Safety and Effectiveness of Ruxolitinib in Patients With Myelofibrosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 51
- 主要终点
- symptoms burden
研究概览
简要总结
Prospective study to evaluate the response of myelofibrosis patients to ruxolitinib and it's adverse events on patients (1 year observational study).
详细描述
Myelofibrosis (MF) is a clonal disorder of the pluripotent hematopoietic stem cell in which the abnormal stem cell population releases several cytokines and growth factors into the bone marrow microenvironment, it is pathologically characterized by bone marrow fibrosis, extramedullary hematopoiesis, and an overactive Janus kinase/signal transducers and activators of transcription( JAK-STAT) pathway, MF is estimated to have an annual incidence of 0.47-1.98 per 100,000, Most patients are aged > 60 years at initial diagnosis tends to be more common in males than females, It may be de novo (primary MF) or secondary to polycythemia vera (PV) or essential thrombocythemia (ET).
Most patients present with anemia, splenomegaly, and constitutional symptoms, but up to 30% of patients are asymptomatic at diagnosis, symptomatic patients develop Splenomegaly-related symptoms such as abdominal distension and pain, early satiety, dyspnea, together with constitutional symptoms such as fatigue, night sweats, cachexia, pruritus, bone pain, weight loss, and fever are the dominant aspects of the clinical picture heavily affecting the functional status and quality of life (QoL) of MF patients, the most frequent cause of death is the evolution to acute myeloid leukemia, also other conditions such as progression without transformation, cytopenia-related complications and cardiovascular events may be fatal.
Approximately 90% of patients with MF carry mutations in any of 3 driver genes: Janus kinase 2 (JAK2) in ~ 60% of cases, calreticulin (CALR) in ~ 20%, and myeloproliferative leukemia virus oncogene (MPL) in ~ 10%, Mutant proteins activate the (JAK-STAT) pathway and other pathways downstream leading to myeloproliferation, proinflammatory cytokine expression, and bone marrow remodeling.
Current diagnosis of PMF is based on the 2016 WHO-criteria and involves a composite assessment of clinical and laboratory features, Prognosis is currently based on three different scoring systems (IPSS, DIPSS, DIPSS PLUS) and recently mutations were considered in the development of three new prognostic models in PMF.
At present the only curative treatment for MF is allogeneic stem cell transplantation. Most patients with MF are considered ineligible for transplantation because of age or comorbidities, so treatment for the majority of patients is focused on symptom control.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PMF was diagnosed according to the 2016 revised International Standard Criteria, and PPV-MF or PET-MF according to standard criteria with JAK2 positive mutation , palpable spleen (≥5 cm below the left costal margin, measured using a soft ruler during quiet respiration), high-risk and intermediate-2 risk PMF, PPV-MF or PET-MF with disease-related symptoms or symptomatic splenomegaly and patients with intermediate-1 risk PMF, PPV-MF or PET-MF who have symptoms not controlled with supportive therapies or symptomatic splenomegaly .
- •patients who previously started Ruxolitinib and still taking it .
排除标准
- •low risk MF patients
- •intermediate risk 1 without splenomegaly or symptoms
- •JAK2 negative mutation
- •inadequate bone marrow reserve at baseline visit, as demonstrated by at least 1 of the following: absolute neutrophil count (ANC) ≤1 × 109/l, platelet count <50 × 109/l, without the assistance of growth factors, thrombopoietic factors or platelet transfusions, and Hb ≤6.5 g/dl despite transfusions
- •severely impaired renal function (defined by creatinine clearance less than 30 ml/min); inadequate liver function (total bilirubin ≥2.5 × upper limit of normal [ULN] and subsequent determination of direct bilirubin ≥2.5 × ULN or alanine aminotransferase >2.5 × ULN or aspartate aminotransferase >2.5 × ULN
- •acute viral hepatitis or active chronic hepatitis B or C infection
- •concurrent treatment with a potent systemic inhibitor or inducer of CYP3A4
结局指标
主要结局
symptoms burden
时间窗: 6 months
change in the burden of the constitutional symptoms assessed by the MF Symptom Assessment Form on a scale of 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be)
decrease of spleen size
时间窗: 6 months
the proportion of patients achieving ≥50% reduction in Spleen size
次要结局
- adverse events of Ruxolitinib on myleofibrosis patients according to WHO criteria of drug toxicity(1 year)
研究者
Marwa Ali Mahmoud Hassan
principle investigator
Assiut University