Real Life Assessment of the Association and Its Determinants Between Side Effects and Plasmatic Concentrations of Two Protein Kinase Inhibitors: Ibrutinib (IMBRUVICA®) and Idelalisib (ZYDELIG®) in Hematological Malignancies Treatment.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib
研究概览
简要总结
Recently, European Medicines Agency approved ibrutinib and idelalisib to treat Chronic Lymphocytic Leukemia (CLL) and two lymphomas: Follicular Lymphoma (FL) for ibrutinib and Mantle cell lymphoma (MCL) for idelalisib.
Clinical trials for ibrutinib and idelalisib were performed with a small number of patients (300-350) and showed several side effects profiles. Since, pharmacokinetic properties of these 2 drugs highlight a interindividual variability of pharmacokinetic. The aim of this study is to determine the association between clinically significant side effects occurrence during the first year of treatment and plasma mean concentration of the steady state of ibrutinib or idelalisib at 1 month.
详细描述
Recently, European medicines agency approved ibrutinib and idelalisib in the treatment of Chronic Lymphocytic Leukemia (CLL) and two lymphomas: Follicular Lymphoma (FL) for ibrutinib and Mantle cell lymphoma (MCL) for idelalisib. Nevertheless, clinical trials for these two drugs were performed for only 300-350 patients and showed several side effects profiles, the most frequent were diarrhea, infection, cutaneous rash... For some patients, treatment had to be reduced or stopped temporary or definitely.
Pharmacokinetic properties of these two drugs highlight an interindividual pharmacokinetic considerable variability. The aim of this clinical research study is to determine the association between clinically significant side effects occurrence during the first year of treatment (serious adverse reaction and/or grade CTCAE ≥ 3 and/or leading a dosage concession) and plasma mean concentration of the steady state of ibrutinib or idelalisib performed at 1 month.
To determine plasma mean concentration of the steady state of ibrutinib or idelalisib, blood tests will be performed every scheduled monitoring at visit 1 month during a pharmacokinetic exploration and during scheduled medical consultation (2, 3, 6 and 12 months) and every unscheduled visit in case of side effect occurrence.
Every scheduled monitoring visit, blood tests will be performed to determine plasma concentration in drug. Complementary blood or salivary samples will be collected before the treatment, 24 months later and in case of relapse to determine genetic characteristics. In parallel, a logbook will be completed by the patient to collect side effects. Finally, an oncology certified nurse call patients every 2 weeks. In case of side effect occurrence a visit will be organized in the next 3 days and a blood test will be performed.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Evidence of Chronic Lymphocytic Leukaemia (CLL), or Follicular Lymphoma (FL) or Mantle cell lymphoma (MCL) and a first prescription of idelalisib or ibrutinib
- •Patients must give written informed consent
- •Patients with Health Insurance System
排除标准
- •Patient who several blood tests can't be performed (poor venous access)
- •Patients under legal guardian
- •Pregnant or breastfeeding women
结局指标
主要结局
Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib
时间窗: 1 months after treatment initiation
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib
时间窗: 1 months after treatment initiation
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
次要结局
- Plasma balance mean concentration in idelalisib with collection of blood samples(1 month after inclusion)
- Effect of patients characteristics on plasma balance mean concentration in idelalisib(1 months after inclusion)
- Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib(Through the completion of study (24 months))
- Clinically significant side effect occurrence (Serious adverse reaction and/or grade CTCAE ≥ 3 and/or leading a dosage concession) as assessed by AMA (Assistance des Malades Ambulatoires) system(through the end of study (24 months))
- Plasma balance mean concentration in ibrutinib with collection of blood samples(1 month after inclusion)
- The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey(24 months after inclusion)
- Effect of patients characteristics on plasma balance mean concentration in ibrutinib(1 months after inclusion)
- Response to treatment assessed by positron emission tomography-Scan(24 months after inclusion)
- Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib(1 months after inclusion)
- Treatment failure rate in relation with mean concentration of idelalisib(1 month after inclusion)
- Forgetting to take medication reported by the patient as recorded in a logbook given to the patient(6 months after inclusion)
- Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib(Through the completion of study (24 months))
- Treatment failure rate in relation with mean concentration of ibrutinib(1 month after inclusion)
- Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state(Through the completion of study (24 months))
- Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib(1 month after inclusion)
- Perception of side effect reported by patient as noted in a logbook by the patient(6 months after inclusion)
- Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state(Through the completion of study (24 months))
- Association of adverse event and quality of life with Short Form (36) Health Survey(Through the completion of study (24 months))
- Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib(1 month after inclusion)