search
Back to results

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

Primary Purpose

AdV Infection, EBV Infection, CMV Infection

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Multivirus (CMV, EBV, AdV)-specific T cells
Sponsored by
Prof. Tobias Feuchtinger
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AdV Infection

Eligibility Criteria

2 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Institut Jules Bordet (JBI)Recruiting
  • UZ BrusselRecruiting
  • Ghent Universal Hospital (UZG)Recruiting
  • UZ LeuvenRecruiting
  • Université de Liège (ULG)Recruiting
  • Hôpital Jeanne de Flandre, CHU LilleRecruiting
  • Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)Recruiting
  • Centre Hospitalier Régional Universitaire de Nancy (CHRU)Recruiting
  • Hôpital de la Pitie-SalpêtrièreRecruiting
  • Hôpital Necker - Enfants MaladesRecruiting
  • Hôpital Robert DebréRecruiting
  • Charité Berlin (Campus Virchow-Klinikum) - Klinik für Pädiatrie mit Schwerpunkt Onkologie und HämatologieRecruiting
  • Universitätsklinikum DresdenRecruiting
  • Universitätsklinikum Düsseldorf - Klinik für Kinder-Onkologie, -Hämatologie und klinische ImmunologieRecruiting
  • Universitätsklinikum Essen - Pädiatrische Hämatologie-OnkologieRecruiting
  • Universitätsklinikum Freiburg - Klinik für Pädiatrische Hämatologie und OnkologieRecruiting
  • Medizinische Hochschule Hannover - Zentrum für Kinderheilkunde und JugendmedizinRecruiting
  • Universitäsklinikum Leipzig - Medizinische Klinik und Poliklinik IRecruiting
  • LMU Klinikum - Dr. v. Haunersches KinderspitalRecruiting
  • Klinikum rechts der Isar der Technischen Universität - Kinderklinik SchwabingRecruiting
  • LMU Klinikum - Medizinische Klinik und Poliklinik IIIRecruiting
  • Klinikum rechts der Isar der Technischen Universität - Klinik und Poliklinik für Innere Medizin IIIRecruiting
  • Universitätsklinikum Regensburg - Pädiatrische Hämatologie, Onkologie und StammzelltransplantationRecruiting
  • Universitätsklinikum Tübingen, Center for Pediatric Clinical Studies (CPCS)Recruiting
  • Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II & Zentrum Innere Medizin (ZIM)Recruiting
  • Universitätsklinikum Würzburg - Pädiatrische Hämatologie, Onkologie und StammzelltransplantationRecruiting
  • Ospedale Pediatrico Bambino Gesù (OPBG)Recruiting
  • Ospedale Infantile Regina Margherita - Oncoematologie PediatricaRecruiting
  • Leiden University Medical Centre (LUMC) - Department of HematologyRecruiting
  • Vall d'Hebron Institute of Oncology (VHIO)Recruiting
  • Hospital Universitario La PazRecruiting
  • Hospital Virgen del RocíoRecruiting
  • Hospital Universitario Politécnico La FeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Sodium chloride

Arm Description

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

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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Incidence of acute GvHD
Incidence of newly occurring acute GvHD grade I from Day 0 to Week 8 and Week 15.
Incidence of chronic GvHD
Incidence of chronic GvHD from Day 7 to Week 8 and to Week 15 after treatment.
Time to newly occuring GvHD
Time to newly occurring acute and chronic GvHD.
Severity of GvHD
Severity of acute GvHD ≥ grade II until Week 8 and Week 15.
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.
Severity of acute toxicity
Monitoring of adverse events infusion.
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.
Time to viral load change of underlying viral infection
Time to 1 log change in viral load.
Percentage of viral decrease
Percentage of patients with ≥1 log decrease in CMV, EBV or AdV viral load at Week 8.
Viral reactivations
Number of reactivations of the underlying viral infection following initial viral clearance until end of follow-up.
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.
Overall survival
Overall survival rate (OS): From Day 0 to end of follow-up.
Necessity of antiviral chemotherapy
Number of days requiring antiviral chemotherapy after T-cell transfer from Day 7 to Week 8 after T-cell transfer.
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.
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.
Days of hospitalization
Number of days hospitalized after IMP transfer from Day 7 to Week 8.
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.
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.
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.
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.
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.
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.
Evaluation of the drop-out rate
Drop-out rate at Day 0 and reasons for drop-out.
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.
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.
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.
Vital Sign - blood pressure
supine systolic and diastolic blood preasure in mm Hg
Vital Signs - heart rate
The resting heart rate in beats/min
Vital Signs - body temperature
Body temperature in °C (aural)
Vital Signs - body weight
body weight in kg
Vital Signs - respiratory rate
respiratory rate in breaths/min.
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.
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.
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.

