The Benefit/Risk Profile of Pegylated Proline-Interferon Alpha-2b (AOP2014) Added to the Best Available Strategy Based on Phlebotomies in Low-risk Patients With Polycythemia Vera (PV). The Low-PV Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 127
- 试验地点
- 23
- 主要终点
- Number of patients who maintains the median value of HCT< 45%, along 12 months, on number of patients randomized in each arm, per cent
研究概览
简要总结
The Low-PV study is a multicenter, phase II, randomized trial aimed to assess whether the addition of Pegylated Proline-interferon-alpha-2b to the best therapeutic current strategy available based on phlebotomies and low dose acetylsalicylic acid (ASA) could improve the efficacy of treatment of patients with PV at low risk of thrombosis (younger than 60 years and without prior vascular events), in term of control of recommended level of hematocrit < 45%, over a period of 12 months.
详细描述
It is an independent, investigator-generated, pragmatic trial including adult PV patients (aged 18-60) diagnosed according to World Health Organization 2008 criteria within the last 3 years before inclusion, without history of thrombosis and younger than 60 years ('low risk' patients).
Eligible patients are randomized to be treated with the best available therapy (recommended for this risk class, standard arm) based on phlebotomy including administration of low-dose (100 mg/daily) of acetylsalicylic acid (ASA, when there are not contraindications) OR Pegylated Proline-Interferon alpha-2b (AOP2014) every 2 weeks in addition to the recommended available regimen (experimental arm), for up to 12 months. The allocation of patients to study arms is 1:1 and stratification at randomization will be performed according to age category (< 50 years old or > 50 years old) and time from diagnosis (naϊve or non-naϊve). Naive patients are defined as new cases coming to observation, diagnosed for the first time just before study entry and never treated; non-naive patients are old cases (diagnosis not older than 3 years before study entry) undergoing therapy with phlebotomy and/or low doses of ASA.
Primary endpoint (PEp) is defined by the proportion (%) of patients who maintain the median value of hematocrit (HCT) below 45% during 12 months of treatment in each arm, without progression of disease and no need of any extra-protocol cytoreductive drug (responder patients).
Secondary endpoints include evaluation of hematological and molecular response, histological remission and safety profile of the protocol therapy.
Before randomization all patients undergo phlebotomies in order to reach an HCT below 45%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-60 years
- •Diagnosis of Polycythemia Vera according to World Health Organization 2016 criteria
- •Diagnosis of Polycythemia Vera including a recent bone marrow (BM) biopsy (performed within 3 years prior randomization in the study) and never treated with cytoreductive drugs
- •Ability and willingness to comply with all study requirements
- •Signed written informed consent.
排除标准
- •Any previous well documented cardiovascular PV-related events (see Appendix 1 for description)
- •Previous cytoreductive drugs
- •Known hypersensitivity or contraindications to the Investigational Medicinal Product (Pegylated Proline-Interferon alpha-2b) including:
- •evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension); thyroid dysfunction not adequately controlled; patients tested positively with Thyroglobulin antibody and / or TPOAb at screening; documented autoimmune disease at screening or in the medical history; history or presence of depression requiring treatment with antidepressant; any risk of suicide at screening or previous suicide attempts;
- •Previous exposure to a non-pegylated or pegylated interferon α
- •Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis
- •Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening
- •Significant liver (AST or alanine aminotransferase > 2.5 times ULN) or renal disease (creatinine > 2 mg/ml)
- •Presence of any life-threatening condition or of any disease (e.g. cancer) that is likely to significantly shorten life expectancy
- •History of active substance or alcohol abuse within the last year
- •Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol
- •Pregnant or lactating women and women*/men of childbearing potential who are not using or are not willing to use any effective means of contraception (i.e. sexual abstinence, hormonal contraceptive, intra-uterine device, barrier method such as diaphragms or condoms, surgical methods).
- •Pregnancy test will be performed in order to ascertain negativity of human chorionic gonadotropin (β-hCG) test and confirm that childbearing women are not pregnant.
研究组 & 干预措施
Phlebotomies + ASA
Conventional treatment based on phlebotomies and low dose (100 mg) of acetylsalicylic acid (ASA)
干预措施: Phlebotomies (Procedure)
Phlebotomies + ASA
Conventional treatment based on phlebotomies and low dose (100 mg) of acetylsalicylic acid (ASA)
干预措施: ASA (Drug)
Phlebotomies + ASA + AOP2014
Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).
干预措施: AOP2014 (Drug)
Phlebotomies + ASA + AOP2014
Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).
干预措施: Phlebotomies (Procedure)
Phlebotomies + ASA + AOP2014
Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).
干预措施: ASA (Drug)
结局指标
主要结局
Number of patients who maintains the median value of HCT< 45%, along 12 months, on number of patients randomized in each arm, per cent
时间窗: 12 months
For each patient the median value of HCT percentage will be calculated from all measurements detected and reported every month (from baseline to 12-month visit or study end). A patient will be defined as responder (achieving PEp) when he maintains the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months. A patient will be defined as non-responder (not achieving PEp) when 1. Does not maintain the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months, or 2. Is in need of any additional chemotherapeutic and/or cytoreductive treatment aimed to manage disease due to disease progression.
次要结局
- Median number of phlebotomies performed(12 months, 24 months)
- Number of patients achieving hematological response (as defined below in 'Description') on number of patients randomized in each arm, per cent,(12 months, 24 months)
- Proportion (rate per cent) of patients with not palpable spleen(12 months, 24 months)
- Janus kinase-2 allele burden reduction or complete molecular remission(12 months, 24 months)
- Bone marrow histological remission(24 months)
- Incidence and frequence of thrombotic and hemorrhagic events occurred(12 months, 24 months)
- Number of adverse events occurred(12 months, 24 months)