Hematopoietic Stem Cell TransplantationNAViReNCT04690933
AntiCMV molécules Monitoring in Real-life in Stem Cell Recipients
An observational study of Hematopoietic Stem Cell Transplantation and Cytomegalovirus Infections, run by University Hospital, Limoges at 16 sites in France.
Trial summary
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that represent a major cause of morbidity in haematopoietic stem cell transplants (HSCT) recipients, mostly through reactivation of the recipient's virus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation, Cytomegalovirus Infections, Antivirals
- What is being tested?
- Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipients
- How many people
- 400 participants
- Where
- 16 sitesFrance
- Study dates
- 24 Sep 2020to 30 Nov 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Candidate (adult) for an allograft of hematopoietic stem cells for which a decision of transplant is made and willing to participate in the cohort.
Who may be able to join
- Candidate (adult) for an allograft of hematopoietic stem cells for which a decision of transplant is made and willing to participate in the cohort.
Who cannot join
- CMV-seronegative patient receiving a negative CMV donor graft ;
- Patient having signed the consent but not grafted ;
- Patient included in a clinical study on an anti-CMV molecule ;
- Non-insured social patient ;
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
France16 sites
CHU
Amiens
CHU
Angers
CHU
Besançon
CHU
Bordeaux
CHU
Caen
CHU
Clermont-Ferrand
CHU
Grenoble
CHU de LIMOGES
Limoges, Limoges, 87045
HCL
Lyon
CHU
Montpellier
CHU
Nancy
APHP
Paris
CHU
Poitiers
CHU
Rouen
CHU
Saint-Etienne
CHU
Strasbourg
About this study
Official title: Real-life Observatory of Efficacy and Resistance to Anti CMV Molecules in Stem Cell Recipients
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that represent a major cause of morbidity in haematopoietic stem cell transplants (HSCT) recipients, mostly through reactivation of the recipient's virus.
If left untreated, 40 to 80% of patients will develop CMV infection, leading to CMV disease in 30 to 35 % patients, and associated with considerable morbi-mortality. Interstitial pneumonia is the most severe and specific manifestation, although CMV replication by itself has also indirect effects such as triggering graft versus host disease and increasing immunosuppression. The current burden of CMV infection increases by 25 to 30% the cost of the graft in France. This also includes the burden for refractory - infections, that represent up to 13% of recipients with CMV infection, including 3% of cases with virological resistance in France (data from the Reference Center cohorts).
Read more
Ganciclovir, or valganciclovir preemptive treatment, guided by CMV viral load follow-up allowed significant reduction of CMV disease to 2-6% but did not prevent CMV indirect effects. In addition, hematotoxicity can compromise post-transplant haematological reconstitution, thus preventing its use as prophylaxis in France. Foscarnet, iv-administered and nephrotoxic, remains less used. There is thus a high expectation from less toxic molecules for prophylaxis The development letermovir recently available for prophylaxis of CMV infection in high risk patients will modify the patients care and follow-up. This new molecule targeting CMV terminases (developed by Merck) was recently marketed in France (Jan 2020). However, the analysis of the letermovir phase III study and further publications show that the risk of emergence of resistance is low, but may occur in case of breakthrough and thus post AMM monitoring is required.
A "real-life" evaluation of these new molecules in terms of efficacy, emergence of resistance, tolerance and morbimortality related to CMV infection, is useful, to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients. To this purpose, the National Reference Center in collaboration with the French Society for marrow graft and cell therapy (SFGMTC) set up a cohort of surveillance of allografted patients, receiving, in prevention or treatment, old and new molecules.
Read the detailed description
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that represent a major cause of morbidity in haematopoietic stem cell transplants (HSCT) recipients, mostly through reactivation of the recipient's virus.
If left untreated, 40 to 80% of patients will develop CMV infection, leading to CMV disease in 30 to 35 % patients, and associated with considerable morbi-mortality. Interstitial pneumonia is the most severe and specific manifestation, although CMV replication by itself has also indirect effects such as triggering graft versus host disease and increasing immunosuppression. The current burden of CMV infection increases by 25 to 30% the cost of the graft in France. This also includes the burden for refractory - infections, that represent up to 13% of recipients with CMV infection, including 3% of cases with virological resistance in France (data from the Reference Center cohorts).
