Hemophagocytic LymphohistiocytosisPhase 3NCT02912702
L-DEP as an Initial Treatment for EBV-HLH
A Phase 3 study testing Pegaspargase, doxorubicin hydrochloride liposome injection and etoposide in people with Hemophagocytic Lymphohistiocytosis, run by Beijing Friendship Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 to 75 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis
- What is being tested?
- Pegaspargase, doxorubicin hydrochloride liposome injection and etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- Sep 2016to Sep 2019
- 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 14 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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, 1 recruiting
- Recruiting
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050
jingshi wang, M.M., 86-13520280731, wangjingshi987@sina.com
About this study
Official title: A Randomized Controlled Trial of L-DEP as an Initial Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis
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
- Being tested
- Pegaspargase, doxorubicin hydrochloride liposome injection, etoposide, methylprednisolone, dexamethasone
- Keywords
- Pegaspargase, hemophagocytic lymphohistiocytosis, Epstein Barr virus, initial treatment
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegaspargaseDrug
2000U/m2 day5
doxorubicin hydrochloride liposome injectionDrug
25 mg/m2 day 1
etoposideDrug
100 mg/m2 was administered once on the first day of every week
15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Etoposide; Drug: dexamethasone |
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 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy
Secondary outcomes (3)
Compare survival between two arms
Measured: 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
Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on.
Measured: through study completion, an average of 1 years
Change of Epstein-Barr virus(EBV)-DNA before and after therapy
Measured: Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP or HLH-94 therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2018 (estimated)
- Study completionSep 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- 120 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
- NCT02912702
- Sponsor's protocol ID
- L-DEP-EBV-HLH-First line
- Status last verified
- Sep 2016
- First submitted
- 9 Sep 2016
- Last updated
- 23 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 26289641
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of L-DEP as an Initial Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis
- ClinicalTrials.gov ID
- NCT02912702
- Acronym / sponsor ID
- L-DEP-EBV-HLH-First line
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Keywords
- Pegaspargase, hemophagocytic lymphohistiocytosis, Epstein Barr virus, initial treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Beijing Friendship HospitalUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Sep 2019 (estimated)
- First posted
- 23 Sep 2016 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-DEP | Experimental | Drug: Pegaspargase, Drug: doxorubicin hydrochloride liposome injection, Drug: etoposide, Drug: methylprednisolonePegaspargase 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 |
| HLH-94 regimen | Active comparator | 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 |
Who may qualify
- Ages
- 14 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
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 |
|---|---|---|
| Pegaspargase2000U/m2 day5 | Drug | L-DEP |
| doxorubicin hydrochloride liposome injection25 mg/m2 day 1 | Drug | L-DEP |
| etoposide100 mg/m2 was administered once on the first day of every week | Drug | L-DEP |
| methylprednisolone15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7 | Drug | L-DEP |
| Etoposide150 mg/m2 twice weekly for 2 weeks and then weekly | Drug | HLH-94 regimen |
| 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 | HLH-94 regimen |
Primary outcome
Overall response(complete response+ partial response) rate of Participants
Time frame: Change from before and 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy
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%.
3 secondary outcomes
Compare survival between two arms
Time frame: 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
Time frame: through study completion, an average of 1 years
Change of Epstein-Barr virus(EBV)-DNA before and after therapy
Time frame: Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP or HLH-94 therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2016.
- Background: PubMed 26289641Wang 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.
- 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.
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 Pegaspargase, doxorubicin hydrochloride liposome injection and etoposide 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 23 Sep 2016. 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?
Contact jingshi wang, M.M. (86-13520280731, wangjingshi987@sina.com), or a site near the patient. 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 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy). 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 NCT02912702, which also lists 1 linked publication.
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 23 Sep 2016.