Back to resultsDEP Combine With PD-1 Antibody as an Treatment for EBV-HLH
Primary Purpose
Hemophagocytic Lymphohistiocytosis
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
DEP combine with PD-1 antibody
Sponsored by
About this trial
This is an interventional treatment trial for Hemophagocytic Lymphohistiocytosis focused on measuring Hemophagocytic Lymphohistiocytosis, DEP, PD-1 antibody
Eligibility Criteria
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.
Sites / Locations
- Beijing Friendship Hospital, Capital Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DEP combine with PD-1 antibody
Arm Description
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.
Outcomes
Primary Outcome Measures
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%.
Secondary Outcome Measures
EBV-DNA
EBV-DNA copies/ml in peripheral blood
Survival
Outcome of patients with EBV-HLH
Adverse events that are related to treatment
Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.
Full Information
NCT ID
NCT05164978
First Posted
June 24, 2021
Last Updated
February 13, 2022
Sponsor
Beijing Friendship Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05164978
Brief Title
DEP Combine With PD-1 Antibody as an Treatment for EBV-HLH
Official Title
DEP Combine With PD-1 Antibody as an Treatment for EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2021 (Actual)
Primary Completion Date
January 1, 2023 (Anticipated)
Study Completion Date
January 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Friendship Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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,
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophagocytic Lymphohistiocytosis
Keywords
Hemophagocytic Lymphohistiocytosis, DEP, PD-1 antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
All patients with EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DEP combine with PD-1 antibody
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DEP combine with PD-1 antibody
Other Intervention Name(s)
DEP+PD-1
Intervention Description
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
Primary Outcome Measure Information:
Title
Evaluation of treatment response
Description
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%.
Time Frame
Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Secondary Outcome Measure Information:
Title
EBV-DNA
Description
EBV-DNA copies/ml in peripheral blood
Time Frame
Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Title
Survival
Description
Outcome of patients with EBV-HLH
Time Frame
3 months after the intervention
Title
Adverse events that are related to treatment
Description
Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.
Time Frame
2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhao Wang
Phone
86-010-63139862
Email
wangzhao@ccmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Yahong You
Phone
17810283962
Email
15332022659@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhao Wang
Organizational Affiliation
Beijing Friendship Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhao Wang, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
DEP Combine With PD-1 Antibody as an Treatment for EBV-HLH
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