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

Phase 3

Not yet recruiting

• Conditions: PD-1 Antibody; Hemophagocytic Lymphohistiocytosis; Lymphoma; Epstein-Barr Virus
• Interventions: Drug: L-DEP and PD-1 antibody

• Registration Number: NCT05775705
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2023-03
• Study First Submitted: 2023-03-08
• Study First Submitted QC: 2023-03-08
• Last Update Submitted: 2023-03-08
• Study First Posted: 2023-03-20
• Last Update Posted: 2023-03-20
• Study Start: 2023-08-01
• Primary Completion: 2026-08-01
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-DEP and PD-1 antibody	L-DEP and PD-1 antibody	PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone administered in 2 week cycles for 2 cycles

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall Survival	1 years	from the date of inclusion to date of death, irrespective of cause
Progression Free Survival	1 years	from date of inclusion to date of progression, relapse, or death from any cause
Response rate of lymphoma	Four weeks after second cycle of L-DEP and PD-1 antibody regimen	complete response (CR) and partial response (PR) rates, using the standard response criteria
Adverse Events	30 days after last administration of cytotoxic drugs	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

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China