Periodic Reporting for period 3 - TRACE (Transfer of multivirus-specific T-cells following transplantation)
Reporting period: 2021-01-01 to 2022-06-30
The objective of the TRACE-Project ("TRansfer of Adenovirus, Cytomegalovirus and Epstein-Barr-virus-specific T cells") is to bring adoptive transfer of virus-specific T cells into clinical routine.
Allogeneic stem cell transplantation (HSCT) is a curative treatment for a variety of diseases. Refractory viral infections, such as Cytomegalovirus (CMV), Epstein-Barr-virus (EBV) and Adenovirus (AdV) post-HSCT are rare, life-threatening conditions due to the deficient T-cell response and lacking effective treatment options. Using T-cell immunotherapy will enable the host to protect himself instead of receiving toxic antiviral chemotherapy.
Although cellular immunotherapy is considered a major recent breakthrough in medicine, none of the cellular treatment approaches has yet become a standard treatment. The reason for this limited translation into daily clinical practice is the lack of controlled, prospective clinical trials investigating efficacy of immunotherapy.
TRACE is the first multi-national clinical trial to prove efficacy and safety of adoptive T-cell transfer in immune-compromized individuals. For the first time, this trial will show that a unique individualized immunotherapy could be included into evidence based clinical routine in rare diseases. Regulatory and structural hurdles will be overcome by standardized GMP-procedures. It will be a major milestone in the development of medicine and health economics to bring such a unique personalized treatment approach into a clinical efficacy trial.
Furthermore the generated data could be used for a potential prophylactic intervention, so in the future patients may be protected in an individualized way, even before the onset of infections.
Allogeneic stem cell transplantation (HSCT) is a curative treatment for a variety of diseases. Refractory viral infections, such as Cytomegalovirus (CMV), Epstein-Barr-virus (EBV) and Adenovirus (AdV) post-HSCT are rare, life-threatening conditions due to the deficient T-cell response and lacking effective treatment options. Using T-cell immunotherapy will enable the host to protect himself instead of receiving toxic antiviral chemotherapy.
Although cellular immunotherapy is considered a major recent breakthrough in medicine, none of the cellular treatment approaches has yet become a standard treatment. The reason for this limited translation into daily clinical practice is the lack of controlled, prospective clinical trials investigating efficacy of immunotherapy.
TRACE is the first multi-national clinical trial to prove efficacy and safety of adoptive T-cell transfer in immune-compromized individuals. For the first time, this trial will show that a unique individualized immunotherapy could be included into evidence based clinical routine in rare diseases. Regulatory and structural hurdles will be overcome by standardized GMP-procedures. It will be a major milestone in the development of medicine and health economics to bring such a unique personalized treatment approach into a clinical efficacy trial.
Furthermore the generated data could be used for a potential prophylactic intervention, so in the future patients may be protected in an individualized way, even before the onset of infections.
The TRACE project started with creating the basis for manufacturing of the multivirus-specific T-cell product investigated in the clinical trial. Regulatory and logistic hurdles of individualized T-cell products were overcome by standardization of GMP-procedures and logistics. All manufacturing centres (except UK) have been approved by local as well as competent national authorities. Work package 1 – Harmonization and validation of GMP-production has been completed. The compliance measures will be continued during the clinical study.
In parallel, the infrastructure for the clinical trial in terms of contact office, eCRF finalization, trial committees, data management, security structure and clinical trial applications has been set-up. Clinical trial approvals have been obtained from the competent authorities as well as central ethics committees for all participating countries (except UK and 2 out of 31 local ethics committees). The IMP for the trial is a personalized therapy, demanding close interaction between the clinical sites and the manufacturing centres, thus special attention was paid to set-up logistic and communication processes minimizing risk of failures.
Site feasibility assessment has been performed and 31 sites have been selected. Until end of the second reporting period 5 sites have been activated and another 6 have already been planned for the first weeks of 2021. 2 patients have finished follow-up in 2020.
Since the TRACE project will contribute evidence-based data on this new treatment option, experimental plans and SOPs for determination of efficacy to restore anti-viral immunity as well as for the analyses of the quality of the T-cell products have been finalized and harmonized within the consortium. First data have already been generated.
For dissemination of know-how and technology beyond the consortium a scientific publication, press-releases, a website and a social media account have been launched. Further, the study has been registered in several public study registries. Within Work package 5 – Communication, dissemination and exploitation of results know-how and technology will be disseminated in an unrestricted way beyond the countries of TRACE participants as soon as the patient recruitment is completed.
The Project Office at LMU ensures a proper overall progress of the project by setting up communication infrastructures within the consortium, monitoring project progress on a daily basis, taking over contractual and financial management, reporting to the European Commission and serving as helpdesk for the consortium.
