Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation

November 27, 2024 updated by: Silvia Deaglio, University of Turin, Italy

Allogeneic hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for people with severe blood-related diseases. However, it comes with serious risks, including a condition called graft-versus-host disease (GVHD), where the transplanted cells attack the patient's body. GVHD can occur in about 50% of patients acutely and 35% in a chronic form, potentially affecting organs like the skin, liver, and gastrointestinal system. Currently, doctors diagnose GVHD based on symptoms, as there are no easy tests available.

Infections can also be a problem after HSCT, as dormant viruses may reactivate. These infections are monitored using specialized tests. Additionally, doctors use advanced methods, like analyzing minimal residual disease (MRD) and chimerism, to check for the risk of the original disease coming back. MRD is tracked by looking for specific genetic markers of the disease in the patient's blood or bone marrow.

Another emerging tool involves analyzing cell-free DNA (cfDNA)-tiny fragments of DNA found in bodily fluids that come from dying cells. This technique, called liquid biopsy, has been revolutionary in areas like cancer detection, pregnancy testing, and organ transplants. For example, in organ transplants, cfDNA can indicate early signs of rejection, helping reduce the need for invasive biopsies.

In HSCT, the use of cfDNA to monitor complications like GVHD or relapse has not been fully explored. This pilot study aims to investigate whether analyzing cfDNA using a technique called epigenomic profiling can help detect acute GVHD, as well as other post-transplant issues like infections, disease relapse, and chronic GVHD. The goal is to compare cfDNA analysis to current testing methods to see if it offers better or earlier detection of complications.

This research could pave the way for improved, less invasive monitoring of HSCT patients, potentially leading to better outcomes and fewer complications.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Milan, Italy, 10132
        • Recruiting
        • Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan
      • Turin, Italy, 10126
        • Recruiting
        • SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients will be enrolled at the Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan and at the SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital in Turin.

Description

Inclusion Criteria:

  • Patient must be affected by an hematological malignancy requiring hematopoietic stem cell transplantation (HSCT).

Exclusion Criteria:

  • Patients can not be 17 years old or yunger

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
GVHD patients
This group gathers all the patients that eventually develop GVHD
Diagnostic test: Sample collation for cfDNA methylation analysis
Sample collation for cfDNA methylation analysis
Diagnostic test: Sample collection for EV phenotype analysis
Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.
Control patients
This group gathers all the patients that will not develop post-HSCT complications and show no signs of relapse.
Diagnostic test: Sample collation for cfDNA methylation analysis
Sample collation for cfDNA methylation analysis
Diagnostic test: Sample collection for EV phenotype analysis
Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.
Infection patients
This group gathers all the patients that develop post-HSCT infections
Diagnostic test: Sample collation for cfDNA methylation analysis
Sample collation for cfDNA methylation analysis
Diagnostic test: Sample collection for EV phenotype analysis
Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.
Relapse patients
This group gathers all the patients that relapse after HSCT
Diagnostic test: Sample collation for cfDNA methylation analysis
Sample collation for cfDNA methylation analysis
Diagnostic test: Sample collection for EV phenotype analysis
Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.
TAD/SOS patients
This goup gathers patients presenting with transplant associated microangiopathy or sinusoidal obstruction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epigenetic profiling of cfDNA in patients developing GVHD
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
Analysis of cfDNA methylation patterns in GVHD patients vs controls to define potential marker regions to be translationally utilized for early detections of the disease.
From enrollment to the end of post-HSCT follow-up of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epigenetic profiling of cfDNA in patients developing post-HSCT infections
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
Analysis of cfDNA methylation patterns in patients developing post-HSCT transplantation infections vs controls to define potential marker regions to be translationally utilized for early detections of the condition.
From enrollment to the end of post-HSCT follow-up of 12 months
Epigenetic profiling of cfDNA in patients with engraftment failure
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
Analysis of cfDNA methylation patterns in patients with engraftment failure vs controls.
From enrollment to the end of post-HSCT follow-up of 12 months
Epigenetic profiling of cfDNA in relapsing patients
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
Description: Analysis of cfDNA methylation patterns in relapsing patients vs controls.
From enrollment to the end of post-HSCT follow-up of 12 months
Epigenetic profiling of cfDNA in patients developing transplant associated microangiopathy or sinusoidal obstruction
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
From enrollment to the end of post-HSCT follow-up of 12 months
Evaluation of EV phenotype
Time Frame: From enrollment to the end of post-HSCT follow-up of 12 months
Evaluation of circulating vesicle phenotype in as potential biomarker for GVHD, engraftment and relapse.
From enrollment to the end of post-HSCT follow-up of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Turin, Italy

Collaborators

San Raffaele IRCCS Hospital, Università Vita â€" Salute, (Milan, Italy)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

November 27, 2024

First Submitted That Met QC Criteria

November 27, 2024

First Posted (Estimated)

December 4, 2024

Study Record Updates

Last Update Posted (Estimated)

December 4, 2024

Last Update Submitted That Met QC Criteria

November 27, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P2022ZRF5H

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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