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

NCT02631109 | Unknown Phase 3 DMC

• 1 other identifier: L-DEP-EBV-HLH
• 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 a salvage therapy for refractory Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Conditions

Hemophagocytic Lymphohistiocytosis

Keywords

Pegaspargase; hemophagocytic lymphohistiocytosis; Epstein Barr virus

Outcome Measures

Primary Outcomes (2)

• Evaluation of treatment response

  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 from before and 2,4,6 and 8 weeks after initiating L-DEP salvage therapy

• Change of Epstein-Barr virus(EBV)-DNA

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

Secondary Outcomes (2)

• 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

Study Arms (1)

L-DEP

EXPERIMENTAL

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; Drug: doxorubicin; Drug: etoposide; Drug: methylprednisolone

Interventions

Pegaspargase DRUG

2000U/m2 day5

L-DEP

doxorubicin DRUG

25mg/m2 day1

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

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 achieve at lease partial response after initial treatment including HLH-94 or DEP no less than 2 weeks
• 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 (2)

• 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

• Wang J, Wang Y, Wu L, Zhang J, Lai W, Wang Z. PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Hematol Oncol. 2016 Sep 9;9(1):84. doi: 10.1186/s13045-016-0317-7.

  PMID: 27613189 DERIVED

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic; Epstein-Barr Virus Infections

Interventions

pegaspargase; Doxorubicin; Etoposide; Methylprednisolone

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)

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

Study Officials

• zhao wang, M.D.

  Beijing Friendship Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

jingshi wang, M.M.

CONTACT

86-13520280731; wangjingshi987@sina.com

Study Design

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

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 16, 2015
• Study Start: December 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2019
• Last Updated: August 4, 2016

Record last verified: 2016-08

Locations

CN (1)