GVHD - Graft-Versus-Host DiseaseNCT06715046
Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation
An observational study of GVHD - Graft-Versus-Host Disease and Infections After HSCT, run by University of Turin, Italy at 2 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GVHD - Graft-Versus-Host Disease, Infections After HSCT, Transplant Associated Microangiopathy TAM
- What is being tested?
- Sample collation for cfDNA methylation analysis and Sample collection for EV phenotype analysis
- How many people
- 30 participants
- Where
- 2 sitesItaly
- Study dates
- 31 Jan 2024to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Patient must be affected by an hematological malignancy requiring hematopoietic stem cell transplantation (HSCT).
Who cannot join
- Patients can not be 17 years old or yunger
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Recruiting
Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan
Milan, Milan, 10132
- Recruiting
SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital
Turin, Turin, 10126
About this study
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.
Read more
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.
- Conditions
- GVHD - Graft-Versus-Host Disease, Infections After HSCT, Transplant Associated Microangiopathy TAM, Sinusoidal Obstruction Syndrome (SOS), HSCT Engraftment
- Being tested
- Sample collation for cfDNA methylation analysis, Sample collection for EV phenotype analysis
- Keywords
- cfDNA, methylation, epigenetic profile, HSCT, liquid biopsy
- Medical subject headings
- Graft vs Host Disease, Hepatic Veno-Occlusive Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sample collation for cfDNA methylation analysisDiagnostic test
Sample collation for cfDNA methylation analysis
Sample collection for EV phenotype analysisDiagnostic test
Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.
| Study group | Role | What they receive |
|---|---|---|
| GVHD patients | This group gathers all the patients that eventually develop GVHD Receives: Diagnostic Test: Sample collation for cfDNA methylation analysis; Diagnostic Test: Sample collection for EV phenotype analysis | |
| Control patients | This group gathers all the patients that will not develop post-HSCT complications and show no signs of relapse. Receives: Diagnostic Test: Sample collation for cfDNA methylation analysis; Diagnostic Test: Sample collection for EV phenotype analysis | |
| Infection patients | This group gathers all the patients that develop post-HSCT infections Receives: Diagnostic Test: Sample collation for cfDNA methylation analysis; Diagnostic Test: Sample collection for EV phenotype analysis | |
| Relapse patients | This group gathers all the patients that relapse after HSCT Receives: Diagnostic Test: Sample collation for cfDNA methylation analysis; Diagnostic Test: Sample collection for EV phenotype analysis | |
| TAD/SOS patients | This goup gathers patients presenting with transplant associated microangiopathy or sinusoidal obstruction. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epigenetic profiling of cfDNA in patients developing GVHD
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.
Measured: From enrollment to the end of post-HSCT follow-up of 12 months
Secondary outcomes (5)
Epigenetic profiling of cfDNA in patients developing post-HSCT infections
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.
Measured: From enrollment to the end of post-HSCT follow-up of 12 months
Epigenetic profiling of cfDNA in patients with engraftment failure
Analysis of cfDNA methylation patterns in patients with engraftment failure vs controls.
Measured: From enrollment to the end of post-HSCT follow-up of 12 months
Epigenetic profiling of cfDNA in relapsing patients
Description: Analysis of cfDNA methylation patterns in relapsing patients vs controls.
Measured: 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
Measured: From enrollment to the end of post-HSCT follow-up of 12 months
Evaluation of EV phenotype
Evaluation of circulating vesicle phenotype in as potential biomarker for GVHD, engraftment and relapse.
Measured: From enrollment to the end of post-HSCT follow-up of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start31 Jan 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for GVHD - Graft-Versus-Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS San Raffaele
- Responsible party
- Principal investigator, Silvia Deaglio, University of Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715046
- Sponsor's protocol ID
- P2022ZRF5H
- Status last verified
- Nov 2024
- First submitted
- 27 Nov 2024
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39009292Jodele 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.
PubMed 35490975Avni 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.
PubMed 37971879Oellerich 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.
PubMed 36339004Cheng 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.
PubMed 35058359
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT06715046
- Acronym / sponsor ID
- P2022ZRF5H
- Conditions
- GVHD - Graft-Versus-Host Disease, Infections After HSCT, Transplant Associated Microangiopathy TAM, Sinusoidal Obstruction Syndrome (SOS), HSCT Engraftment
- Keywords
- cfDNA, methylation, epigenetic profile, HSCT, liquid biopsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Collaborators
- IRCCS San Raffaele
- Study start
- 31 Jan 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| GVHD patients | – | Diagnostic Test: Sample collation for cfDNA methylation analysis, Diagnostic Test: Sample collection for EV phenotype analysisThis group gathers all the patients that eventually develop GVHD |
| Control patients | – | Diagnostic Test: Sample collation for cfDNA methylation analysis, Diagnostic Test: Sample collection for EV phenotype analysisThis group gathers all the patients that will not develop post-HSCT complications and show no signs of relapse. |
| Infection patients | – | Diagnostic Test: Sample collation for cfDNA methylation analysis, Diagnostic Test: Sample collection for EV phenotype analysisThis group gathers all the patients that develop post-HSCT infections |
| Relapse patients | – | Diagnostic Test: Sample collation for cfDNA methylation analysis, Diagnostic Test: Sample collection for EV phenotype analysisThis group gathers all the patients that relapse after HSCT |
| TAD/SOS patients | – | –This goup gathers patients presenting with transplant associated microangiopathy or sinusoidal obstruction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Patient must be affected by an hematological malignancy requiring hematopoietic stem cell transplantation (HSCT).
Key exclusion criteria (1 listed)
- Patients can not be 17 years old or yunger
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sample collation for cfDNA methylation analysisSample collation for cfDNA methylation analysis | Diagnostic test | Control patients, GVHD patients, Infection patients, Relapse patients |
| Sample collection for EV phenotype analysisAnalysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment. | Diagnostic test | Control patients, GVHD patients, Infection patients, Relapse patients |
Primary outcome
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.
5 secondary outcomes
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
Epigenetic profiling of cfDNA in patients with engraftment failure
Time frame: 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
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
Evaluation of EV phenotype
Time frame: From enrollment to the end of post-HSCT follow-up of 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Background: PubMed 39009292Wang 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.
- Background: PubMed 35490975Jodele 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.
- Background: PubMed 37971879Avni 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.
- Background: PubMed 36339004Oellerich 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.
- Background: PubMed 35058359Cheng 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of GVHD - Graft-Versus-Host Disease and Infections After HSCT, run by University of Turin, Italy at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Silvia Deaglio, MD/PhD (+39 0116709535, silvia.deaglio@unito.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epigenetic profiling of cfDNA in patients developing GVHD (time frame: From enrollment to the end of post-HSCT follow-up of 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06715046, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.