Prospective Survey of CMV, Herpesviruses Infections and Diseases in Allo-HSCT

Hematologic Diseases Clinical Trial

— CYTOALLOSURVEY  

Official title:

A Prospective, Multicenter Survey of Cytomegalovirus (CMV) and Other Herpesviruses Infections and Diseases in Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT) Recipients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04412811
• Other study ID #: CYTOALLO GITMO-AMCLI SURVEY
• Status: Completed
• Start date: January 1, 2021
• Est. completion date: July 31, 2022

Study information

• Verified date: November 2022
• Source: Gruppo Italiano Trapianto di Midollo Osseo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Viremia
• Hematologic Diseases
• Herpesviridae Infections
• Herpesvirus Infection
• Infections
• Stem Cell Transplant Complications
• Viremia

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti	Ancona
Italy	Ospedale Mazzoni	Ascoli Piceno
Italy	A.O.S. G. Moscati	Avellino
Italy	Policlinico di Bari-Ematologia con trapianti	Bari
Italy	Divisione di Ematologia - Ospedali Papa Giovanni XXIII	Bergamo
Italy	A.O.U. Policlinico S.Orsola-Malpighi	Bologna
Italy	Ospedale San Orsola	Bologna
Italy	Ospedale Regionale Generale- Divisione Ematologia	Bolzano
Italy	AO Spedali Civili di Brescia- USD - TMO Adulti	Brescia
Italy	Azienda Sanitaria Locale Br1 Ospedale "A. Perrino	Brindisi
Italy	CTMO PO "Businco" A.O. "G. Brotzu"	Cagliari
Italy	Ospedale Ferrarotto	Catania
Italy	Struttura Complessa di Ematologia, Azienda Ospedaliera Santa Croce e Carle	Cuneo
Italy	Azienda Ospedaliera di Careggi	Firenze
Italy	Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza	Foggia
Italy	AOU-IRCCS San Martino-IST	Genova
Italy	Ospedale Gaslini	Genova
Italy	Policlinico VIto Fazzi	Lecce
Italy	AOU Integrata	Mestre
Italy	Divisione di Ematologia - Istituto Nazionale dei Tumori	Milano
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -	Modena
Italy	Ospedale San Gerardo	Monza
Italy	A.O.U. Policlinico Federico II	Napoli
Italy	AOU S. Giovanni di Dio e Ruggi D'Aragona	Napoli
Italy	Uoc Sit Tmo	Napoli
Italy	UOSC Ematologia con Trapianto CSE, AORN A. Cardarelli, AORN Cardarelli	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	CTMO Osp. V. Cervello Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello	Palermo
Italy	Azienda ospedaliera Universitaria di Parma	Parma
Italy	Fondazione IRCCS San Matteo	Pavia
Italy	Policlinico San Matteo	Pavia
Italy	Ospedale S. Maria della Misericordia	Perugia
Italy	Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara	Pescara
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Ospedale San Carlo	Potenza
Italy	Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli	Reggio Calabria
Italy	Arciospedale S. M. Novella	Reggio Emilia
Italy	Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli	Roma
Italy	Ospedale Bambin Gesù	Roma
Italy	Policlinico Tor Vergata	Roma
Italy	Policlinico Umberto I	Roma
Italy	Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas	Rozzano (MI)
Italy	Ospedale Moscati	Taranto
Italy	AOU CIttà della Salute e della Scienza	Torino
Italy	Ospedale Regina Margherita	Torino
Italy	UO Ematologia e TMO - Ospedale C. Panico	Tricase	Lecce
Italy	A.O. Santa Maria della Misericordia	Udine
Italy	Policlinico GB Rossi	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Gruppo Italiano Trapianto di Midollo Osseo	Azienda Policlinico Umberto I

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cytomegalovirus infection	incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Primary	Cytomegalovirus disease	incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Primary	Herpesvirus human 6 infection	incidence of human 6 infection after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Primary	Herpesvirus human 6 disease	incidence of human 6 disease after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Primary	Virus Epstein-Barr infection	incidence of Virus Epstein-Barr infections after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Primary	Virus Epstein-Barr disease	incidence of Virus Epstein-Barr disease after allogeneic haematopoietic stem cell transplantation	6 months from transplant
Secondary	Overall Survival (OS)	OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis	These outcome measures will be assessed at 1 year from transplant
Secondary	Disease Free Survival (DFS)	DFS is defined as the probability of being alive free of disease at any point in time.	These outcome measures will be assessed at 1 year from transplant
Secondary	Transplant Related Mortality (TRM)	TRM was defined as death due to any transplantation-related cause other than disease	These outcome measures will be assessed at 1 year from transplant
Secondary	Relapse risk (RR)	RR or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group.	These outcome measures will be assessed at 1 year from transplant
Secondary	Acute Graft-versus-Host Disease	cumulative incidence of acute GvHD (grade II-IV)	These outcome measures will be assessed at 100 days from transplant
Secondary	chronic graft-versus-host disease	cumulative incidence and severity of chronic graft-versus-host disease	These outcome measures will be assessed at 1 year from transplant