NCT03205267Unknown2 期
Multicenter, Open-label Single Arm Phase II Study Testing the Tolerability and the Efficacy of Bosutinib step-in Dosing in Chronic Phase CML Patients Intolerant or Refractory to Previous Imatinib, Nilotinib or Dasatinib Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 入组人数
- 127
- 试验地点
- 1
- 主要终点
- Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities)
研究概览
简要总结
Bosutinib is a 2nd generation tyrosine kinase inhibitor that has shown promising results from first up to fourth line treatment in patients with in chronic phase of chronic myelogenous leukaemia. Most patients discontinuing the treatment with Bosutinib do so because of side effects occuring early after starting the treatment. A step in dosing scheme could improve these early toxicities. The aim of this study therefore is to demonstrate that temporary lowering of the Bosutinib dose during early treatment may help to reduce or prevent side effects while preserving efficacy.
详细描述
Objectives:
The objective of the BODO trial is to assess the tolerability and efficacy of a step-in dosing concept of the dual SRC-ABL kinase inhibitor Bosutinib in CP-CML patients who either developed intolerance or treatment failure to previous Imatinib, Dasatinib or Nilotinib as 1st line therapy.
Primary endpoint:
• Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities) within the first 6 months of treatment
Secondary endpoints:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Male or female patients aged ≥18 years
- •ECOG performance status of 0 to 2
- •CML in 1st or late chronic phase
- •Intolerant or resistant to pretreatment with one of the approved 1st line TKIs (Imatinib, Nilotinib or Dasatinib). Imatinib therapy prior to 2nd generation TKI therapy for a maximum of 6 weeks is allowed.
- •Patients must have a serum creatinine of ≤ 2 x ULN, SGOT/SGPT ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (except known Gilbert's syndrome), and Lipase ≤ 1.5 x ULN
- •Female patients of childbearing potential must have a negative pregnancy test performed during screening period
- •Male and female patients of reproductive potential must currently use a highly effective contraceptive method and be willing to keep on using it throughout the study and for 6 months following discontinuation of study drug.
排除标准
- •Hypersensitivity against Bosutinib or other ingredients of the medicinal product
- •Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion
- •Patients with BCR-ABL negative CML
- •Patients having received Imatinib for more than 6 weeks prior to initiation of 2nd generation TKI (either Nilotinib or Dasatinib)
- •Patients with known T315I or V299L mutation
- •Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4
- •History of pancreatitis, inflammatory bowel disease requiring systemic or topical immunosuppressive therapy within the last 12 months
- •Impaired cardiac function, including any of the following:
- •History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG
- •ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG
- •Congenital long QT syndrome
- •QTc> 450 msec in the screening ECG
- •QT-prolonging concomitant medication
- •History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG
- •History of or presence of clinically significant resting bradycardia (< 50 beats per minute)
- •Myocardial infarction within 6 months prior to inclusion
- •Unstable angina diagnosed or treated during the past 12 months
- •Uncontrolled hypertension, history of labile hypertension
- •Known HIV and/or active viral hepatitis (hepatitis B or C). Hepatitis B screening will be performed at screening. Patients with history of hepatitis B with negative HBV DNA may be included when using antiviral prophylaxis
- •Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
- •Treatment with another investigational product during this study or during the last 30 days prior to study start, except treatment with Interferon alpha within the TIGER (CML V) protocol, which must be stopped at least 7 days prior to study entry
- •Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study
- •Patient must not have any active bacterial, viral or fungal infection at screening
- •Patient must not have severe cerebral dysfunction and/or legal incapacity
- •Conditions which interfere with the study treatment at the discretion of the investigator
- •Women who are pregnant or breast feeding
研究组 & 干预措施
Bosutinib
Experimental
Drug: Bosulif 100 mg or 500 mg tablets step in dosing scheme
干预措施: Bosulif (Drug)
结局指标
主要结局
Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities)
时间窗: within the first 6 months of treatment
calculation of the incidence rate of grade 2 to 4 GI toxicity with and without regard to causality
次要结局
- overall Tolerability (i.e. all grade, grade 2 to 4 and grade 3 and 4 toxicities)(at month 6, 12 and 24)
- Molecular response mesured by efficacy parametern(at month 3, 6, 12, 18 and 24)
- Overall Survival (OS)(at month 3, 6, 9, 12, 15, 18, 21 and 24)
- Patient-reported outcome measures (QoL)(at month 3 and 6)
- Progression-free survival (PFS)(at month 3, 6, 9, 12, 15, 18, 21 and 24)
- The rate of emerging mutations during Bosutinib treatment(at month 3, 6, 9, 12, 15, 18, 21 and 24)
研究者
Prof. Dr. Dominik Wolf
Principal Investigator Prof. Dr. med. D. Wolf
University of Bonn
研究点 (1)
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