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

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Criteria

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