• Patient with Haemophagocytic lymphohistiocytosis (HLH) or lymphohistiocytic syndrome
Conditions
Interventions
Pharmaceutical Form:
Sponsors
Assistance Publique Hopitaux Paris - APHP
Eligibility
Sex/Gender
All
Inclusion 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: o Fever o Splenomegaly o Cytopenia (affecting at least two cell lineages) ? Haemoglobin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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: o History of hypersensitivity to the active substance or to any of the excipients • Pregnant or lactating female patient • Contraindication to receive methylprednisolone or prednisolone o History of hypersensitivity to the active substance or to any of the excipients o 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 1.Evaluation of the efficacy of Ruxolitinib through the rate of patients achieving a complete or partial response at Day 14, Day 28, Week 8 and at Day-1 of the conditioning for HSCT, and through the delay that is necessary to obtain a response. 2.Estimation of the incidence and timing of HLH reactivation 3.Evaluation of treatment tolerance and adverse effects 4.Study of pharmacokinetics of Ruxolitinib and the link between the pharmacokinetic and treatment efficacy. 5.Study of the cytokine profile and gene expression at different time points during treatment and the link to treatment efficacy. ;Primary end point(s): The primary endpoint is the survival until HSCT. All causes of death will be taken into account, whether or not related to the course of the disease. ;Timepoint(s) of evaluation of this end point: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Evaluation of the efficacy through the rate of patients achieving a complete or partial response at Day 14, Day 28, Week 8 and Day-1 of the conditioning for HSCT and through the delay that is necessary to obtain a response: The response will be evaluated in accordance with the following definitions. Importantly, the treating physician must determine that continued or new symptoms are related to active HLH and not due to infection or other causes. • Complete response (CR) is defined by the normalization of clinical and laboratory parameters, as measured by: o Resolution of fever o Resolution of splenomegaly or reduced and isolated splenomegaly o Improvement of cytopenias: absolute neutrophil count = 500/µl AND platelets count = 100.000/µl (unsupported by transfusions), in the absence of myelotoxic treatments or other non-HLH related reasons as judged by the treating physician o Normalization of serum fibrinogen level (fibrinogen = 1.5 g/l) o Resolution of hyperferritinemia (ferritin level < 2000 µg/l) o Absence of activated T cells OR normalization of CD25 soluble (sIL-2 receptor) < 2400 U/ml o Normalization of CSF pleocytosis (WBC < 5/µl and absence of haemophagocytosis) AND decrease of CSF protein by = 50% • Partial response (PR) is defined by an improvement without complete normalization of the clinical and biological parameters in comparison to the initial status of the patient at inclusion. Patient must meet at least 3 of the below mentioned criteria with no worsening of clinical aspects of disease (i.e. worsening CNS disease, new requirement for intensive care support such as mechanical ventilation, vasopressor support, renal replacement therapy), as determined by the treating physician: o Resolution of fever o Improvement of cytopenias: absolute neutrophil count = 500/µl OR platelets count = 50.000/µl (unsupported by transfusions), in the absence of myelotoxic treatments or other non-HLH related reasons as judged by the treat | — |
Countries
France
Contacts
Public ContactPROJECT MANAGER
APHP
Outcome results
None listed