A Phase 3 interventional study of Etoposide (Early strategy) and Etoposide (Delayed strategy) in Hemophagocytic Lymphohistiocytosis, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-23.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
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Among 13 studies testing etoposide in Lymphohistiocytosis, Hemophagocytic — 3 open to participants now, 3 under way, 1 of them phase 3. Etoposide · Lymphohistiocytosis, Hemophagocytic.
Among the 13 studies testing etoposide in Lymphohistiocytosis, Hemophagocytic, this one is the 3rd largest by planned enrollment, is the only one that started in 2026, is one of 5 in phase 3, and was the 13th registered.
111 studies on the registry are indexed under Lymphohistiocytosis, Hemophagocytic; 41 are open to participants now.
Browse Lymphohistiocytosis, Hemophagocytic studies →3 of the 13 studies testing etoposide in Lymphohistiocytosis, Hemophagocytic are open now, in 2 countries. Recruiting first, the newest first:
The Children's Hospital of Zhejiang University School of Medicine · Sites in China
Ages 1 days–18 yrs
Beijing Friendship Hospital · Sites in China
Ages 18+
By country, each count listing its studies:
Etoposide: first FDA approval 1983 (VEPESID). What it is approved for, and how studies give it, is on its page →
Of the 26 Lymphohistiocytosis, Hemophagocytic studies recruiting now, 14 (54%) set no upper age limit and 8 (31%) stop at 75 or younger; 15 take children under 18; 2 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
13 studies; the count open now beside each. This study's row is marked.
First in 2004; this study’s year is marked. 1 started in 2026.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 176 is above the median of 30 across 75 interventional studies indexed under Lymphohistiocytosis, Hemophagocytic.
Median enrollment 31 across the 13 interventional studies. Of the 5 that completed or were terminated, 3 (60%) have results posted.
This tab as a report to print or save as PDF → With an account.
None of the 13 has an industry lead sponsor. The 10 most frequent:
Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,596 studies on the registry; 1,037 are open to participants now.
Assistance Publique - Hôpitaux de Paris has 6 studies filed under Lymphohistiocytosis, Hemophagocytic — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 13 studies testing etoposide in Lymphohistiocytosis, Hemophagocytic, from their registry updates:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder characterized by hyperactivation of the immune system, leading to a cytokine storm responsible for organ failures. Consequently, patients with HLH often require intensive care management, where their short-term prognosis is compromised (1-month mortality: 30 to 40%).
Therapeutic management is urgent and consists in treating associated pathologies and employing immunomodulatory therapy. Currently, there are no clear and consistent recommendations for guiding immunomodulatory treatment in HLH due to the lack of high-level evidence studies. Experts recommend corticosteroid therapy for mild forms, whereas etoposide is proposed for severe cases, especially those with organ failures. However, in clinical practice, its use in patients with multi-organ failure is not systematic due to concerns about potential severe side effects and uncertainty regarding the contribution of severe sepsis to the clinical and biological presentation. Consequently, initiation of etoposide is sometimes delayed.
Our hypothesis is that early treatment of severe HLH associated with organ failure using etoposide could reduce organ failures associated with this syndrome. Therefore, we aim to compare two strategies for initiating etoposide in severe HLH in intensive care: an early strategy where etoposide is prescribed at the onset of HLH-related organ failure, and a delayed strategy where etoposide is prescribed only if there is unfavorable progression (or lack of improvement) after treating associated pathologies, associated with corticosteroid therapy.
Objectives
Primary Objective: To compare the effect on the evolution of organ failures of two initiation strategies of etoposide in severe HLH in intensive care:
The occurrence of an event defined as the onset or worsening of organ failures, evaluated using the modified Sequential Organ Failure Assessment (SOFA) score (excluding the hematologic component, from 0 to 20 points), calculated every 12 hours from Day 1 to Day 5 (Day 0 = inclusion), and then every 24 hours from Day 6 to Day 14. An event will be defined as an increase of at least 1 point for at least two organ systems compared to Day 0. In the delayed arm, the use of rescue etoposide treatment or in case of secondary aggravation during follow-up will also be considered an event.
Secondary objectives:
Evaluate the effect of these 2 strategies on:
Investigational treatment
Etoposide is used at a dose of 100 mg/m², administered via slow intravenous infusion over 30 to 60 minutes on Day 0 or Day 2 depending on the arm (early strategy or delayed strategy).
