Targeting metabolic vulnerability of BCR: ABL negative myeloproliferative neoplasms: Focus on Primary Myelofibrosis.
试验速览
- 阶段
- 1/2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Proportion of subjects achieving above 35% reduction in spleen volume from baseline to Week 24 as measured by ultrasound (or CT scan in applicable subjects)
研究概览
简要总结
Aim
To target the metabolic vulnerability of BCR: ABL negative myeloproliferative neoplasms: Focus on Primary Myelofibrosis
Patients and Methods:
Early phase II open-labeled single arm study design will be utilized to study the impact of arsenic trioxide and artesunate on PMF. Patients with advanced disease scheduled to start treatment with Ruxolitinib or to undergo an alloHCT will be given a 6-month course of the novel intervention after validation of the findings before those mentioned above, as well as more standard interventions to assess response.
This exploratory early-phase trial will enroll 25 patients over two years.
Expected outcome:
The proposed study aims to validate the metabolic and phenotypic vulnerabilities of JAK2 V617F+ cells using FDA-approved drugs and novel drug combinations. This study will also determine the effect of promising drugs on bone marrow fibrosis in PMF. This would have the potential to translate into a novel therapeutic strategy in the clinical management of PMF, which otherwise does not have therapies that alter the clinical course of the disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects age ≥ 18 years of age (adults) Subjects must be diagnosed with Primary Myelofibrosis according to the 2008 World Health Organization criteria (Table 2 in Tefferi and Vardiman, 2008) irrespective of JAK2 mutation status.
- •Subjects with an ECOG performance status of 0, 1, or
- •Subjects with peripheral blood blast count of less than 10% at the Screening and Baseline visits.
排除标准
- •Subjects with a life expectancy of less than six months.
- •Subjects in whom MF disease is well controlled with current therapy.
- •Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid becoming pregnant or fathering a child.
- •Subjects with inadequate bone marrow reserve as demonstrated by: a.
- •Absolute neutrophil count (ANC) that is less than 500 b.
- •Platelet count less than 30,000 without the assistance of growth factors, thrombopoietic factors, or platelet transfusions.
- •Subjects with inadequate liver or renal function as demonstrated by: a.
- •Direct bilirubin above 2 X upper limit of laboratory normal (ULN).
- •(NOTE: Direct bilirubin will only be determined if total bilirubin is above 2.0 x ULN).
- •Alanine aminotransferase (ALT) above 2.5x upper limit of laboratory normal (ULN).
结局指标
主要结局
Proportion of subjects achieving above 35% reduction in spleen volume from baseline to Week 24 as measured by ultrasound (or CT scan in applicable subjects)
时间窗: Assessed at 3 months 6 months and at 1 year
次要结局
- Duration of maintenance of a above 35% reduction from baseline in spleen volume among subjects receiving intervention.(Proportion of subjects who have above 50% reduction in total symptom score from baseline to Week 24 as measured by the Modified MFSAF.)
研究者
Vikram Mathews
Christian Medical College Vellore Ranipet campus