AdV InfectionPhase 3TRACENCT04832607
Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections
A Phase 3 study testing Multivirus (CMV, EBV, AdV)-specific T cells in people with AdV Infection and EBV Infection, run by Tobias Feuchtinger at 33 sites in 6 countries.
Trial summary
Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Read more about this study
- Who is it for?
- Ages 2 months and older
- Conditions the study is for
- AdV Infection, EBV Infection, CMV Infection
- What is being tested?
- Multivirus (CMV, EBV, AdV)-specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149 participants
- Where
- 33 sitesin 6 countries
- Study dates
- 27 Aug 2019to Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adult or paediatric patients (> 2 months of age) after allogeneic stem cell transplantation (SCT) (no time restrictions apply) suffering from new or reactivated CMV or EBV or AdV infection refractory to standard antiviral treatment for two weeks (defined as no decrease or insignificant decrease of less than 1log in viral load over two weeks) as confirmed by quantitative blood PCR analysis.
- Original HSCT-donor available with an immune response at least to the virus causing the therapy-refractory (=underlying) infection.
- Written informed consent given (patient or legal representative) prior to any study-related procedures.
Who cannot join
- Patient with acute GvHD > grade II or extensive chronic GvHD at the time of IMP transfer
- Patient receiving steroids (>1 mg/kg BW Prednisone equivalent) at Screening.
- Therapeutic donor lymphocyte infusion (DLI) from 4 weeks prior to IMP infusion until 8 weeks post IMP infusion. Prescheduled prophylactic DLI ≤3x105 T cells/kg BW in case of T-cell depleted HSCT is not considered an exclusion criterion.
- Patient with organ dysfunction or failure as determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30%
- Concomitant enrolment in another clinical trial interfering with the endpoints of this study
- Any medical condition which could compromise participation in the study according to the investigator's assessment
Show all 13Show fewer
- Progression of underlying disease (disease that has led to the indication of HSCT, e.g. leukaemia) that will limit the life expectance below the duration of the study
- Second line or experimental antiviral treatment other than Ganciclovir/Valganciclovir, Foscarnet, Cidofovir and Rituximab until 8 weeks after IMP Infusion or prophylactic Treatment other than Aciclovir or Letermovir throughout the study except approved by sponsor
- Known HIV infection. In case patients do not have a negative HIV test performed within 6 months before enrolment in the study, HIV negativity has to be confirmed by a negative laboratory test.
- Female patient who is pregnant or breast-feeding. Female patient of child-bearing potential (i.e. post menarche and not surgically sterilized) or male patient of reproductive potential not willing to use an effective method of birth control from Screening until the last follow-up visit (FU6, Visit 8).
- Note: Women of childbearing potential must have a negative serum pregnancy test at study entry ≤7 days before IMP administration on Day 0. Acceptable birth control methods are hormonal oral contraceptive ('pill'), contraceptive injection or patch, intrauterine pessar or the combination of two barrier methods. The combination of female and male condomes is NOT acceptable. If the male partner is sterilized, no further contraceptive is required. Women of post-menopausal status (no menses for 12 months without an alternative medical cause) are also not required to use contraceptives during the study.
- Known hypersensitivity to iron dextran
- Patients unwilling or unable to comply with the protocol or unable to give informed consent.
Trial locations and contacts
33 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
33 sites in 6 countries
Germany15 sites, 15 recruiting
- Recruiting
Charité Berlin (Campus Virchow-Klinikum) - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
Berlin, 13353
Johannes Schulte, Prof., johannes.schulte@charite.de
Johannes Schulte, Prof.
- Recruiting
Universitätsklinikum Dresden
Dresden, 01307
Martin Bornhäuser, Prof., Martin.Bornhaeuser@uniklinikum-dresden.de
Martin Bornhäuser, Prof.
- Recruiting
Universitätsklinikum Düsseldorf - Klinik für Kinder-Onkologie, -Hämatologie und klinische Immunologie
Düsseldorf, 40225
Roland Meisel, Prof., meisel@med.uni-duesseldorf.de
Roland Meisel, Prof.