Full Information

First Posted
March 19, 2021
Last Updated
October 2, 2023
Sponsor
Prof. Tobias Feuchtinger
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, Centre Hospitalier Universitaire de Nancy, CHU, Vandoeuvre-Lès-Nancy, France, Ghent University Hospital, UZG, Ghent, Belgium, Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy, Newcastle University, UNEW, Newcastle, UK, Vall d'Hebron Institute of Oncology (VHIO) and Banc de Sang I Teixits (BST), Barcelona, Spain
search

1. Study Identification

Unique Protocol Identification Number
NCT04832607
Brief Title
Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections
Acronym
TRACE
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 27, 2019 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Tobias Feuchtinger
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, Centre Hospitalier Universitaire de Nancy, CHU, Vandoeuvre-Lès-Nancy, France, Ghent University Hospital, UZG, Ghent, Belgium, Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy, Newcastle University, UNEW, Newcastle, UK, Vall d'Hebron Institute of Oncology (VHIO) and Banc de Sang I Teixits (BST), Barcelona, Spain

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AdV Infection, EBV Infection, CMV Infection, Stem Cell Transplant Complications

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
2 (verum): 1 (Placebo) randomization
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
149 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Multivirus (CMV, EBV, AdV)-specific T cells
Arm Type
Experimental
Arm Description
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
Arm Title
Sodium chloride
Arm Type
Placebo Comparator
Arm Description
Suspension of multivirus-specific T cells in 20 mL of 0.9% NaCl + 0.5% HSA
Intervention Type
Other
Intervention Name(s)
Multivirus (CMV, EBV, AdV)-specific T cells
Intervention Description
Cell therapy product which is individually produced for each patient and administered via IV bolus injection.
Primary Outcome Measure Information:
Title
Viral clearance
Description
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
Time Frame
8 weeks after treatment
Title
Disease Progression
Description
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
Time Frame
day 7 until week 8 after treatment
Secondary Outcome Measure Information:
Title
Incidence of acute GvHD
Description
Incidence of newly occurring acute GvHD grade I from Day 0 to Week 8 and Week 15.
Time Frame
15 weeks after treatment
Title
Incidence of chronic GvHD
Description
Incidence of chronic GvHD from Day 7 to Week 8 and to Week 15 after treatment.
Time Frame
15 weeks after treatment
Title
Time to newly occuring GvHD
Description
Time to newly occurring acute and chronic GvHD.
Time Frame
15 weeks after treatment
Title
Severity of GvHD
Description
Severity of acute GvHD ≥ grade II until Week 8 and Week 15.
Time Frame
week 8 and 15 week after treatment
Title
Incidence of acute toxicity
Description
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.
Time Frame
15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Title
Severity of acute toxicity
Description
Monitoring of adverse events infusion.
Time Frame
15 minutes, 30 minutes, 2 hours and 4 hours post T-cell/placebo transfer
Title
Change in viral load of underlying viral infection
Description
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.
Time Frame
8 weeks after treatment
Title
Time to viral load change of underlying viral infection
Description
Time to 1 log change in viral load.
Time Frame
15 weeks after treatment
Title
Percentage of viral decrease
Description
Percentage of patients with ≥1 log decrease in CMV, EBV or AdV viral load at Week 8.
Time Frame
8 weeks after treatment
Title
Viral reactivations
Description
Number of reactivations of the underlying viral infection following initial viral clearance until end of follow-up.
Time Frame
15 weeks after treatment
Title
Clinical response/resolution of symptoms of underlying viral infection
Description
