Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
Hemophagocytic Lymphohistiocytosis, DEP, PD-1 antibody
Brief summary
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
PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH,
Interventions
DRUGDEP combine with PD-1 antibody
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
Sponsors
Beijing Friendship Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients with EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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). 2. . The expected survival time is more than 1 month. 3. Age \>18 years old, gender is not limited. 4. Serum creatinine ≤ 1.5 times normal； 5. 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. 6. No thyroid dysfunction. The left ventricular ejection fraction (LVEF) was normal. 7. No uncontrollable infection. 8. Contraception for both male or female. 8\. Informed consent obtained.
Exclusion criteria
1. Allergic to doxorubicin, etoposide and sintilimab Injection 2. Serious immunoreaction: myocardial damage, hepatitis, pneumonia 3. Central nervous system symptoms 4. Serious mental illness; 5. Central nervous system symptoms 6. Serious mental illness; 7. Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2； 8. Pancreatitis history. Patients unable to comply during the trial and/or follow-up phase; 9. Participate in other clinical research at the same time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of treatment response | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EBV-DNA | Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy | EBV-DNA copies/ml in peripheral blood |
| Survival | 3 months after the intervention | Outcome of patients with EBV-HLH |
| Adverse events that are related to treatment | 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy | Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on. |
Countries
China
Contacts
Primary ContactZhao Wang
Backup ContactYahong You
Outcome results
None listed