Patients in the "early strategy" arm will receive etoposide treatment within 12 hours of inclusion.
In the "delayed strategy" arm, patients will be reassessed 48 hours after inclusion. If there is persistence or deterioration of organ failures (similar or higher modified SOFA score), patients will receive etoposide treatment within 12 hours of this reassessment in the absence of formal contraindications. In cases of rapidly deteriorating clinical status with short-term life-threatening prognosis (defined as an increase of 6 or more points in modified SOFA score), patients may receive rescue treatment (before 48 hours) with etoposide at the discretion of the medical team managing the patient; in such cases, the Day-2 infusion will not be administered. This practice will be exceptional and documented, following consultation with the hotline if possible.
In the unlikely event of subsequent clinical deterioration from Day 2 to Day 14, etoposide infusion may be considered for patients who did not receive etoposide previously in the "delayed strategy" group. This situation will also be documented.
Patients in both arms will routinely receive systemic corticosteroid therapy with dexamethasone 10 mg/m² in a daily injection for the duration of the study, unless contraindicated (adjuvant investigational drug).
Standard treatment
In case of persistence of HLH signs, a first (for patients in the "delayed strategy" arm) or subsequent (for patients in both arms) injections of etoposide may be performed during follow-up at the discretion of the patient's care team.
Other treatments will be:
Inclusion and randomization will be conducted through a computer server accessible to all study investigators. This will be a 1:1 randomization into two groups, with stratification based on the SOFA score (\<9 or ≥9), prior administration of corticosteroid therapy, and the centers.
The 2 groups will be:
Data will be collected as part of routine care for HLH management (clinical and biological characteristics, dates of HLH onset and diagnosis, underlying immunosuppression, HLH-associated pathologies, HScore and Henter criteria, immunomodulatory treatments [date, duration], daily assessment of organ support, occurrence of infectious or hemorrhagic events) by the investigator, and recorded in an e-CRF. Data collection will continue up to 14 days post-randomization. SOFA score and modified SOFA score (excluding hematological component) will be calculated and recorded by the investigator every 12 hours from Day 1 to Day 5, then daily from Day 6 to Day 14. Adverse events will be reported from inclusion to Day 14. Vital status will be collected on Day 14 and Day 60, with a maximum follow-up duration of 60 days. A systematic minimal assessment for HLH-associated pathologies will be proposed to each team.
The protocol also includes the establishment of a biobank (serotheca and DNAtheca) at the PRB of Avicenne Hospital.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Confirmed diagnosis of HLH:
Presence of one or more organ failures:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Etoposide treatment will be administered within 12 hours of inclusion.
Drug: Etoposide (Early strategy)
The need for etoposide treatment will be reassessed after 48 hours of management. If organ failure worsens or fails to improve (modified SOFA increase ≥1 point or stable), etoposide will be administered within 12 hours of reassessment. In cases of rapidly deteriorating clinical status with short-term life-threatening prognosis (defined as an increase of 6 or more points in modified SOFA score), patients may receive rescue treatment (before 48 hours) with etoposide at the discretion of the medical team managing the patient; in such cases, the Day-2 infusion will not be administered.
Drug: Etoposide (Delayed strategy)
early strategy arm: patients will receive etoposide treatment within 12 hours of inclusion.
Also known as: Etoposide is used at a dose of 100 mg/m², administered via slow intravenous infusion over 30 to 60 minutes on Day 0 or Day 2 depending on the arm.
delayed strategy arm: patients will be reassessed 48 hours after inclusion. If there is persistence or deterioration of organ failures (similar or higher modified SOFA score), patients will receive etoposide treatment within 12 hours of this reassessment in the absence of formal contraindications. In cases of rapidly deteriorating clinical status with short-term life-threatening prognosis (defined as an increase of 6 or more points in modified SOFA score), patients may receive rescue treatment (before 48 hours) with etoposide at the discretion of the medical team managing the patient; in such cases, the Day-2 infusion will not be administered. This practice will be exceptional and documented, following consultation with the hotline if possible.
Also known as: Etoposide is used at a dose of 100 mg/m², administered via slow intravenous infusion over 30 to 60 minutes on Day 0 or Day 2 depending on the arm.
