ClinicalTrials.gov record NCT05762640

Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

Efficacy of Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (HLH) in Children: a Phase 2, Multicentre, Non-comparative Study

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
AgeUp to 22 years old
SexAll
LocationFrance
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This phase II study gives ruxolitinib together with corticosteroids as first-line therapy to children and young people (0–22 years) with primary haemophagocytic lymphohistiocytosis (HLH). All participants receive the same treatment in a single-group, open-label design and are followed until they undergo allogeneic haematopoietic stem cell transplantation (HSCT) or for up to nine weeks if HSCT is not planned. The study measures survival until HSCT, response rates, safety, drug concentrations, and inflammatory markers.

What it is studying. Whether ruxolitinib combined with corticosteroids as first-line therapy can be used in primary HLH, by measuring survival until HSCT, response rates, safety, drug levels, and inflammatory markers.

What the researchers hope to learn. Measure survival until HSCT; determine rates and timing of complete and partial responses; record incidence and timing of HLH reactivation; collect safety and adverse-event data, including new or worsening viral infections; measure ruxolitinib concentrations in blood and cerebrospinal fluid; and describe cytokine profiles and gene-expression changes.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Ruxolitinib

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • 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
  • 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.

Exclusion criteria

  • 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
  • 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

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants receive oral ruxolitinib tablets (given twice daily; dosing set by body surface area with a maximum daily dose) together with intravenous methylprednisolone or oral prednisolone. Treatment continues until the day before conditioning for allogeneic haematopoietic stem cell transplant (HSCT) or for up to 9 weeks if not eligible for HSCT. Study procedures include regular blood tests (including weekly samples through week 8), drug level measurements in blood and cerebrospinal fluid, monitoring for infections and side effects, and assessments of HLH response; cerebrospinal fluid sampling may be performed. Participants will be followed until HSCT or the specified treatment period.

How the study is structured. Phase II, non-randomized, open-label, single-group trial using Simon's optimal two-stage design. Every participant receives ruxolitinib plus methylprednisolone (IV) or prednisolone (oral); there is no comparison or placebo group. Participants are followed from treatment start through HSCT or for up to nine weeks if not proceeding to HSCT, with regular clinical and laboratory assessments and planned blood and cerebrospinal fluid sampling for drug levels and inflammatory studies.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in France. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on hemophagocytic lymphohistiocytosis

Clinical trials34 trials listed for hemophagocytic lymphohistiocytosisEvery trial the registry lists for hemophagocytic lymphohistiocytosis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in hemophagocytic lymphohistiocytosis researchLatest monthly update: September 2026. Includes: Multiple test results. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Nov 10, 2024
Primary completion
May 2027 (estimated)
Study completion
March 2028 (estimated)
Target enrollment
20 participants (estimated)
Last updated on registry
Apr 23, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
  • URC-CIC Paris Descartes Necker Cochin

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

corticosteroids
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
Absolute neutrophil count
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
legal representative
A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
Contraindication
A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
Creatinine Clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
investigational agent
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
HSCT
A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
refractory
A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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