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

NCT ID: NCT06715046

Last Updated: 2024-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-01-31

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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GVHD - Graft-Versus-Host Disease Infections After HSCT Transplant Associated Microangiopathy TAM Sinusoidal Obstruction Syndrome (SOS) HSCT Engraftment

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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GVHD patients

This group gathers all the patients that eventually develop GVHD

Sample collation for cfDNA methylation analysis

Intervention Type DIAGNOSTIC_TEST

Sample collation for cfDNA methylation analysis

Sample collection for EV phenotype analysis

Intervention Type DIAGNOSTIC_TEST

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.

Sample collation for cfDNA methylation analysis

Intervention Type DIAGNOSTIC_TEST

Sample collation for cfDNA methylation analysis

Sample collection for EV phenotype analysis

Intervention Type DIAGNOSTIC_TEST

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

Sample collation for cfDNA methylation analysis

Intervention Type DIAGNOSTIC_TEST

Sample collation for cfDNA methylation analysis

Sample collection for EV phenotype analysis

Intervention Type DIAGNOSTIC_TEST

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

Sample collation for cfDNA methylation analysis

Intervention Type DIAGNOSTIC_TEST

Sample collation for cfDNA methylation analysis

Sample collection for EV phenotype analysis

Intervention Type DIAGNOSTIC_TEST

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.

No interventions assigned to this group

Interventions

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Sample collation for cfDNA methylation analysis

Sample collation for cfDNA methylation analysis

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS San Raffaele

OTHER

Sponsor Role collaborator

University of Turin, Italy

OTHER

Sponsor Role lead

Responsible Party

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Silvia Deaglio

Professor of Medical Genetics

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan

Milan, Milan, Italy

Site Status RECRUITING

SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital

Turin, Turin, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Silvia Deaglio, MD/PhD

Role: CONTACT

+39 0116709535

References

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Wang X, He B. Insight into endothelial cell-derived extracellular vesicles in cardiovascular disease: Molecular mechanisms and clinical implications. Pharmacol Res. 2024 Sep;207:107309. doi: 10.1016/j.phrs.2024.107309. Epub 2024 Jul 14.

Reference Type BACKGROUND
PMID: 39009292 (View on PubMed)

Jodele S, Dandoy CE, Sabulski A, Koo J, Lane A, Myers KC, Wallace G, Chima RS, Teusink-Cross A, Hirsch R, Ryan TD, Benoit S, Davies SM. Transplantation-Associated Thrombotic Microangiopathy Risk Stratification: Is There a Window of Opportunity to Improve Outcomes? Transplant Cell Ther. 2022 Jul;28(7):392.e1-392.e9. doi: 10.1016/j.jtct.2022.04.019. Epub 2022 Apr 29.

Reference Type BACKGROUND
PMID: 35490975 (View on PubMed)

Avni B, Neiman D, Shaked E, Gal-Rosenberg O, Grisariu S, Kuzli M, Avni I, Fracchia A, Stepensky P, Zuckerman T, Lev-Sagie A, Fox-Fisher I, Piyanzin S, Moss J, Salpeter SJ, Glaser B, Shemer R, Dor Y. Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers. J Clin Invest. 2024 Jan 16;134(2):e163541. doi: 10.1172/JCI163541.

Reference Type BACKGROUND
PMID: 37971879 (View on PubMed)

Oellerich M, Budde K, Osmanodja B, Bornemann-Kolatzki K, Beck J, Schutz E, Walson PD. Donor-derived cell-free DNA as a diagnostic tool in transplantation. Front Genet. 2022 Oct 21;13:1031894. doi: 10.3389/fgene.2022.1031894. eCollection 2022.

Reference Type BACKGROUND
PMID: 36339004 (View on PubMed)

Cheng AP, Cheng MP, Loy CJ, Lenz JS, Chen K, Smalling S, Burnham P, Timblin KM, Orejas JL, Silverman E, Polak P, Marty FM, Ritz J, De Vlaminck I. Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2113476118. doi: 10.1073/pnas.2113476118.

Reference Type BACKGROUND
PMID: 35058359 (View on PubMed)

Other Identifiers

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P2022ZRF5H

Identifier Type: -

Identifier Source: org_study_id