Clinical trial NCT02997280: Ruxolitinib for Steroid-refractory GVHD
Official title: Treatment of Steroid-refractory Acute and Chronic Graft-versus-host Disease With Inhibitor of Janus Kinases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Vs Host Disease
Keywords: acute graft-versus-host disease
chronic graft-versus-host disease
Steroid-refractory GVHD
ruxolitinib
JAK inhibitors
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Russian Federation
First posted: 2016-12-20
Enrollment: 75
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Steroid-refractory acute GVHD (srGVHD) is one of the causes of mortality after allogeneic stem cell transplantation, while steroid-refractory chronic GVHD significantly increases morbidity, aggravates quality of life and may also impact survival. Currently there is no standard treatment of srGVHD. One of the most promising agents is Janus kinase (JAK) inhibitor ruxolitinib, which in the retrospective study demonstrated excellent response rate and survival of patients with either acute or chronic srGVHD. This study prospectively evaluates the efficacy of ruxolitinib in srGVHD patients.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of graft-versus-host disease established based on tissue biopsy
* Steroid-refractory acute or chronic graft-versus-host disease according to EBMT/ELN criteria (T. Ruutu et al, 2014)
* Age 1 to 70 years
* Karnofsky index \>30%.
* Ability for oral drug intake
* Life expectancy \> 1 month
* Signed informed consent

Exclusion Criteria:

* Severe organ dysfunction: AST or ALT \>5 upper normal limits (excluding cases related to liver GVHD), creatinine \>2 upper normal limits
* Requirement for vasopressor support at the time of enrollment
* Uncontrolled bacterial or fungal infection at the time of enrollment
* Pregnancy
* Somatic or psychiatric disorder making the patient (or legal guardian) unable to sign informed consent

Primary outcomes:
measure: Overall response rate
timeFrame: 84 days
Secondary outcomes:
measure: 6-month overall survival
timeFrame: 6 months
measure: Toxicity based NCI CTC grades
timeFrame: 6 months
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: 6 months
measure: GVHD relapse incidence after complete response
timeFrame: 6 months
measure: Relapse incidence of underlying hematologic malignancy
timeFrame: 12 months
measure: Quality of life measured by FACT BMT ver. 4 questionnaire in adults
timeFrame: 6 months
measure: Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children
timeFrame: 6 months
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University
name: Boris V Afanasyev, Prof
role: STUDY_DIRECTOR
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.