Haemophagocytic LymphohistiocytosisPhase 2R-HLHNCT05762640
Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH)
A Phase 2 study testing Ruxolitinib in people with Haemophagocytic Lymphohistiocytosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this project is to study the survival of patients until Haematopoietic Stem Cell Transplantation following the use of Ruxolitinib as first-line treatment associated to corticosteroids in primary HLH. Read more about this study
- Who is it for?
- Ages Up to 22 years
- Conditions the study is for
- Haemophagocytic Lymphohistiocytosis
- What is being tested?
- Ruxolitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 10 Nov 2024to Mar 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 Up to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient aged 0 to 22 years
- Patient with HLH syndrome confirmed by at least one of the two criteria:
- Confirmed genetic diagnosis of a condition predisposing to primary HLH (see table 1 and table 2) or abnormal expression of perforin, MUNC13-4, SAP or XIAP in FACS and/or positive family history OR
- Presence of at least 5 of the 8 following HLH diagnostic criteria:
- Fever
- Splenomegaly
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- Cytopenia (affecting at least two cell lineages)
- Haemoglobin < 9 g/dl (<10 g/dL in neonates)
- Platelets < 100,000/µL
- Absolute neutrophil count (ANC) < 1,000/µL
- Hypertriglyceridemia and/or hypofibrinogenemia
- Fasting triglycerides ≥ 3 mmol/l
- Fibrinogen <1.5 g/L
- Haemophagocytosis found in a histological sample (without evidence of a malignant process or an underlying rheumatic disorder)
- Decreased or absent NK function
- Ferritin ≥ 500 µg/l
- Presence of activated T cells in the immune phenotyping as evidenced by expression of the activation marker DR (superior to the normal value of the laboratory) OR CD25 soluble (sIL-2 receptor) ≥ 2,400 U/mL.
- Patient with no previous specific treatment for HLH syndrome
- For patients of childbearing age : using an effective method of contraception during the trial, and through to 90 days after EOS for male participants and 30 days after EOS for female participants
- Freely given, informed and written consent of legal representative of the participant or consent of the adult participant
- Affiliation to Social Security.
Who cannot join
- Previous treatment with ATG, Alemtuzumab, Etoposide, JAK-inhibitors, rifampicin and/or anti-Interferon gamma antibodies. St. John's Wort, or any other strong CYP3A4 inducers.
- Previous treatment with corticosteroids and/or cyclosporine A for more than 14 days
- Isolated CNS disease.
- Contraindication to receive Ruxolitinib:
- History of hypersensitivity to the active substance or to any of the excipients
- Pregnant or lactating female patient
Show all 16Show fewer
- Contraindication to receive methylprednisolone or prednisolone
- History of hypersensitivity to the active substance or to any of the excipients
- Any infectious condition with the exception of infections, which are the trigger for lymphohistiocytic activation.
- Patient with acute very severe renal impairment (Creatinine Clearance <15 mL/min/1.73m²) who are NOT receiving dialysis.
- Patient with Grade 4 hepatic failure according to the CTCAE v5.0 of 27 November 2017 (Life-threatening consequences; moderate to severe encephalopathy; coma)
- Past or know active tuberculosis
- Known rheumatologic disorder.
- Known active malignancy.
- Patient who is taking another investigational agent or is enrolled in another treatment protocol.
- Patient who cannot tolerate administration of drugs PO or through NG
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hopital Necker Enfants malades
Paris, Île-de-France Region, 75015
Despina MOSHOUS, MD, PHD, 01 44 49 48 23 ext. +33, despina.mouhous@aphp.fr
About this study
Official title: Efficacy of Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (HLH) in Children: a Phase 2, Multicentre, Non-comparative Study
The purpose of this project is to study the survival of patients until Haematopoietic Stem Cell Transplantation following the use of Ruxolitinib as first-line treatment associated to corticosteroids in primary HLH.
Read the detailed description
Haemophagocytic lymphohistiocytosis (HLH) is a devastating inflammatory condition caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines.
Treatment of HLH aims at decreasing inflammation and requires also treatment of the underlying trigger, if any.
The principal goal of the induction therapy is to suppress the life-threatening inflammatory process. Once remission of HLH achieved, patients require allogeneic haematopoietic stem cell transplantation (HSCT), the only curative therapy to date.
