Etoposide in the First-line Treatment of Adult EBV-HLH

Study Overview
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Brief Summary
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his study aimed to investigate the efficacy of etoposide as the first line therapy for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Official Title
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A Randomized Controlled Trial of Etoposide in the First-line Treatment of Adult Epstein-barr Virus Associated Hemophagocytic Lymphohistiocytosis

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Etoposide
* Drug: Dexamethasone
* Drug: Etoposide
* Drug: IVIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were older than 18 years of age Diagnosed as EBV-Hemophagocytic Lymphohistiocytosis (HLH) Patients did not receive any treatment for HLH before Informed consent Exclusion Criteria: Heart function above grade II (NYHA) Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2 Pregnancy or lactating Women Allergic to Pegaspargase, doxorubicin or etoposide Active bleeding of the internal organs uncontrollable infection history of acute and chronic pancreatitis Participate in other clinical research at the same time

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etoposide standard group<br>Etoposide 150 mg/m2 twice weekly for 2 weeks and then weekly; dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering | Drug: Etoposide<br>* 150 mg/m2 twice weekly for 2 weeks and then weekly<br>Drug: Dexamethasone<br>* initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering<br>|
| Experimental: Etoposide reduction group<br>Etoposide 150 mg/m2 once a week; dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering | Drug: Dexamethasone<br>* initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering<br>Drug: Etoposide<br>* 150 mg/m2 weekly<br>|
| Active Comparator: Corticosteroid group<br>dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering, with or without IvIG (0.5 g/kg IV, once every 4 weeks) | Drug: Dexamethasone<br>* initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering<br>Drug: IVIG<br>* 0.5 g/kg, once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response(complete response+ partial response) rate of Participants | A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25(pg/ml), ferritin(μg/L), and triglyceride(mmol/L); hemoglobin(g/L); neutrophil counts(×109/L); platelet counts(×109/L); and alanine aminotransferase (ALT(U/L)). A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25(pg/ml) response was>1.5-fold decreased; ferritin (μg/L)and triglyceride(mmol/L) 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 (U/L)decrease of at least 50%. | Change from before and 2,4 weeks after initiating thearpy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare survival between two arms |  | from the time patients received therapy up to 12 months or December 2020 |