L-DEP Regimen as a Salvage Therapy for Refractory Epstein Barr Virus-induced Hemophagocytic Lymphohistiocytosis

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 a salvage therapy for refractory Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Official Title
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L-DEP Regimen as a Salvage Therapy for Refractory Epstein Barr Virus-induced Hemophagocytic Lymphohistiocytosis

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Pegaspargase
* Drug: doxorubicin
* Drug: etoposide
* Drug: methylprednisolone


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 achieve at lease partial response after initial treatment including HLH-94 or DEP no less than 2 weeks 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-DEP<br>Pegaspargase 2000U/m2 day5; doxorubicin (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<br>* 25mg/m2 day1<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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of treatment response | 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 L-DEP salvage therapy | 
| Change of Epstein-Barr virus(EBV)-DNA |  | Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP salvage therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | from the time patients received L-DEP salvage therapy up to 24 months or November 2019 | 
| Adverse events that are related to treatment | Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on. | through study completion, an average of 2 years | 

 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