NCT03831776已完成2 期
A Study of Efficacy and Safety of Long-acting Low Dose Ropeginterferon in Patients With Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis: a Randomized Prospective Trial
St. Olavs Hospital18 个研究点 分布在 4 个国家目标入组 212 人开始时间: 2019年3月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 212
- 试验地点
- 18
- 主要终点
- Rate of molecular response 4 (MR4)
研究概览
简要总结
To study the efficacy and safety of combination of Ro-Peg-interferon-α2b (RoPegIFN) with Bosutinib (BOS) in comparison to BOS monotherapy, as frontline therapy for newly diagnosed chronic myeloid leukemia patients, and to estimate efficacy of the addition of RoPegIFN to BOS in terms of deep molecular response with the aim of increasing the proportion of patients who may achieve treatment free remission. (NCMLSG study #NordCML012)
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent form (ICF) before any procedure related to the study
- •Newly diagnosed (≤ 3 months) BCR-ABL positive chronic myeloid leukemia (CML) in chronic phase
- •Major BCR-ABL transcripts (p210 b2a2(e13a2) and/or b3a2 (e14a2)
- •Not previously treated for CML except with hydroxyurea or anagrelide
- •ECOG Performance Status (ECOG PS) ≤ 2
- •Adequate organ function: Total bilirubin < 1,5 times the institutional Upper Limit of Normal (ULN); Hepatic enzymes ASAT and ALAT < 2 times the institutional ULN; Serum Creatinine < 1.5 time the institutional ULN; Lipase < 1.5 time the institutional ULN
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study.
- •WOCBP must have a negative serum or urine pregnancy test at screening.
- •Free subject, without guardianship nor subordination
- •Health insurance coverage
排除标准
- •Patients with BCR-ABL transcript other than M-BCR-ABL
- •Patients previously treated with tyrosine kinase inhibitors (TKIs).
- •Inability to freely provide consent through judiciary or administrative condition.
- •Ongoing participation to another clinical investigational study.
- •Medical history and concurrent diseases: a) Hypersensitivity to any of the excipients of BOS or RoPegIFN, b) Prior treatment with Interferon-α, contraindication to interferon-α, c) Autoimmune disorder, concomitant immunosuppressive treatment or corticosteroids, d) Pre-existing thyroid disease unless controlled with conventional treatment, auto-immune thyroiditis, e) Chronic liver disease, f) Prior or ongoing severe psychiatric disease, g) HIV positivity, chronic hepatitis B or C, h) Uncontrolled or severe cardiac (NYHA Class III or IV) or pulmonary disease, echocardiography with LVF < 45% or LLN, peak velocity of tricuspid regurgitant flow > 2,8 m/s, pulmonary arterial hypertension (PAH), QTc>450 ms (by Barrets correction)
- •Other malignant disease during the last 5 years prior to the inclusion except non-melanoma skin carcinoma or carcinoma in situ of the cervix,
- •History of significant bleeding disorder unrelated to CML or diagnosed congenital bleeding disorder,
- •Subjects with an uncontrolled undercurrent illness or any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.
- •Prohibited treatments and/or therapies: strong inhibitors/inducers of the CYP 3A4,
- •History / any condition for poor compliance to medical treatment.
- •Women who are pregnant or breastfeeding are not eligible for this study
研究组 & 干预措施
Bosutinib-Ropeginterferon combination
Experimental
干预措施: Bosutinib (Drug)
Bosutinib-Ropeginterferon combination
Experimental
干预措施: Ropeginterferon (Drug)
Bosutinib monotherapy
Active Comparator
干预措施: Bosutinib (Drug)
结局指标
主要结局
Rate of molecular response 4 (MR4)
时间窗: 12 months
Molecular response 4 (MR4) is defined by either a positive BCR-ABL/ABL ratio ≤ 0.01% on the international scale (IS) or by undetectable BCR-ABL with the analysis of at least 10000 copies of ABL or 24000 copies of GUS (according to the ELN recommendations by N. Cross et al., Leukemia 2015)
次要结局
- Dose intensity of RoPegIFN and Bosutinib(2 years)
- Rate of molecular response MR2, MR3, MR4, MR4.5 from 1 month up to 24 months and every 6 months thereafter(2 years)
- Cumulative incidence of molecular response MR3, MR4, MR4.5(2 years)
- Rate of complete cytogenetic response (CCyR) up to 12 months(12 months)
- Rate of undetectable molecular response for patients who achieved molecular response MR4 and MR4.5(2 years)
- Time to and duration of CCyR, MR3, MR4, MR4.5(2 years)
- proportion of patients eligible for randomization after 3 months of Bosutinib(3 months)
- rate and characteristics of severe adverse events (SAE)(2 years)
- Cumulative incidence of discontinuation of the therapies, incl. reasons for discontinuation(2 years)
- Quality of life assessment by QLQC30 questionnaire up to 6 years at key time point (Day 1, month 3, month 6, month 12, month 24, month 48, month 54, month 72)(6 years)
- Quality of life assessment by CML24 questionnaire up to 6 years at key time point (Day 1, month 3, month 6, month 12, month 24, month 48, month 54, month 72)(6 years)
- The proportion of patients achieving a durable deep molecular response and being eligible for treatment discontinuation at month 48(4 years)
研究者
研究点 (18)
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