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.
Time Frame
8 weeks after treatment
Title
Overall survival
Description
Overall survival rate (OS): From Day 0 to end of follow-up.
Time Frame
15 weeks after treatment
Title
Necessity of antiviral chemotherapy
Description
Number of days requiring antiviral chemotherapy after T-cell transfer from Day 7 to Week 8 after T-cell transfer.
Time Frame
Day 7 until Week 8
Title
Duration of antiviral chemotherapy
Description
Time to last administration of defined antiviral medication or switch to prophylactic treatment from Day 0 to Week 8 after IMP transfer.
Time Frame
8 weeks after treatment
Title
Incidence of viral infections other than underlying viral infection
Description
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.
Time Frame
15 weeks
Title
Days of hospitalization
Description
Number of days hospitalized after IMP transfer from Day 7 to Week 8.
Time Frame
8 weeks
Title
Life quality in adults
Description
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.
Time Frame
Screening and Week 8.
Title
Life quality in adults
Description
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.
Time Frame
Screening and Week 8
Title
Life quality in children
Description
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.
Time Frame
Screening and Week 8
Title
Effect on the patient's T-cell phenotype in vivo
Description
T-cell phenotyping, samples taken at Screening, Day 0 and each visit from Day 7 to Week 15 after treatment.
Time Frame
Screening until Week 15
Title
Effect on the patient's number of expanded T cells
Description
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.
Time Frame
Screening until Week 15
Title
Quality of the IMP and performance of the CliniMACS® Prodigy
Description
Assessment of the cellular composition, in particular the percentage of IFN-gamma+ cells, in the IMP.
Time Frame
Before IMP release (between Screening and Day 0)
Title
Evaluation of the drop-out rate
Description
Drop-out rate at Day 0 and reasons for drop-out.
Time Frame
at Day 0 (planned treatment day)
Title
Time from inclusion to administration of the IMP
Description
Number of days from Screening to Day 0 (day of IMP transfer) to evaluate the required time frame.
Time Frame
Screening until Day 0 (treatment day)
Title
Adverse events
Description
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.
Time Frame
15 weeks
Title
Physical examination
Description
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.
Time Frame
Screening to Week 8
Title
Vital Sign - blood pressure
Description
supine systolic and diastolic blood preasure in mm Hg
Time Frame
Screening to Week 8
Title
Vital Signs - heart rate
Description
The resting heart rate in beats/min
Time Frame
Screening to Week 8
Title
Vital Signs - body temperature
Description
Body temperature in °C (aural)
Time Frame
Screening to Week 8
Title
Vital Signs - body weight
Description
body weight in kg
Time Frame
Screening to Week 8
Title
Vital Signs - respiratory rate
Description
respiratory rate in breaths/min.
Time Frame
Screening to Week 8
Title
Incidence of abnormal laboratory values
Description
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.
Time Frame
Screening to Week 8
Title
Concomitant medication until Week 8
Description
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.
Time Frame
8 weeks after treatment
Title
Concomitant medication until Week 15
Description
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.
Time Frame
15 weeks after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tobias Feuchtinger, Prof
Phone
0049 (0)89 4400
Ext
57945
Email
onkostudien.hauner@med.uni-muenchen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Theresa Käuferle, Dr
Phone
0049 (0)89 4400
Ext
52338
Email
info@trace-study.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tobias Feuchtinger, Prof
Organizational Affiliation
Klinikum der Universität München
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Jules Bordet (JBI)
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Lewalle, Prof