- Recruiting
Universitätsklinikum Essen - Pädiatrische Hämatologie-Onkologie
Essen, 45147
Stefan Schönberger, Dr., Stefan.Schoenberger@uk-essen.de
Stefan Schönberger, Dr.
- Recruiting
Universitätsklinikum Freiburg - Klinik für Pädiatrische Hämatologie und Onkologie
Freiburg im Breisgau, 79106
Brigitte Strahm, PD Dr., brigitte-strahm@uniklinik-freiburg.de
Brigitte Strahm, PD Dr.
- Recruiting
Medizinische Hochschule Hannover - Zentrum für Kinderheilkunde und Jugendmedizin
Hanover, 30625
Britta Maecker-Kolhoff, Prof., Maecker.Britta@MH-Hannover.de
Britta Maecker-Kolhoff, Prof.
- Recruiting
Universitäsklinikum Leipzig - Medizinische Klinik und Poliklinik I
Leipzig, 04103
Vladan Vucinic, Dr., Vladan.Vucinic@medizin.uni-leipzig.de
Vladan Vucinic, Dr.
- Recruiting
LMU Klinikum - Medizinische Klinik und Poliklinik III
München, 81377
Johanna Tischer, Dr., johanna.tischer@med.uni-muenchen.de
Johanna Tischer, Dr.
- Recruiting
Klinikum rechts der Isar der Technischen Universität - Klinik und Poliklinik für Innere Medizin III
München, 81675
Mareike Verbeek, Dr., Mareike.Verbeek@tum.de
Mareike Verbeek, Dr.
- Recruiting
LMU Klinikum - Dr. v. Haunersches Kinderspital
Munich, 80337
Tobias Feuchtinger, Prof., info@trace-study.de
Tobias Feuchtinger, Prof.
- Recruiting
Klinikum rechts der Isar der Technischen Universität - Kinderklinik Schwabing
Munich, 80804
Irene Teichert von Lüttichau, PD Dr., Irene.Teichert-vonluettichau@mri.tum.de
Irene Teichert von Lüttichau, PD Dr.
- Recruiting
Universitätsklinikum Regensburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
Regensburg, 93053
Jürgen Föll, Prof., juergen.foell@klinik.uni-regensburg.de
Jürgen Föll, Prof.
- Recruiting
Universitätsklinikum Tübingen, Center for Pediatric Clinical Studies (CPCS)
Tübingen, 72076
Peter Lang, Prof., peter.lang@med.uni-tuebingen.de
Peter Lang, Prof.
- Recruiting
Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II & Zentrum Innere Medizin (ZIM)
Würzburg, 97080
Hermann Einsele, Prof., einsele_h@klinik.uni-wuerzburg.de
Hermann Einsele, Prof.
- Recruiting
Universitätsklinikum Würzburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
Würzburg, 97080
Matthias Wölfl, Prof., Woelfl_M@kw.de
Matthias Wölfl, Prof.
France6 sites, 6 recruiting
- Recruiting
Hôpital Jeanne de Flandre, CHU Lille
Lille, 59037
Bénédicte Bruno, Dr., benedicte.bruno@chru-lille.fr
Bénédicte Bruno, Dr.
- Recruiting
Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)
Lyon, 69008
Marie Ouachée-Chardin, Dr., marie.ouachee-chardin@ihope.fr
Marie Ouachée-Chardin, Dr.
- Recruiting
Centre Hospitalier Régional Universitaire de Nancy (CHRU)
Nancy, 54035
Daniele Bensoussan, Prof., d.bensoussan@chru-nancy.fr
Maud D'Aveni-Piney, Dr.
- Recruiting
Hôpital de la Pitie-Salpêtrière
Paris, 75013
Stéphanie Nguyen Quoc, Prof., stephanie.nguyen-quoc@aphp.fr
Stéphanie Nguyen Quoc, Prof.
- Recruiting
Hôpital Necker - Enfants Malades
Paris, 75015
Bendedicte Neven, Prof., benedicte.neven@aphp.fr
Bendedicte Neven, Prof.
