Ruxolitinib as add-on Therapy in Steroid-refractory Graft-vs-host Disease

Study Overview
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Brief Summary
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Steroid-refractory graft-vs-host disease (SR-GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We sought to evaluate the effect and safety of ruxolitinib (RUX) add-on in the treatment of patients with SR-GVHD.

Detailed Description
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Nowadays, second-line treatment for SR-GVHD differs between centers and depends on the physician's experience. The agents commonly used as second and further lines of therapy include anti-thymocyte globulin, mycophenolate mofetil, calcineurin inhibitor, or extracorporeal photopheresis. However, the response varied. This study highlighted that corticosteroid (CS) is not a panacea for treating GVHD, and some patients with remission still experience further relapse. Additionally, the identification of multiple infections adds complexity. Hope was supposed to come in 2019 after the Food and Drug Administration (FDA) approved RUX for the therapy of SR-GVHD in adult and pediatric patients > 12 years. RUX add-on should be withheld as the risks outweigh the benefits, especially for patients who developed scleroderma and bronchiolitis obliterans. RUX can be added on as needed for the treatment of GVHD, especially in patients receiving DLI as relapse therapy with the conversion from mixed chimerism to complete chimerism. Despite some studies showing the efficacy of RUX across affected organs, some other data bring the opposite results. Thus we conducted this study to reinforce the efficacy of RUX as an add-on therapy for SR-GVHD.

Official Title
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Ruxolitinib Add-on in Steroid-refractory Graft-vs-host Disease After Allogeneic Stem Cell Transplantation: a Single Institutional Experience

Conditions
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Steroid Refractory GVHD

Intervention / Treatment
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* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with hematologic disorder Exclusion Criteria: Those who are not applicable of receiving Ruxolitinib as immunodeficiency-modulation therapy Those who are actively encountering acute infectious illness

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 30 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Cases with steroid-refractory GVHD would be given an add-on therapy of age/weight adjusted dosage of Ruxolitinib
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib add-on group<br>Once diagnosed with steroid-refractory GVHD, after discussion with family, as per their willing, Ruxolitinib will be administered as add-on therapy. Its dose depends on participants' age and body weight. Usually a dosage of 5mg once per day will be applied as initiation and titrated in accordance with clinical response. | Drug: Ruxolitinib<br>* A dosage of 5mg once daily will be applied as initiation. After one week use, dose escalation or de-escalation would depend on clinical response.<br>* Other names: Jakavi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI symptoms secondary to GVHD | Diarrhea, abnormal liver enzyme tests, or abdominal discomfort were viewed as GI GVHD after exclusion of other etiology | 3 years | 
| Skin symptoms secondary to GVHD | Rash, petechiae, erosion, ulcer hyperpigmentation, or scleroderma were viewed as skin GVHD after exclusion of other etiology | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From diagnosis of SR-GVHD to mortality due to any cause | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia, hematopoietic stem cell transplantation