HU-F-AIM - A Prospective, Interventional Study to Evaluate HU-resistance in Polycythemia Vera Patients Who Meet Predictive Parameters Identified in the Machine Learning Project PV-AIM
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 76
- 试验地点
- 23
- 主要终点
- Proportion of PV patients with HU-resistance/intolerance within 6-9 months after start of de novo HU- treatment in presence of the PV-AIM HU-resistance predictors at the start of HU treatment.
研究概览
简要总结
The purpose of this study is to confirm the predictive factors for hydroxyurea (HU) failure (hemoglobin (HGB) <15.5 g/dL (9.62 mmol/L) and red blood cell distribution width (RDW) ≥17%) identified by machine learning in the polycythemia vera advanced integrated model (PV-AIM) project in the real-life setting.
详细描述
The study consists of three periods: Screening period, treatment period (observation for HU-resistance/intolerance) and follow-up (FU) period.
Eligible participants will enter the treatment period (observation period for HU-resistance/intolerance) and start receiving the de novo HU treatment. The maximum treatment duration for each participant in the study will be up to 15 months.
This study will be conducted in a total of 300 adult PV patients and approximately at 30 to 40 sites in Germany. If necessary, the study will be extended to other countries to achieve the target population.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study
- •Patients ≥18 years
- •Confirmed diagnosis of Polycythemia vera (according to WHO 2008, 2016, or 2022 criteria) (Tefferi and Vardiman 2008, Arber et al 2016, Khoury et al 2022)
- •Eastern Cooperative Oncology Group (ECOG) ≤ 2
- •No previous pharmacologic cytoreductive therapy (including investigational drugs)
- •No phlebotomy in last 14 days
- •HU-eligible
- •High-risk: age ≥ 60 years and/or prior history of thrombosis
- •Low-risk: showing at least one of the defined criteria
- •Signs of disease progression (myeloproliferation):
- •Increase in spleen size or symptomatic splenomegaly
- •Platelet increase to > 1,000,000/µl
- •WBC increase to > 15,000/µl or higher
- •Frequent (> 10 per year) or increasing frequency of phlebotomies
- •Increasing risk of thromboembolism and bleeding:
- •New thromboembolism and/or hemorrhagic complications
- •Microcirculation disorders despite acetyl salicylic acid (ASA) 2x 100 mg/day
- •Restricted feasibility or intolerance of phlebotomies
- •Symptomatic iron deficiency
- •Uncontrolled increase in hematocrit
- •Severe or distressing disease-related symptoms
- •Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study treatment.
排除标准
- •Patients with post-polycythemia vera myelofibrosis (post-PV MF) or accelerated phase/ blast phase myeloproliferative neoplasm acute myeloid leukemia (AP/BP-MPN AML).
- •Patients with a contraindication to HU according to the SmPC (severe bone marrow depression, leukopenia (< 2.5 x 109 leukocytes/l), thrombocytopenia (< 100 x 109 platelets/L), severe anemia (< 10 g/dL HGB).
- •Patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption in their past medical history.
- •Active uncontrolled infection that is considered by the Investigator as a reason for exclusion.
- •Active malignancies (except for carcinoma in situ; prostate cancer and breast cancer in remission and - where necessary - ongoing hormonal therapy).
- •Inadequate renal function as demonstrated by Modification of Diet in Renal Disease estimate glomerular filtration rate (MDRDeGFR) < 30 mL/min/1.73m2 or on dialysis.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test.
- •Sexually active males unwilling to use a condom during intercourse while taking study treatment and for at least 3 months after stopping study treatment.
- •HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine.
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Hydroxyurea (HU)
Participants will be treated with HU capsules, orally taken, for a maximum duration of 15 months.
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
Proportion of PV patients with HU-resistance/intolerance within 6-9 months after start of de novo HU- treatment in presence of the PV-AIM HU-resistance predictors at the start of HU treatment.
时间窗: From 6 to 9 months after start of de novo HU-treatment
Proportion of PV participants with HU resistance/intolerance within 6-9 months after start of de novo HU treatment in presence of the PV-AIM HU resistance predictors at the start of HU treatment. The proportion will be assessed calculating the rate together with the respective 95% confidence interval (CI).
次要结局
- Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment(Baseline)
- Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months(Up to 15 months)
- Proportion of "non-switchers"(Up to 15 months)
- Timepoint of therapy switch (after confirmation of HU resistance/intolerance)(Up to 15 months)
- Reasons for therapy switch / non-switch(Up to 15 months)
- Therapies applied during follow-up period(Up to 3 months after treatment discontinuation)