- Recruiting
Hôpital Robert Debré
Paris, 75019
Jean Hugues Dalle, Prof., jean-hugues.dalle@aphp.fr
Jean Hugues Dalle, Prof.
Belgium5 sites, 5 recruiting
- Recruiting
Institut Jules Bordet (JBI)
Brussels, 1000
Philippe Lewalle, Prof, philippe.lewalle@bordet.be
Philippe Lewalle, Prof
- Recruiting
UZ Brussel
Brussels, 1090
Ann De Becker, Dr., ann.debecker@uzbrussel.be
Ann De Becker, Dr.
- Recruiting
Ghent Universal Hospital (UZG)
Ghent, 9000
Tessa Kerre, Prof, tessa.kerre@ugent.be
Tessa Kerre, Prof
- Recruiting
UZ Leuven
Leuven, 3000
Johan Maertens, Prof. Dr., johan.maertens@uzleuven.be
Johan Maertens, Prof.
- Recruiting
Université de Liège (ULG)
Liège, 4000
Yves Beguin, Prof., yves.beguin@chu.ulg.ac.be
Yves Beguin, Prof.
Spain4 sites, 4 recruiting
- Recruiting
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona, 119-129
Pere Barba, Dr., pbarba@vhio.net
María Laura Fox, Dr., mlfox@vhio.net
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
Antonio Pérez-Martinez, Dr., aperezmartinez@salud.madrid.org
Antonio Pérez-Martinez, Dr.
- Recruiting
Hospital Virgen del Rocío
Seville, 41013
José Antonio Pérez Simón, Dr., josea.perez.simon.sspa@juntadeandalucia.es
José Antonio Pérez Simón, Dr.
- Recruiting
Hospital Universitario Politécnico La Fe
Valencia, 46026
Juan Montoro Gómez, Dr., juanmontorogomez@gmail.com
Juan Montoro Gómez, Dr.
Italy2 sites, 2 recruiting
- Recruiting
Ospedale Pediatrico Bambino Gesù (OPBG)
Rome, 00165
Franco Locatelli, Prof., franco.locatelli@opbg.net
Franco Locatelli, Prof.
- Recruiting
Ospedale Infantile Regina Margherita - Oncoematologie Pediatrica
Turin, 10126
Franca Fagioli, Prof., franca.fagioli@unito.it
Franca Fagioli, Prof.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Centre (LUMC) - Department of Hematology
Leiden, 2333
Peter van Balen, Dr., P.van_Balen@lumc.nl
Peter van Balen, Dr.
About this study
Official title: Treatment of Chemo-refractory Viral Infections After Allogeneic Stem Cell Transplantation With Multispecific T Cells Against CMV, EBV and AdV: A Phase III, Prospective, Multicentre Clinical Trial
Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T-cell immunity in patients with refractory viral infections after allogeneic HSCT. The aim of this Phase III trial is to confirm efficacy of this treatment in children and adults.
Read the detailed description
For a growing number of patients suffering from various conditions as, e.g., haematological malignancies or diverse genetic disorders, haematopoietic stem cell transplantation (HSCT) or bone marrow transplantation offer the only possible curative options. However, HSCT is associated with three major risks: graft rejection, graft-versus-host disease (GvHD) and opportunistic, mostly viral, infections or reactivations resulting from delayed immune reconstitution. Delayed immune reconstitution, however, often is the direct result of the severe pre-transplantation conditioning treatment and T-cell depletion of the transplant necessary to fight the risks of graft rejection and GvHD. Therefore, the risk for life-threatening opportunistic, mostly viral, infections is increased in post-transplantation patients. The most common infections after HSCT are Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Adenovirus (AdV).
The standard treatment approach for viral infections/reactivations is chemotherapy which shows limited efficacy and does not restore immunity. Therefore, effective new treatment options are required for this condition.
