Ruxolitinib as first-line treatment for primary haemophagocytic lymphohistiocytosis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 interventional study gives ruxolitinib together with corticosteroids as first-line induction therapy for patients with primary HLH aged 0–22 years, with the main outcome being survival until allogeneic haematopoietic stem cell transplantation (HSCT). The approach aims to suppress the life-threatening hyperinflammation while using a targeted JAK1/2 inhibitor that may be less myeloablative than conventional etoposide- or ATG-based regimens. Ruxolitinib has reduced disease manifestations and improved survival in HLH animal models and has been used in isolated human cases, so this protocol tests it prospectively as initial therapy. Patients are treated and followed at a tertiary pediatric centre in Paris, with standardized criteria for HLH diagnosis and requirement for HSCT once remission is achieved.

Why it matters

Who can join: the full rules

Inclusion Criteria

* Patient aged 0 to 22 years
* Patient with HLH syndrome confirmed by at least one of the two criteria:

  1. 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
  2. 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

Where it's running

• Hopital Necker Enfants malades
  Paris, Île-de-France Region, France Recruiting

Study contacts

• Study coordinator: Despina MOSHOUS, MD, PhD
• Email: despina.moshous@aphp.fr
• Phone: 01 44 49 48 23

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Graft-versus-host disease after stem cell transplant: testing LBP-MARCO with ruxolitinib

  We are testing whether combining LBP-MARCO with ruxolitinib is safe for adults with GVHD after a stem cell transplant.

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• DMR-001 in CALR-mutant myeloproliferative neoplasms

  This study tests DMR-001 alone for CALR-mutant essential thrombocythemia or myelofibrosis, and in combination with ruxolitinib for CALR-mutant myelofibrosis.

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• Testing WJ01024 Alone and with Ruxolitinib for Myelofibrosis with Splenomegaly

  This early-phase study tests whether WJ01024, by itself or with ruxolitinib, is safe and tolerable and whether it shows signs of activity in adults with myelofibrosis and enlarged spleen.

  Recruiting Phase 1 Henan Cancer Hospital · Zhengzhou, Henan · NCT07802405

• Belumosudil vs. Ruxolitinib for hepatic cGVHD after HSCT

  This trial tests whether belumosudil or ruxolitinib works better for hepatic chronic GVHD after a stem cell transplant in people 12 and older.

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• Topical ruxolitinib for adults with pyoderma gangrenosum

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  Recruiting Phase 2 Oregon Health and Science University · Portland, Oregon · NCT07783412

• Ruxolitinib Cream Plus Corticosteroids for Facial Non-Segmental Vitiligo in Real-World Practice

  This real-world study tests whether adding 1.5% ruxolitinib cream to corticosteroids helps people 12 and older with active facial non-segmental vitiligo.

  Recruiting at 6 sites Dermavon Holdings Limited · Shenzhen, Guangdong and 19 other locations · NCT07673640

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.