Ganciclovir, or valganciclovir preemptive treatment, guided by CMV viral load follow-up allowed significant reduction of CMV disease to 2-6% but did not prevent CMV indirect effects. In addition, hematotoxicity can compromise post-transplant haematological reconstitution, thus preventing its use as prophylaxis in France. Foscarnet, iv-administered and nephrotoxic, remains less used. There is thus a high expectation from less toxic molecules for prophylaxis The development letermovir recently available for prophylaxis of CMV infection in high risk patients will modify the patients care and follow-up. This new molecule targeting CMV terminases (developed by Merck) was recently marketed in France (Jan 2020). However, the analysis of the letermovir phase III study and further publications show that the risk of emergence of resistance is low, but may occur in case of breakthrough and thus post AMM monitoring is required.
A "real-life" evaluation of these new molecules in terms of efficacy, emergence of resistance, tolerance and morbimortality related to CMV infection, is useful, to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients. To this purpose, the National Reference Center in collaboration with the French Society for marrow graft and cell therapy (SFGMTC) set up a cohort of surveillance of allografted patients, receiving, in prevention or treatment, old and new molecules.
- Conditions
- Hematopoietic Stem Cell Transplantation, Cytomegalovirus Infections, Antivirals, Antiviral Drug Resistance
- Being tested
- Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipients
- Keywords
- Hematopoietic Stem Cell Transplantation, Cytomegalovirus Infections, Antivirals, Antiviral Drug Resistance
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipientsOther
Signing of consent at the time of the pre-transplant consultation (1 month before grafting). Inclusion of patients during conditioning (around D-8 of transplantation). Samples related to the cohort:one blood sample from the donor (only familial donors) for genetic SNPs analysis. 5 samples: D-8, D20, D100, D200 (+/-10 days), 1 year : 1 tube of 7ml of whole blood on EDTA: Biobanking of whole blood for genetic SNPs analysis (D-8) of specific transporters for GCV, and of plasma for TTV viral load at all times. In routine care:samples taken in the event of a therapeutic escape (2 x 7 ml EDTA tubes, for resistance genotype, and ganciclovir dosage, 3 x 1 ml for Quantiferon CMV, according to CNR Herpesvirus recommendations. 1 x Paxgene tube (2.5 ml) for subsequent CMV genomic and transcriptomic studies. Cell preservation plasma and whole blood for biocollection (2 tubes EDTA de 7ml). Samples stored by the centers' virology laboratories are periodically sent to the CNR for analysis.
| Study group | Role | What they receive |
|---|---|---|
| Multicentric NAViRe cohort with biocollection | The National Reference Center (CNR) for cytomegalovirus with the French Society for Medullary Transplantation and Cell Therapy (SFGM-TC) has set up a surveillance cohort of allografted patients (NAViRe cohort) receiving, as prevention or treatment, Anti-Cytomegalovirus (Anti-CMV) molecules, "new or less recent", thus allowing the development of a new observatory evaluating in real life the potentials of these drugs in terms of efficacy, emergence of resistance, tolerance and morbidity and mortality associated with CMV infection.This work is useful to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients and allows the emergence of an real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipients. Receives: Other: Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipients |
What is being measured
The primary outcome is the main question the study is designed to answer.
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: between Day-30 and Day -8
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: between Day-8 and Day 0
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: at Day20
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: at Day100
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: at Day 200 (Month 6)
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: Month12
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
Measured: Month24
Secondary outcomes (24)
Uses of anti-CMV molecules : preemptive treatment
% of patients having received preemptive treatment
Measured: at Day200
Uses of anti-CMV molecules : prophylaxis
% of patients having received prophylaxis
Measured: at Day200
Uses of anti-CMV molecules : curative treatment
% of patients having received curative treatment
Measured: at Day200
Uses of anti-CMV molecules
Cumulative duration of exposure (number of day) for each drug administered
Measured: at Day200
Uses of anti-CMV molecules : preemptive treatment
% of patients having received preemptive treatment
Measured: at Month12
Uses of anti-CMV molecules : prophylaxis
% of patients having received prophylaxis
Measured: at Month12
Uses of anti-CMV molecules : curative treatment
% of patients having received curative treatment
Measured: at Month12
Uses of anti-CMV molecules
Cumulative duration of exposure (number of day) for each drug administered
Measured: at Month12
Uses of anti-CMV molecules : preemptive treatment
% of patients having received preemptive treatment
Measured: at Month24
Uses of anti-CMV molecules : prophylaxis
% of patients having received prophylaxis
Measured: at Month24
Uses of anti-CMV molecules : curative treatment
% of patients having received curative treatment
Measured: at Month24
Uses of anti-CMV molecules
Cumulative duration of exposure (number of day) for each drug administered
Measured: at Month24
Incidence of the non-response and resistance to antivirals with risk factors associated (virological, pharmacological, immunological). Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in
Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in :
- Refractory CMV infection CMV viremia that increases after at least 2 wk of appropriately dosed antiviral therapy.