Previous investigations have shown that sufficient T-cell immunity is essential for the control and prevention of viral reactivations and newly occurring infections after HSCT. The infusion of T-cells is therefore a promising new approach to treat immune-comprised patients. However, infusion with unselected T cells is associated with an increased risk for GvHD due to the high content of alloreactive T cells. A very promising approach to minimize this problem is to remove alloreactive T cells and enrich, isolate and purify virus-specific T cells.
This approach has been studied for nearly two decades and the data published up to date indicate that virus-specific T-cell responses after adoptive T-cell transfer protect against virus-related complications post HSCT and restore T-cell immunity, in particular for AdV-, CMV- and EBV-infections. Despite these promising results, virus-specific T-cell transfer is not yet translated into daily clinical practice due to the lack of prospective clinical trials confirming the efficacy of this treatment approach.
The overall goal of this Phase III, double-blind placebo-controlled study is to test efficacy of multivirus-specific T cells to bring this treatment method in clinical routine. Multivirus-specific T cells generated in this study will be directed against all three most common post-HSCT viral infections: AdV, CMV and EBV. Thus, T-cell immunity will be restored to fight and prevent new viral infections.
After an initial screening visit, patients eligible to participate in the study will be treated within 28 days after screening. Patients will be randomized in a 2:1 (treatment: placebo) ratio and receive a single infusion with either multivirus-specific T cells or placebo. Patients will be followed up on the day of treatment, 1 day after and 1, 2, 4, 8 and 15 weeks after treatment. Treatment success will be measured by assessing different parameters including symptoms, quality of life, viral load and T-cell immunity in blood samples.
Patients eligible to participate in this study are adult and paediatric patients who have received allogeneic stem cell transplantation and suffer from new or reactivated EBV, AdV or CMV infection refractory to standard antiviral treatment for two weeks. Patients from the six European countries Germany, Belgium, Netherlands, UK, France and Italy will be enrolled. In total 130 patients plus 19 screening failures are expected to participate in the study.
- Being tested
- Multivirus (CMV, EBV, AdV)-specific T cells
- Medical subject headings
- Adenoviridae Infections, Epstein-Barr Virus Infections, Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multivirus (CMV, EBV, AdV)-specific T cellsOther
Cell therapy product which is individually produced for each patient and administered via IV bolus injection.
| Study group | Role | What they receive |
|---|---|---|
| Multivirus (CMV, EBV, AdV)-specific T cells | Experimental | Allogeneic CD4+ and CD8+ T lymphocytes ex vivo incubated with synthetic peptides of the viral antigens of Cytomegalovirus, Adenovirus and Epstein-Barr Virus
Max dose:
* HLA-matched (8/8) donors: 1.0 x 10e5 T cells/kg recipient BW
* HLA-mismatched donors: 2.5 x 10e4 T cells/kg recipient BW
Min. dose:
- 10 T cells/kg recipient BW Receives: Other: Multivirus (CMV, EBV, AdV)-specific T cells |
| Sodium chloride | Placebo comparator | Suspension of multivirus-specific T cells in 20 mL of 0.9% NaCl + 0.5% HSA Receives: Other: Multivirus (CMV, EBV, AdV)-specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral clearance
Percentage of patients with viral clearance (defined as two consecutive negative PCRs) to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation
Measured: 8 weeks after treatment
Disease Progression
Percentage of patients with progression between Day 7 and Week 8 after T-cell Transfer to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation
Measured: day 7 until week 8 after treatment
Secondary outcomes (34)
Incidence of acute GvHD
Incidence of newly occurring acute GvHD grade I from Day 0 to Week 8 and Week 15.
Measured: 15 weeks after treatment
Incidence of chronic GvHD
Incidence of chronic GvHD from Day 7 to Week 8 and to Week 15 after treatment.
Measured: 15 weeks after treatment
Time to newly occuring GvHD
Time to newly occurring acute and chronic GvHD.
Measured: 15 weeks after treatment
Severity of GvHD
Severity of acute GvHD ≥ grade II until Week 8 and Week 15.
Measured: week 8 and 15 week after treatment
Incidence of acute toxicity
Acute maximum toxicity on the day of T-cell transfer evaluated by measuring vital signs prior to and at different times after the T-cell transfer from 1 hour prior to T-cell transfer to 4 hours post infusion.
Measured: 15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Severity of acute toxicity
Monitoring of adverse events infusion.
Measured: 15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Change in viral load of underlying viral infection
Change in viral load of underlying viral infection as assessed by quantitative PCR analysis of peripheral blood; samples taken weekly from Day 7 to Week 8 after IMP transfer as compared to samples taken at Day 0.
Measured: 8 weeks after treatment
Time to viral load change of underlying viral infection
Time to 1 log change in viral load.
Measured: 15 weeks after treatment
Percentage of viral decrease
Percentage of patients with ≥1 log decrease in CMV, EBV or AdV viral load at Week 8.
Measured: 8 weeks after treatment
Viral reactivations
Number of reactivations of the underlying viral infection following initial viral clearance until end of follow-up.
Measured: 15 weeks after treatment
Clinical response/resolution of symptoms of underlying viral infection
Number of patients with reduction or clearance of clinical symptoms of underlyingviral infection from Day 7 to Week 8 after IMP transfer as compared to Day 0.
Measured: 8 weeks after treatment
Overall survival
Overall survival rate (OS): From Day 0 to end of follow-up.
Measured: 15 weeks after treatment
Necessity of antiviral chemotherapy
Number of days requiring antiviral chemotherapy after T-cell transfer from Day 7 to Week 8 after T-cell transfer.
Measured: Day 7 until Week 8
Duration of antiviral chemotherapy
Time to last administration of defined antiviral medication or switch to prophylactic treatment from Day 0 to Week 8 after IMP transfer.
Measured: 8 weeks after treatment
Incidence of viral infections other than underlying viral infection
Number of new viral reactivations (CMV, AdV or EBV) other than the underlying viral infection per patient as assessed by PCR analysis and clinical symptoms throughout the study to evaluate the putative prophylactic effect of the treatment.
Measured: 15 weeks
Days of hospitalization
Number of days hospitalized after IMP transfer from Day 7 to Week 8.
Measured: 8 weeks
Life quality in adults
EQ-5D for adult patients (≥18 years) at Screening and Week 8 to evaluate life quality in adults. A scale from 0 to 100 is used with 100 being best value and 0 the worst.
Measured: Screening and Week 8.
Life quality in adults
FACT-BMT for adult patients (≥18 years) at Screening and Week 8 to evaluate life quality in adults.
The patients have to answer questions about their physicial, social, emotional and functional wellbeing. A scale from 0 to 4 is used with 0= not at all, 1= a little bit, 2=somewhat, 3=quite a bit, 4=very much.
Measured: Screening and Week 8
Life quality in children
PEDS-QL for paediatric patients (<18 years) at Screening and Week 8 to evaluate life quality in children.
The patients and /or their parents have to answer questions about pain and hurt, fatigue and sleep, nausea, worry, Nutrition, thinking and communication.
A scale from 0 to 4 is used with 0=never a Problem, 1=almost never a problem, 2= sometimes a problem, 3=often a problem, 4= almost always a problem.
Measured: Screening and Week 8
Effect on the patient's T-cell phenotype in vivo
T-cell phenotyping, samples taken at Screening, Day 0 and each visit from Day 7 to Week 15 after treatment.
Measured: Screening until Week 15
Effect on the patient's number of expanded T cells
Analysis of virus-specific T cells: frequencies of in vivo expanded virus-specific T cells in peripheral blood samples taken at Screening, Day 0, Day 7 to Week 15 after treatment.
Measured: Screening until Week 15
Quality of the IMP and performance of the CliniMACS® Prodigy
Assessment of the cellular composition, in particular the percentage of IFN-gamma+ cells, in the IMP.
Measured: Before IMP release (between Screening and Day 0)
Evaluation of the drop-out rate
Drop-out rate at Day 0 and reasons for drop-out.
Measured: at Day 0 (planned treatment day)
Time from inclusion to administration of the IMP
Number of days from Screening to Day 0 (day of IMP transfer) to evaluate the required time frame.
