Identification of Novel Targetable Kinases in SR-a GvHD

NCT ID: NCT04342442

Last Updated: 2020-04-13

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

COMPLETED

Total Enrollment

24 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-01-01

Study Completion Date

2019-12-31

Brief Summary

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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

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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

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Graft Versus Host Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Steroid-refractory a GvHD

Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-refractory a GvHD

No interventions assigned to this group

Steroid-responsive a GvHD

Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-responsive a GvHD

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* age \< 18 years
* lack of informed consent
* patients that cannot be classified in one of the 2 groups (steroid-refractory, steroid-responsive)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Freiburg

OTHER

Sponsor Role lead

Responsible Party

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Robert Zeiser

Director of Division of Tumor Immunology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Robert Zeiser, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Freiburg

References

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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.

Reference Type BACKGROUND
PMID: 26228813 (View on PubMed)

Hulsdunker 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.

Reference Type BACKGROUND
PMID: 29463561 (View on PubMed)

Zeiser 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.

Reference Type BACKGROUND
PMID: 29171820 (View on PubMed)

Schwab 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.

Reference Type BACKGROUND
PMID: 24836575 (View on PubMed)

Other Identifiers

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KIN-SR-GvHD

Identifier Type: -

Identifier Source: org_study_id

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