- Probable refractory CMV infection : persistent viral load after at least 2 wk of appropriately dosed antiviral therapy.
- Refractory CMV end organ disease : worsening in signs and symptoms or progression into end-organ disease after at least 2 wk of appropriately dosed antiviral therapy.
- Probable refractory CMV end-organ disease : lack of improvement in signs and symptoms after at least 2 wk of appropriately dosed antiviral drugs.
- Antiviral drug resistance : viral genetic alteration that decreases susceptibility to one or more antiviral drugs.
Resistance : presence of a resistance-related mutation by resistance genotyping of UL97, UL54, UL56, UL89, UL27 genes, carried out or validated by the Limoges Herpesviruses reference laboratory. In blood or any other sample.
Measured: at Month12
Incidence of the non-response and resistance to antivirals with risk factors associated (virological, pharmacological, immunological). Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in
Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in :
- Refractory CMV infection CMV viremia that increases after at least 2 wk of appropriately dosed antiviral therapy.
- Probable refractory CMV infection : persistent viral load after at least 2 wk of appropriately dosed antiviral therapy.
- Refractory CMV end organ disease : worsening in signs and symptoms or progression into end-organ disease after at least 2 wk of appropriately dosed antiviral therapy.
- Probable refractory CMV end-organ disease : lack of improvement in signs and symptoms after at least 2 wk of appropriately dosed antiviral drugs.
- Antiviral drug resistance : viral genetic alteration that decreases susceptibility to one or more antiviral drugs.
Resistance : presence of a resistance-related mutation by resistance genotyping of UL97, UL54, UL56, UL89, UL27 genes, carried out or validated by the Limoges Herpesviruses reference laboratory. In blood or any other sample.
Measured: at Month24
Adverse effects leading to interruption of treatment
Incidence of treatment emergent adverse event as assessed by interruption of treatment
Measured: at Month12
Adverse effects leading to interruption of treatment
Incidence of treatment emergent adverse event as assessed by interruption of treatment
Measured: at Month24
CMV related mortality
Number of patients who died from CMV related desease
Measured: at Month12
CMV related mortality
Number of patients who died from CMV related desease
Measured: at Month24
CMV associated morbidity : delay engraftment
number of days bettwen graft and engraftment
Measured: at Month12
CMV associated morbidity : GVHD
Incidence of GVHD
Measured: at Month12
CMV associated morbidity : CMV infection/disease
Incidence of CMV infection/disease (infection or disease will be combined to report this outcome).
CMV infection : positive diagnostic test (CMV culture, antigen detection or CMV PCR), in any body fluid or tissue, in the absence of symptoms.
CMV disease : CMV infection associated with end-organ disease (clinical signs and oriented virological diagnosis).
Measured: at Month12
CMV associated morbidity : delay engraftment
number of days bettwen graft and engraftment
Measured: at Month24
CMV associated morbidity : GVHD
Incidence of GVHD
Measured: at Month24
CMV associated morbidity : CMV infection/disease
Incidence of CMV infection/disease (infection or disease will be combined to report this outcome).
CMV infection : positive diagnostic test (CMV culture, antigen detection or CMV PCR), in any body fluid or tissue, in the absence of symptoms.
CMV disease : CMV infection associated with end-organ disease (clinical signs and oriented virological diagnosis).
Measured: at Month24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2020
- Study start24 Sep 2020
- Primary completion24 Sep 2025
- Study completion30 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascal TURLURE, Principal investigator, Service d'Hématologie Clinique et de Thérapie Cellulaire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04690933
- Sponsor's protocol ID
- 87RI18_0011 (NAViRe)
- Acronym
- NAViRe
- Status last verified
- Sep 2020
- First submitted
- 14 Sep 2020
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.
