Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma (PMR-MM-002)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma|
- number of cytotoxic T cells and regulatory T cells in the blood of patients [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.
- safety and toxicity [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2009|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Experimental: DC immunotherapy + CTX
Patients with mesothelioma who are fit enough to be treated with chemotherapy and enough tumor material was available are asked for participation in this study. After 4 cycles of Alimta chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using different cytokines. The procedure to grow DCs in vitro and pulse them with tumor lysate is performed according to our earlier performed phase I study that was approved by our local ethics committee. Three doses of properly pulsed autologous DCs (MesoCancerVac) are then re-injected every two weeks. Patients will be treated with a low dose of CTX for seven day in a row the week before the 1st vaccination, the weeks in between the 2nd, and for one week after the 3rd vaccination.
Biological: DC + CTX
3x 50x10e6 DC + cyclophosphamide
Other Name: Endoxan
Currently there is no satisfactory low-toxicity treatment for patients with mesothelioma (MM). Based on studies in other types of cancer in humans where beneficial effects were obtained, and based on our pre-clinical data in a mouse model for MM, led to the introduction of DC-immunotherapy for human MM in 2005. A beneficial effect of immunotherapy in MM patients without major side effects was found, however, research has shown that DC immunotherapy might be further improved. The objectives of the here proposed phase study are:
- To define the safety and toxicity of low dose CTX in combination with MesoCancerVac in patients with MM.
- To determine if vaccination with low dose CTX in combination with MesoCancerVac results in a detectable immune response by skin DTH reactions on MM crude antigen and KLH and by in vitro laboratory analysis.
- To observe and document anti-cancer activity by laboratory evaluation (e.g. decrease in Tregs, increase in CTLs using 51Cr release and IFN-gamma ELISPOT)
- To observe and document anti-cancer activity by clinical evaluation (e.g. CT scan)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01241682
|Erasmus Medical Center|
|Rotterdam, Zuid-Holland, Netherlands, 3000 CA|
|Principal Investigator:||Joachim Aerts, PhD MD||Erasmus Medical Center|