Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Overall Survival at 2 Months
研究概览
简要总结
This is a pilot study to determine the efficacy of Ruxolitinib in secondary hemophagocytic syndrome. The primary objective is to assess the efficacy of ruxolitinib 15 mg PO twice daily in patients with HPS. The primary endpoint is overall survival at two months.
详细描述
Hemophagocytic Syndrome (HPS) is a disorder characterized by pathological activation of the immune system resulting in a systemic disorder characterized by excessive cytokine production and macrophage activation, culminating in cytopenias and evidence of hemophagocytosis on tissue specimens. The disorder can be sporadic or familial due to one of several mutations and is primarily seen in the pediatric population, with a reported incidence of 1 case per 3000 admissions. The actual incidence in adults is unknown and can be rarely sporadic, or secondary to viral infections, malignancy, or autoimmune disease.
HPS is a universally fatal disease if untreated. In adults, the median survival has been reported to be less than 2 months if diagnosis and treatment is delayed. Adult patients are treated with pediatric protocols with early institution of etoposide and steroids and consolidation with allogeneic stem cell transplant in appropriately selected patients if a familial form is identified. Other treatment strategies have been attempted, including rituximab, infliximab, entaracept, tocilizumab, and alemtuzumab. These anecdotal reports highlight the therapeutic potential of cytokine-targeted therapies in this disorder.
This is a pilot study to determine the efficacy of Ruxolitinib in secondary hemophagocytic syndrome. The primary objective is to assess the efficacy of ruxolitinib 15 mg PO twice daily in patients with HPS. The primary endpoint is overall survival at two months.
Patients will receive Ruxolitinib at 15 mg twice daily orally either on an empty stomach or with food for 4 weeks (28 days) in a 4 week (28 day) cycle. Ruxolitinib will be administered in continuous 28-day cycles.
In the absence of treatment delays or cessation due to adverse events, treatment may continue indefinitely or until one of the following criteria applies:
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, or their legally authorized representative, must voluntarily provide written IRB-approved informed consent.
- •Males and females, 18 years of age or older at the time of enrollment.
- •Patients must meet the diagnostic criteria for HPS (at least 5 of the following): fever, splenomegaly, cytopenia involving ≥2 cell lines (Hemoglobin <9 g/dL; platelets <100,000/μL; absolute neutrophil count <1000/μL), hypertriglyceridemia or hypofibrinogenemia, tissue demonstration of hemophagocytosis, low or absent NK (Natural Killer) cell activity, serum ferritin ≥3000 ug/L, soluble IL-2 receptor (CD25) >2400 U/mL.
- •In the investigator's opinion, the patient has the ability to participate fully in the study, and comply with all its requirements.
排除标准
- •CNS (Central Nervous System) involvement
- •Malabsorption
- •Known secondary HPS (Hemophagocytic Syndrome) that is otherwise treatable (e.g. non-Hodgkin's lymphoma).
- •Pregnant or lactating female: all females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment; lactating females must discontinue breast feeding.
- •Estimated creatinine clearance <15mL/min
- •Has received any prior systemic therapy, excluding corticosteroids, within 7 days (or 5 half-lives) of treatment.
- •No active malignancy at the time of enrollment, except nonmelanoma skin cancers or carcinoma in situ. Patients with a prior history of malignancy are eligible if their malignancy has been definitely treated or is in remission and does not require ongoing adjuvant or cancer-directed therapies.
- •Active hepatitis B or hepatitis C or known HIV infection
- •Known (and biopsy-confirmed) liver cirrhosis; or, a reported history of liver cirrhosis with a Model for End-stage Liver Disease (MELD) score >20.
研究组 & 干预措施
Ruxolitinib
Ruxolitinib 15 mg by mouth twice daily.
For patients unable to ingest tablets, ruxolitinib suspended in water may be administered through a nasogastric (NG) or percutaneous endoscopy gastrostomy (PEG) tube.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Overall Survival at 2 Months
时间窗: 2 Months
Number of Patients Alive at 2 Months after the first administration of ruxolitinib.
次要结局
- Percentage of Patients With a Response to Treatment With Ruxolitinib(2 Months)
- Duration of Response(Up to 3 years (Due to funding and other constraints, participant follow-up was discontinued in 2020. Thus, not all participants were followed for a full three years.))
- Progression Free Survival Time(Up to 3 years (Due to funding and other constraints, participant follow-up was discontinued in 2020. Thus, not all participants were followed for a full three years.))
- Regimen Related Toxicities(Up to 30 days after last treatment administration)