Clinical trial NCT04412811: Prospective Survey of CMV, Herpesviruses Infections and Diseases in Allo-HSCT
Official title: A Prospective, Multicenter Survey of Cytomegalovirus (CMV) and Other Herpesviruses Infections and Diseases in Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) Recipients.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematologic Diseases
Stem Cell Transplant Complications
Cytomegalovirus Viremia
Herpesvirus Infection
Keywords: Haematopoietic transplantation, CMV, Herpesviruses
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
Collaborators: name: Azienda Policlinico Umberto I
First posted: 2020-06-02
Enrollment: 1310
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult and children allogenic Hematopoietic stem cell transplantation recipients

Brief summary: Prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, Italian with objective to describe the incidence of CMV infections and diseases in adult and pediatric patients undergoing allo-HSCT during the first 6 months from transplant. This study will evaluate approximately 1500 subjects (with competitive enrolment) from GITMO investigational centers.

Detailed description: This is a prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, italian on patients submitted to allogeneic haematopoietic stem cell transplantation organized under the auspices of the Gruppo Italiano Trapianti di Midollo Osseo that involves the principal Centres active in transplantation of any kind of hematopoietic stem cells in Italy.

Allogeneic haematopoietic stem cell transplantation patients continue to be one of the highest risk categories for developing viral infections. Cytomegalovirus infection is the leading viral cause of morbidity and mortality and HHV6 and EBV are other major causes of complications in transplant. The risk of these infections is directly related to the type of transplant.

A better and continuous monitoring of Cytomegalovirus and other herpesviruses complication in this setting would contribute to a better knowledge of the evolving epidemiology and would lead to a better use of diagnostic strategies and of preventive and therapeutic measures.

This study is aimed to identify epidemiological characteristics of allogeneic haematopoietic stem cell transplantation patients developing cytomegalovirus and other herpesviruses infections, risk factors, diagnostic peculiarities and factors that may guide to pre-emptive therapy versus prophylaxis strategies.

Virological monitoring and health care resources utilization in Allogeneic haematopoietic stem cell transplantation recipients according to the different risk of viral infection will be also assessed. This prospective analysis will provide useful information for local clinicians to define tailored antiviral strategies in line with the change of transplantation procedures.

All consecutive patients submitted to allogeneic haematopoietic stem cell transplantation will be prospectively monitored for Cytomegalovirus Cytomegalovirus, Herpesvirus human 6 and Virus Epstein-Barr infections and diseases during the six months from transplant, because most of viral infections and diseases occur within this period after transplant. Risk factors, incidence and prognostic factors of each viral infection and disease, as well as diagnostic and therapeutic strategies employed in the various transplant centers, will be evaluated in the overall population and in subpopulations according to different transplant characteristics.

The incidence of these infections and diseases will be also collected and described according to the different types of transplant and underlying disease conditions.

The Secondary Objectives are:

To assess the factors that may affect the incidence and the prognosis of allogeneic haematopoietic stem cell transplantation infections and diseases, as well as of Herpesvirus human 6 and Virus Epstein-Barr infections and related diseases To assess the impact of allogeneic haematopoietic stem cell transplantation infections and diseases on the overall and attributable mortality at 12 months from the transplant To describe the virological diagnostic strategies of allogeneic haematopoietic stem cell transplantation, Herpesvirus human 6 and Virus Epstein-Barr infections and the allogeneic haematopoietic stem cell transplantation specific immunological reconstitution tests used in the various centres To describe the antiviral strategies employed in the various centers and in the various subpopulations of transplant patients with focus on use of antiviral drugs in prophylaxis and therapy and use of allogeneic haematopoietic stem cell transplantation -specific intravenous IVIG in prophylaxis and therapy To evaluate the impact of a local strategy about use of antiviral drugs and allogeneic haematopoietic stem cell transplantation -specific IVIG in prophylaxis and therapy on the epidemiological findings, the clinical evolution of the allogeneic haematopoietic stem cell transplantation infections and diseases and on the Health Care Resources utilization (diagnostic procedures, pharmaco-utilization, hospitalization, outpatient visits).

A web system data entry will be used for this study. Data will be stored using specific e-CRFs designed by GITMO committee and includes mainly descriptive variables. Data Center will perform extensive consistency checks and issue electronic Query Forms in case of inconsistent data. Follow-up period for the evaluation of survival will be from the date of transplant until 12 months post-transplant or death. However, patients may not have 12 months follow up and if the patients are not having 12 months of observation due to lost to follow up and not due to mortality, these patients characteristics will be compared with the rest of the patients in order to ascertain there is no bias or estimate the bias.

