Mesothelioma was designated as orphan disease by both the EMA and the FDA, a designation that has the goal to speed up the developmental process from laboratory to patient treatment. This phase III clinical trial aims to serve as final registration study, which is the last step to be taken before dendritic cell immunotherapy can be made available to mesothelioma patients worldwide. Since it is of outmost importance that the European Medicine Agency (EMA) and Food and Drug Authority (FDA) will accept the results of this study, the consortium has made tremendous effort to perfect the study protocol to ensure that it will meet all criteria of EMA and FDA. Obtaining approvals for the clinical study was more time consuming and complex than anticipated based on previous studies.
Patients were randomized to receive either dendritic cell-based immunotherapy or standard care. Inclusion of patients in the first centers started mid 2018, and more centers started including subsequently. From early 2020, COVID-19 has had a tremendous impact on the project. Inclusion was temporarily stopped between mid-March and mid-May 2020, while treatment, care and follow-up of already included patients continued as much as possible, taking into account local (travel)restrictions and hospital visit policies. Continuously changing travel restrictions and hospital policies throughout 2020 and 2021 made it extremely challenging to complete the inclusion of patients for this project, as patients randomized to the dendritic cell-based immunotherapy had to travel to The Netherlands to undergo leukapheresis. Also, even when travel restrictions were lifted slightly, hospital policies still made it difficult to facilitate inclusion of the study, as non-urgent care was scaled down to facilitate COVID-19 related care and other urgent care. However, since the consortium was committed to complete the study, a strategy was developed to complete inclusion. This involved decreasing the sample size. The original sample size was based on a specific number of events that would be required to draw firm conclusions from the study. As the study was taking longer than expected, the follow up of included patients could be extended and more events took place with a lower number of patients. This meant that the sample size could be decreased to a total of 176, while maintaining the statistical power of the study. This made it feasible to complete inclusion, despite the challenging COVID-19 situation. The final patient was included in June 2021.This means that follow up has been completed, and that follow up is still ongoing. Once the follow up of all patients has been completed, the database will be closed and final analyses will be performed. These data will be used to complete the registration files, which will be submitted to the EMA and FDA in order to request approval for registration of this dendritic cell-based immunotherapy for treatment for malignant mesothelioma.