Email
philippe.lewalle@bordet.be
First Name & Middle Initial & Last Name & Degree
Philippe Lewalle, Prof
Facility Name
UZ Brussel
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ann De Becker, Dr.
Email
ann.debecker@uzbrussel.be
First Name & Middle Initial & Last Name & Degree
Ann De Becker, Dr.
Facility Name
Ghent Universal Hospital (UZG)
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tessa Kerre, Prof
Email
tessa.kerre@ugent.be
First Name & Middle Initial & Last Name & Degree
Tessa Kerre, Prof
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Maertens, Prof. Dr.
Email
johan.maertens@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Johan Maertens, Prof.
Facility Name
Université de Liège (ULG)
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Beguin, Prof.
Email
yves.beguin@chu.ulg.ac.be
First Name & Middle Initial & Last Name & Degree
Yves Beguin, Prof.
Facility Name
Hôpital Jeanne de Flandre, CHU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bénédicte Bruno, Dr.
Email
benedicte.bruno@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Bénédicte Bruno, Dr.
Facility Name
Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Ouachée-Chardin, Dr.
Email
marie.ouachee-chardin@ihope.fr
First Name & Middle Initial & Last Name & Degree
Marie Ouachée-Chardin, Dr.
Facility Name
Centre Hospitalier Régional Universitaire de Nancy (CHRU)
City
Nancy
ZIP/Postal Code
54035
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniele Bensoussan, Prof.
Email
d.bensoussan@chru-nancy.fr
First Name & Middle Initial & Last Name & Degree
Maud D'Aveni-Piney, Dr.
Facility Name
Hôpital de la Pitie-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stéphanie Nguyen Quoc, Prof.
Email
stephanie.nguyen-quoc@aphp.fr
First Name & Middle Initial & Last Name & Degree
Stéphanie Nguyen Quoc, Prof.
Facility Name
Hôpital Necker - Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bendedicte Neven, Prof.
Email
benedicte.neven@aphp.fr
First Name & Middle Initial & Last Name & Degree
Bendedicte Neven, Prof.
Facility Name
Hôpital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Hugues Dalle, Prof.
Email
jean-hugues.dalle@aphp.fr
First Name & Middle Initial & Last Name & Degree
Jean Hugues Dalle, Prof.
Facility Name
Charité Berlin (Campus Virchow-Klinikum) - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johannes Schulte, Prof.
Email
johannes.schulte@charite.de
First Name & Middle Initial & Last Name & Degree
Johannes Schulte, Prof.
Facility Name
Universitätsklinikum Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Bornhäuser, Prof.
Email
Martin.Bornhaeuser@uniklinikum-dresden.de
First Name & Middle Initial & Last Name & Degree
Martin Bornhäuser, Prof.
Facility Name
Universitätsklinikum Düsseldorf - Klinik für Kinder-Onkologie, -Hämatologie und klinische Immunologie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roland Meisel, Prof.
Email
meisel@med.uni-duesseldorf.de
First Name & Middle Initial & Last Name & Degree
Roland Meisel, Prof.
Facility Name
Universitätsklinikum Essen - Pädiatrische Hämatologie-Onkologie
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Schönberger, Dr.
Email
Stefan.Schoenberger@uk-essen.de
First Name & Middle Initial & Last Name & Degree
Stefan Schönberger, Dr.
Facility Name
Universitätsklinikum Freiburg - Klinik für Pädiatrische Hämatologie und Onkologie
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brigitte Strahm, PD Dr.
Email
brigitte-strahm@uniklinik-freiburg.de
First Name & Middle Initial & Last Name & Degree
Brigitte Strahm, PD Dr.
Facility Name
Medizinische Hochschule Hannover - Zentrum für Kinderheilkunde und Jugendmedizin
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Britta Maecker-Kolhoff, Prof.
Email
Maecker.Britta@MH-Hannover.de
First Name & Middle Initial & Last Name & Degree
Britta Maecker-Kolhoff, Prof.
Facility Name
Universitäsklinikum Leipzig - Medizinische Klinik und Poliklinik I
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vladan Vucinic, Dr.
Email
