R-Hlh

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Nov 2024 → ongoing

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS _ ministère de la santé _ PHRC

External identifiers

EU CT number

2024-516105-23-01

EudraCT number

2021-006878-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

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 objectives 5

1. 1. Evaluation of the efficacy of Ruxolitinib through the rate of patients achieving a complete or partial response at Day 7, Day 14, Day 21, Day 28, Week 8 and at Day-1 of the conditioning for HSCT, and through the delay necessary to obtain a response. The last evaluation will be performed at the last day of Ruxolitinib 50 mg/m2/day (Maximum dose: 100 mg/day) prior to the weaning
2. 2. Estimation of the incidence and timing of HLH reactivation
3. 3. Evaluation of treatment tolerance and adverse effects
4. 4. Study of pharmacokinetics of Ruxolitinib and the link between the pharmacokinetic and treatment efficacy
5. 5. Study of the cytokine profile and gene expression at different time points during treatment and the link to treatment efficacy.

Conditions and MedDRA coding

haemophagocytic lymphohistiocytosis (HLH) in children

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. • Patient aged 0 to 22 years
2. • 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 < 9 g/dl (<10 g/dL in neonates)  Platelets < 100.000/µL  Absolute neutrophil count (ANC) < 1.000/µL o Hypertriglyceridemia and/or hypofibrinogenemia  Fasting triglycerides ≥ 3 mmol/l  Fibrinogen <1.5 g/L o Haemophagocytosis found in a histological sample (without evidence of a malignant process or an underlying rhematic disorder) o Decreased or absent NK function o Ferritin ≥ 500 µg/l o 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.
3. • Patient with no previous specific treatment for HLH syndrom
4. • For 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
5. • Freely given, informed and written consent of the participant’s legal representative(s) or of the adult participant • Affiliation to Social Security

Exclusion criteria 13

1. • 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
2. • Previous treatment with corticosteroids and/or cyclosporine A for more than 14 days
3. • Isolated CNS disease
4. • Contraindication to receive Ruxolitinib: o History of hypersensitivity to the active substance or to any of the excipients
5. • Pregnant or lactating female patient
6. • 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
7. • Patient with acute very severe renal impairment (Creatinine Clearance <15 mL/min/1.73m²) who are NOT receiving dialysis
8. • Patient with Grade 4 hepatic failure according to the CTCAE v5.0 of 27 November 2017 (Life-threatening consequences; moderate to severe encephalopathy; coma)
9. • Past or know active tuberculosis
10. • Known rheumatologic disorder.
11. • Known active malignancy.
12. • Patient who is taking another investigational agent or is enrolled in another treatment protocol
13. • Patient who cannot tolerate administration of drugs PO or through NG

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Survival until HSCT. All causes of death will be taken into account, whether or not related to the course of the disease.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

MEDECIN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

MEDECIN

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications