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

Sponsor

Beijing Friendship Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05315336

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: L-DEP and PD-1 antibody	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-DEP and PD-1 antibody 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.	Drug: L-DEP and PD-1 antibody 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.

Arm

Intervention/Treatment

Experimental: L-DEP and PD-1 antibody

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.

Drug: L-DEP and PD-1 antibody

Outcome Measures

Primary Outcome Measures

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

EBV-DNA [Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy]
Outcome of patients with EBV-HLH
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.