Graft Versus Host DiseaseNCT04342442
Identification of Novel Targetable Kinases in SR-a GvHD
An observational study of Graft Versus Host Disease, run by University of Freiburg.
Trial summary
In this study, the investigators aim to identify novel targetable kinases in SR-a GvHD patient samples and investigate their role in different immune cell subtypes. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Graft Versus Host Disease
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2017to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adult patients with acute GvHD, steroid-refractory or steroid-responsive
Who may be able to join
- allo-transplanted
- confirmed diagnosis of a GvHD
- age ≥ 18 years
- peripheral blood samples and biopsies available
- written informed consent
- ability to understand the nature of the study and the study-related procedures and to comply with them
Who cannot join
- age < 18 years
- lack of informed consent
- patients that cannot be classified in one of the 2 groups (steroid-refractory, steroid-responsive)
About this study
Official title: Investigation of Novel Targetable Kinases in Steroid-refractory Acute Graft-versus-host Disease
In this study, the investigators aim to identify novel targetable kinases in SR-a GvHD patient samples and investigate their role in different immune cell subtypes.
Read the detailed description
Corticosteroids are the first-line treatment of a GvHD, however many patients do not respond to corticosteroids. Patients with steroid-refractory a GvHD (SR-a GVHD) have a low 1-year survival rate. In this study, the investigators aim to identify and validate novel targetable kinases in SR-a GvHD patient peripheral blood mononuclear cells (PBMCs) by using a kinase-specific proteomic approach, and thereafter to investigate the role of the identified kinases in different immune cell subtypes by analyzing biopsies taken from SR- a GvHD patients.
- Conditions
- Graft Versus Host Disease
- Keywords
- Steroid-refractory GvHD, Myeloid cells, Allogeneic hematopoietic cell transplantation (allo-HCT)
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Steroid-refractory a GvHD | Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-refractory a GvHD | |
| Steroid-responsive a GvHD | Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-responsive a GvHD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of differentially regulated kinases
Bead-based Kinase Assay enrichment (Knet beads) of PBMC lysates
Measured: 3 years
Secondary outcomes (2)
Analysis of protein expression
Analysis of PBMC lysates by western blot
Measured: 3 years
Analysis of immune cell subtype
Immunohistochemistry of intestinal biopsies
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2020
- Study start1 Jan 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Zeiser, University of Freiburg
- Investigators
- Robert Zeiser, Prof. Dr., Principal investigator, University Medical Center Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04342442
- Sponsor's protocol ID
- KIN-SR-GvHD
- Status last verified
- Apr 2020
- First submitted
- 8 Apr 2020
- Last updated
- 13 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.
PubMed 26228813Hulsdunker J, Ottmuller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, Dierbach H, Kirschnek S, Lammermann T, Blaser MJ, Fife BT, Blazar BR, Beilhack A, Hill GR, Hacker G, Zeiser R. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018 Apr 19;131(16):1858-1869. doi: 10.1182/blood-2017-10-812891. Epub 2018 Feb 20.
PubMed 29463561Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available.
PubMed 29171820Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hacker H, Hildebrandt GC, Hacker G, Zeiser R. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014 Jun;20(6):648-54. doi: 10.1038/nm.3517. Epub 2014 May 18.
PubMed 24836575
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Novel Targetable Kinases in Steroid-refractory Acute Graft-versus-host Disease
- ClinicalTrials.gov ID
- NCT04342442
- Acronym / sponsor ID
- KIN-SR-GvHD
- Conditions
- Graft Versus Host Disease
- Keywords
- Steroid-refractory GvHD, Myeloid cells, Allogeneic hematopoietic cell transplantation (allo-HCT)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of FreiburgUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 13 Apr 2020 (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.
In this study, the investigators aim to identify novel targetable kinases in SR-a GvHD patient samples and investigate their role in different immune cell subtypes.
Detailed description
Corticosteroids are the first-line treatment of a GvHD, however many patients do not respond to corticosteroids. Patients with steroid-refractory a GvHD (SR-a GVHD) have a low 1-year survival rate. In this study, the investigators aim to identify and validate novel targetable kinases in SR-a GvHD patient peripheral blood mononuclear cells (PBMCs) by using a kinase-specific proteomic approach, and thereafter to investigate the role of the identified kinases in different immune cell subtypes by analyzing biopsies taken from SR- a GvHD patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Steroid-refractory a GvHD | – | –Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-refractory a GvHD |
| Steroid-responsive a GvHD | – | –Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-responsive a GvHD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with acute GvHD, steroid-refractory or steroid-responsive
Key inclusion criteria (6 listed)
- allo-transplanted
- confirmed diagnosis of a GvHD
- age ≥ 18 years
- peripheral blood samples and biopsies available
- written informed consent
Key exclusion criteria (3 listed)
- age < 18 years
- lack of informed consent
- patients that cannot be classified in one of the 2 groups (steroid-refractory, steroid-responsive)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of differentially regulated kinases
Time frame: 3 years
Bead-based Kinase Assay enrichment (Knet beads) of PBMC lysates
2 secondary outcomes
Analysis of protein expression
Time frame: 3 years
Analysis of immune cell subtype
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2020.
- Background: PubMed 26228813Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.
- Background: PubMed 29463561Hulsdunker J, Ottmuller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, Dierbach H, Kirschnek S, Lammermann T, Blaser MJ, Fife BT, Blazar BR, Beilhack A, Hill GR, Hacker G, Zeiser R. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018 Apr 19;131(16):1858-1869. doi: 10.1182/blood-2017-10-812891. Epub 2018 Feb 20.
- Background: PubMed 29171820Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available.
- Background: PubMed 24836575Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hacker H, Hildebrandt GC, Hacker G, Zeiser R. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014 Jun;20(6):648-54. doi: 10.1038/nm.3517. Epub 2014 May 18.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Robert Zeiser, Prof. Dr. principal investigator
University Medical Center Freiburg
Questions about this trial
What is this clinical trial studying?
An observational study of Graft Versus Host Disease, run by University of Freiburg.
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 6 inclusion and 3 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: finished, as of the sponsor's last update on 13 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of differentially regulated kinases (time frame: 3 years). 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 NCT04342442, which also lists 4 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 13 Apr 2020.