Ruxolitinib for Primary haemophagocytic lymphohistiocytosis (HLH)

Inclusion criteria

• {"criterion_text":"- •\tPatient aged 0 to 22 years\n- •\tPatient with HLH syndrome confirmed by at least one of the two criteria: 1)\tConfirmed 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: o\tFever o\tSplenomegaly o\tCytopenia (affecting at least two cell lineages)\t \tHaemoglobin < 9 g/dl (<10 g/dL in neonates) \tPlatelets < 100.000/µL \tAbsolute neutrophil count (ANC) < 1.000/µL o\tHypertriglyceridemia and/or hypofibrinogenemia \tFasting triglycerides ≥ 3 mmol/l \tFibrinogen <1.5 g/L o\tHaemophagocytosis found in a histological sample (without evidence of a malignant process or an underlying rhematic disorder) o\tDecreased or absent NK function o\tFerritin ≥ 500 µg/l o\tPresence 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.\n- •\tPatient with no previous specific treatment for HLH syndrom\n- •\tFor patients in childbearing age : use of an effective contraception method during the trial, and until 90 days after EOS for male participants and 30 days after EOS for female participants\n- •\tFreely given, informed and written consent of the participant’s legal representative(s) or of the adult participant •\tAffiliation to Social Security"}

Exclusion criteria

• {"criterion_text":"- •\tPrevious treatment with ATG, Alemtuzumab, Etoposide, JAK-inhibitors, rifampicin and/or anti-Interferon gamma antibodies. St. John’s Wort, or any other strong CYP3A4 inducers\n- •\tPrevious treatment with corticosteroids and/or cyclosporine A for more than 14 days\n- •\tIsolated CNS disease\n- •\tContraindication to receive Ruxolitinib: o\tHistory of hypersensitivity to the active substance or to any of the excipients\n- •\tPregnant or lactating female patient\n- •\tContraindication to receive methylprednisolone or prednisolone o\tHistory of hypersensitivity to the active substance or to any of the excipients o\tAny infectious condition with the exception of infections, which\n- •\tPatient with acute very severe renal impairment (Creatinine Clearance <15 mL/min/1.73m²) who are NOT receiving dialysis\n- •\tPatient with Grade 4 hepatic failure according to the CTCAE v5.0 of 27 November 2017 (Life-threatening consequences; moderate to severe encephalopathy; coma)\n- •\tPast or know active tuberculosis\n- •\tKnown rheumatologic disorder.\n- •\tKnown active malignancy.\n- •\tPatient who is taking another investigational agent or is enrolled in another treatment protocol\n- •\tPatient who cannot tolerate administration of drugs PO or through NG"}

Primary endpoints

• {"endpoint_text":"- Survival until HSCT. All causes of death will be taken into account, whether or not related to the course of the disease.","definition_or_measurement_approach":"Survival until HSCT measured as time to death from any cause up to Haematopoietic Stem Cell Transplantation; all-cause mortality will be counted whether or not related to disease."}

France

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

16-12-2024

Processing Time Days

20

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France