Vladan.Vucinic@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name & Degree
Vladan Vucinic, Dr.
Facility Name
LMU Klinikum - Dr. v. Haunersches Kinderspital
City
Munich
ZIP/Postal Code
80337
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Feuchtinger, Prof.
Email
info@trace-study.de
First Name & Middle Initial & Last Name & Degree
Tobias Feuchtinger, Prof.
Facility Name
Klinikum rechts der Isar der Technischen Universität - Kinderklinik Schwabing
City
Munich
ZIP/Postal Code
80804
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irene Teichert von Lüttichau, PD Dr.
Email
Irene.Teichert-vonluettichau@mri.tum.de
First Name & Middle Initial & Last Name & Degree
Irene Teichert von Lüttichau, PD Dr.
Facility Name
LMU Klinikum - Medizinische Klinik und Poliklinik III
City
München
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johanna Tischer, Dr.
Email
johanna.tischer@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Johanna Tischer, Dr.
Facility Name
Klinikum rechts der Isar der Technischen Universität - Klinik und Poliklinik für Innere Medizin III
City
München
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mareike Verbeek, Dr.
Email
Mareike.Verbeek@tum.de
First Name & Middle Initial & Last Name & Degree
Mareike Verbeek, Dr.
Facility Name
Universitätsklinikum Regensburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Föll, Prof.
Email
juergen.foell@klinik.uni-regensburg.de
First Name & Middle Initial & Last Name & Degree
Jürgen Föll, Prof.
Facility Name
Universitätsklinikum Tübingen, Center for Pediatric Clinical Studies (CPCS)
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Lang, Prof.
Email
peter.lang@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Peter Lang, Prof.
Facility Name
Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II & Zentrum Innere Medizin (ZIM)
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hermann Einsele, Prof.
Email
einsele_h@klinik.uni-wuerzburg.de
First Name & Middle Initial & Last Name & Degree
Hermann Einsele, Prof.
Facility Name
Universitätsklinikum Würzburg - Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Wölfl, Prof.
Email
Woelfl_M@kw.de
First Name & Middle Initial & Last Name & Degree
Matthias Wölfl, Prof.
Facility Name
Ospedale Pediatrico Bambino Gesù (OPBG)
City
Rom
ZIP/Postal Code
00165
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Franco Locatelli, Prof.
Email
franco.locatelli@opbg.net
First Name & Middle Initial & Last Name & Degree
Franco Locatelli, Prof.
Facility Name
Ospedale Infantile Regina Margherita - Oncoematologie Pediatrica
City
Turin
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Franca Fagioli, Prof.
Email
franca.fagioli@unito.it
First Name & Middle Initial & Last Name & Degree
Franca Fagioli, Prof.
Facility Name
Leiden University Medical Centre (LUMC) - Department of Hematology
City
Leiden
ZIP/Postal Code
2333
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter van Balen, Dr.
Email
P.van_Balen@lumc.nl
First Name & Middle Initial & Last Name & Degree
Peter van Balen, Dr.
Facility Name
Vall d'Hebron Institute of Oncology (VHIO)
City
Barcelona
ZIP/Postal Code
119-129
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pere Barba, Dr.
Email
pbarba@vhio.net
First Name & Middle Initial & Last Name & Degree
María Laura Fox, Dr.
Email
mlfox@vhio.net
First Name & Middle Initial & Last Name & Degree
María Laura Fox, Dr.
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Pérez-Martinez, Dr.
Email
aperezmartinez@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Antonio Pérez-Martinez, Dr.
Facility Name
Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Antonio Pérez Simón, Dr.
Email
josea.perez.simon.sspa@juntadeandalucia.es
First Name & Middle Initial & Last Name & Degree
José Antonio Pérez Simón, Dr.
Facility Name
Hospital Universitario Politécnico La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Montoro Gómez, Dr.
Email
juanmontorogomez@gmail.com
First Name & Middle Initial & Last Name & Degree
Juan Montoro Gómez, Dr.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs