Clinical trial NCT04342442: Identification of Novel Targetable Kinases in SR-a GvHD
Official title: Investigation of Novel Targetable Kinases in Steroid-refractory Acute Graft-versus-host Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Graft Versus Host Disease
Keywords: Steroid-refractory GvHD
Myeloid cells
Allogeneic hematopoietic cell transplantation (allo-HCT)
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2020-04-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with acute GvHD, steroid-refractory or steroid-responsive

Brief 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Identification of differentially regulated kinases
timeFrame: 3 years
Secondary outcomes:
measure: Analysis of protein expression
timeFrame: 3 years
measure: Analysis of immune cell subtype
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: University Medical Center Freiburg
name: Robert Zeiser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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, 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.
citation: 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.
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. No abstract available.
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, 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.