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

Sponsor

Beijing Friendship Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02631109

Collaborator

(none)

120

Enrollment

Location

Arm

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: Pegaspargase Drug: doxorubicin Drug: etoposide Drug: methylprednisolone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Nov 1, 2017

Anticipated Study Completion Date :

Nov 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-DEP 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	Drug: Pegaspargase 2000U/m2 day5 Drug: doxorubicin 25mg/m2 day1 Drug: etoposide 100 mg/m2 was administered once on the first day of every week Drug: methylprednisolone 15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7

Arm

Intervention/Treatment

Experimental: L-DEP

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

Drug: Pegaspargase

2000U/m2 day5

Drug: doxorubicin

25mg/m2 day1

Drug: etoposide

100 mg/m2 was administered once on the first day of every week

Drug: methylprednisolone

15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7

Outcome Measures

Primary Outcome Measures

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

Survival [from the time patients received L-DEP salvage therapy up to 24 months or November 2019]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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