L-DEP as an Initial Treatment for EBV-HLH

Study Overview
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Brief Summary
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This study aimed to investigate the efficacy and safety of Pegaspargase together with liposomal doxorubicin, etoposide and high dose methylprednisolone (L-DEP) as an initial treatment for Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Official Title
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A Randomized Controlled Trial of L-DEP as an Initial Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Pegaspargase
* Drug: doxorubicin hydrochloride liposome injection
* Drug: etoposide
* Drug: methylprednisolone
* Drug: Etoposide
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were older than 14 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: 14 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: L-DEP<br>Pegaspargase 2000U/m2 day5; doxorubicin hydrochloride liposome injection 25 mg/m2 day 1; etoposide 100 mg/m2 was administered once on the first day of every week; methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7 | Drug: Pegaspargase<br>* 2000U/m2 day5<br>Drug: doxorubicin hydrochloride liposome injection<br>* 25 mg/m2 day 1<br>Drug: etoposide<br>* 100 mg/m2 was administered once on the first day of every week<br>Drug: methylprednisolone<br>* 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7<br>|
| Active Comparator: HLH-94 regimen<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>|

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 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare survival between two arms |  | from the time patients received L-DEP or HLH-94 therapy up to 12 months or September 2019 | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on. | through study completion, an average of 1 years | 
| Change of Epstein-Barr virus(EBV)-DNA before and after therapy |  | Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP or HLH-94 therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pegaspargase, hemophagocytic lymphohistiocytosis, Epstein Barr virus, initial treatment