Treatment of nonsevere sporadic Hemophagocytosis Lymphohistiocytosis (HLHs) with ITACITINIB: a phase II prospective trial.

Phase 1

• Conditions: Adults patients having non severe sporadic Hemophagocytosis Lymphohistiocytosis; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2021-000407-20-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE HOPITAUX DE PARIS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-23
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

1.Patients age >= 18 years, with front line or recurrent sporadic HLH, without or awaiting diagnosis of associated pathologies that may benefit from specific treatment, without severity criteria, without organ failure
2.Inclusion criteria were adapted from the revised Diagnostic Guidelines for Hemophagocytic lymphohistiocytosis. Are request to be included:
1 major and 2 minors criteria including hyperferritinemia or/and hypertriglyceridemia
or
3 minors criteria including hyper ferritinemia or/and hypertriglyceridemia
Major criteria:
a. Cytological features of hemophagocytosis
b. Fever
c. Splenomegaly
Minor criteria:
d. Adenopathies
e. Cytopenia> 2 lineages:
Haemoglobin < 9 g/dl,
Platelets < 100 000/mm3
Neutrophils < 1000/mm3
f. Hypertriglyceridemia > 3 mmol/l and/or hypofibrigenemia < 1.5 g/l
g. Ferritin>500 ng/l

3.Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol
4.Patient known to have systemic juvenile idiopathic arthritis are classified as having HLH if they met the following criteria
Ferritin >684 ng/mL
And any 2 of the following:
Platelet count < 181 000/mm3
ASAT > 48 UI/ml
Triglyceride > 4 mmol/L
Fibrinogen 3.6 g/L

5.Be willing to avoid pregnancy or fathering children based on 1 of the following criteria:
a. Women of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or
bilateral oophorectomy OR = 12 months of amenorrhea).
b. Women of childbearing potential who has a negative serum pregnancy test at
screening and who agrees to take appropriate precautions to avoid pregnancy (with at
least 99% certainty) from screening through safety follow-up. Permitted methods that
are at least 99% effective in preventing pregnancy (see Appendix 4) should be
communicated to the subject and their understanding confirmed.
c. Man who agrees to take appropriate precautions to avoid fathering children (with at
least 99% certainty) from screening through safety follow-up. Permitted methods that
are at least 99% effective in preventing pregnancy (see Appendix 4) should be
communicated to the subject and their understanding confirmed.
6.Be either affiliated to, or a beneficiary of, a social security category

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1.Organ failure: Confusion, organic kidney failure KADIGO 2liver failure (Factor V < 50%), heart failure, respiratory failure.

2.Fibrinogenemia < 0.5 g/dl or platelets < 20G/L

3.Indication to intensive care unit transfer on an organ failure requiring assistance (dialysis, Ventilation (assisted or VNI), shock regardless of the origin

4.Participation in another interventional study involving human

5.Breastfeeding women
6.Women with a positive pregnancy test or not willing to take contraceptive measures
7.Known allergies, hypersensitivity, or intolerance to any of the ITACITINIB or excipients, or similar compounds
8.Current or history of recurrent infections, including HBV, HCV

9.Participants with active HBV or HCV infection that requires treatment or who are at risk for HBV reactivation (ie Positive HBs Ag serology)

10.Candidates positive for HCV antibody and positive PCR RNA HCV
11.HIV infection with positive viral charge
12.Protected adults (including individual under guardianship by court order)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified