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

Sponsor

Gruppo Italiano Trapianto di Midollo Osseo (Other)

Overall Status

Recruiting

CT.gov ID

NCT04412811

Collaborator

Azienda Policlinico Umberto I (Other)

1,500

Enrollment

Locations

28.9

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Diseases Stem Cell Transplant Complications Cytomegalovirus Viremia Herpesvirus Infection

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Patients with hematological disease Adult and children allogenic Hematopoietic stem cell transplantation recipients

Outcome Measures

Primary Outcome Measures

Cytomegalovirus infection [6 months from transplant]
incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation
Cytomegalovirus disease [6 months from transplant]
incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation
Herpesvirus human 6 infection [6 months from transplant]
incidence of human 6 infection after allogeneic haematopoietic stem cell transplantation
Herpesvirus human 6 disease [6 months from transplant]
incidence of human 6 disease after allogeneic haematopoietic stem cell transplantation
Virus Epstein-Barr infection [6 months from transplant]
incidence of Virus Epstein-Barr infections after allogeneic haematopoietic stem cell transplantation
Virus Epstein-Barr disease [6 months from transplant]
incidence of Virus Epstein-Barr disease after allogeneic haematopoietic stem cell transplantation

Secondary Outcome Measures

Overall Survival (OS) [These outcome measures will be assessed at 1 year from transplant]
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
Disease Free Survival (DFS) [These outcome measures will be assessed at 1 year from transplant]
DFS is defined as the probability of being alive free of disease at any point in time.
Transplant Related Mortality (TRM) [These outcome measures will be assessed at 1 year from transplant]
TRM was defined as death due to any transplantation-related cause other than disease
Relapse risk (RR) [These outcome measures will be assessed at 1 year from transplant]
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.
Acute Graft-versus-Host Disease [These outcome measures will be assessed at 100 days from transplant]
cumulative incidence of acute GvHD (grade II-IV)
chronic graft-versus-host disease [These outcome measures will be assessed at 1 year from transplant]
cumulative incidence and severity of chronic graft-versus-host disease

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UO Ematologia e TMO - Ospedale C. Panico	Tricase	Lecce	Italy
2	Azienda Ospedaliero-Universitaria Ospedali Riuniti	Ancona		Italy
3	Ospedale Mazzoni	Ascoli Piceno		Italy
4	A.O.S. G. Moscati	Avellino		Italy
5	Policlinico di Bari-Ematologia con trapianti	Bari		Italy
6	Divisione di Ematologia - Ospedali Papa Giovanni XXIII	Bergamo		Italy
7	A.O.U. Policlinico S.Orsola-Malpighi	Bologna		Italy
8	Ospedale San Orsola	Bologna		Italy
9	Ospedale Regionale Generale- Divisione Ematologia	Bolzano		Italy
10	AO Spedali Civili di Brescia- USD - TMO Adulti	Brescia		Italy
11	Azienda Sanitaria Locale Br1 Ospedale "A. Perrino	Brindisi		Italy
12	CTMO PO "Businco" A.O. "G. Brotzu"	Cagliari		Italy
13	Ospedale Ferrarotto	Catania		Italy
14	Struttura Complessa di Ematologia, Azienda Ospedaliera Santa Croce e Carle	Cuneo		Italy
15	Azienda Ospedaliera di Careggi	Firenze		Italy
16	Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza	Foggia		Italy
17	AOU-IRCCS San Martino-IST	Genova		Italy
18	Ospedale Gaslini	Genova		Italy
19	Policlinico VIto Fazzi	Lecce		Italy
20	AOU Integrata	Mestre		Italy
21	Divisione di Ematologia - Istituto Nazionale dei Tumori	Milano		Italy
22	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy
23	Ospedale San Raffaele	Milano		Italy
24	Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -	Modena		Italy
25	Ospedale San Gerardo	Monza		Italy
26	A.O.U. Policlinico Federico II	Napoli		Italy
27	AOU S. Giovanni di Dio e Ruggi D'Aragona	Napoli		Italy
28	Uoc Sit Tmo	Napoli		Italy
29	UOSC Ematologia con Trapianto CSE, AORN A. Cardarelli, AORN Cardarelli	Napoli		Italy
30	Azienda Ospedaliera di Padova	Padova		Italy
31	CTMO Osp. V. Cervello Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello	Palermo		Italy
32	Azienda ospedaliera Universitaria di Parma	Parma		Italy
33	Fondazione IRCCS San Matteo	Pavia		Italy	27100
34	Policlinico San Matteo	Pavia		Italy
35	Ospedale S. Maria della Misericordia	Perugia		Italy
36	Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara	Pescara		Italy
37	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy
38	Ospedale San Carlo	Potenza		Italy
39	Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli	Reggio Calabria		Italy
40	Arciospedale S. M. Novella	Reggio Emilia		Italy
41	Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli	Roma		Italy
42	Ospedale Bambin Gesù	Roma		Italy
43	Policlinico Tor Vergata	Roma		Italy
44	Policlinico Umberto I	Roma		Italy
45	Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas	Rozzano (MI)		Italy
46	Ospedale Moscati	Taranto		Italy
47	AOU CIttà della Salute e della Scienza	Torino		Italy
48	Ospedale Regina Margherita	Torino		Italy
49	A.O. Santa Maria della Misericordia	Udine		Italy
50	Policlinico GB Rossi	Verona		Italy