Ruxolitinib and Steroid as First Line Therapy for Acute GVHD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of ruxolitinib in combination with methylprednisolone as first line therapy in patients with Grades II to IV acute graft-versus-host disease (GVHD).

Detailed Description
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Treatment: Once patients are diagnosed with grade II IV acute GVHD, the combination therapy should be initiated as soon as possible. Methylprednisolone: 2mg/kg/d, iv or iv gtt, in two or three divided doses. Taper steroid every one or two weeks according to patient's response. Ruxolitinib 5 10mg bid po for at least 28 days. If patient's ANC<0.5×10e9/L or PLT< 20×10e9/L, cease ruxolitinib until recovery of ANC higher than 0.5×10e9/L or PLT higher than 20×10e9/L. Indication for stopping Ruxolitinib treatment: No response after ruxolitinib treatment for 28 days. Develop life-threatening complication. ANC<0.5×10e9/L or PLT< 20×10e9/L. Indication for second line acute GVHD treatment: deterioration of acute GVHD in 3 days no response after 7 days no complete remission after 2 weeks. Suggestions of second line therapy: Basiliximab 20mg, d1, d4, d8.

Official Title
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Ruxolitinib and Methylprednisolone as First Line Therapy for Acute Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation

Conditions
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Acute GVHD

Intervention / Treatment
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* Drug: Ruxolitinib Oral Tablet
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with hematological diseases. recipients of allogeneic peripheral blood stem cell transplantation. new onset of grade II IV acute graft versus host disease within 100 days post-transplantation. exclusion criteria: recipients of second allogeneic stem cell transplant. acute GVHD induced by donor lymphocyte infusion, interferon. received treatment other than steroid before enrollment. overlap GVHD syndrome. pregnant or breast-feeding women. absolute neutrophil count (ANC) <0.5×10e9/L or platelet count (PLT) < 20×10e9/L non-GVHD related liver dysfunction: glutamic pyruvic transaminase>= 4 times of upper normal limit, direct bilirubin >= 4 times of upper normal limit renal dysfunction: creatinine clearance < 15 mL/min or glomerular filtration rate< 15 mL/min uncontrolled infection human immunodeficiency virus infection active hepatitis b virus, hepatitis C virus infection and need antivirus treatment. relapse of primary malignant hematological diseases, or graft rejection. allergic history to Janus kinase inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination therapy<br>There is only 1 arm. Combination therapy arm includes ruxolitinib and methylprednisolone. Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response. Ruxolitinib oral tablet, 5 10mg bid orally, for at least 28 days. | Drug: Ruxolitinib Oral Tablet<br>* Ruxolitinib Oral Tablet （Jakafi）, 5 10mg bid po for at least 28 days.<br>* Other names: Jakafi;Drug: Methylprednisolone<br>* Methylprednisolone: 2mg/kg/d , iv or iv gtt, for at least 1 week, then taper accordingly.<br>* Other names: steroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate | overall response rate of acute GVHD treatment, including complete response rate and partial response rate after combination therapy. | 28 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to response | days from beginning to the first day of maximum response | 28 days after treatment | 
| reactivation rate of cytomegalovirus | reactivation rate of cytomegalovirus infection | 100 days within transplant | 
| 1 year incidence of chronic GVHD | incidence of chronic GVHD 1 year after transplant | 1 year within transplant |