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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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PD-1 Antibody, Hemophagocytic Lymphohistiocytosis, Epstein-Barr Virus, Lymphoma

Intervention / Treatment
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* Drug: L-DEP and PD-1 antibody


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-DEP and PD-1 antibody<br>PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone administered in 2 week cycles for 2 cycles | Drug: L-DEP and PD-1 antibody<br>* 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.<br>|

What is the study measuring?
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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 |