Despite significant treatment progress, mortality remains high. The study aims to implement a targeted treatment that is less aggressive than conventional approaches (Etoposide / ATG / Alemtuzumab).
A better understanding of the pathophysiology of primary HLH has opened new avenues for targeted therapy. The central cytokine of the HLH process is IFNγ. IFNγ as well as most cytokines that are elevated in HLH, signal via Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-associated receptors. Ruxolitinib, a selective JAK1/2 inhibitor has shown its efficacy in mouse models of HLH, where it significantly reduced disease manifestations and enhanced survival. Notably, Ruxolitinib diminished CD8+ T-cell accumulation and cytokine production, while sparing degranulation and cytotoxicity. Recently, Ruxolitinib has also been used successfully in humans in isolated cases of refractory primary and secondary HLH.
This is a National, phase II, non-comparative and non-randomized, study in France with 9 participating centers. The chosen experimental plan is a Simon's Optimal 2-Step Design.
- Conditions
- Haemophagocytic Lymphohistiocytosis
- Being tested
- Ruxolitinib
- Keywords
- Haemophagocytic Lymphohistiocytosis, Lymphohistiocytic activation syndrome, Ruxolitinib, Jakavi
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Form: tablets, 50 mg/m2/day in two administrations. Maximum dose is 100 mg/day. Administration in association with Methylprednisolone IV (or Prednisolone PO) starting at 2 mg/kg/day in two administrations.
Duration of treatment: until D-1 of conditioning for allogeneic HSCT OR 9weeks for patients who are not eligible for HSCT.
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib | Experimental | Not described Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival until HSCT
Measured: Day 0 until HSCT, up to 8 weeks
Secondary outcomes (11)
Rate of patients achieving a complete response
To evaluate the efficacy of Ruxolitinib
Measured: Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT
Rate of patients achieving a partial response
To evaluate the efficacy of Ruxolitinib
Measured: Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT
Delay to obtain complete response
To evaluate the efficacy of Ruxolitinib
Measured: Day 0 up to Day-1 of the conditioning for HSCT
Delay to obtain partial response
To evaluate the efficacy of Ruxolitinib
Measured: Day 0 up to Day-1 of the conditioning for HSCT
Incidence of HLH reactivation
HLH reactivation after achieving complete or partial response.
Measured: Day 0 up to Day-1 of the conditioning for HSCT
Timing of HLH reactivation
HLH reactivation after achieving complete or partial response.
Measured: Day 0 up to Day-1 of the conditioning for HSCT
Occurrence of a viral infection de novo or worsening of pre-existing viral infection(s)
To evaluate treatment tolerance
Measured: During Ruxolitinib treatment
Occurrence of adverse effects reported in the product information for Ruxolitinib
To evaluate treatment tolerance
Measured: During Ruxolitinib treatment
Concentration of Ruxolitinib in blood
to evaluate Pharmacokinetics
Measured: Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT
Concentration of Ruxolitinib in cerebrospinal fluid
to evaluate Pharmacokinetics
Measured: Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT
Cytokine profile and gene expression
Assess through measurement of IFNγ, TNFα, Interleukin (IL)-6, IL-2, IL-10, IL-18, IL-1b, and CXCL9
Measured: Day 0, Weekly until week 8 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2023
- Study start10 Nov 2024
- Primary completionMay 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Despina MOSHOUS, MD, PhD, Study chair, Hôpital Necker-Enfants Malades
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05762640
- Sponsor's protocol ID
- APHP200023
- Other IDs
- 2021-006878-23
- Acronym
- R-HLH
- Status last verified
- Mar 2026
- First submitted
- 3 Jan 2023
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (HLH) in Children: a Phase 2, Multicentre, Non-comparative Study
- ClinicalTrials.gov ID
- NCT05762640
- Acronym / sponsor ID
- R-HLH / APHP200023
- Conditions
- Haemophagocytic Lymphohistiocytosis
- Keywords
- Haemophagocytic Lymphohistiocytosis, Lymphohistiocytic activation syndrome, Ruxolitinib, Jakavi
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 10 Nov 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 9 Mar 2023 (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.
