Etoposide in the First-line Treatment of Adult EBV-HLH

A Randomized Controlled Trial of Etoposide in the First-line Treatment of Adult Epstein-barr Virus Associated Hemophagocytic Lymphohistiocytosis

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

Study Overview

• Status: Unknown
• Conditions: Hemophagocytic Lymphohistiocytosis
• Intervention / Treatment: Drug: Etoposide; Drug: Dexamethasone; Drug: Etoposide; Drug: IVIG

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: Yue Song, M.M.; Phone Number: +8601063139862 86-18810253070; Email: xueqifeng1992@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients were older than 18 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etoposide standard group; 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; Drug: Etoposide; 150 mg/m2 weekly
Experimental: Etoposide reduction group; 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: 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; Drug: Etoposide; 150 mg/m2 weekly
Active Comparator: Corticosteroid group; 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: 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: IVIG; 0.5 g/kg, once every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Compare survival between two arms	from the time patients received therapy up to 12 months or December 2020

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on.	through study completion, an average of 1 years

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): November 15, 2018
• Last Update Submitted That Met QC Criteria: November 13, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dexamethasone; Etoposide; Etoposide phosphate
• Other Study ID Numbers: VP-16-adult EBV-HLH-first line

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No