A Prospective Observational Study for Evaluating CGVHD

Chronic Graft-Versus-Host Disease Clinical Trial

— GITMO-GVCrOSy  

Official title:

A Prospective Observational Study for Evaluating Incidence, Severity and Outcomes of Chronic Graft-versus-Host Disease According to 2015 NIH Consensus Criteria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02991846
• Other study ID #: GITMO-GVCrOSy
• Status: Completed
• Start date: September 1, 2017
• Est. completion date: November 22, 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, 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: November 22, 2022
• Est. primary completion date: November 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Graft-Versus-Host Disease
• Graft vs Host Disease

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera SS Antonio e Biagio	Alessandria
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti	Ancona
Italy	Policlinico di Bari-Ematologia con trapianti	Bari
Italy	Divisione di Ematologia - Ospedali Papa Giovanni XXIII	Bergamo
Italy	Ospedale San Orsola	Bologna
Italy	Ospedale Regionale Generale- Divisione Ematologia	Bolzano
Italy	AO Spedali Civili di Brescia- USD - TMO Adulti	Brescia
Italy	Ospedale Ferrarotto - Ematologia	Catania
Italy	S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle	Cuneo
Italy	Cattedra di Ematologia - Azienda Ospedaliera di Careggi	Firenze
Italy	Ospedale Gaslini	Genova
Italy	Osp. Card. Panico	Lecce
Italy	Ospedale Maggiore - Policlinico	Milano
Italy	Ospedale San Raffaele	Milano
Italy	CTMO Fond MBBM Clinica pediatrica	Monza
Italy	Uoc Sit Tmo	Napoli
Italy	Azienda ospedaliera Universitaria di Parma	Parma
Italy	Ospedale G. Da Saliceto di Piacenza	Piacenza
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli	Reggio Calabria
Italy	Arciospedale S. M. Novella	Reggio Emilia
Italy	Cattedra di Ematologia - Policlinico Umberto I	Roma
Italy	A.O.U. Citta della Salute e della Scienza	Torino
Italy	Ospedale Regina Margherita	Torino
Italy	A.O. Santa Maria della Misericordia	Udine
Italy	Policlinico GB Rossi	Verona
Italy	Ospedale S. Bortolo-Divisione Ematologia	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Trapianto di Midollo Osseo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure free survival (FFS)	To estimate the failure free survival measured from the start of 1st line immunosuppressive treatment for cGVHD, defined as the probability of survival free of any of the following events: cGVHD progression, need of a new immunosuppressive treatment, need of treatment dose escalation, relapse of the underlying hematological disease, severe (CTCAE grade 3-4) toxicity.	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	Response rate (RR)	Global and organ-specific response rate (RR), evaluated 3 and 6 months after starting systemic treatment, by the 2015 NIH criteria	3 and 6 months
Secondary	Incidence and grade of cGVHD	Incidence and grade of cGVHD, by the 2015 NIH criteria at 1 year after Hematopoietic stem cell transplantation (HSCT)	at 1 year from transplant
Secondary	relapse	Cumulative incidence of relapse of underlying haematological malignancy	1 year from transplant
Secondary	non-relapse mortality	Cumulative incidence of non-relapse mortality (NRM), defined as any death not due to disease relapse or progression	1 year from transplant
Secondary	treatment change	Cumulative incidence of treatment change, measured from the start of first-line and subsequent treatment lines	measured from the start of first-line and subsequent treatment lines for 1 year
Secondary	Successful withdrawal of immunosuppressive treatment	Cumulative incidence of successful withdrawal of immunosuppressive treatment, measured from the start of first-line and subsequent treatment lines.	Measured from the start of firs-tline and subsequent treatment lines for 1 year
Secondary	Overall Survival	Overall Survival, measured from cGVHD diagnosis.	measured from cGVHD diagnosis until 1 year
Secondary	Severe Adverse Events (SAE) and Toxicities	Incidence of Severe Adverse Events (SAE), toxicities (by the Common Terminology Criteria for Adverse Events - CTCAE), infections during treatments.	Measured from first treatment for cGVHD until 1 year