Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections

NCT ID: NCT04832607

Last Updated: 2025-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-27

Study Completion Date

2028-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

AdV Infection EBV Infection CMV Infection Stem Cell Transplant Complications

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2 (verum): 1 (Placebo) randomization
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Randomization will be stratified with respect to three age groups: Children up to 6 years, children \>6 and up to 18 years, and adults \>18 years. Accordingly, for each stratum, a separate randomization list will be provided. Randomization will be performed by a representative of the Simbec-Orion Group who will be independent in the sense that he / she will otherwise not be involved in the TRACE trial.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Multivirus (CMV, EBV, AdV)-specific T cells

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

Group Type EXPERIMENTAL

Multivirus (CMV, EBV, AdV)-specific T cells

Intervention Type OTHER

Cell therapy product which is individually produced for each patient and administered via IV bolus injection.

Sodium chloride

Suspension of multivirus-specific T cells in 20 mL of 0.9% NaCl + 0.5% HSA

Group Type PLACEBO_COMPARATOR

Multivirus (CMV, EBV, AdV)-specific T cells

Intervention Type OTHER

Cell therapy product which is individually produced for each patient and administered via IV bolus injection.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Multivirus (CMV, EBV, AdV)-specific T cells

Cell therapy product which is individually produced for each patient and administered via IV bolus injection.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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.
2. Original HSCT-donor available with an immune response at least to the virus causing the therapy-refractory (=underlying) infection.
3. Written informed consent given (patient or legal representative) prior to any study-related procedures.

Exclusion Criteria

1. Patient with acute GvHD \> grade II or extensive chronic GvHD at the time of IMP transfer
2. Patient receiving steroids (\>1 mg/kg BW Prednisone equivalent) at Screening.
3. 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.
4. Patient with organ dysfunction or failure as determined by Karnofsky (patients \>16 years) or Lansky (patients ≤16 years) score ≤30%
5. Concomitant enrolment in another clinical trial interfering with the endpoints of this study
6. Any medical condition which could compromise participation in the study according to the investigator's assessment
7. 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
8. 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
9. 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.
10. 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.
11. Known hypersensitivity to iron dextran
12. Patients unwilling or unable to comply with the protocol or unable to give informed consent.
Minimum Eligible Age

2 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

European Commission

OTHER

Sponsor Role collaborator

Simbec-Orion Group Ltd, Merthyr Tydfil, UK

UNKNOWN

Sponsor Role collaborator

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany

UNKNOWN

Sponsor Role collaborator

Leiden University Medical Center, LUMC, Leiden, The Netherlands

UNKNOWN

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

Ghent University Hospital, UZG, Ghent, Belgium

UNKNOWN

Sponsor Role collaborator

Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy

UNKNOWN

Sponsor Role collaborator

Newcastle University, UNEW, Newcastle, UK

UNKNOWN

Sponsor Role collaborator

Vall d'Hebron Institute of Oncology

OTHER

Sponsor Role collaborator

Tobias Feuchtinger

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Tobias Feuchtinger

Prof. Dr. med Tobias Feuchtinger

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Tobias Feuchtinger, Prof

Role: PRINCIPAL_INVESTIGATOR

Medical Center - University of Freiburg

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Institut Jules Bordet (JBI)

Brussels, , Belgium

Site Status RECRUITING

UZ Brussel

Brussels, , Belgium

Site Status RECRUITING

Ghent Universal Hospital (UZG)

Ghent, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Université de Liège (ULG)

Liège, , Belgium

Site Status RECRUITING

Hôpital Jeanne de Flandre, CHU Lille

Lille, , France

Site Status RECRUITING

Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)

Lyon, , France

Site Status RECRUITING

Centre Hospitalier Régional Universitaire de Nancy (CHRU)

Nancy, , France

Site Status RECRUITING

Hôpital de la Pitie-Salpêtrière

Paris, , France

Site Status RECRUITING

Hôpital Necker - Enfants Malades

Paris, , France

Site Status RECRUITING

Hôpital Robert Debré

Paris, , France

Site Status RECRUITING

Charité Berlin (Campus Virchow-Klinikum) - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie

Berlin, , Germany

Site Status RECRUITING

Universitätsklinikum Dresden

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf - Klinik für Kinder-Onkologie, -Hämatologie und klinische Immunologie

Düsseldorf, , Germany

Site Status RECRUITING

Universitätsklinikum Essen - Pädiatrische Hämatologie-Onkologie

Essen, , Germany

Site Status RECRUITING

Universitätsklinikum Freiburg - Klinik für Pädiatrische Hämatologie und Onkologie

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover - Zentrum für Kinderheilkunde und Jugendmedizin

Hanover, , Germany

Site Status RECRUITING

Universitäsklinikum Leipzig - Medizinische Klinik und Poliklinik I

Leipzig, , Germany

Site Status RECRUITING

LMU Klinikum - Dr. v. Haunersches Kinderspital

Munich, , Germany

Site Status RECRUITING

Klinikum rechts der Isar der Technischen Universität - Kinderklinik Schwabing

Munich, , Germany

Site Status RECRUITING

LMU Klinikum - Medizinische Klinik und Poliklinik III

München, , Germany

Site Status RECRUITING

Klinikum rechts der Isar der Technischen Universität - Klinik und Poliklinik für Innere Medizin III

München, , Germany

Site Status RECRUITING

Universitätsklinikum Regensburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation

Regensburg, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen, Center for Pediatric Clinical Studies (CPCS)

Tübingen, , Germany

Site Status RECRUITING

Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II & Zentrum Innere Medizin (ZIM)

Würzburg, , Germany

Site Status RECRUITING

Universitätsklinikum Würzburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation

Würzburg, , Germany

Site Status RECRUITING

Ospedale Pediatrico Bambino Gesù (OPBG)

Rome, , Italy

Site Status RECRUITING

Ospedale Infantile Regina Margherita - Oncoematologie Pediatrica

Turin, , Italy

Site Status RECRUITING

Leiden University Medical Centre (LUMC) - Department of Hematology

Leiden, , Netherlands

Site Status RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Hospital Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Hospital Universitario Politécnico La Fe

Valencia, , Spain

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Belgium France Germany Italy Netherlands Spain

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Tobias Feuchtinger, Prof

Role: CONTACT

0049 (0)761 270 ext. 43641

Theresa Käuferle, Dr

Role: CONTACT

0049 (0)761 270 ext. 43369

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Philippe Lewalle, Prof

Role: primary

Ann De Becker, Dr.

Role: primary

Tessa Kerre, Prof

Role: primary

Johan Maertens, Prof. Dr.

Role: primary

Yves Beguin, Prof.

Role: primary

Bénédicte Bruno, Dr.

Role: primary

Marie Ouachée-Chardin, Dr.

Role: primary

Daniele Bensoussan, Prof.

Role: primary

Stéphanie Nguyen Quoc, Prof.

Role: primary

Bendedicte Neven, Prof.

Role: primary

Jean Hugues Dalle, Prof.

Role: primary

Johannes Schulte, Prof.

Role: primary

Martin Bornhäuser, Prof.

Role: primary

Roland Meisel, Prof.

Role: primary

Stefan Schönberger, Dr.

Role: primary

Brigitte Strahm, PD Dr.

Role: primary

Britta Maecker-Kolhoff, Prof.

Role: primary

Vladan Vucinic, Dr.

Role: primary

Tobias Feuchtinger, Prof.

Role: primary

Irene Teichert von Lüttichau, PD Dr.

Role: primary

Johanna Tischer, Dr.

Role: primary

Mareike Verbeek, Dr.

Role: primary

Jürgen Föll, Prof.

Role: primary

Peter Lang, Prof.

Role: primary

Hermann Einsele, Prof.

Role: primary

Matthias Wölfl, Prof.

Role: primary

Franco Locatelli, Prof.

Role: primary

Franca Fagioli, Prof.

Role: primary

Peter van Balen, Dr.

Role: primary

Pere Barba, Dr.

Role: primary

María Laura Fox, Dr.

Role: backup

Antonio Pérez-Martinez, Dr.

Role: primary

José Antonio Pérez Simón, Dr.

Role: primary

Juan Montoro Gómez, Dr.

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2018-000853-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00018985

Identifier Type: OTHER

Identifier Source: secondary_id

TRACE

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.