Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH)
Efficacy of Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (HLH) in Children: a Phase 2, Multicentre, Non-comparative Study
Assistance Publique - Hôpitaux de Paris
20 participants
Nov 10, 2024
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria21
- 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 Criteria16
- 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
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Interventions
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05762640