L-DEP as an Initial Treatment for EBV-HLH

NCT02912702 | Unknown Phase 3 DMC

• 1 other identifier: L-DEP-EBV-HLH-First line
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophagocytic Lymphohistiocytosis

Keywords

Pegaspargase; hemophagocytic lymphohistiocytosis; Epstein Barr virus; initial treatment

Outcome Measures

Primary Outcomes (1)

• Overall response(complete response+ partial response) rate of Participants

  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%.

  Change from before and 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy

Secondary Outcomes (3)

• 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

• 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

Study Arms (2)

L-DEP

EXPERIMENTAL

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; Drug: doxorubicin hydrochloride liposome injection; Drug: etoposide; Drug: methylprednisolone

HLH-94 regimen

ACTIVE COMPARATOR

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; Drug: dexamethasone

Interventions

Pegaspargase DRUG

2000U/m2 day5

L-DEP

doxorubicin hydrochloride liposome injection DRUG

25 mg/m2 day 1

L-DEP

Etoposide DRUG

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

L-DEP

methylprednisolone DRUG

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

L-DEP

dexamethasone DRUG

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

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients were older than 14 years of age
• Diagnosed as EBV-Hemophagocytic Lymphohistiocytosis (HLH)
• Patients did not receive any treatment for HLH before
• Informed consent

You may not qualify if:

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

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

Related Publications (1)

• Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, Shen J, Wei N, Wang Z. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015 Nov 5;126(19):2186-92. doi: 10.1182/blood-2015-05-644914. Epub 2015 Aug 19.

  PMID: 26289641 BACKGROUND

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic; Epstein-Barr Virus Infections

Interventions

pegaspargase; Etoposide; Methylprednisolone; Dexamethasone

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Central Study Contacts

jingshi wang, M.M.

CONTACT

86-13520280731; wangjingshi987@sina.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 23, 2016
• Study Start: September 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2019
• Last Updated: September 23, 2016

Record last verified: 2016-09

Locations

CN (1)