L-DEP as an Initial Treatment for EBV-HLH

Sponsor

Beijing Friendship Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02912702

Collaborator

(none)

120

Enrollment

Location

Arms

Duration (Months)

3.3

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 an initial treatment for Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: Pegaspargase Drug: doxorubicin hydrochloride liposome injection Drug: etoposide Drug: methylprednisolone Drug: Etoposide Drug: dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled Trial of L-DEP as an Initial Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis

Study Start Date :

Sep 1, 2016

Anticipated Primary Completion Date :

Sep 1, 2018

Anticipated Study Completion Date :

Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-DEP Pegaspargase 2000U/m2 day5; 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 hydrochloride liposome injection 25 mg/m2 day 1 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
Active Comparator: HLH-94 regimen Etoposide 150 mg/m2 twice weekly for 2 weeks and then weekly; dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering	Drug: Etoposide 150 mg/m2 twice weekly for 2 weeks and then weekly Drug: dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering

Arm

Intervention/Treatment

Experimental: L-DEP

Pegaspargase 2000U/m2 day5; 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 hydrochloride liposome injection

25 mg/m2 day 1

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

Active Comparator: HLH-94 regimen

Etoposide 150 mg/m2 twice weekly for 2 weeks and then weekly; dexamethasone initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering

Drug: Etoposide

150 mg/m2 twice weekly for 2 weeks and then weekly

Drug: dexamethasone

initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering

Outcome Measures

Primary Outcome Measures

Overall response(complete response+ partial response) rate of Participants [Change from before and 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy]
A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25(pg/ml), ferritin(μg/L), and triglyceride(mmol/L); hemoglobin(g/L); neutrophil counts(×109/L); platelet counts(×109/L); and alanine aminotransferase (ALT(U/L)). A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25(pg/ml) response was>1.5-fold decreased; ferritin (μg/L)and triglyceride(mmol/L) 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 (U/L)decrease of at least 50%.

Secondary Outcome Measures

Compare survival between two arms [from the time patients received L-DEP or HLH-94 therapy up to 12 months or September 2019]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [through study completion, an average of 1 years]
Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on.
Change of Epstein-Barr virus(EBV)-DNA before and after therapy [Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP or HLH-94 therapy]