Measured: Screening until Day 0 (treatment day)
Adverse events
Documentation of incidence, severity and type of adverse events from Day 0 to Week 8 and serious adverse events throughout the study to evaluate safety.
Measured: 15 weeks
Physical examination
Physical examinations will be conducted to identify possible clinically significant pathologies. These findings will be recorded at each visit. The Karnofsky/Lansky index will be included in the physical examination at Screening and at Week 8 only.
Measured: Screening to Week 8
Vital Sign - blood pressure
supine systolic and diastolic blood preasure in mm Hg
Measured: Screening to Week 8
Vital Signs - heart rate
The resting heart rate in beats/min
Measured: Screening to Week 8
Vital Signs - body temperature
Body temperature in °C (aural)
Measured: Screening to Week 8
Vital Signs - body weight
body weight in kg
Measured: Screening to Week 8
Vital Signs - respiratory rate
respiratory rate in breaths/min.
Measured: Screening to Week 8
Incidence of abnormal laboratory values
haemoglobin, leukocytes, thrombocytes, dirfferential blood count (neutrophil granulocytes, lymphocytes, monocytes and easinophil granulocytes), total and conjugated Bilirubin, C reactive Protein (CRP), creatinine, Alanin aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl Transferase (GGT), Lactate Dehydrase (LDH), Urea.
A list of normal ranges will be provided from each site.
Measured: Screening to Week 8
Concomitant medication until Week 8
All concomitant medication will be recorded from Screening until Week 8. The generic name, indication, route of administration, dose/ unit, start and stop date or ongoing, way of application will be documented.
Measured: 8 weeks after treatment
Concomitant medication until Week 15
During follow-up Week 15, only antiviral therapy, immunosuppression and SAE-related concomitant medication as well as chemotherapy will be documented.
The generic name, indication, route of administration, dose/ unit, start and stop date or ongoing, way of application will be documented.
Cellular treatment also has to be documented as concomitant medication.
Measured: 15 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start27 Aug 2019
- Primary completionMar 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AdV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2 (verum): 1 (Placebo) randomization
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 149 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tobias Feuchtinger
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, Simbec-Orion Group Ltd, Merthyr Tydfil, UK, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany, Leiden University Medical Center, LUMC, Leiden, The Netherlands, Central Hospital, Nancy, France, University Hospital, Ghent, Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy, Newcastle University, Vall d'Hebron Institute of Oncology
- Responsible party
- Sponsor-investigator, Tobias Feuchtinger, University Hospital Freiburg
- Investigators
- Tobias Feuchtinger, Prof, Principal investigator, Medical Center - University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04832607
- Sponsor's protocol ID
- TRACE
- Other IDs
- 2018-000853-29, DRKS00018985, 2018
- Acronym
- TRACE
- Status last verified
- Jul 2025
- First submitted
- 19 Mar 2021
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Chemo-refractory Viral Infections After Allogeneic Stem Cell Transplantation With Multispecific T Cells Against CMV, EBV and AdV: A Phase III, Prospective, Multicentre Clinical Trial
- ClinicalTrials.gov ID
- NCT04832607
- Acronym / sponsor ID
- TRACE / TRACE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 149 participants (estimated)
- Lead sponsor
- Tobias FeuchtingerUniversity, hospital or other
- Collaborators
- European Commission, Simbec-Orion Group Ltd, Merthyr Tydfil, UK, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany, Leiden University Medical Center, LUMC, Leiden, The Netherlands, Central Hospital, Nancy, France, University Hospital, Ghent, Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy, Newcastle University, Vall d'Hebron Institute of Oncology
- Study start
- 27 Aug 2019 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 6 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T-cell immunity in patients with refractory viral infections after allogeneic HSCT. The aim of this Phase III trial is to confirm efficacy of this treatment in children and adults.
