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Ruxolitinib for Steroid-refractory GVHD

Primary Purpose

Graft Vs Host Disease

Status

Completed

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Ruxolitinib Oral Tablet

About this trial

This is an interventional treatment trial for Graft Vs Host Disease focused on measuring acute graft-versus-host disease, chronic graft-versus-host disease, Steroid-refractory GVHD, ruxolitinib, JAK inhibitors

Eligibility Criteria

1 Year - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

First Pavlov State Medical University of St. Petersburg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

6-month overall survival

Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.

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).

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

GVHD relapse incidence after complete response

Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.

Relapse incidence of underlying hematologic malignancy

Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates

Quality of life measured by FACT BMT ver. 4 questionnaire in adults

Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children

Full Information

NCT ID

NCT02997280

First Posted

December 14, 2016

Last Updated

April 3, 2019

Sponsor

St. Petersburg State Pavlov Medical University

Collaborators

Ministry of Health, Russian Federation

1. Study Identification

Unique Protocol Identification Number

NCT02997280

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

August 2016 (Actual)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St. Petersburg State Pavlov Medical University

Collaborators

Ministry of Health, Russian Federation

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Vs Host Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ruxolitinib treatment

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib Oral Tablet

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall response rate

Description

Time Frame

84 days

Secondary Outcome Measure Information:

Title

6-month overall survival

Description

Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.

Time Frame

6 months

Title

Toxicity based NCI CTC grades

Description

Time Frame

6 months

Title

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

Time Frame

6 months

Title

GVHD relapse incidence after complete response

Description

Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.

Time Frame

6 months

Title

Relapse incidence of underlying hematologic malignancy

Description

Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates

Time Frame

12 months

Title

Quality of life measured by FACT BMT ver. 4 questionnaire in adults

Time Frame

6 months

Title

Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boris V Afanasyev, Prof

Organizational Affiliation

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

Official's Role

Study Director

Facility Information:

Facility Name

First Pavlov State Medical University of St. Petersburg

City

Saint-Petersburg

ZIP/Postal Code

197089

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26228813

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.

Results Reference

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Ruxolitinib for Steroid-refractory GVHD

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