Identification of Novel Targetable Kinases in SR-a GvHD

Graft Versus Host Disease Clinical Trial

Official title:

Investigation of Novel Targetable Kinases in Steroid-refractory Acute Graft-versus-host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04342442
• Other study ID #: KIN-SR-GvHD
• Status: Completed
• Start date: January 1, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: April 2020
• Source: University of Freiburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Freiburg

References & Publications (4)

Hülsdünker J, Ottmüller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, Dierbach H, Kirschnek S, Lämmermann T, Blaser MJ, Fife BT, Blazar BR, Beilhack A, Hill GR, Häcker 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. — View Citation

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, Schönle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Häcker H, Hildebrandt GC, Häcker 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. — View Citation

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. Review. — View Citation

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, Lübbert M, Wäsch R, Scheid C, Stölzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Gräff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kröger N, Passweg J, Halter J, Socié 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of differentially regulated kinases	Bead-based Kinase Assay enrichment (Knet beads) of PBMC lysates	3 years
Secondary	Analysis of protein expression	Analysis of PBMC lysates by western blot	3 years
Secondary	Analysis of immune cell subtype	Immunohistochemistry of intestinal biopsies	3 years