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

Capital Medical University

Status and phase: Not yet enrolling; Phase 3

Conditions: Hemophagocytic Lymphohistiocytosis

Treatments: Drug: L-DEP and PD-1 antibody

Study type: Interventional

Funder types: Other

Identifiers

NCT05315336

L-DEP, PD-1, HLH

Details and patient eligibility

About

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.

Full description

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

Enrollment: 50 estimated patients

Sex: All

Ages: 1 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

L-DEP and PD-1 antibody

Experimental group

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.

Treatment:

Drug: L-DEP and PD-1 antibody