Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB

NCT ID: NCT05063110

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-03

Study Completion Date

2025-10-01

Brief Summary

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This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs)

Detailed Description

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This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs). The existence of an IFN-γ signature, in HLHs, is a strong rational for testing the use of a JAK1 inhibitor in the treatment of HLHs. We hypothesize that ITACITINIB, an inhibitor of JAK-1, may be a therapeutic of interest in the treatment of non-severe HLHs in replacement of corticosteroids by inhibiting the production and effects of IFN-γ but also those of other pro-inflammatory cytokines. The use JAK-1 inhibitor instead of corticosteroids in patients with HLHs without any sign of severity is justified by its probable lesser toxicity and higher efficiency.

In this proof of concept study, because of the vital risk associated with severe HLH and the efficacy of Etoposide in this setting, we will first include only patients with moderate HLHs

Conditions

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Adults Patients Having Non Severe HLH

Keywords

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Hemophagocytosis lymphohistiocytosis JAK 1 Itacitinib

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment arm

300 mg of ITACITINIB will be administrated per os every day for 30 days, dose with reduction to 200 mg per safety is allowed if AEs are observed or if co-administered a strong CYP3A inhibitor

Group Type EXPERIMENTAL

Itacitinib

Intervention Type DRUG

Administration of 300 mg of ITACITINIB per os every day for 30 days.

Interventions

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Itacitinib

Administration of 300 mg of ITACITINIB per os every day for 30 days.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients age \> 18 years,
* Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol
* Patient known to have systemic juvenile idiopathic arthritis are classified as having HLH
* Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception for the duration of the study
* Be either affiliated to, or a beneficiary of, a social security category

Exclusion Criteria

* Organ failure: confusion, organic kidney failure KDIGO 2 criteria, liver failure (Factor V \< 50%), heart failure, respiratory failure.
* Fibrinogen \< 0.50 g/l, platelets \<20G/L
* Indication to intensive care unit transfer on an organ failure requiring assistance (dialysis, Ventilation (assisted or VNI), shock regardless of the origin.
* Breastfeeding women
* Patient participating in another investigational therapeutic study
* Women with a positive pregnancy test or not willing to take contraceptive measures
* Known allergies, hypersensitivity, or intolerance to any of the ITACITINIB or excipients, or similar compounds
* Current or history of recurrent infections, including HBV, HCV
* Participants with active HBV or HCV infection that requires treatment or who are at risk for HBV reactivation (ie Positive HBs Ag serology)
* Candidates positive for HCV antibody and positive PCR RNA HCV
* HIV infection with positive viral charge
* Protected adults (including individual under guardianship by court order)
* Vulnerable adults, under a safeguard of justice measure
* Adults deprived of their liberty by judicial or administrative decision
* Persons under psychiatric care without their consent
* Persons admitted to social institution for purposes other this research
* Adults under legal protection (guardianship or curatorship)
* Persons unable to express their consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Avicenne

Bobigny, Bobigny, France

Site Status

Countries

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France

References

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Menasche G, Feldmann J, Fischer A, de Saint Basile G. Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis. Immunol Rev. 2005 Feb;203:165-79. doi: 10.1111/j.0105-2896.2005.00224.x.

Reference Type RESULT
PMID: 15661029 (View on PubMed)

Pachlopnik Schmid J, Ho CH, Chretien F, Lefebvre JM, Pivert G, Kosco-Vilbois M, Ferlin W, Geissmann F, Fischer A, de Saint Basile G. Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol Med. 2009 May;1(2):112-24. doi: 10.1002/emmm.200900009.

Reference Type RESULT
PMID: 20049711 (View on PubMed)

Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C. Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages. Blood. 2005 Feb 15;105(4):1648-51. doi: 10.1182/blood-2004-08-2997. Epub 2004 Oct 5.

Reference Type RESULT
PMID: 15466922 (View on PubMed)

Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene. 2013 May 23;32(21):2601-13. doi: 10.1038/onc.2012.347. Epub 2012 Aug 6.

Reference Type RESULT
PMID: 22869151 (View on PubMed)

Maschalidi S, Sepulveda FE, Garrigue A, Fischer A, de Saint Basile G. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016 Jul 7;128(1):60-71. doi: 10.1182/blood-2016-02-700013. Epub 2016 May 24.

Reference Type RESULT
PMID: 27222478 (View on PubMed)

Other Identifiers

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2021-000407-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP 201454

Identifier Type: -

Identifier Source: org_study_id