PubMed 27682069Chemaly RF, Chou S, Einsele H, Griffiths P, Avery R, Razonable RR, Mullane KM, Kotton C, Lundgren J, Komatsu TE, Lischka P, Josephson F, Douglas CM, Umeh O, Miller V, Ljungman P; Resistant Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019 Apr 8;68(8):1420-1426. doi: 10.1093/cid/ciy696.
PubMed 30137245Billat PA, Ossman T, Saint-Marcoux F, Essig M, Rerolle JP, Kamar N, Rostaing L, Kaminski H, Fabre G, Otyepka M, Woillard JB, Marquet P, Trouillas P, Picard N. Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. Pharmacol Res. 2016 Sep;111:501-508. doi: 10.1016/j.phrs.2016.07.012. Epub 2016 Jul 9.
PubMed 27402191Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-2444. doi: 10.1056/NEJMoa1706640. Epub 2017 Dec 6.
PubMed 29211658Robin C, Hemery F, Dindorf C, Thillard J, Cabanne L, Redjoul R, Beckerich F, Rodriguez C, Pautas C, Toma A, Maury S, Durand-Zaleski I, Cordonnier C. Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients. BMC Infect Dis. 2017 Dec 5;17(1):747. doi: 10.1186/s12879-017-2854-2.
PubMed 29207952Billat PA, Woillard JB, Essig M, Sauvage FL, Picard N, Alain S, Neely M, Marquet P, Saint-Marcoux F. Plasma and intracellular exposure to ganciclovir in adult renal transplant recipients: is there an association with haematological toxicity? J Antimicrob Chemother. 2016 Feb;71(2):484-9. doi: 10.1093/jac/dkv342. Epub 2015 Nov 3.
PubMed 26538506Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.
PubMed 29596116
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-life Observatory of Efficacy and Resistance to Anti CMV Molecules in Stem Cell Recipients
- ClinicalTrials.gov ID
- NCT04690933
- Acronym / sponsor ID
- NAViRe / 87RI18_0011 (NAViRe)
- Conditions
- Hematopoietic Stem Cell Transplantation, Cytomegalovirus Infections, Antivirals, Antiviral Drug Resistance
- Keywords
- Hematopoietic Stem Cell Transplantation, Cytomegalovirus Infections, Antivirals, Antiviral Drug Resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 24 Sep 2025 (actual)
- Study completion
- 30 Nov 2025 (actual)
- First posted
- 31 Dec 2020 (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.
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that represent a major cause of morbidity in haematopoietic stem cell transplants (HSCT) recipients, mostly through reactivation of the recipient's virus.
If left untreated, 40 to 80% of patients will develop CMV infection, leading to CMV disease in 30 to 35 % patients, and associated with considerable morbi-mortality. Interstitial pneumonia is the most severe and specific manifestation, although CMV replication by itself has also indirect effects such as triggering graft versus host disease and increasing immunosuppression. The current burden of CMV infection increases by 25 to 30% the cost of the graft in France. This also includes the burden for refractory - infections, that represent up to 13% of recipients with CMV infection, including 3% of cases with virological resistance in France (data from the Reference Center cohorts).
Ganciclovir, or valganciclovir preemptive treatment, guided by CMV viral load follow-up allowed significant reduction of CMV disease to 2-6% but did not prevent CMV indirect effects. In addition, hematotoxicity can compromise post-transplant haematological reconstitution, thus preventing its use as prophylaxis in France. Foscarnet, iv-administered and nephrotoxic, remains less used. There is thus a high expectation from less toxic molecules for prophylaxis The development letermovir recently available for prophylaxis of CMV infection in high risk patients will modify the patients care and follow-up. This new molecule targeting CMV terminases (developed by Merck) was recently marketed in France (Jan 2020). However, the analysis of the letermovir phase III study and further publications show that the risk of emergence of resistance is low, but may occur in case of breakthrough and thus post AMM monitoring is required.
A "real-life" evaluation of these new molecules in terms of efficacy, emergence of resistance, tolerance and morbimortality related to CMV infection, is useful, to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients. To this purpose, the National Reference Center in collaboration with the French Society for marrow graft and cell therapy (SFGMTC) set up a cohort of surveillance of allografted patients, receiving, in prevention or treatment, old and new molecules.
Detailed description
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that represent a major cause of morbidity in haematopoietic stem cell transplants (HSCT) recipients, mostly through reactivation of the recipient's virus.
