Multi-centre trial

The initiation of a multi partner trial is planned and data will be generated. The DC-THERA trial will compare the use of ‘TRI-MIX’ RNA in clinical trials that were already underway at each of the three centres (Nijmegen Medical School, Nijmegen; Friedrich-Alexander University, Erlangen; Vrije Universiteit Brussel, Brussels).

It was decided that Friedrich-Alexander University, Erlangen, would apply for a licence to prepare GMP-grade ‘TRI-MIX’ RNA and subsequently supply this for all three centres.

The multi-centre trial is a well-standardised, two-arm, multi-centre clinical trial in melanoma patients comparing DC transfected with mRNA coding for constitutively active TLR-4, CD40 and CD70 (‘TRI-MIX’) with other modalities. The trial will be conducted across the 3 centres mentioned above using standardised SOPs – both for preparation of DC and for subsequent immunomonitoring. At these respective centres the following will be compared:

1) peptide-pulsed DC, matured either with the standard maturation cocktail (IL-1, IL-6, TNF-alpha, PGE2) or transfected with ‘TRI-MIX’, and administered intra-nodally under ultrasound guidance (Nijmegen)
2) antigen mRNA-transfected DC, matured either with the standard maturation cocktail (IL-1, IL-6, TNF-alpha, PGE2) or transfected with ‘TRI-MIX’, and administered subcutaneously (Erlangen)
3) antigen mRNA-transfected DC, co-transfected with ‘TRI-MIX’, comparing intradermal vaccination with intradermal plus intravenous vaccination (Brussels).

The analyses of all DC vaccination trials published has shown that this general vaccination strategy is clearly promising given the fact that the adoptive transfer of antigen-loaded DC (i.e. DC vaccination) appears more immunogenic than other vaccination strategies and clinical effects have also been observed even with first generation DC vaccines. The major deficit in this field is that the obvious variables are simply not addressed in a well-coordinated fashion to allow rapid optimization. This is a pity as DC vaccination is rather unique in that it allows to control ex vivo many biological aspects of DC relevant for optimized DC vaccination but also for other more conventional vaccine strategies (which also depend on DC as antigen in various formats + adjuvant is injected which has to reach and activate DC in situ). The reason for the lack of coordinated testing including combination strategies appears to differ in industry and academia. Biotech companies naturally focus on strategies which are covered by their intellectual property and patents, and in academia there are people with different ideas and visions who in addition have to “publish and perish” even if dealing with mid- to long-term efforts such as clinical trials for which in addition there is insufficient funding.

After treatment of 50% of the patients (i.e. 15 patients in the Tri-Mix-DC arm) or by the end of 2009, whichever comes first, we will perform an interim analysis of this immunogenicity trial. A final immunogenicity analysis, which might identify a particularly immunogenic superior DC vaccine, will be available by mid 2010. The clinical fate of the patients will be followed further but this is not the endpoint of this immunogenicity trial.

created over 15 years ago (10 December 2009)    last modified over 12 years ago (26 November 2012)   [ RDF ]   [ RelFinder ]