In parallel, the infrastructure for the clinical trial in terms of contact office, eCRF finalization, trial committees, data management, security structure and clinical trial applications has been set-up. Clinical trial approvals have been obtained from the competent authorities as well as central ethics committees for all participating countries (except UK and 2 out of 31 local ethics committees). The IMP for the trial is a personalized therapy, demanding close interaction between the clinical sites and the manufacturing centres, thus special attention was paid to set-up logistic and communication processes minimizing risk of failures.
Site feasibility assessment has been performed and 31 sites have been selected. Until end of the second reporting period 5 sites have been activated and another 6 have already been planned for the first weeks of 2021. 2 patients have finished follow-up in 2020.
Since the TRACE project will contribute evidence-based data on this new treatment option, experimental plans and SOPs for determination of efficacy to restore anti-viral immunity as well as for the analyses of the quality of the T-cell products have been finalized and harmonized within the consortium. First data have already been generated.
For dissemination of know-how and technology beyond the consortium a scientific publication, press-releases, a website and a social media account have been launched. Further, the study has been registered in several public study registries. Within Work package 5 – Communication, dissemination and exploitation of results know-how and technology will be disseminated in an unrestricted way beyond the countries of TRACE participants as soon as the patient recruitment is completed.
The Project Office at LMU ensures a proper overall progress of the project by setting up communication infrastructures within the consortium, monitoring project progress on a daily basis, taking over contractual and financial management, reporting to the European Commission and serving as helpdesk for the consortium.
Virus-specific T cells are a new curative treatment option for patients suffering from life-threatening viral infections such as AdV, EBV and CMV after allogeneic stem cell transplantation. Due to the promising previous results, the avoidance of antiviral pharmacotherapy side effects and the manufacturing procedure doing without genetic engineering, public acceptance of adoptive transfer of multivirus-specific T cells is high and without any ethical concerns.
For the individual patient the prognosis of viral infection after allogeneic stem cell transplantation will be improved, since a successful adoptive transfer of multivirus-specific T cells will lead to reduced in-patient days, reduced intensive care, reduced toxic antiviral medication, improved quality of life and improved survival. European patient health will benefit through a safe, curative and innovative individualized treatment option, that has not been available for the majority of eligible patients in the past. The reason for this limitation was the restriction to very few specialized centres due to regulatory and financial hurdles. The TRACE project will cover all eligible patients in the participating countries as long as they can be transferred to one of the treating centres.
Further the project will contribute evidence-based data on this new treatment to current treatment recommendations. Apart from the recovery from the underlying viral infection, the trial will contribute novel evidence-based data on other expected benefits such as reduced rate of new CMV, EBV or AdV infections/reactivations, reduced frequency of hospitalizations, reduced medication intake and a GvHD rate which is not increased compared to an untreated population. Already during the TRACE project, the knowledge will yet be disseminated through an open source policy, so that also centres of non-participating countries will be able to adapt the approach of adoptive T-cell transfer and provide this technology to their patient population.
The major objective of TRACE is to provide data, ethical and regulatory approvals and logistic infrastructure to build the basis for market authorization of the product “multivirus-specific T cells” and thus bring adoptive transfer of virus-specific T cells into clinical routine.
For the individual patient the prognosis of viral infection after allogeneic stem cell transplantation will be improved, since a successful adoptive transfer of multivirus-specific T cells will lead to reduced in-patient days, reduced intensive care, reduced toxic antiviral medication, improved quality of life and improved survival. European patient health will benefit through a safe, curative and innovative individualized treatment option, that has not been available for the majority of eligible patients in the past. The reason for this limitation was the restriction to very few specialized centres due to regulatory and financial hurdles. The TRACE project will cover all eligible patients in the participating countries as long as they can be transferred to one of the treating centres.
Further the project will contribute evidence-based data on this new treatment to current treatment recommendations. Apart from the recovery from the underlying viral infection, the trial will contribute novel evidence-based data on other expected benefits such as reduced rate of new CMV, EBV or AdV infections/reactivations, reduced frequency of hospitalizations, reduced medication intake and a GvHD rate which is not increased compared to an untreated population. Already during the TRACE project, the knowledge will yet be disseminated through an open source policy, so that also centres of non-participating countries will be able to adapt the approach of adoptive T-cell transfer and provide this technology to their patient population.
The major objective of TRACE is to provide data, ethical and regulatory approvals and logistic infrastructure to build the basis for market authorization of the product “multivirus-specific T cells” and thus bring adoptive transfer of virus-specific T cells into clinical routine.