Ruxolitinib for Steroid-refractory GVHD

Graft Vs Host Disease Clinical Trial

Official title:

Treatment of Steroid-refractory Acute and Chronic Graft-versus-host Disease With Inhibitor of Janus Kinases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02997280
• Other study ID #: 2016-29-1
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: April 2019

Study information

• Verified date: April 2019
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: April 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft Vs Host Disease

Intervention

Drug:
• Ruxolitinib Oral Tablet
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.

Locations

Country	Name	City	State
Russian Federation	First Pavlov State Medical University of St. Petersburg	Saint-Petersburg

Sponsors (2)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University	Ministry of Health, Russian Federation

Country where clinical trial is conducted

Russian Federation, 

References & 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, 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	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	6-month overall survival	Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.	6 months
Secondary	Toxicity based NCI CTC grades	Toxicity parameters based on NCI CTCAE 4.03 grades: nasea, vomiting, anemia, thrombocytopenia, leukopenia, neutropenia, hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), hemorrhagic cystitis (attending physician assessment).	6 months
Secondary	Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence		6 months
Secondary	GVHD relapse incidence after complete response	Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.	6 months
Secondary	Relapse incidence of underlying hematologic malignancy	Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates	12 months
Secondary	Quality of life measured by FACT BMT ver. 4 questionnaire in adults		6 months
Secondary	Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children		6 months