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

Phase 3

Not yet recruiting

• Conditions: Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: L-DEP and PD-1 antibody

• Registration Number: NCT05315336
• Lead Sponsor: Beijing Friendship Hospital

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

Study Timeline

• Study First Submitted: 2022-03-30
• Study First Submitted QC: 2022-03-30
• Status Verified: 2022-04
• Study First Posted: 2022-04-07
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-26
• Study Start: 2022-06-01
• Primary Completion: 2025-06-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-DEP and PD-1 antibody	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Survival	3 months after the intervention	Outcome of patients with EBV-HLH
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
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.

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, China