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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05775705
• Other study ID #: BFH20220920001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 1, 2023
• Est. completion date: October 1, 2026

Study information

• Verified date: March 2023
• Source: Beijing Friendship Hospital
• Contact: Zhao Wang, MD
• Phone: 63138303
• Email: wangzhao[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: October 1, 2026
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Epstein-Barr Virus Infections
• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic
• Lymphoma
• PD-1 Antibody

Intervention

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.

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Friendship Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	complete response (CR) and partial response (PR) rates	Two weeks after initiation of L-DEP regimen combined with PD-1 antibody
Secondary	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
Secondary	Progression Free Survival	from date of inclusion to date of progression, relapse, or death from any cause	1 years
Secondary	Overall Survival	from the date of inclusion to date of death, irrespective of cause	1 years
Secondary	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