Detailed description
For a growing number of patients suffering from various conditions as, e.g., haematological malignancies or diverse genetic disorders, haematopoietic stem cell transplantation (HSCT) or bone marrow transplantation offer the only possible curative options. However, HSCT is associated with three major risks: graft rejection, graft-versus-host disease (GvHD) and opportunistic, mostly viral, infections or reactivations resulting from delayed immune reconstitution. Delayed immune reconstitution, however, often is the direct result of the severe pre-transplantation conditioning treatment and T-cell depletion of the transplant necessary to fight the risks of graft rejection and GvHD. Therefore, the risk for life-threatening opportunistic, mostly viral, infections is increased in post-transplantation patients. The most common infections after HSCT are Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Adenovirus (AdV).
The standard treatment approach for viral infections/reactivations is chemotherapy which shows limited efficacy and does not restore immunity. Therefore, effective new treatment options are required for this condition.
Previous investigations have shown that sufficient T-cell immunity is essential for the control and prevention of viral reactivations and newly occurring infections after HSCT. The infusion of T-cells is therefore a promising new approach to treat immune-comprised patients. However, infusion with unselected T cells is associated with an increased risk for GvHD due to the high content of alloreactive T cells. A very promising approach to minimize this problem is to remove alloreactive T cells and enrich, isolate and purify virus-specific T cells.
This approach has been studied for nearly two decades and the data published up to date indicate that virus-specific T-cell responses after adoptive T-cell transfer protect against virus-related complications post HSCT and restore T-cell immunity, in particular for AdV-, CMV- and EBV-infections. Despite these promising results, virus-specific T-cell transfer is not yet translated into daily clinical practice due to the lack of prospective clinical trials confirming the efficacy of this treatment approach.
The overall goal of this Phase III, double-blind placebo-controlled study is to test efficacy of multivirus-specific T cells to bring this treatment method in clinical routine. Multivirus-specific T cells generated in this study will be directed against all three most common post-HSCT viral infections: AdV, CMV and EBV. Thus, T-cell immunity will be restored to fight and prevent new viral infections.
After an initial screening visit, patients eligible to participate in the study will be treated within 28 days after screening. Patients will be randomized in a 2:1 (treatment: placebo) ratio and receive a single infusion with either multivirus-specific T cells or placebo. Patients will be followed up on the day of treatment, 1 day after and 1, 2, 4, 8 and 15 weeks after treatment. Treatment success will be measured by assessing different parameters including symptoms, quality of life, viral load and T-cell immunity in blood samples.
Patients eligible to participate in this study are adult and paediatric patients who have received allogeneic stem cell transplantation and suffer from new or reactivated EBV, AdV or CMV infection refractory to standard antiviral treatment for two weeks. Patients from the six European countries Germany, Belgium, Netherlands, UK, France and Italy will be enrolled. In total 130 patients plus 19 screening failures are expected to participate in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2 (verum): 1 (Placebo) randomization
| Arm | Type | Receives |
|---|---|---|
| Multivirus (CMV, EBV, AdV)-specific T cells | Experimental | Other: Multivirus (CMV, EBV, AdV)-specific T cellsAllogeneic CD4+ and CD8+ T lymphocytes ex vivo incubated with synthetic peptides of the viral antigens of Cytomegalovirus, Adenovirus and Epstein-Barr Virus Max dose: * HLA-matched (8/8) donors: 1.0 x 10e5 T cells/kg recipient BW * HLA-mismatched donors: 2.5 x 10e4 T cells/kg recipient BW Min. dose: - 10 T cells/kg recipient BW |
| Sodium chloride | Placebo comparator | Other: Multivirus (CMV, EBV, AdV)-specific T cellsSuspension of multivirus-specific T cells in 20 mL of 0.9% NaCl + 0.5% HSA |
Who may qualify
- Ages
- 2 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Adult or paediatric patients (> 2 months of age) after allogeneic stem cell transplantation (SCT) (no time restrictions apply) suffering from new or reactivated CMV or EBV or AdV infection refractory to standard antiviral treatment for two weeks (defined as no decrease or insignificant decrease of less than 1log in viral load over two weeks) as confirmed by quantitative blood PCR analysis.
- Original HSCT-donor available with an immune response at least to the virus causing the therapy-refractory (=underlying) infection.
- Written informed consent given (patient or legal representative) prior to any study-related procedures.