The study will be conducted according to the principles of Good Clinical Practice, the current Italian and European laws and regulations, in agreement with the declaration of Helsinki. The protocol has been written and the study will be conducted according to The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonized Tripartite Guideline for Good Clinical Practice, issued by the European Union. The responsible Local Ethical Committee approval must be obtained before starting the trial. A copy of the patient informed consent form must be submitted to the appropriate authority or committee, together with the protocol for written approval. Written approval of the protocol and informed consent by the responsible and appropriate authority or committee must be obtained prior to recruitment of patients to the study.

Eligibility criteria: Inclusion Criteria:

* Prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, Italian with objective to describe the incidence of CMV infections and diseases in adult and pediatric patients undergoing allo-HSCT during the first 6 months from transplant. This study will evaluate approximately 1500 subjects, with competitive enrolment from GITMO investigational centers.

Exclusion Criteria:

* Absence of consent Written information

Primary outcomes:
measure: Cytomegalovirus infection
timeFrame: 6 months from transplant
measure: Cytomegalovirus disease
timeFrame: 6 months from transplant
measure: Herpesvirus human 6 infection
timeFrame: 6 months from transplant
measure: Herpesvirus human 6 disease
timeFrame: 6 months from transplant
measure: Virus Epstein-Barr infection
timeFrame: 6 months from transplant
measure: Virus Epstein-Barr disease
timeFrame: 6 months from transplant
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: These outcome measures will be assessed at 1 year from transplant
measure: Disease Free Survival (DFS)
timeFrame: These outcome measures will be assessed at 1 year from transplant
measure: Transplant Related Mortality (TRM)
timeFrame: These outcome measures will be assessed at 1 year from transplant
measure: Relapse risk (RR)
timeFrame: These outcome measures will be assessed at 1 year from transplant
measure: Acute Graft-versus-Host Disease
timeFrame: These outcome measures will be assessed at 100 days from transplant
measure: chronic graft-versus-host disease
timeFrame: These outcome measures will be assessed at 1 year from transplant
Other outcomes:
Locations:
city: Tricase
country: Italy
facility: UO Ematologia e TMO - Ospedale C. Panico
state: Lecce
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria Ospedali Riuniti
city: Ascoli Piceno
country: Italy
facility: Ospedale Mazzoni
city: Avellino
country: Italy
facility: A.O.S. G. Moscati
city: Bari
country: Italy
facility: Policlinico di Bari-Ematologia con trapianti
city: Bergamo
country: Italy
facility: Divisione di Ematologia - Ospedali Papa Giovanni XXIII
city: Bologna
country: Italy
facility: A.O.U. Policlinico S.Orsola-Malpighi
city: Bologna
country: Italy
facility: Ospedale San Orsola
city: Bolzano
country: Italy
facility: Ospedale Regionale Generale- Divisione Ematologia
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia- USD - TMO Adulti
city: Brindisi
country: Italy
facility: Azienda Sanitaria Locale Br1 Ospedale "A. Perrino
city: Cagliari
country: Italy
facility: CTMO PO "Businco" A.O. "G. Brotzu"
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Cuneo
country: Italy
facility: Struttura Complessa di Ematologia, Azienda Ospedaliera Santa Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera di Careggi
city: Foggia
country: Italy
facility: Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza
city: Genova
country: Italy
facility: AOU-IRCCS San Martino-IST
city: Genova
country: Italy
facility: Ospedale Gaslini
city: Lecce
country: Italy
facility: Policlinico VIto Fazzi
city: Mestre
country: Italy
facility: AOU Integrata
city: Milano
country: Italy
facility: Divisione di Ematologia - Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Modena
country: Italy
facility: Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Napoli
country: Italy
facility: A.O.U. Policlinico Federico II
city: Napoli
country: Italy
facility: AOU S. Giovanni di Dio e Ruggi D'Aragona
city: Napoli
country: Italy
facility: Uoc Sit Tmo
city: Napoli
country: Italy
facility: UOSC Ematologia con Trapianto CSE, AORN A. Cardarelli, AORN Cardarelli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: CTMO Osp. V. Cervello Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
city: Parma
country: Italy
facility: Azienda ospedaliera Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS San Matteo
city: Pavia
country: Italy
facility: Policlinico San Matteo
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia
city: Pescara
country: Italy
facility: Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Potenza
country: Italy
facility: Ospedale San Carlo
city: Reggio Calabria
country: Italy
facility: Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli
city: Reggio Emilia
country: Italy
facility: Arciospedale S. M. Novella
city: Roma
country: Italy
facility: Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Ospedale Bambin Gesù
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Rozzano (MI)
country: Italy
facility: Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas
city: Taranto
country: Italy
facility: Ospedale Moscati
city: Torino
country: Italy
facility: AOU CIttà della Salute e della Scienza
city: Torino
country: Italy
facility: Ospedale Regina Margherita
city: Udine
country: Italy
facility: A.O. Santa Maria della Misericordia
city: Verona
country: Italy
facility: Policlinico GB Rossi
Study officials:
affiliation: Azienda Policlinico Umberto I
name: Corrado Girmenia
role: PRINCIPAL_INVESTIGATOR
References: