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

• Sponsor: Beijing Friendship Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05164978
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 20
• Patients Per Site Per Month: 1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: DEP combine with PD-1 antibody	N/A

Detailed Description

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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All patients with EBV- HLH receive DEP combine with PD-1 antibody as an treatment.All patients with EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: DEP Combine With PD-1 Antibody as an Treatment for EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
• Actual Study Start Date: May 1, 2021
• Anticipated Primary Completion Date: Jan 1, 2023
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. Survival [3 months after the intervention]

   Outcome of patients with EBV-HLH

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

9. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Friendship Hospital, Capital Medical University	Beijing		China

Sponsors and Collaborators

• Beijing Friendship Hospital

Investigators

• Principal Investigator: Zhao Wang, Beijing Friendship Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zhao Wang, Department of Hematology, Beijing Friendship Hospital, Beijing Friendship Hospital
• ClinicalTrials.gov Identifier: NCT05164978
• Other Study ID Numbers: DEP,PD-1, HLH
• First Posted: Dec 21, 2021
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zhao Wang, Department of Hematology, Beijing Friendship Hospital, Beijing Friendship Hospital: Hemophagocytic Lymphohistiocytosis; DEP; PD-1 antibody
• Additional relevant MeSH terms: Lymphohistiocytosis, Hemophagocytic; Antibodies

Study Results

No Results Posted as of Mar 2, 2022