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L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH

Primary Purpose

Hemophagocytic Lymphohistiocytosis

Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
L-DEP and PD-1 antibody
Sponsored by
Beijing Friendship Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophagocytic Lymphohistiocytosis focused on measuring Hemophagocytic Lymphohistiocytosis, DEP, L-Asparaginasum, PD-1 antibody

Eligibility Criteria

1 Year - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria;patients were diagnosed with EBV associated HLH (EBV-HLH).
  2. EBV-DNA in peripheral blood or EBER in tissue were positive.
  3. Treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least partial response
  4. 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.)
  5. The expected survival time is more than 1 month.
  6. Age ≤ years old, gender is not limited.
  7. Serum creatinine ≤ 1.5 times normal；After infusion, fibrinogen can be corrected to ≥0.6g/L.
  8. 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.
  9. The left ventricular ejection fraction (LVEF) was normal.
  10. No uncontrollable infection.
  11. Contraception for both male or female.
  12. Informed consent obtained.

Exclusion Criteria:

  1. Allergic to doxorubicin and/or etoposide and/or PD-1 antibody Injection
  2. Severe myocardial injury, myocardial enzymes CK, CK-MB increased more than 3 times ULN (upper limit of normal)
  3. Heart function above grade II (NYHA).
  4. Thyroid dysfunction
  5. Serious mental illness;
  6. Active hemorrhage of internal organs
  7. Previously received L-DEP regimen for HLH-targeted treatment, but the treatment was ineffective or relapsed
  8. Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2
  9. Participate in other clinical research at the same time.

Sites / Locations

  • Beijing Friendship Hospital, Capital Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

L-DEP and PD-1 antibody

Arm Description

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.

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
Outcome of patients with EBV-HLH
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

First Posted
March 30, 2022
Last Updated
April 19, 2022
Sponsor
Beijing Friendship Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05315336
Brief Title
L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH
Official Title
L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2022 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2026 (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 L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory 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, L-Asparaginasum, PD-1 antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-DEP and 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 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.
Intervention Type
Drug
Intervention Name(s)
L-DEP and PD-1 antibody
Intervention Description
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.
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
Outcome of patients with EBV-HLH
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
1 Year
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhao Wang
Phone
86-010-63139862
Email
wangzhao@ccmu.edu.cn
Facility Information:
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
Country
China

12. IPD Sharing Statement

Learn more about this trial

L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH

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