Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma
MPM patients are not eligible for surgical procedures like decortication or pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP which serves as target structure in MPM.
- Trial with immunomodulatory product / biological
|Malignant Pleural Mesothelioma||Genetic: Adoptive Transfer of re-directed T cells||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Intervention Model Description:
Adoptive Transfer of re-directed FAP-specific T cellsMasking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.|
- Safety [ Time Frame: until 35 days after transfer of re-directed T cells ]Incidence and severity of treatment-related laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version v4.03 criteria as grade III-IV. In the case of one AE grade III/IV or one SAE the safety monitoring board will judge whether the case is treatment related and whether it have to be counted as DLT.
|Study Start Date:||October 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Adoptive Transfer of re-directed T cells
Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion
Genetic: Adoptive Transfer of re-directed T cells
Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion
This is a phase I trial for patients with malignant pleural mesothelioma. A fixed single dose of adoptively transferred FAP-specific CD8 positive re-directed T cells will be given in the pleural effusion.
Three patients who are at the time point of screening not operable will be treated with re-directed T cells administered into the pleural effusion after completion of 3 cycles of palliative chemotherapy. In the case of one AE grade III/IV or one SAE - and the occurrence of DLT both judged to be treatment related by an independent safety monitoring board - the patient number will be expanded to 6 patients. The study will be stopped if one additional DLT occurs also judged to be treatment related.
Patients will be treated with 1x10e6 re-directed FAP-specific T cells injected in the pleural effusion. The study ends 35 days after adoptive T cell transfer. Re-directed FAP-specific T cells will be administered at day 0 (day 14 of the third cycle of palliative chemotherapy). The study is designed to demonstrate safety of 1x10e6 re-directed FAP-specific T cells. The next patient will be enrolled earliest, when the previous patient completed day +14 and the safety monitoring board has not declared any DLTs. The palliative chemotherapy is not part of the study protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01722149
|Contact: Alessandra Curioni, MDfirstname.lastname@example.org|
|Contact: Helga Bachmann, Study Coordinationemail@example.com|
|University Hospital Zurich, Division of Oncology||Recruiting|
|Zurich, ZH, Switzerland, 8091|
|Principal Investigator:||Alessandra Curioni, MD||University Hospital Zurich, Division of Oncology|