The purpose of this project is to study the survival of patients until Haematopoietic Stem Cell Transplantation following the use of Ruxolitinib as first-line treatment associated to corticosteroids in primary HLH.
Detailed description
Haemophagocytic lymphohistiocytosis (HLH) is a devastating inflammatory condition caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines.
Treatment of HLH aims at decreasing inflammation and requires also treatment of the underlying trigger, if any.
The principal goal of the induction therapy is to suppress the life-threatening inflammatory process. Once remission of HLH achieved, patients require allogeneic haematopoietic stem cell transplantation (HSCT), the only curative therapy to date.
Despite significant treatment progress, mortality remains high. The study aims to implement a targeted treatment that is less aggressive than conventional approaches (Etoposide / ATG / Alemtuzumab).
A better understanding of the pathophysiology of primary HLH has opened new avenues for targeted therapy. The central cytokine of the HLH process is IFNγ. IFNγ as well as most cytokines that are elevated in HLH, signal via Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-associated receptors. Ruxolitinib, a selective JAK1/2 inhibitor has shown its efficacy in mouse models of HLH, where it significantly reduced disease manifestations and enhanced survival. Notably, Ruxolitinib diminished CD8+ T-cell accumulation and cytokine production, while sparing degranulation and cytotoxicity. Recently, Ruxolitinib has also been used successfully in humans in isolated cases of refractory primary and secondary HLH.
This is a National, phase II, non-comparative and non-randomized, study in France with 9 participating centers. The chosen experimental plan is a Simon's Optimal 2-Step Design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib | Experimental | Drug: Ruxolitinib |
Who may qualify
- Ages
- Up to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Patient aged 0 to 22 years
- Patient with HLH syndrome confirmed by at least one of the two criteria:
- Fever
- Splenomegaly
- Cytopenia (affecting at least two cell lineages)
Key exclusion criteria (16 listed)
- Previous treatment with ATG, Alemtuzumab, Etoposide, JAK-inhibitors, rifampicin and/or anti-Interferon gamma antibodies. St. John's Wort, or any other strong CYP3A4 inducers.
- Previous treatment with corticosteroids and/or cyclosporine A for more than 14 days
- Isolated CNS disease.
- Contraindication to receive Ruxolitinib:
- History of hypersensitivity to the active substance or to any of the excipients
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 |
|---|---|---|
| RuxolitinibForm: tablets, 50 mg/m2/day in two administrations. Maximum dose is 100 mg/day. Administration in association with Methylprednisolone IV (or Prednisolone PO) starting at 2 mg/kg/day in two administrations. Duration of treatment: until D-1 of conditioning for allogeneic HSCT OR 9weeks for patients who are not eligible for HSCT. | Drug | Ruxolitinib |
Primary outcome
Survival until HSCT
Time frame: Day 0 until HSCT, up to 8 weeks
11 secondary outcomes
Rate of patients achieving a complete response
Time frame: Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT
Rate of patients achieving a partial response
Time frame: Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT
Delay to obtain complete response
Time frame: Day 0 up to Day-1 of the conditioning for HSCT
Delay to obtain partial response
Time frame: Day 0 up to Day-1 of the conditioning for HSCT
Incidence of HLH reactivation
Time frame: Day 0 up to Day-1 of the conditioning for HSCT
Timing of HLH reactivation
Time frame: Day 0 up to Day-1 of the conditioning for HSCT
Occurrence of a viral infection de novo or worsening of pre-existing viral infection(s)
Time frame: During Ruxolitinib treatment
Occurrence of adverse effects reported in the product information for Ruxolitinib
Time frame: During Ruxolitinib treatment
Concentration of Ruxolitinib in blood
Time frame: Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT
Concentration of Ruxolitinib in cerebrospinal fluid
Time frame: Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT
Cytokine profile and gene expression
Time frame: Day 0, Weekly until week 8 of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Despina MOSHOUS, MD, PhD study chair
Hôpital Necker-Enfants Malades
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib in people with Haemophagocytic Lymphohistiocytosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 21 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 23 Apr 2026. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Despina MOSHOUS, MD, PhD (01 44 49 48 23 ext. +33, despina.moshous@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival until HSCT (time frame: Day 0 until HSCT, up to 8 weeks). 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 23 Apr 2026.