Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB

Phase 2

• Conditions: Adults Patients Having Non Severe HLH
• Interventions: Drug: Itacitinib

• Registration Number: NCT05063110
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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 Timeline

• Study First Submitted: 2021-09-02
• Study First Submitted QC: 2021-09-22
• Study First Posted: 2021-09-30
• Study Start: 2022-05-01
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-22
• Last Update Posted: 2022-08-23
• Primary Completion: 2023-11-01
• Study Completion: 2024-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 63

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Itacitinib	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

Primary Outcome Measures

Name	Time	Method
Efficacy of ITACITINIB	At day 15	Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH

Secondary Outcome Measures

Name	Time	Method
Response rate of ITACITINIB at D8 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria	day 8	Response rate at D8 of treatment
Efficacy at the day of etiologic treatment if patients received at least 7 days of treatment (ITACITINIB taken until J15)	At day 15	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
Toxicity of ITACITINIB	21 months	Toxicity of ITACITINIB not related to evolution of HLH (cytopenia, worsening of hepatic balance, secondary infections)
Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15	At day 15	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
Rescue therapy	21 months	In the case of worsening, treatment will be stopped and switch for HLH specific treatment as VP16, (etoposide)
Clinical, biological, associated diseases characteristics of patients having CR, PR, Progression	21 months	Clinical, biological, associated diseases and evolutions characteristics of patients in each response
Overall survival at 3	3 months	Overall survival at 3
Response rate of ITACITINIB at D30 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria	day 30	Response rate at D30 of treatment
Response rate of ITACITINIB at D90 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria	day 90	Response rate at D90 of treatment

Trial Locations

Locations (1)

Hôpital Avicenne; 🇫🇷 Bobigny, France