Hemophagocytic LymphohistiocytosisPhase 3NCT05315336
L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH
A Phase 3 study testing L-DEP and PD-1 antibody 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 L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory EBV associated hemophagocytic lymphohistiocytosis. Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis
- What is being tested?
- L-DEP and PD-1 antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2022to 1 Jun 2026
- 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 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria;patients were diagnosed with EBV associated HLH (EBV-HLH).
- EBV-DNA in peripheral blood or EBER in tissue were positive.
- Treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least partial response
- The patient is expected to be unable to undergo allogeneic hematopoietic stem cell transplantation in the short term due to various reasons (physical status, economic reasons, donor reasons, etc.)
- The expected survival time is more than 1 month.
- Age ≤ years old, gender is not limited.
Show all 12Show fewer
- Serum creatinine ≤ 1.5 times normal；After infusion, fibrinogen can be corrected to ≥0.6g/L.
- Serum human immunodeficiency virus(HIV) antigen or antibody negative； Hepatitis C virus (HCV) antibody is negative, or HCV antibody is positive, but HCV RNA is negative；HBV copies less than 1E+03 copies/ml.
- The left ventricular ejection fraction (LVEF) was normal.
- No uncontrollable infection.
- Contraception for both male or female.
- Informed consent obtained.
Who cannot join
- Allergic to doxorubicin and/or etoposide and/or PD-1 antibody Injection
- Severe myocardial injury, myocardial enzymes CK, CK-MB increased more than 3 times ULN (upper limit of normal)
- Heart function above grade II (NYHA).
- Thyroid dysfunction
- Serious mental illness;
- Active hemorrhage of internal organs
Show all 9Show fewer
- Previously received L-DEP regimen for HLH-targeted treatment, but the treatment was ineffective or relapsed
- Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2
- Participate in other clinical research at the same time.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
This study aimed to investigate the efficacy and safety of L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory EBV associated hemophagocytic lymphohistiocytosis.
Read the detailed description
PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Being tested
- L-DEP and PD-1 antibody
- Keywords
- Hemophagocytic Lymphohistiocytosis, DEP, L-Asparaginasum, PD-1 antibody
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-DEP and PD-1 antibodyDrug
Doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; PD-1 antibody injection 200mg day 5; L-asparaginases 6000iu/m2 day2, day4. This regimen was repeated after 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| L-DEP and PD-1 antibody | Experimental | Doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; PD-1 antibody injection 200mg day 5; L-asparaginases 6000iu/m2 day2, day4. This regimen was repeated after 2 weeks. Receives: Drug: L-DEP and PD-1 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of treatment response
The primary observed endpoint is the objective remission rate (ORR): cases that include complete remission (CR) and partial remission (PR).CR 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). PR 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%.
Measured: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Secondary outcomes (3)
EBV-DNA
Outcome of patients with EBV-HLH
Measured: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Survival
Outcome of patients with EBV-HLH
Measured: 3 months after the intervention
Adverse events that are related to treatment
Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.
Measured: 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start1 Jun 2022 (estimated)
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
- Masking
- None (open label)
- Enrolment
- 50 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
- NCT05315336
- Sponsor's protocol ID
- L-DEP, PD-1, HLH
- Status last verified
- Apr 2022
- First submitted
- 30 Mar 2022
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV Associated Hemophagocytic Lymphohistiocytosis (HLH)
- ClinicalTrials.gov ID
- NCT05315336
- Acronym / sponsor ID
- L-DEP, PD-1, HLH
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Keywords
- Hemophagocytic Lymphohistiocytosis, DEP, L-Asparaginasum, PD-1 antibody
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Beijing Friendship HospitalUniversity, hospital or other
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 7 Apr 2022 (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.
This study aimed to investigate the efficacy and safety of L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory EBV associated hemophagocytic lymphohistiocytosis.
Detailed description
PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients with R/R EBV- HLH receive DEP combine with PD-1 antibody as an treatment.
| Arm | Type | Receives |
|---|---|---|
| L-DEP and PD-1 antibody | Experimental | Drug: L-DEP and PD-1 antibodyDoxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; PD-1 antibody injection 200mg day 5; L-asparaginases 6000iu/m2 day2, day4. This regimen was repeated after 2 weeks. |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria;patients were diagnosed with EBV associated HLH (EBV-HLH).
- EBV-DNA in peripheral blood or EBER in tissue were positive.
- Treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least partial response
- The patient is expected to be unable to undergo allogeneic hematopoietic stem cell transplantation in the short term due to various reasons (physical status, economic reasons, donor reasons, etc.)
- The expected survival time is more than 1 month.
Key exclusion criteria (9 listed)
- Allergic to doxorubicin and/or etoposide and/or PD-1 antibody Injection
- Severe myocardial injury, myocardial enzymes CK, CK-MB increased more than 3 times ULN (upper limit of normal)
- Heart function above grade II (NYHA).
- Thyroid dysfunction
- Serious mental illness;
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 |
|---|---|---|
| L-DEP and PD-1 antibodyDoxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2mg/kg days 1 to 3,then 0.25mg/kg day 4 to 14; PD-1 antibody injection 200mg day 5; L-asparaginases 6000iu/m2 day2, day4. This regimen was repeated after 2 weeks. | Drug | L-DEP and PD-1 antibody |
Primary outcome
Evaluation of treatment response
Time frame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
The primary observed endpoint is the objective remission rate (ORR): cases that include complete remission (CR) and partial remission (PR).CR 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). PR 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%.
3 secondary outcomes
EBV-DNA
Time frame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Survival
Time frame: 3 months after the intervention
Adverse events that are related to treatment
Time frame: 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
Related trials for Hemophagocytic Lymphohistiocytosis
RecruitingObservational study
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
Lymphohistiocytosis, Hemophagocytic, Secondary Hemophagocytic Lymphohistiocytosis
Not yet recruitingObservational study
Long Term Safety Study in Patients With HLH/MAS in Still's Disease Exposed to Gamifant.
Hemophagocytic Lymphohistiocytosis (HLH), Macrophage Activation Syndrome (MAS)
RecruitingObservational study
Hemophagocytic Lymphohistiocytosis After Allogeneic Stem Cell Transplantation
Hemophagocytic Lymphohistiocytosis (HLH)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
CytOSorb TreatMent Of Critically Ill PatientS Registry
Septic Shock, Acute Respiratory Distress Syndrome
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 L-DEP and PD-1 antibody 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 12 inclusion and 9 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 26 Apr 2022. 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 Zhao Wang (86-010-63139862, wangzhao@ccmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of treatment response (time frame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Apr 2022.