L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH

April 19, 2022 updated by: Zhao Wang, Beijing Friendship Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PD-1 antibody added to the DEP regimen （with or without asparaginases） in EBV-HLH

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Beijing Friendship hospital, Capital Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria;patients were diagnosed with EBV associated HLH (EBV-HLH).
  2. EBV-DNA in peripheral blood or EBER in tissue were positive.
  3. Treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least partial response
  4. 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.)
  5. The expected survival time is more than 1 month.
  6. Age ≤ years old, gender is not limited.
  7. Serum creatinine ≤ 1.5 times normal；After infusion, fibrinogen can be corrected to ≥0.6g/L.
  8. 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.
  9. The left ventricular ejection fraction (LVEF) was normal.
  10. No uncontrollable infection.
  11. Contraception for both male or female.
  12. Informed consent obtained.

Exclusion Criteria:

  1. Allergic to doxorubicin and/or etoposide and/or PD-1 antibody Injection
  2. Severe myocardial injury, myocardial enzymes CK, CK-MB increased more than 3 times ULN (upper limit of normal)
  3. Heart function above grade II (NYHA).
  4. Thyroid dysfunction
  5. Serious mental illness;
  6. Active hemorrhage of internal organs
  7. Previously received L-DEP regimen for HLH-targeted treatment, but the treatment was ineffective or relapsed
  8. Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2
  9. Participate in other clinical research at the same time.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: L-DEP and PD-1 antibody
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.
Drug: L-DEP and PD-1 antibody
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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%.
Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
EBV-DNA
Time Frame: Change from before and 2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy
Outcome of patients with EBV-HLH
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
Outcome of patients with EBV-HLH
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
Incidence of events that are related to treatment including myelosuppression, infection, bleeding and so on.
2,4,6 and 8 weeks after initiating DEP combine with PD-1 antibody therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Friendship Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2025

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2022

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2022

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 26, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • L-DEP, PD-1, HLH

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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