Key exclusion criteria (13 listed)
- Patient with acute GvHD > grade II or extensive chronic GvHD at the time of IMP transfer
- Patient receiving steroids (>1 mg/kg BW Prednisone equivalent) at Screening.
- Therapeutic donor lymphocyte infusion (DLI) from 4 weeks prior to IMP infusion until 8 weeks post IMP infusion. Prescheduled prophylactic DLI ≤3x105 T cells/kg BW in case of T-cell depleted HSCT is not considered an exclusion criterion.
- Patient with organ dysfunction or failure as determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30%
- Concomitant enrolment in another clinical trial interfering with the endpoints of this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multivirus (CMV, EBV, AdV)-specific T cellsCell therapy product which is individually produced for each patient and administered via IV bolus injection. | Other | Multivirus (CMV, EBV, AdV)-specific T cells, Sodium chloride |
Primary outcome
Viral clearance
Time frame: 8 weeks after treatment
Percentage of patients with viral clearance (defined as two consecutive negative PCRs) to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation
Disease Progression
Time frame: day 7 until week 8 after treatment
Percentage of patients with progression between Day 7 and Week 8 after T-cell Transfer to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation
34 secondary outcomes
Incidence of acute GvHD
Time frame: 15 weeks after treatment
Incidence of chronic GvHD
Time frame: 15 weeks after treatment
Time to newly occuring GvHD
Time frame: 15 weeks after treatment
Severity of GvHD
Time frame: week 8 and 15 week after treatment
Incidence of acute toxicity
Time frame: 15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Severity of acute toxicity
Time frame: 15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Change in viral load of underlying viral infection
Time frame: 8 weeks after treatment
Time to viral load change of underlying viral infection
Time frame: 15 weeks after treatment
Percentage of viral decrease
Time frame: 8 weeks after treatment
Viral reactivations
Time frame: 15 weeks after treatment
Clinical response/resolution of symptoms of underlying viral infection
Time frame: 8 weeks after treatment
Overall survival
Time frame: 15 weeks after treatment
Necessity of antiviral chemotherapy
Time frame: Day 7 until Week 8
Duration of antiviral chemotherapy
Time frame: 8 weeks after treatment
Incidence of viral infections other than underlying viral infection
Time frame: 15 weeks
Days of hospitalization
Time frame: 8 weeks
Life quality in adults
Time frame: Screening and Week 8.
Life quality in adults
Time frame: Screening and Week 8
Life quality in children
Time frame: Screening and Week 8
Effect on the patient's T-cell phenotype in vivo
Time frame: Screening until Week 15
Effect on the patient's number of expanded T cells
Time frame: Screening until Week 15
Quality of the IMP and performance of the CliniMACS® Prodigy
Time frame: Before IMP release (between Screening and Day 0)
Evaluation of the drop-out rate
Time frame: at Day 0 (planned treatment day)
Time from inclusion to administration of the IMP
Time frame: Screening until Day 0 (treatment day)
Adverse events
Time frame: 15 weeks
Physical examination
Time frame: Screening to Week 8
Vital Sign - blood pressure
Time frame: Screening to Week 8
Vital Signs - heart rate
Time frame: Screening to Week 8
Vital Signs - body temperature
Time frame: Screening to Week 8
Vital Signs - body weight
Time frame: Screening to Week 8
Vital Signs - respiratory rate
Time frame: Screening to Week 8
Incidence of abnormal laboratory values
Time frame: Screening to Week 8
Concomitant medication until Week 8
Time frame: 8 weeks after treatment
Concomitant medication until Week 15
Time frame: 15 weeks after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tobias Feuchtinger, Prof principal investigator
Medical Center - University of Freiburg
33 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Multivirus (CMV, EBV, AdV)-specific T cells in people with AdV Infection and EBV Infection, run by Tobias Feuchtinger at 33 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Germany, France, Belgium, Spain, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tobias Feuchtinger, Prof (0049 (0)761 270 ext. 43641, kjk.trace-study@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Viral clearance (time frame: 8 weeks after treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.