Clinical trial NCT02991846: A Prospective Observational Study for Evaluating CGVHD
Official title: A Prospective Observational Study for Evaluating Incidence, Severity and Outcomes of Chronic Graft-versus-Host Disease According to 2015 NIH Consensus Criteria
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Graft-Versus-Host Disease
Keywords: chronic graft-versus-host disease cGVHD
Hematopoietic stem cell transplantation HSCT
NIH consensus criteria
GITMO
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
First posted: 2016-12-14
Enrollment: 248
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients undergoing sllogenic stem cell transplant for any underlyng disease who develop chronic graft-versus-host disease (cGVHD)

Brief summary: Prospective, observational, multicentre, spontaneous, non-interventional study This study will evaluate all consecutive patients who develop chronic graft-versus-host disease, reported by the Italian GITMO centers according to a standardized Web platform for real-time, onsite data collection. The platform for data collection will be based on a software prototype developed by the Clinica di Ematologia di Ancona Transplant Center for the management of patients with chronic graft-versus-host disease. This software has been integrated with algorithms that automatically determine: severity of chronic graft-versus-host disease and overall response according to the 2015 NIH consensus criteria.

Detailed description: Chronic Graft-versus-Host Disease represents the first cause of transplant-related mortality and reduced quality of life after transplant (HSCT). The epidemiology of Chronic Graft-versus-Host Disease is largely unknown; moreover, diagnosis of Chronic Graft-versus-Host Disease can be easily missed because its onset is often late in the post-transplant period, requires specific follow up, and general practitioners are usually not familiar with this entity. Successful treatment of Chronic Graft-versus-Host Disease represents an unmet clinical need in the field of allogeneic transplantation. Steroids are standard treatment, but up to 60% of the patients will require second-line treatment but there is no standard second-line treatment for Chronic Graft-versus-Host Disease steroid refractory. To help standardise the management Chronic Graft-versus-Host Disease, the NIH Consortium proposed consensus definitions for diagnosis, scoring and response criteria in 2006 revised in 2015 which offers a shared framework to study this rare disease. These criteria are not yet validated and thus not suitable for clinical trials.

This study is prospective, observational, multicentre, spontaneous, non-interventional study that will evaluate all consecutive patients who develop chronic graft-versus-host disease, reported by the Italian GITMO centers according to a standardized Web platform for real-time, on-site data collection. The platform for data collection will be based on a software prototype developed by the Ancona Transplant Center for the management of patients with Chronic Graft-versus-Host Disease. This software has been integrated with algorithms that automatically determine: severity of Chronic Graft-versus-Host Disease and overall response by the 2015 NIH consensus criteria. Historical controls to compare Chronic Graft-versus-Host Disease incidence, toxicities, response rate and hard outcomes will be used.

The aim of this project is to evaluate prospectively the long-term effectiveness of different therapies by the hard outcome "failure free survival" commonly considered the most reliable one. The failure free survival is the result of a number of factors that influence the treatment failure and has been shown a reliable predictor of long-term survival. Main cause of failure is the change in immunosuppressive treatment although recurrent disease, treatment toxicity and mortality from Chronic Graft-versus-Host Disease (or other infectious complications) also contribute to failure free survival. Second, we aim to evaluate the prognostic ability of the latest NIH response criteria to predict main hard survival outcomes and to assess their suitability as a tool for decision-making that ultimately leads to treatment changes. Finally, we aim to evaluate the feasibility of the use of an electronic tool for data collection in daily clinical practice.

Eligibility criteria: Inclusion Criteria:

* Any age
* All patients who develop cGVHD (any grade) by the NIH criteria after allogeneic transplantation
* Written and signed informed consent

Exclusion Criteria:

* Absence of informed consent

Primary outcomes:
measure: Failure free survival (FFS)
timeFrame: Measured from the start of 1st line immunosuppressive treatment for cGVHD until the date of first documented progression or date of death from any cause whichever came first, assessed up to 1 years from transplant
Secondary outcomes:
measure: Response rate (RR)
timeFrame: 3 and 6 months
measure: Incidence and grade of cGVHD
timeFrame: at 1 year from transplant
measure: relapse
timeFrame: 1 year from transplant
measure: non-relapse mortality
timeFrame: 1 year from transplant
measure: treatment change
timeFrame: measured from the start of first-line and subsequent treatment lines for 1 year
measure: Successful withdrawal of immunosuppressive treatment
timeFrame: Measured from the start of firs-tline and subsequent treatment lines for 1 year
measure: Overall Survival
timeFrame: measured from cGVHD diagnosis until 1 year
measure: Severe Adverse Events (SAE) and Toxicities
timeFrame: Measured from first treatment for cGVHD until 1 year
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS Antonio e Biagio
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria Ospedali Riuniti
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: 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: Catania
country: Italy
facility: Ospedale Ferrarotto - Ematologia
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: Cattedra di Ematologia - Azienda Ospedaliera di Careggi
city: Genova
country: Italy
facility: Ospedale Gaslini
city: Lecce
country: Italy
facility: Osp. Card. Panico
city: Milano
country: Italy
facility: Ospedale Maggiore - Policlinico
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Monza
country: Italy
facility: CTMO Fond MBBM Clinica pediatrica
city: Napoli
country: Italy
facility: Uoc Sit Tmo
city: Parma
country: Italy
facility: Azienda ospedaliera Universitaria di Parma
city: Piacenza
country: Italy
facility: Ospedale G. Da Saliceto di Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
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: Cattedra di Ematologia - Policlinico Umberto I
city: Torino
country: Italy
facility: A.O.U. Citta 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
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo-Divisione Ematologia
Study officials:
affiliation: AOU Ospedali Riuniti di Ancona
name: Attilio Olivieri, MD
role: PRINCIPAL_INVESTIGATOR
References: