Chidamide Combines With VP-16 and Methylprednisolone in the Treatment of HLH

Study Overview
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Brief Summary
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Chidamide combines with VP-16 and methylprednisolone in HLH

Detailed Description
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This study aimed to investigate the efficacy and safety of Chidamide together with Etoposide and methylprednisolone for hemophagocytic lymphohistiocytosis

Official Title
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Chidamide Combines With Etoposide and Methylprednisolone in the Treatment of Hemophagocytic Lymphohistiocytosis

Conditions
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Chidamide, Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Chidamide combines with VP-16 and methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria; patients were diagnosed with EBV associated HLH (EBV-HLH) and lymphoma associated HLH.Age ≥18 years old, gender is not limited. Serum creatinine ≤ 1.5 times normal；NT-proBNP ≤ normal；Informed consent obtained. - Exclusion Criteria: Active bleeding of the internal organs or patients with new thrombotic diseases；Allergic to Chidamide and etoposide；Participate in other clinical research at the same time；HIV , HBV and HCV infected patients (HIV antibody positive)；History of QT interval prolongation, atrioventricular block, ventricular tachycardia, coronary atherosclerotic heart disease；Pregnant or lactating women and patients of childbearing age who refuse to take appropriate contraceptive measures during this trial. If the patient was male, he refused to use adequate contraceptive methods or donate semen during the study period and within 3 months after receiving the last cycle of drug study；patients judged by the investigator to be unsuitable to participate in this study. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Assigned Interventions<br>Chidamide combines with VP-16 and methylprednisolone | Drug: Chidamide combines with VP-16 and methylprednisolone<br>* Chidamide 30mg TIW po，etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.75mg/kg day 4 to 6，0.25mg/kg day 7 to 9，and 0.1mg/kg day 10 to 21<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%.Overall response rate (ORR) is defined as the ratio of patients with CR and PR to overall patients | 4 weeks after Chidamide combines with VP-16 and methylprednisolone was used | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EBV-DNA copies | EBV-DNA copies in peripheral blood for patients with EBV positive when they enrolled | 4 weeks after Chidamide combines with VP-16 and methylprednisolone was used | 
| relapsed rate of HLH |  | 4 weeks after Chidamide combines with VP-16 and methylprednisolone was used | 
| the response rate of lymphoma | lymphoma associated HLH | 4 weeks after Chidamide combines with VP-16 and methylprednisolone was used |