If left untreated, 40 to 80% of patients will develop CMV infection, leading to CMV disease in 30 to 35 % patients, and associated with considerable morbi-mortality. Interstitial pneumonia is the most severe and specific manifestation, although CMV replication by itself has also indirect effects such as triggering graft versus host disease and increasing immunosuppression. The current burden of CMV infection increases by 25 to 30% the cost of the graft in France. This also includes the burden for refractory - infections, that represent up to 13% of recipients with CMV infection, including 3% of cases with virological resistance in France (data from the Reference Center cohorts).
Ganciclovir, or valganciclovir preemptive treatment, guided by CMV viral load follow-up allowed significant reduction of CMV disease to 2-6% but did not prevent CMV indirect effects. In addition, hematotoxicity can compromise post-transplant haematological reconstitution, thus preventing its use as prophylaxis in France. Foscarnet, iv-administered and nephrotoxic, remains less used. There is thus a high expectation from less toxic molecules for prophylaxis The development letermovir recently available for prophylaxis of CMV infection in high risk patients will modify the patients care and follow-up. This new molecule targeting CMV terminases (developed by Merck) was recently marketed in France (Jan 2020). However, the analysis of the letermovir phase III study and further publications show that the risk of emergence of resistance is low, but may occur in case of breakthrough and thus post AMM monitoring is required.
A "real-life" evaluation of these new molecules in terms of efficacy, emergence of resistance, tolerance and morbimortality related to CMV infection, is useful, to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients. To this purpose, the National Reference Center in collaboration with the French Society for marrow graft and cell therapy (SFGMTC) set up a cohort of surveillance of allografted patients, receiving, in prevention or treatment, old and new molecules.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multicentric NAViRe cohort with biocollection | – | Other: Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipientsThe National Reference Center (CNR) for cytomegalovirus with the French Society for Medullary Transplantation and Cell Therapy (SFGM-TC) has set up a surveillance cohort of allografted patients (NAViRe cohort) receiving, as prevention or treatment, Anti-Cytomegalovirus (Anti-CMV) molecules, "new or less recent", thus allowing the development of a new observatory evaluating in real life the potentials of these drugs in terms of efficacy, emergence of resistance, tolerance and morbidity and mortality associated with CMV infection.This work is useful to propose recommendations on management strategies, in particular for the most at-risk patients i.e. CMV-seropositive recipients and allows the emergence of an real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Candidate (adult) for an allograft of hematopoietic stem cells for which a decision of transplant is made and willing to participate in the cohort.
Key inclusion criteria (1 listed)
- Candidate (adult) for an allograft of hematopoietic stem cells for which a decision of transplant is made and willing to participate in the cohort.
Key exclusion criteria (4 listed)
- CMV-seronegative patient receiving a negative CMV donor graft ;
- Patient having signed the consent but not grafted ;
- Patient included in a clinical study on an anti-CMV molecule ;
- Non-insured social patient ;
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 |
|---|---|---|
| Real-life observatory of efficacy and resistance to anti CMV molecules in stem cell recipientsSigning of consent at the time of the pre-transplant consultation (1 month before grafting). Inclusion of patients during conditioning (around D-8 of transplantation). Samples related to the cohort:one blood sample from the donor (only familial donors) for genetic SNPs analysis. 5 samples: D-8, D20, D100, D200 (+/-10 days), 1 year : 1 tube of 7ml of whole blood on EDTA: Biobanking of whole blood for genetic SNPs analysis (D-8) of specific transporters for GCV, and of plasma for TTV viral load at all times. In routine care:samples taken in the event of a therapeutic escape (2 x 7 ml EDTA tubes, for resistance genotype, and ganciclovir dosage, 3 x 1 ml for Quantiferon CMV, according to CNR Herpesvirus recommendations. 1 x Paxgene tube (2.5 ml) for subsequent CMV genomic and transcriptomic studies. Cell preservation plasma and whole blood for biocollection (2 tubes EDTA de 7ml). Samples stored by the centers' virology laboratories are periodically sent to the CNR for analysis. | Other | Multicentric NAViRe cohort with biocollection |
Primary outcome
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: between Day-30 and Day -8
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: between Day-8 and Day 0
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: at Day20
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: at Day100
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: at Day 200 (Month 6)
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: Month12
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017).
