Adults Patients Having Non Severe HLHPhase 2HLH-JAKNCT05063110
Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB
A Phase 2 study testing Itacitinib in people with Adults Patients Having Non Severe HLH, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adults Patients Having Non Severe HLH
- What is being tested?
- Itacitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteFrance
- Study dates
- 3 May 2022to 1 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB a Phase II Prospective Trial
This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs)
Read the detailed description
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
- Adults Patients Having Non Severe HLH
- Being tested
- Itacitinib
- Keywords
- Hemophagocytosis lymphohistiocytosis, JAK 1, Itacitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItacitinibDrug
Administration of 300 mg of ITACITINIB per os every day for 30 days.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Itacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of ITACITINIB
Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH
Measured: 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
Response rate at D8 of treatment
Measured: day 8
Efficacy at the day of etiologic treatment if patients received at least 7 days of treatment (ITACITINIB taken until J15)
Rate of complete response to ITACITINIB treatment for HLHs in adults without any sign of severity at the day of etiologic treatment if patients have been treated by ITACITINIB at least during seven days. Response to ITACITINIB is evaluated at the day of etiologic treatment on the major and minor diagnostic criteria of HLH
Measured: At day 15
Toxicity of ITACITINIB
Toxicity of ITACITINIB not related to evolution of HLH (cytopenia, worsening of hepatic balance, secondary infections)
Measured: 21 months
Rescue therapy
In the case of worsening, treatment will be stopped and switch for HLH specific treatment as VP16, (etoposide)
Measured: 21 months
Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15
Range of decrease in plasma rate of IFN-Gamma, IP-10, Il-1, Il-6, IL-10, TNF-alpha, between D0 and D15 of ITACITINIB treatment in each patient group: response and progression
Measured: At day 15
Clinical, biological, associated diseases characteristics of patients having CR, PR, Progression
Clinical, biological, associated diseases and evolutions characteristics of patients in each response
Measured: 21 months
Overall survival at 3
Overall survival at 3
Measured: 3 months
Response rate of ITACITINIB at D30 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria
Response rate at D30 of treatment
Measured: day 30
Response rate of ITACITINIB at D90 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria
Response rate at D90 of treatment
Measured: day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2021
- Study start3 May 2022
- Primary completion3 Apr 2025
- Study completion1 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Adults Patients Having Non Severe HLHStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063110
- Sponsor's protocol ID
- APHP 201454
- Other IDs
- 2021-000407-20
- Acronym
- HLH-JAK
- Status last verified
- Oct 2025
- First submitted
- 2 Sep 2021
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 15661029Pachlopnik 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.
PubMed 20049711Billiau 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.
PubMed 15466922Vainchenker 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.
PubMed 22869151Maschalidi 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.
PubMed 27222478
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB a Phase II Prospective Trial
- ClinicalTrials.gov ID
- NCT05063110
- Acronym / sponsor ID
- HLH-JAK / APHP 201454
- Conditions
- Adults Patients Having Non Severe HLH
- Keywords
- Hemophagocytosis lymphohistiocytosis, JAK 1, Itacitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 3 May 2022 (actual)
- Primary completion
- 3 Apr 2025 (actual)
- Study completion
- 1 Oct 2025 (actual)
- First posted
- 30 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs)
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Itacitinib300 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ItacitinibAdministration of 300 mg of ITACITINIB per os every day for 30 days. | Drug | Treatment arm |
Primary outcome
Efficacy of ITACITINIB
Time frame: At day 15
Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH
9 secondary outcomes
Response rate of ITACITINIB at D8 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria
Time frame: day 8
Efficacy at the day of etiologic treatment if patients received at least 7 days of treatment (ITACITINIB taken until J15)
Time frame: At day 15
Toxicity of ITACITINIB
Time frame: 21 months
Rescue therapy
Time frame: 21 months
Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15
Time frame: At day 15
Clinical, biological, associated diseases characteristics of patients having CR, PR, Progression
Time frame: 21 months
Overall survival at 3
Time frame: 3 months
Response rate of ITACITINIB at D30 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria
Time frame: day 30
Response rate of ITACITINIB at D90 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria
Time frame: day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Results publication: PubMed 15661029Menasche 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.
- Results publication: PubMed 20049711Pachlopnik 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.
- Results publication: PubMed 15466922Billiau 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.
- Results publication: PubMed 22869151Vainchenker 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.
- Results publication: PubMed 27222478Maschalidi 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.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Itacitinib in people with Adults Patients Having Non Severe HLH, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of ITACITINIB (time frame: At day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05063110, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.