Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB

NCT05063110 | Completed Phase 2 DMC

• 2 other identifiers: APHP 2014542021-000407-20
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adults Patients Having Non Severe HLH

Keywords

Hemophagocytosis lymphohistiocytosis; JAK 1; Itacitinib

Outcome Measures

Primary Outcomes (1)

• Efficacy of ITACITINIB

  Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH

  At day 15

Secondary Outcomes (9)

• Response rate of ITACITINIB at D8 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria

  day 8

• Efficacy at the day of etiologic treatment if patients received at least 7 days of treatment (ITACITINIB taken until J15)

  At day 15

• Toxicity of ITACITINIB

  21 months

• Rescue therapy

  21 months

• Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15

  At day 15

Study Arms (1)

Treatment arm

EXPERIMENTAL

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

Drug: Itacitinib

Interventions

Itacitinib DRUG

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

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Incyte Corporation: collaborator

Study Sites (1)

Hôpital Avicenne

Bobigny, Bobigny, 93000, France

Location

Related Publications (5)

• 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.

  PMID: 15661029 RESULT

• 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.

  PMID: 20049711 RESULT

• 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.

  PMID: 15466922 RESULT

• 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.

  PMID: 22869151 RESULT

• 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.

  PMID: 27222478 RESULT

MeSH Terms

Interventions

itacitinib

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: September 2, 2021
• First Posted: September 30, 2021
• Study Start: May 3, 2022
• Primary Completion: April 3, 2025
• Study Completion: October 1, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-10

Locations

FR (1)