Ruxolitinib for Steroid-refractory GVHD

NCT02997280 | Completed Phase 2

• 1 other identifier: 2016-29-1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Vs Host Disease

Keywords

acute graft-versus-host disease; chronic graft-versus-host disease; Steroid-refractory GVHD; ruxolitinib; JAK inhibitors

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Partial response for acute GVHD is defined as the improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ. A response had to last for at least 3 weeks. Partial response for chronic GVHD was defined as reduction in GVHD National Institute of Health (NIH) severity score at east for one organ without deterioration in any other organ. A complete response was defined as the absence of any symptoms related to GVHD. Overall response is defined as presence of partial or complete response

  84 days

Secondary Outcomes (7)

• 6-month overall survival

  6 months

• Toxicity based NCI CTC grades

  6 months

• Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

  6 months

• GVHD relapse incidence after complete response

  6 months

• Relapse incidence of underlying hematologic malignancy

  12 months

Study Arms (1)

Ruxolitinib treatment

EXPERIMENTAL

Ruxolitinib 10 mg bid for adults and children with body weight \> 40 kg, 0.15 mg/kg bid for children with body weight \< 40 kg.

Drug: Ruxolitinib Oral Tablet

Interventions

Ruxolitinib Oral Tablet DRUG

Dose reduction criteria for acute GVHD: grade 4 neutropenia or grade 4 thrombocytopenia related to ruxolitinib administration based on the decision of attending physician. Dose reduction criteria for chronic GVHD: grade 3 neutropenia, grade 3 thrombocytopenia or anemia requiring transfusion, related to ruxolitinib administration based on the decision of attending physician. Reduced dose schedule: 5 mg bid for adults and children with body weight \> 40 kg, 0.08 mg/kg bid for children with body weight \< 40 kg. Treatment discontinuation criteria: complete response; absence of response after 28 days or progressive disease after 7 days for acute GVHD; absence of response after 84 days or progressive disease after 28 days for chronic GVHD; life-threatening complications.

Ruxolitinib treatment

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead
• Ministry of Health, Russian Federation: collaborator

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Location

Related Publications (1)

• 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.

  PMID: 26228813 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Study Officials

• Boris V Afanasyev, Prof

  R.M.Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of oncology, hematology and transplantation department for adults

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 20, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: April 1, 2019
• Last Updated: April 5, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)