NCT03742115

Brief Summary

his study aimed to investigate the efficacy of etoposide as the first line therapy for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Dec 2018

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 13, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 15, 2018

Completed
16 days until next milestone

Study Start

First participant enrolled

December 1, 2018

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

November 15, 2018

Status Verified

November 1, 2018

Enrollment Period

1 year

First QC Date

November 13, 2018

Last Update Submit

November 13, 2018

Conditions

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 weeks after initiating thearpy

Secondary Outcomes (1)

  • Compare survival between two arms

    from the time patients received therapy up to 12 months or December 2020

Other Outcomes (1)

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    through study completion, an average of 1 years

Study Arms (3)

Etoposide standard group

EXPERIMENTAL

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: EtoposideDrug: Dexamethasone

Etoposide reduction group

EXPERIMENTAL

Etoposide 150 mg/m2 once a week; 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: DexamethasoneDrug: Etoposide

Corticosteroid group

ACTIVE COMPARATOR

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, with or without IvIG (0.5 g/kg IV, once every 4 weeks)

Drug: DexamethasoneDrug: IVIG

Interventions

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

Etoposide standard group

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

Corticosteroid groupEtoposide reduction groupEtoposide standard group
IVIGDRUG

0.5 g/kg, once every 4 weeks

Corticosteroid group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients were older than 18 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Related Publications (3)

  • Imashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Kato M, Sako M, Hibi S. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001 May 15;19(10):2665-73. doi: 10.1200/JCO.2001.19.10.2665.

    PMID: 11352958BACKGROUND
  • Imashuku S, Kuriyama K, Sakai R, Nakao Y, Masuda S, Yasuda N, Kawano F, Yakushijin K, Miyagawa A, Nakao T, Teramura T, Tabata Y, Morimoto A, Hibi S. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003 Aug;41(2):103-9. doi: 10.1002/mpo.10314.

    PMID: 12825212BACKGROUND
  • Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002 Oct 1;100(7):2367-73. doi: 10.1182/blood-2002-01-0172.

    PMID: 12239144BACKGROUND

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

EtoposideDexamethasoneImmunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-CellHistiocytosisLymphatic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

PodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsSteroids, FluorinatedImmunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

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
Dr.

Study Record Dates

First Submitted

November 13, 2018

First Posted

November 15, 2018

Study Start

December 1, 2018

Primary Completion

December 1, 2019

Study Completion

December 1, 2020

Last Updated

November 15, 2018

Record last verified: 2018-11

Locations