Time frame: Month24
CMV detection (CMV DNAemia or antigen detection) in any body fluid or tissue specimen
24 secondary outcomes
Uses of anti-CMV molecules : preemptive treatment
Time frame: at Day200
Uses of anti-CMV molecules : prophylaxis
Time frame: at Day200
Uses of anti-CMV molecules : curative treatment
Time frame: at Day200
Uses of anti-CMV molecules
Time frame: at Day200
Uses of anti-CMV molecules : preemptive treatment
Time frame: at Month12
Uses of anti-CMV molecules : prophylaxis
Time frame: at Month12
Uses of anti-CMV molecules : curative treatment
Time frame: at Month12
Uses of anti-CMV molecules
Time frame: at Month12
Uses of anti-CMV molecules : preemptive treatment
Time frame: at Month24
Uses of anti-CMV molecules : prophylaxis
Time frame: at Month24
Uses of anti-CMV molecules : curative treatment
Time frame: at Month24
Uses of anti-CMV molecules
Time frame: at Month24
Incidence of the non-response and resistance to antivirals with risk factors associated (virological, pharmacological, immunological). Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in
Time frame: at Month12
Incidence of the non-response and resistance to antivirals with risk factors associated (virological, pharmacological, immunological). Criteria recently published by Chemaly et al. CID 2018 will be used to classify cases in
Time frame: at Month24
Adverse effects leading to interruption of treatment
Time frame: at Month12
Adverse effects leading to interruption of treatment
Time frame: at Month24
CMV related mortality
Time frame: at Month12
CMV related mortality
Time frame: at Month24
CMV associated morbidity : delay engraftment
Time frame: at Month12
CMV associated morbidity : GVHD
Time frame: at Month12
CMV associated morbidity : CMV infection/disease
Time frame: at Month12
CMV associated morbidity : delay engraftment
Time frame: at Month24
CMV associated morbidity : GVHD
Time frame: at Month24
CMV associated morbidity : CMV infection/disease
Time frame: at Month24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Background: PubMed 27682069Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.
- Background: PubMed 30137245Chemaly RF, Chou S, Einsele H, Griffiths P, Avery R, Razonable RR, Mullane KM, Kotton C, Lundgren J, Komatsu TE, Lischka P, Josephson F, Douglas CM, Umeh O, Miller V, Ljungman P; Resistant Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019 Apr 8;68(8):1420-1426. doi: 10.1093/cid/ciy696.
- Background: PubMed 27402191Billat PA, Ossman T, Saint-Marcoux F, Essig M, Rerolle JP, Kamar N, Rostaing L, Kaminski H, Fabre G, Otyepka M, Woillard JB, Marquet P, Trouillas P, Picard N. Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. Pharmacol Res. 2016 Sep;111:501-508. doi: 10.1016/j.phrs.2016.07.012. Epub 2016 Jul 9.
- Background: PubMed 29211658Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-2444. doi: 10.1056/NEJMoa1706640. Epub 2017 Dec 6.
- Background: PubMed 29207952Robin C, Hemery F, Dindorf C, Thillard J, Cabanne L, Redjoul R, Beckerich F, Rodriguez C, Pautas C, Toma A, Maury S, Durand-Zaleski I, Cordonnier C. Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients. BMC Infect Dis. 2017 Dec 5;17(1):747. doi: 10.1186/s12879-017-2854-2.
- Results publication: PubMed 26538506Billat PA, Woillard JB, Essig M, Sauvage FL, Picard N, Alain S, Neely M, Marquet P, Saint-Marcoux F. Plasma and intracellular exposure to ganciclovir in adult renal transplant recipients: is there an association with haematological toxicity? J Antimicrob Chemother. 2016 Feb;71(2):484-9. doi: 10.1093/jac/dkv342. Epub 2015 Nov 3.
- Results publication: PubMed 29596116Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.
- 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. This study is not recruiting at the moment.
Pascal TURLURE principal investigator
Service d'Hématologie Clinique et de Thérapie Cellulaire
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematopoietic Stem Cell Transplantation and Cytomegalovirus Infections, run by University Hospital, Limoges at 16 sites in France.
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 1 inclusion and 4 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: finished, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in France. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CMV infection according to criteria defined by the European EBMT group (Ljungman et al., 2017). (time frame: between Day-30 and Day -8). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04690933, which also lists 7 linked publications.
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 15 Dec 2025.