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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophagocytic Lymphohistiocytosis
• Intervention / Treatment: Drug: L-DEP and PD-1 antibody

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of treatment response	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%.	Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EBV-DNA	Outcome of patients with EBV-HLH	Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Survival	Outcome of patients with EBV-HLH	3 months after the intervention
Adverse events that are related to treatment	Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.	2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2025
• Study Completion (ANTICIPATED): June 1, 2026

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (ACTUAL): April 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: PD-1 antibody; Hemophagocytic Lymphohistiocytosis; DEP; L-Asparaginasum
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: L-DEP, PD-1, HLH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No