Clinical trial NCT05775705: L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: PD-1 Antibody
Hemophagocytic Lymphohistiocytosis
Epstein-Barr Virus
Lymphoma
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2023-03-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response rate
timeFrame: Two weeks after initiation of L-DEP regimen combined with PD-1 antibody
Secondary outcomes:
measure: Response rate of lymphoma
timeFrame: Four weeks after second cycle of L-DEP and PD-1 antibody regimen
measure: Progression Free Survival
timeFrame: 1 years
measure: Overall Survival
timeFrame: 1 years
measure: Adverse Events
timeFrame: 30 days after last administration of cytotoxic drugs
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Friendship Hospital
name: Zhao Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: