NCT04832607

Brief 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. 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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
149

participants targeted

Target at P25-P50 for phase_3

Timeline
28mo left

Started Aug 2019

Longer than P75 for phase_3

Geographic Reach
6 countries

33 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress74%
Aug 2019Sep 2028

Study Start

First participant enrolled

August 27, 2019

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

March 19, 2021

Completed
18 days until next milestone

First Posted

Study publicly available on registry

April 6, 2021

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2028

Last Updated

July 18, 2025

Status Verified

July 1, 2025

Enrollment Period

8.5 years

First QC Date

March 19, 2021

Last Update Submit

July 15, 2025

Conditions

AdV InfectionEBV InfectionCMV InfectionStem Cell Transplant Complications

Outcome Measures

Primary Outcomes (2)

  • 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

    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

    day 7 until week 8 after treatment

Secondary Outcomes (34)

  • Incidence of acute GvHD

    15 weeks after treatment

  • Incidence of chronic GvHD

    15 weeks after treatment

  • Time to newly occuring GvHD

    15 weeks after treatment

  • Severity of GvHD

    week 8 and 15 week after treatment

  • Incidence of acute toxicity

    15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer

  • +29 more secondary outcomes

Study Arms (2)

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

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

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

Interventions

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

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

Multivirus (CMV, EBV, AdV)-specific T cellsSodium chloride

Eligibility Criteria

Age2 Months+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

Institut Jules Bordet (JBI)

Brussels, 1000, Belgium

RECRUITING

UZ Brussel

Brussels, 1090, Belgium

RECRUITING

Ghent Universal Hospital (UZG)

Ghent, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Université de Liège (ULG)

Liège, 4000, Belgium

RECRUITING

Hôpital Jeanne de Flandre, CHU Lille

Lille, 59037, France

RECRUITING

Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)

Lyon, 69008, France

RECRUITING

Centre Hospitalier Régional Universitaire de Nancy (CHRU)

Nancy, 54035, France

RECRUITING

Hôpital de la Pitie-Salpêtrière

Paris, 75013, France

RECRUITING

Hôpital Necker - Enfants Malades

Paris, 75015, France

RECRUITING

Hôpital Robert Debré

Paris, 75019, France

RECRUITING

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

Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Dresden

Dresden, 01307, Germany

RECRUITING

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

Düsseldorf, 40225, Germany

RECRUITING

Universitätsklinikum Essen - Pädiatrische Hämatologie-Onkologie

Essen, 45147, Germany

RECRUITING

Universitätsklinikum Freiburg - Klinik für Pädiatrische Hämatologie und Onkologie

Freiburg im Breisgau, 79106, Germany

RECRUITING

Medizinische Hochschule Hannover - Zentrum für Kinderheilkunde und Jugendmedizin

Hanover, 30625, Germany

RECRUITING

Universitäsklinikum Leipzig - Medizinische Klinik und Poliklinik I

Leipzig, 04103, Germany

RECRUITING

LMU Klinikum - Dr. v. Haunersches Kinderspital

Munich, 80337, Germany

RECRUITING

Klinikum rechts der Isar der Technischen Universität - Kinderklinik Schwabing

Munich, 80804, Germany

RECRUITING

LMU Klinikum - Medizinische Klinik und Poliklinik III

München, 81377, Germany

RECRUITING

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

München, 81675, Germany

RECRUITING

Universitätsklinikum Regensburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation

Regensburg, 93053, Germany

RECRUITING

Universitätsklinikum Tübingen, Center for Pediatric Clinical Studies (CPCS)

Tübingen, 72076, Germany

RECRUITING

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

Würzburg, 97080, Germany

RECRUITING

Universitätsklinikum Würzburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation

Würzburg, 97080, Germany

RECRUITING

Ospedale Pediatrico Bambino Gesù (OPBG)

Rome, 00165, Italy

RECRUITING

Ospedale Infantile Regina Margherita - Oncoematologie Pediatrica

Turin, 10126, Italy

RECRUITING

Leiden University Medical Centre (LUMC) - Department of Hematology

Leiden, 2333, Netherlands

RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 119-129, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitario Politécnico La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Adenoviridae InfectionsEpstein-Barr Virus InfectionsCytomegalovirus Infections

Condition Hierarchy (Ancestors)

DNA Virus InfectionsVirus DiseasesInfectionsHerpesviridae InfectionsTumor Virus Infections

Study Officials

  • Tobias Feuchtinger, Prof

    Medical Center - University of Freiburg

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Feuchtinger, Prof

CONTACT

0049 (0)761 270kjk.trace-study@uniklinik-freiburg.de

Theresa Käuferle, Dr

CONTACT

0049 (0)761 270kjk.trace-study@uniklinik-freiburg.de

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 2 (verum): 1 (Placebo) randomization
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Prof. Dr. med Tobias Feuchtinger

Study Record Dates

First Submitted

March 19, 2021

First Posted

April 6, 2021

Study Start

August 27, 2019

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

September 1, 2028

Last Updated

July 18, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)ES(4)BE(5)FR(6)DE(15)IT(2)