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

NCT05315336 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: L-DEP, PD-1, HLH
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophagocytic Lymphohistiocytosis

Keywords

Hemophagocytic Lymphohistiocytosis; DEP; L-Asparaginasum; PD-1 antibody

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• EBV-DNA

  Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

• Survival

  3 months after the intervention

• Adverse events that are related to treatment

  2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Study Arms (1)

L-DEP and PD-1 antibody

EXPERIMENTAL

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

Interventions

L-DEP and PD-1 antibody DRUG

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.

L-DEP and PD-1 antibody

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Zhao Wang

CONTACT

86-010-63139862; wangzhao@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Hematology, Beijing Friendship Hospital

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

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 7, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 26, 2022

Record last verified: 2022-04

Locations

CN (1)