Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH)
- Conditions
- Haemophagocytic Lymphohistiocytosis
- Interventions
- Registration Number
- NCT05762640
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief 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.
- Detailed Description
Haemophagocytic lymphohistiocytosis (HLH) is a devastating inflammatory condition caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines.
Treatment of HLH aims at decreasing inflammation and requires also treatment of the underlying trigger, if any.
The principal goal of the induction therapy is to suppress the life-threatening inflammatory process. Once remission of HLH achieved, patients require allogeneic haematopoietic stem cell transplantation (HSCT), the only curative therapy to date.
Despite significant treatment progress, mortality remains high. The study aims to implement a targeted treatment that is less aggressive than conventional approaches (Etoposide / ATG / Alemtuzumab).
A better understanding of the pathophysiology of primary HLH has opened new avenues for targeted therapy. The central cytokine of the HLH process is IFNγ. IFNγ as well as most cytokines that are elevated in HLH, signal via Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-associated receptors. Ruxolitinib, a selective JAK1/2 inhibitor has shown its efficacy in mouse models of HLH, where it significantly reduced disease manifestations and enhanced survival. Notably, Ruxolitinib diminished CD8+ T-cell accumulation and cytokine production, while sparing degranulation and cytotoxicity. Recently, Ruxolitinib has also been used successfully in humans in isolated cases of refractory primary and secondary HLH.
This is a National, phase II, non-comparative and non-randomized, study in France with 9 participating centers. The chosen experimental plan is a Simon's Optimal 2-Step Design.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ruxolitinib Ruxolitinib -
- Primary Outcome Measures
Name Time Method Survival until HSCT Day 0 until HSCT, up to 8 weeks
- Secondary Outcome Measures
Name Time Method Occurrence of adverse effects reported in the product information for Ruxolitinib During Ruxolitinib treatment To evaluate treatment tolerance
Rate of patients achieving a partial response Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT To evaluate the efficacy of Ruxolitinib
Delay to obtain complete response Day 0 up to Day-1 of the conditioning for HSCT To evaluate the efficacy of Ruxolitinib
Concentration of Ruxolitinib in blood Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT to evaluate Pharmacokinetics
Rate of patients achieving a complete response Day 7, Day 14, Day 21, Day 28, Week 8, and Day-1 of the conditioning for HSCT To evaluate the efficacy of Ruxolitinib
Cytokine profile and gene expression Day 0, Weekly until week 8 of treatment Assess through measurement of IFNγ, TNFα, Interleukin (IL)-6, IL-2, IL-10, IL-18, IL-1b, and CXCL9
Delay to obtain partial response Day 0 up to Day-1 of the conditioning for HSCT To evaluate the efficacy of Ruxolitinib
Occurrence of a viral infection de novo or worsening of pre-existing viral infection(s) During Ruxolitinib treatment To evaluate treatment tolerance
Concentration of Ruxolitinib in cerebrospinal fluid Blood sampling: Day 0, weekly until week 8 of treatment and at Day-8 prior to the conditioning for HSCT to evaluate Pharmacokinetics
Incidence of HLH reactivation Day 0 up to Day-1 of the conditioning for HSCT HLH reactivation after achieving complete or partial response.
Timing of HLH reactivation Day 0 up to Day-1 of the conditioning for HSCT HLH reactivation after achieving complete or partial response.