Increase of at least 1 point in the modified SOFA score (excluding the hematologic component) for at least two organ systems compared to Day 0. In the delayed arm, the use of rescue etoposide treatment or in case of secondary aggravation during follow-up
The occurrence of an event defined as the onset or worsening of organ failures, evaluated using the modified Sequential Organ Failure Assessment (SOFA) score (excluding the hematologic component, from 0 to 20 points), calculated every 12 hours from Day 1 to Day 5 (Day 0 = inclusion), and then every 24 hours from Day 6 to Day 14. An event will be defined as an increase of at least 1 point for at least two organ systems compared to Day 0. In the delayed arm, the use of rescue etoposide treatment or in case of secondary aggravation during follow-up will also be considered an event.
Time frame: every 12 hours from Day 1 to Day 5 (Day 0 = inclusion), and then every 24 hours from Day 6 to Day 14
Survival
Time to death after inclusion (with a maximum follow-up duration of 60 days)
Time frame: 60 days
Duration of mechanical ventilation
Number of ventilator-free days between inclusion and Day 14. A live discharge from the intensive care unit will be considered equivalent to no mechanical ventilation (event) from the date of discharge. Patients who died before day 14 will be assigned a value of 0 days, corresponding to no days alive without ventilation.
Time frame: 14 days after inclusion
Duration of catecholamine therapy
Number of catecholamine-free days between inclusion and Day 14. A live discharge from the intensive care unit will be considered equivalent to an absence of catecholamines (event) from the date of discharge. Patients who died before D14 will be assigned a value of 0 days, corresponding to an absence of live days without catecholamines.
Time frame: 14 days after inclusion
Need for renal replacement therapy.
Proportion of patients receiving at least one session of renal replacement therapy between inclusion and Day 14. Discharge from intensive care without prior extrarenal purification will be considered a non-event. Death without prior extrarenal purification will be considered a non-event.
Time frame: 14 days after inclusion
Length of stay in the intensive care unit
Length of stay in the intensive care unit
Time frame: 60 days
Length of hospital stay
Length of hospital stay
Time frame: 60 days
Proportion of patients receiving etoposide treatment
Proportion of patients receiving a dose of etoposide
Time frame: 60 days
Cumulative dose of etoposide
Cumulative dose of etoposide over the first 14 days, within the total study population and among those receiving at least one dose of treatment
Time frame: 14 days after inclusion
Time to initiation of etoposide treatment
Number of days between inclusion and initiation of etoposide treatment in patients who received etoposide.
Time frame: 60 days
Number of patients receiving another immunosuppressive treatment
Number of patients receiving another immunosuppressive treatment during the intensive care unit stay up to Day 14. Treatment received outside the intensive care unit will not be taken into account.
Time frame: 60 days
Normalization of HLH-related biological abnormalities
Time from inclusion to normalization of fibrinogen (\> 2 g/L), decrease in ferritin (\< 2000 µg/L), and decrease in triglycerides (\< 1.5 mg/dL) during the intensive care unit stay up to Day 14. These blood tests will be performed daily as part of routine care during the period of intensive care.
Time frame: 14 days after inclusion
Evolution of the HScore (probability score for HLH)
HScore at Days 2, 7, and 14. In the event of missing data (particularly for hemophagocytosis), the latest available data will be used
Time frame: 2, 7, and 14 days after inclusion
Potential side effects attributable to etoposide, such as healthcare-associated infections, incidence of neutropenia, and bleeding events
Proportion of patients with at least one healthcare-associated infection, neutropenia acquired after inclusion and its duration, if applicable (defined by PNN \<500/mm³), a bleeding event after inclusion requiring transfusion and/or surgery. Patients with neutropenia on admission will be excluded from the neutropenia analysis. Complete blood counts, bleeding events, and transfusions will be monitored daily.
Time frame: 60 days
Evolution of the SOFA score and modified SOFA score.
Delta SOFA at Days 2 and 5, maximum SOFA score, including both SOFA and modified SOFA. The SOFA score will be calculated daily, in accordance with the protocol for the primary endpoint. The maximum SOFA score during the first 14 days will be used.
Time frame: 14 days after inclusion
Start is estimated for Apr 2026; primary completion for Dec 2029, 44 months later.
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Studies of the drug tested here: Etoposide
Lymphohistiocytosis, Hemophagocytic →
Assistance Publique - Hôpitaux de Paris →