Treatment of Non Severe Hemophagocytosis Lymphohistiocytosis With ITACITINIB a Phase II Prospective Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Efficacy of ITACITINIB
研究概览
简要总结
This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs)
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Itacitinib (Drug)
结局指标
主要结局
Efficacy of ITACITINIB
时间窗: At day 15
Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH
次要结局
- 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)
- Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15(At day 15)
- Rescue therapy(21 months)
- Clinical, biological, associated diseases characteristics of patients having CR, PR, Progression(21 months)
- Overall survival at 3(3 months)
- Response rate of ITACITINIB at D30 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria(day 30)
- Response rate of ITACITINIB at D90 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria(day 90)