Clinical trial NCT04888286: DSAs in Patients Undergoing Allo-HSCT From Mismatched Donors
Official title: Donor-specific Anti-HLA Antibodies (DSAS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation From Mismatched Donors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematologic Diseases
Stem Cell Transplant Complications
Keywords: Retrospective survey
GITMO
Hematological disease
Allogeneic stem cell transplantation
anti-HLA antibodies
mismatched donors
DSAs searching
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
Collaborators: name: Azienda Policlinico Umberto I
First posted: 2021-05-17
Enrollment: 912
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult and children allogenic Hematopoietic stem cell transplantation recipients

Brief summary: Retrospective observational multicentric, spontaneous non-interventional non-pharmacological Italian study. The primary objective is analysis of Anti-HLA antibodies and DSAs searching and monitoring activities in haematological adult and paediatric patients undergoing allo-HSCT from January 2014 to June 2017. This study will evaluate approximately 1000 subjects (with competitive enrolment) from GITMO investigational centers.

Detailed description: The aim of the study is to evaluate, retrospectively, the activity of the Italian Centres in the search for donor-specific anti-HLA antibodies (DSAs) in patients undergoing allogeneic hematopoietic stem cell transplantation from mismatched donors and the strategy of treatment employed in case of DSAs positivity. Moreover, the study aims are to evaluate the role of DSAs on the engraftment. The interest in the study arises from the absence of knowledge on the MFI cut-off value clinically significant, and from the absence of the knowledge on the role of DSAs against each HLA locus on the engraftment and post-transplant survival. Furthermore, shared desensitization protocols and common donor selection strategies are lacking.

In recent years, with the increase of haploidentical and mismatched unrelated donor transplants, is also increasing the interest for DSAs at the time of HSCT, considering their potential role on graft failure by cell-mediated or antibody-mediated mechanisms.

Having a picture of the policy about DSAs management in Italian Transplant Centers, and of the indications reported by the Histocompatibility and Immunogenetic Laboratories, will allow to define, in collaboration with GITMO / AIBT, a consensus strategy. This strategy could be the platform for prospective studies.

The study involves the enrolment of patients (adults and paediatrics) undergoing mismatched allogeneic transplant, in the period 2014-2017 regardless of the source of stem cells and the search for DSAs. The sample size includes all the transplants recorded in the Gruppo Italiano Trapianti di Midollo Osseo and European group for Blood and Marrow Transplantation database.

Primary objectives are two: the analysis of Anti-HLA antibodies and DSAs searching and monitoring activities in haematological patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) performed by Histocompatibility and Immunogenetic Laboratories in collaboration with Italian transplant centres and assess to the impact of DSAs on neutrophil and platelet engraftment.

The secondary objectives are to study the probability and times to neutrophils and platelets engraftment, reject, poor engraftment in patients undergoing HSCT among different transplant centres, according to anti-HLA antibodies and DSA testing practice and assess the Overall Survival (OS) in patients undergoing HSCT with or without DSAs.

The analysis of continuous and categorical variables will be performed according to the criteria of descriptive statistics, including mean, median, standard deviation, range, minimum and maximum values for continuous variables, absolute and relative values for categorical variables. For the comparison of continuous and categorical variables, parametric and non-parametric statistical tests (Chi-square test, Fisher exact test and rank correlation coefficient of Spearman) will be applied. Competitive risk analysis will be used to assess the cumulative incidence (CI) of engraftment, considering death within 60 days as a competitive event.

OS will be estimated according to the Kaplan-Meier method and calculated from the date of the transplant; the comparison between different groups will be performed with the log-rank test.

The Cox regression model for proportional hazards will be used for multivariate analysis in order to evaluate the prognostic effect of the various variables in terms of engraftment. For the statistical analysis, a p-value \<0.05 will be considered statistically significant.

This trial is being 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 (HSCT) in Italy.

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 (ICH) 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:

* patients who underwent mismatched allogeneic transplantation, from January 2014 to June 2017
* signed the informed consent

Exclusion Criteria:

* Absence of consent Written information

Primary outcomes:
measure: Analysis of the monitoring practice of DSAs
timeFrame: 6 months from allogeneic hematopoietic stem cell transplantation
measure: Role of DSAs on neutrophils and platelets engraftment
timeFrame: 28 days from allogeneic hematopoietic stem cell transplantation
measure: Graft failure
timeFrame: 28 days from allogeneic hematopoietic stem cell transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Clinica di Ematologia. AOU Ospedali Riuniti di Ancona
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 Seragnoli Malpighi
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia- USD - TMO Adulti
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera di Careggi
city: Genova
country: Italy
facility: AOU IRCCS San Martino - IST
city: Genova
country: Italy
facility: Ospedale Gaslini
city: Milano
country: Italy
facility: Div. di Ematologia e TMO, Istituto Nazionale Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Unità Operativa di Ematologia e Trapianto Midollo Osseo (UTMO), Ospedale San Raffaele di Milano
city: Napoli
country: Italy
facility: Azienda ospedaliera Santobono Pausilipon
city: Parma
country: Italy
facility: Azienda ospedaliera Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS San Matteo
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: Roma
country: Italy
facility: A.O. San Camillo Forlanini
city: Roma
country: Italy
facility: Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Roma
country: Italy
facility: Policlinico Umberto I - Università La Sapienza
city: Torino
country: Italy
facility: Azienda ospedaliera Città della Salute e della Scienza
city: Udine
country: Italy
facility: Clinica Ematologica - AOU Santa Maria Della Misericordia
city: Verona
country: Italy
facility: Policlinico GB Rossi
Study officials:
affiliation: Azienda Policlinico Umberto I
name: Anna Paola Iori
role: PRINCIPAL_INVESTIGATOR
References: