Hemophagocytic LymphohistiocytosisPhase 3NCT03742115
Etoposide in the First-line Treatment of Adult EBV-HLH
A Phase 3 study testing Etoposide, Dexamethasone and IVIG in people with Hemophagocytic Lymphohistiocytosis, run by Beijing Friendship Hospital at 1 site in China.
Trial summary
his study aimed to investigate the efficacy of etoposide as the first line therapy for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis
- What is being tested?
- Etoposide, Dexamethasone and IVIG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2018to 1 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050
Yue Song, M.M., 86-18810253070 ext. +8601063139862, xueqifeng1992@163.com
About this study
Official title: 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.
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Being tested
- Etoposide, Dexamethasone, IVIG
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoposideDrug
150 mg/m2 twice weekly for 2 weeks and then weekly
DexamethasoneDrug
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
EtoposideDrug
150 mg/m2 weekly
IVIGDrug
0.5 g/kg, once every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Etoposide; Drug: 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 Receives: Drug: Dexamethasone; Drug: 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) Receives: Drug: Dexamethasone; Drug: IVIG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: Change from before and 2,4 weeks after initiating thearpy
Secondary outcomes (1)
Compare survival between two arms
Measured: from the time patients received therapy up to 12 months or December 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start1 Dec 2018 (estimated)
- Primary completion1 Dec 2019 (estimated)
- Study completion1 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Beijing Friendship HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Friendship Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Wang, Beijing Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03742115
- Sponsor's protocol ID
- VP-16-adult EBV-HLH-first line
- Status last verified
- Nov 2018
- First submitted
- 13 Nov 2018
- Last updated
- 15 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 11352958Imashuku 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.
PubMed 12825212Henter 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.
PubMed 12239144
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Etoposide in the First-line Treatment of Adult Epstein-barr Virus Associated Hemophagocytic Lymphohistiocytosis
- ClinicalTrials.gov ID
- NCT03742115
- Acronym / sponsor ID
- VP-16-adult EBV-HLH-first line
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Beijing Friendship HospitalUniversity, hospital or other
- Study start
- 1 Dec 2018 (estimated)
- Primary completion
- 1 Dec 2019 (estimated)
- Study completion
- 1 Dec 2020 (estimated)
- First posted
- 15 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
his study aimed to investigate the efficacy of etoposide as the first line therapy for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Etoposide standard group | Experimental | Drug: Etoposide, Drug: DexamethasoneEtoposide 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 |
| Etoposide reduction group | Experimental | Drug: Dexamethasone, Drug: EtoposideEtoposide 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 |
| Corticosteroid group | Active comparator | Drug: Dexamethasone, Drug: IVIGdexamethasone 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) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etoposide150 mg/m2 twice weekly for 2 weeks and then weekly | Drug | Etoposide standard group |
| Dexamethasoneinitially 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 | Corticosteroid group, Etoposide reduction group, Etoposide standard group |
| Etoposide150 mg/m2 weekly | Drug | Etoposide reduction group |
| IVIG0.5 g/kg, once every 4 weeks | Drug | Corticosteroid group |
Primary outcome
Overall response(complete response+ partial response) rate of Participants
Time frame: Change from before and 2,4 weeks after initiating thearpy
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%.
1 secondary outcome
Compare survival between two arms
Time frame: from the time patients received therapy up to 12 months or December 2020
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- Background: PubMed 11352958Imashuku 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.
- Background: PubMed 12825212Imashuku 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.
- Background: PubMed 12239144Henter 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beijing Friendship Hospital, Capital Medical University
Beijing, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etoposide, Dexamethasone and IVIG in people with Hemophagocytic Lymphohistiocytosis, run by Beijing Friendship Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response(complete response+ partial response) rate of Participants (time frame: Change from before and 2,4 weeks after initiating thearpy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03742115, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2018.