In this 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.
|First Received Date||December 7, 2015|
|Last Changed Date||January 24, 2017|
|Start Date||October 2015|
|Anticipated Primary Completion Date||October 2020|
|Primary Outcome Measures||
Number of MPM patients with feasible and safe DC vaccine production [Time Frame: 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)]
|Secondary Outcome Measures||
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]
Overall survival (clinical efficacy) [Time Frame: 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)]
Local immunogenicity [Time Frame: Upon surgery (P/D)]
|Phase||Phase 1/Phase 2|
|Study Arms / Comparison Groups||1 / 0|
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 November 2015. Study-related follow-up of the included patients is intended to be until death. 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.
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
Zwi N Berneman, MD, PhD
Phone: 0032 3 821 39 15
- 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 within 72 hours prior to the first dose of study treatment/surgery. They should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least three months after the last study treatment. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until three months 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
- 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
|Sponsor||University Hospital, Antwerp|
|Verification Date||January 2017|