DEP Combine With PD-1 Antibody as an 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 DEP (liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for EBV associated hemophagocytic lymphohistiocytosis.

Detailed Description
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PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH,

Official Title
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DEP Combine With PD-1 Antibody as an Treatment for EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: DEP combine with PD-1 antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria; EBV-DNA in peripheral blood or EBER in tissue were positive, patients were diagnosed with EBV associated HLH (EBV-HLH). . The expected survival time is more than 1 month. Age >18 years old, gender is not limited. 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. No thyroid dysfunction. The left ventricular ejection fraction (LVEF) was normal. No uncontrollable infection. Contraception for both male or female. 8. Informed consent obtained. Exclusion Criteria: Allergic to doxorubicin, etoposide and sintilimab Injection Serious immunoreaction: myocardial damage, hepatitis, pneumonia Central nervous system symptoms Serious mental illness; Central nervous system symptoms Serious mental illness; Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2； Pancreatitis 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
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Minimum Age: 18 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: All patients with EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEP combine with PD-1 antibody<br>doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 1.5mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; sintilimab injection 200mg day 4. This regimen was repeated after 2 weeks. | Drug: DEP combine with PD-1 antibody<br>* Doxorubicin hydrochloride liposome injection 25 mg/m2 day 1 Etoposide 100 mg/m2 day1 Methylprednisolone 1.5 mg/kg days 1 to day 3, 0.25mg/kg days 4 to 14 Sintilimab Injection 200mg d4<br>* Other names: DEP+PD-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of treatment response | The primary observed endpoint is the objective remission rate (ORR): cases that include complete remission (CR) and partial remission (PR).CR 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). PR 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 DEP combine with PD-1 antibody therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EBV-DNA | EBV-DNA copies/ml in peripheral blood | Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy | 
| Survival | Outcome of patients with EBV-HLH | 3 months after the intervention | 
| Adverse events that are related to treatment | Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on. | 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophagocytic Lymphohistiocytosis, DEP, PD-1 antibody