DEP Combine With PD-1 Antibody as an Treatment for EBV-HLH

DEP Combine With PD-1 Antibody as an Treatment for EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)

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.

Study Overview

• Status: Recruiting
• Conditions: Hemophagocytic Lymphohistiocytosis
• Intervention / Treatment: Drug: DEP combine with PD-1 antibody

Detailed Description

PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH,

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yahong You; Phone Number: 17810283962; Email: 15332022659@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Friendship Hospital, Capital Medical University
    • Contact: Zhao Wang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEP combine with PD-1 antibody; 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.	Drug: DEP 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; Other Names: DEP+PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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%.	Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Outcome of patients with EBV-HLH	3 months after the intervention
Adverse events that are related to treatment	Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.	2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
EBV-DNA	EBV-DNA copies/ml in peripheral blood	Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: PD-1 antibody; Hemophagocytic Lymphohistiocytosis; DEP
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: DEP,PD-1, HLH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No