tumor 1 (WT1)
Medical subject headings
Mesothelioma, Malignant, Wilms Tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dendritic cell vaccination plus chemotherapyBiological

    Also called chemoimmunotherapy

    1. Chemoimmunotherapy:
    2. 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.
    3. 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.
    4. Surgery: pleurectomy/decortication; in case of resectable disease, 4-6 weeks after start of the last chemotherapy cycle.
Study groups in NCT02649829
Study groupRoleWhat they receive
Single ArmExperimentaldendritic cell vaccination plus chemotherapy
Receives: Biological: dendritic cell vaccination plus chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of MPM patients with feasible and safe DC vaccine production

    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.

    Measured: Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)

  2. Number of patients receiving investigational DC vaccine administration combined with standard of care chemotherapy within the proposed time frame

    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.

    Measured: After the chemoimmunotherapy treatment (+/- 15 weeks after entry to trial)

Secondary outcomes (4)

  1. Objective clinical responses by tumor evaluation (clinical efficacy)

    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).

    Measured: 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

  2. Overall survival (clinical efficacy)

    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.

    Measured: Through study completion, an average of 1 year

  3. Systemic immunogenicity

    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.

    Measured: After the fourth DC vaccine (i.e. post chemoimmunotherapy, prior to surgery in case of resectable disease)

  4. Local immunogenicity

    Local immunogenicity will be evaluated by detection of immune profile in tumor biopsies and/or pleurectomy specimens (in case of resectable disease).

    Measured: Upon surgery (P/D)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2016 (estimated)
  2. Study start3 Oct 2017
  3. Primary completion9 Mar 2025
  4. Study completion9 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02649829
Sponsor's protocol ID
CCRG13-002
Acronym
MESODEC
Status last verified
Apr 2025
First submitted
7 Dec 2015
Last updated
29 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005 Jul 30-Aug 5;366(9483):397-408. doi: 10.1016/S0140-6736(05)67025-0.

    PubMed 16054941

  • Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005 Oct 13;353(15):1591-603. doi: 10.1056/NEJMra050152. No abstract available.

    PubMed 16221782

  • Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.

    PubMed 12860938

  • Musk AW, Olsen N, Alfonso H, Reid A, Mina R, Franklin P, Sleith J, Hammond N, Threlfall T, Shilkin KB, de Klerk NH. Predicting survival in malignant mesothelioma. Eur Respir J. 2011 Dec;38(6):1420-4. doi: 10.1183/09031936.00000811. Epub 2011 Jul 7.

    PubMed 21737558

  • Bagia M, Nowak AK. Novel targeted therapies and vaccination strategies for mesothelioma. Curr Treat Options Oncol. 2011 Jun;12(2):149-62. doi: 10.1007/s11864-011-0149-1.

    PubMed 21424750

  • Bograd AJ, Suzuki K, Vertes E, Colovos C, Morales EA, Sadelain M, Adusumilli PS. Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma. Cancer Immunol Immunother. 2011 Nov;60(11):1509-27. doi: 10.1007/s00262-011-1103-6. Epub 2011 Sep 13.

    PubMed 21913025

  • Izzi V, Masuelli L, Tresoldi I, Foti C, Modesti A, Bei R. Immunity and malignant mesothelioma: from mesothelial cell damage to tumor development and immune response-based therapies. Cancer Lett. 2012 Sep 1;322(1):18-34. doi: 10.1016/j.canlet.2012.02.034. Epub 2012 Mar 3.

    PubMed 22394996

  • Gregoire M. What's the place of immunotherapy in malignant mesothelioma treatments? Cell Adh Migr. 2010 Jan-Mar;4(1):153-61. doi: 10.4161/cam.4.1.11361. Epub 2010 Jan 30.

    PubMed 20179421

  • Kushitani K, Takeshima Y, Amatya VJ, Furonaka O, Sakatani A, Inai K. Immunohistochemical marker panels for distinguishing between epithelioid mesothelioma and lung adenocarcinoma. Pathol Int. 2007 Apr;57(4):190-9. doi: 10.1111/j.1440-1827.2007.02080.x.

    PubMed 17316414

  • Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014 Jun;15(7):e257-67. doi: 10.1016/S1470-2045(13)70585-0.

    PubMed 24872109

  • Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. doi: 10.1164/rccm.200501-057OC. Epub 2005 Mar 11.

    PubMed 15764728

  • Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90. doi: 10.1164/rccm.200909-1465OC. Epub 2010 Feb 18.

    PubMed 20167848

  • Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.

    PubMed 19656053

  • Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN. Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood. 2001 Jul 1;98(1):49-56. doi: 10.1182/blood.v98.1.49.

    PubMed 11418462

  • Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.

    PubMed 20631300

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing dendritic cell vaccination plus chemotherapy in people with Malignant Pleural Mesothelioma, run by University Hospital, Antwerp at 3 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of MPM patients with feasible and safe DC vaccine production (time frame: Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02649829, which also lists 43 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.

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