Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Wilms Tumor

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

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Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Wilms' Tumor

Antineoplastic Agents

All Drugs and Chemicals

Pemetrexed

Cisplatin

Immunomodulating Agents

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.

Zwi N Berneman, MD, PhD

Eva Lion, MSc, PhD

Evelien LJ Smits, MSc, PhD

Sébastien Anguille, MD, PhD

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.

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.

Autologous Dendritic Cell Vaccination in Mesothelioma

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

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.

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.

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).

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.

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.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous Dendritic Cell Vaccination in Mesothelioma	NCT02649829	Malignant Pleur...	dendritic cell ...	18 Years -	University Hospital, Antwerp
Autologous Dendritic Cell Vaccination in Mesothelioma	NCT02649829	Malignant Pleur...	dendritic cell ...	18 Years -	University Hospital, Antwerp
Autologous Dendritic Cell Vaccination in Mesothelioma	NCT02649829	Malignant Pleur...	dendritic cell ...	18 Years -	University Hospital, Antwerp

Spots Global Cancer Trial Database for wilms' tumor 1 (wt1)