Clinical trial NCT05315336: L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH
Official title: L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hemophagocytic Lymphohistiocytosis
Keywords: Hemophagocytic Lymphohistiocytosis
DEP
L-Asparaginasum
PD-1 antibody
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of treatment response
timeFrame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Secondary outcomes:
measure: EBV-DNA
timeFrame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
measure: Survival
timeFrame: 3 months after the intervention
measure: Adverse events that are related to treatment
timeFrame: 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
Study officials:
References: