L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Evaluation of treatment response
研究概览
简要总结
This study aimed to investigate the efficacy and safety of L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory EBV associated hemophagocytic lymphohistiocytosis.
详细描述
PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria;patients were diagnosed with EBV associated HLH (EBV-HLH).
- •EBV-DNA in peripheral blood or EBER in tissue were positive.
- •Treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least partial response
- •The patient is expected to be unable to undergo allogeneic hematopoietic stem cell transplantation in the short term due to various reasons (physical status, economic reasons, donor reasons, etc.)
- •The expected survival time is more than 1 month.
- •Age ≤ years old, gender is not limited.
- •Serum creatinine ≤ 1.5 times normal；After infusion, fibrinogen can be corrected to ≥0.6g/L.
- •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.
- •The left ventricular ejection fraction (LVEF) was normal.
- •No uncontrollable infection.
- •Contraception for both male or female.
- •Informed consent obtained.
排除标准
- •Allergic to doxorubicin and/or etoposide and/or PD-1 antibody Injection
- •Severe myocardial injury, myocardial enzymes CK, CK-MB increased more than 3 times ULN (upper limit of normal)
- •Heart function above grade II (NYHA).
- •Thyroid dysfunction
- •Serious mental illness;
- •Active hemorrhage of internal organs
- •Previously received L-DEP regimen for HLH-targeted treatment, but the treatment was ineffective or relapsed
- •Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2
- •Participate in other clinical research at the same time.
研究组 & 干预措施
L-DEP and PD-1 antibody
Doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; PD-1 antibody injection 200mg day 5; L-asparaginases 6000iu/m2 day2, day4. This regimen was repeated after 2 weeks.
干预措施: L-DEP and PD-1 antibody (Drug)
结局指标
主要结局
Evaluation of treatment response
时间窗: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
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%.
次要结局
- Survival(3 months after the intervention)
- EBV-DNA(Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy)
- Adverse events that are related to treatment(2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy)
研究者
Zhao Wang
Department of Hematology, Beijing Friendship Hospital
Beijing Friendship Hospital