L-DEP Regimen as a Salvage Therapy for Refractory Epstein Barr Virus-induced Hemophagocytic Lymphohistiocytosis

Phase 3

• Conditions: Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: Pegaspargase; Drug: doxorubicin; Drug: etoposide; Drug: methylprednisolone

• Registration Number: NCT02631109
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

This study aimed to investigate the efficacy and safety of Pegaspargase together with liposomal doxorubicin, etoposide and high dose methylprednisolone (L-DEP) as a salvage therapy for refractory Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-03
• Study First Submitted QC: 2015-12-11
• Study First Posted: 2015-12-16
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-03
• Last Update Posted: 2016-08-04
• Primary Completion: 2017-11
• Study Completion: 2019-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Patients were older than 14 years of age
2. Diagnosed as EBV-Hemophagocytic Lymphohistiocytosis (HLH)
3. Patients did not achieve at lease partial response after initial treatment including HLH-94 or DEP no less than 2 weeks
4. Informed consent

Exclusion Criteria

1. Heart function above grade II (NYHA)
2. Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2
3. Pregnancy or lactating Women
4. Allergic to Pegaspargase, doxorubicin or etoposide
5. Active bleeding of the internal organs
6. uncontrollable infection
7. history of acute and chronic pancreatitis
8. Participate in other clinical research at the same time

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-DEP	Pegaspargase	Pegaspargase 2000U/m2 day5; doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered once on the first day of every week; methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7
L-DEP	doxorubicin	Pegaspargase 2000U/m2 day5; doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered once on the first day of every week; methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7
L-DEP	etoposide	Pegaspargase 2000U/m2 day5; doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered once on the first day of every week; methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7
L-DEP	methylprednisolone	Pegaspargase 2000U/m2 day5; doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered once on the first day of every week; methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7

Primary Outcome Measures

Name	Time	Method
Evaluation of treatment response	Change from before and 2,4,6 and 8 weeks after initiating L-DEP salvage therapy	A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25, ferritin, and triglyceride; hemoglobin; neutrophil counts; platelet counts; and alanine aminotransferase (ALT).; A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25 response was\>1.5-fold decreased; ferritin and triglyceride decreased at least 25%; for patients with an initial neutrophil count of\<0.5 ×109/L, a response was defined as an increase by at least 100% to\>0.5× 109/L; for patients with a neutrophil count of 0.5 to 2.0 × 109/L, an increase by at least 100% to \>2.0 × 109/L was considered a response; and for patients with ALT \>400 U/L, response was defined as an ALT decrease of at least 50%.
Change of Epstein-Barr virus(EBV)-DNA	Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP salvage therapy

Secondary Outcome Measures

Name	Time	Method
Adverse events that are related to treatment	through study completion, an average of 2 years	Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on.
Survival	from the time patients received L-DEP salvage therapy up to 24 months or November 2019

Trial Locations

Locations (1)

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