L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH

The Efficacy and Safety of L-DEP Regimen Combined With PD-1 Antibody an Induction Therapy for Epstein-Barr Virus (EBV)-Positive Lymphoma-associated Hemophagocytic Lymphohistiocytosis

The efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; Hemophagocytic Lymphohistiocytosis; PD-1 Antibody; Epstein-Barr Virus
• Intervention / Treatment: Drug: L-DEP and PD-1 antibody

Detailed Description

Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Without early intervention, the median survival time is less than 2 months. Currently, HLH-94 or HLH-04 are the standard HLH treatment regimens, which have improved the disease response rate to approximately 70% and increased the 5-year OS rate to 50%. However, approximately, 30% of the patients remain unresponsive to standard therapy, especially if HLH is lymphoma-associated. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhao Wang, MD; Phone Number: 63138303; Email: wangzhao@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed as lymphoma-Hemophagocytic Lymphohistiocytosis.
• EBV-DNA in peripheral blood > 1000 copies/ml or EBER detected in tissue specimens.
• Age 18~65，gender is not limited.
• Estimated survival time ≥ 1 month.
• Cardiac ultrasound LVEF≥50%; No Active bleeding of the internal organs(digestive tract, lung, brain, etc.); If the patient has dyspnea, oxygenation index >250.
• Signed informed consent.

Exclusion Criteria:

• Heart function above grade II (NYHA).
• Severe myocardial injury：TNT、TNI、CK-MB > 3 ULN.
• Accumulated dose of doxorubicin above 400mg/m2 、epirubicin above 750mg/m2、pirarubicin above 800mg/m2 or the patients treated with anthracycline induced cardiovascular disease.
• Pregnancy or lactating Women.
• Allergic to pegylated liposomal doxorubicin，etoposide，or PD-1 antibody.
• Thyroid dysfunction.
• HIV antibody positivity.
• Acute or chronic active hepatitis B (HBsAg positivity, HBV DNA negative acceptable), acute or chronic active hepatitis C (HCV antibody negatively acceptable; HCV antibody positivity, HCV RNA negative acceptable).
• Participate in other clinical research at the same time.
• The researchers considered that patients are not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-DEP and PD-1 antibody; PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone administered in 2 week cycles for 2 cycles	Drug: L-DEP and PD-1 antibody; Doxorubicin (doxorubicin hydrochloride liposome injection) 35 mg/m2 day 1; etoposide 75 mg/m2 day1; methylprednisolone 1.5mg/kg days 1 to 3, 0.25mg/kg day 4 to 14; PEG-aspargase 6000iu/m2 day2, day4; PD-1 antibody injection 200mg day 5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	complete response (CR) and partial response (PR) rates	Two weeks after initiation of L-DEP regimen combined with PD-1 antibody

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of lymphoma	complete response (CR) and partial response (PR) rates, using the standard response criteria	Four weeks after second cycle of L-DEP and PD-1 antibody regimen
Progression Free Survival	from date of inclusion to date of progression, relapse, or death from any cause	1 years
Overall Survival	from the date of inclusion to date of death, irrespective of cause	1 years
Adverse Events	any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure	30 days after last administration of cytotoxic drugs

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhao Wang, MD, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2023
• Primary Completion (Anticipated): August 1, 2026
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphoma; Epstein-Barr Virus Infections; Lymphohistiocytosis, Hemophagocytic; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: BFH20220920001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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