Ruxolitinib and Methylprednisolone as a First-line Treatment for Macrophage Activation Syndrome

Study Overview
=================
Brief Summary
-----------------
The present study was a single-center, prospective, non-comparative in which macrophage activation syndrome patients were selected as the main subjects to evaluate the effect and safety of Ruxolitinib and methylprednisolone regimens as the first-line therapy .

Official Title
-----------------
A Single-center, Prospective, Non-comparative Clinical Trial of Ruxolitinib and Methylprednisolone as a First-line Treatment for Macrophage Activation Syndrome

Conditions
-----------------
Macrophage Activation Syndrome

Intervention / Treatment
-----------------
* Drug: Ruxolitinib
* Drug: methylprednisolone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria; patients were diagnosed with autoimmune disease associated HLH (Macrophage activation syndrome, MAS). No HLH induction therapy was performed. The expected survival time is more than 1 month. Serum creatinine ≤ 1.5 times normal；Serum human immunodeficiency virus(HIV) antigen or antibody negative； Hepatitis C virus (HCV) antibody is negative, or HCV antibody is positive, but HCV RNA is negative；HBV copies less than 1E+03 copies/ml. Total bilirubin ≤10 times the upper limit of normal; serum creatinine ≤1.5 times the normal value The left ventricular ejection fraction (LVEF) was normal. No uncontrollable infection. Contraception for both male or female. Informed consent obtained. Exclusion Criteria: Pregnancy or lactating Women； Allergic to ruxolitinib； Active bleeding of the internal organs； uncontrollable infection； Serious mental illness; Non-melanoma skin cancer history; Patients unable to comply during the trial and/or follow-up phase; Participate in other clinical research at the same time.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib+methylprednisolone<br>Ruxolitinib and methylprednisolone administered as the first-line therapy | Drug: Ruxolitinib<br>* 0.3mg/kg/d, iv.gtt, for at least 2 weeks<br>Drug: methylprednisolone<br>* 2mg/kg, d1-d5, gradually reduced, for at least 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25, ferritin, and triglyceride; hemoglobin; neutrophil counts; platelet counts; and alanine aminotransferase (ALT). A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25 response was>1.5-fold decreased; ferritin and triglyceride decreased at least 25%; for patients with an initial neutrophil count of<0.5 ×109/L, a response was defined as an increase by at least 100% to>0.5× 109/L; for patients with a neutrophil count of 0.5 to 2.0 × 109/L, an increase by at least 100% to >2.0 × 109/L was considered a response; and for patients with ALT >400 U/L, response was defined as an ALT decrease of at least 50%. | Change from before and 2,4,6 and 8 weeks after initiating Ruxolitinib combined with methylprednisolone therapy | 
| Progression Free Survival | from date of inclusion to date of progression, relapse, or death from any cause | 2 years | 
| Adverse events | Adverse events including myelosuppression, infection, hemorrhage | 2 years |