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

NCT05762640 | Recruiting Phase 2 DMC

• 2 other identifiers: APHP2000232021-006878-23
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Haemophagocytic Lymphohistiocytosis

Keywords

Haemophagocytic Lymphohistiocytosis; Lymphohistiocytic activation syndrome; Ruxolitinib; Jakavi

Outcome Measures

Primary Outcomes (1)

• Survival until HSCT

  Day 0 until HSCT, up to 8 weeks

Secondary Outcomes (11)

• 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

• 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

• Delay to obtain complete response

  Day 0 up to Day-1 of the conditioning for HSCT

• Delay to obtain partial response

  Day 0 up to Day-1 of the conditioning for HSCT

• Incidence of HLH reactivation

  Day 0 up to Day-1 of the conditioning for HSCT

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

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.

Ruxolitinib

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hopital Necker Enfants malades

Paris, Île-de-France Region, 75015, France

RECRUITING

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Despina MOSHOUS, MD, PhD

  Hôpital Necker-Enfants Malades

  STUDY CHAIR

Central Study Contacts

Despina MOSHOUS, MD, PhD

CONTACT

01 44 49 48 23; despina.moshous@aphp.fr

Laure CHOUPEAUX

CONTACT

01 44 38 17 11; laure.choupeaux@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: March 9, 2023
• Study Start: November 10, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)