DSAs in Patients Undergoing Allo-HSCT From Mismatched Donors

Hematologic Diseases Clinical Trial

— AIBT_DSAs  

Official title:

Donor-specific Anti-HLA Antibodies (DSAS) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation From Mismatched Donors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04888286
• Other study ID #: GITMO-AIBT DSAs
• Status: Completed
• Start date: October 15, 2018
• Est. completion date: June 22, 2021

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

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 912
• Est. completion date: June 22, 2021
• Est. primary completion date: June 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Diseases
• Stem Cell Transplant Complications

Locations

Country	Name	City	State
Italy	Clinica di Ematologia. AOU Ospedali Riuniti di Ancona	Ancona
Italy	Policlinico di Bari-Ematologia con trapianti	Bari
Italy	Divisione di Ematologia - Ospedali Papa Giovanni XXIII	Bergamo
Italy	Ospedale Seragnoli Malpighi	Bologna
Italy	AO Spedali Civili di Brescia- USD - TMO Adulti	Brescia
Italy	S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle	Cuneo
Italy	Azienda Ospedaliera di Careggi	Firenze
Italy	AOU IRCCS San Martino - IST	Genova
Italy	Ospedale Gaslini	Genova
Italy	Div. di Ematologia e TMO, Istituto Nazionale Tumori	Milano
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Unità Operativa di Ematologia e Trapianto Midollo Osseo (UTMO), Ospedale San Raffaele di Milano	Milano
Italy	Azienda ospedaliera Santobono Pausilipon	Napoli
Italy	Azienda ospedaliera Universitaria di Parma	Parma
Italy	Fondazione IRCCS San Matteo	Pavia
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	A.O. San Camillo Forlanini	Roma
Italy	Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli	Roma
Italy	Policlinico Tor Vergata	Roma
Italy	Policlinico Umberto I - Università La Sapienza	Roma
Italy	Azienda ospedaliera Città della Salute e della Scienza	Torino
Italy	Clinica Ematologica - AOU 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	Analysis of the monitoring practice of DSAs	The variables that will be collected are: Type of transplant in which the search for DSAs is carried out, Laboratory methods used, Positivity cut-off used, Donor selection criteria if DSAs present, Desensitization protocol employed	6 months from allogeneic hematopoietic stem cell transplantation
Primary	Role of DSAs on neutrophils and platelets engraftment	Time to reach an absolute neutrophil count > 0.5 109/L from day of HSCT. Neutrophil recovery end-point will be defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 x109/L.; Time engraftment of platelet count will be defined as PTLS >20.9 x 109/L without transfusion requirements for at least 5 days.	28 days from allogeneic hematopoietic stem cell transplantation
Primary	Graft failure	graft failure is defined as peripheral blood ANC < 0.5 × 109/L by after allogeneic hematopoietic stem cell transplantation without evidence of relapse	28 days from allogeneic hematopoietic stem cell transplantation