L-DEP as an Initial Treatment for EBV-HLH

Phase 3

• Conditions: Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: Pegaspargase; Drug: doxorubicin hydrochloride liposome injection; Drug: dexamethasone; Drug: Etoposide; Drug: methylprednisolone

• Registration Number: NCT02912702
• 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 an initial treatment for Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Detailed Description

Not available

Study Timeline

• Status Verified: 2016-09
• Study Start: 2016-09
• Study First Submitted: 2016-09-09
• Study First Submitted QC: 2016-09-21
• Last Update Submitted: 2016-09-21
• Study First Posted: 2016-09-23
• Last Update Posted: 2016-09-23
• Primary Completion: 2018-09
• Study Completion: 2019-09

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 receive any treatment for HLH before
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: PARALLEL

Arm && Interventions

Group	Intervention	Description
L-DEP	Pegaspargase	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
L-DEP	methylprednisolone	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
L-DEP	doxorubicin hydrochloride liposome injection	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
L-DEP	Etoposide	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
HLH-94 regimen	Etoposide	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
HLH-94 regimen	dexamethasone	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Compare survival between two arms	from the time patients received L-DEP or HLH-94 therapy up to 12 months or September 2019
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
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.

Trial Locations

Locations (1)

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