The Effect of Active Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - A Prospective Observational Multicenter Study (TAKE-IT)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 7
- 主要终点
- Clinically relevant change in MEMS-measured adherence
研究概览
简要总结
Adherence to tyrosine kinase inhibitors is associated with improved outcomes in chronic myeloid leukemia patients. Hence, improved adherence might improve CML patients' prognosis.
Decreased adherence is a common problem in such patients, with non-adherence in up to 30% of patients in several studies. Recently, an emphasis has been placed on improving patient's adherence to tyrosine kinase inhibitors in these patients. However, there is no prospective high-quality evidence showing that adherence can be improved in these patients.
Therefore, the investigators hypothesize that adherence-encouraging interventions improve adherence to tyrosine kinase inhibitors in chronic myeloid leukemia patients.
详细描述
The cytogenetic hallmark of chronic myeloid leukemia (CML) is the reciprocal translocation between chromosomes 9 and 22 creating the Philadelphia (Ph(1)) chromosome. The BCRABL1 fusion gene is the result of this translocation and encodes for a constitutively active tyrosine kinase responsible for the development of CML. Tyrosine kinase inhibitors (TKIs) targeting the protein product of this aberrant gene, the BCRABL-1 protein, have revolutionized the therapeutic approach to chronic myeloid leukemia (CML). Treatment with the first FDA approved TKI, imatinib mesylate (Gleevec, Novartis), in chronic phase CML results in a projected 8 year overall survival of 85%. Recently, two second generation TKIs, Dasatinib and Nilotinib, have been approved for use in newly diagnosed chronic phase CML, as a result of studies showing improved molecular and cytogenetic outcomes. Importantly, in each of the above studies there was a substantial number of dropouts due to drug intolerance and resistance, among other reasons. In a prospective observational study of 169 CML patients, only 14% of patients were fully adherent with prescribed imatinib. Moreover, one third of patients were considered to be non-adherent, which is similar to the proportion of dropouts in the landmark studies on TKIs in CML. Thus, it is clear that there is a subgroup of patients who do not properly adhere to treatment. This is especially significant because the contemporary approach to CML in complete cytogenetic remission (CCyR) and major molecular remission (MMR) necessitates long-term, chronic treatment with TKIs.
Therefore, although hematologists have the luxury of an armamentarium of highly effective drugs, one of the most challenging aspects of treating CML is the management of non-compliance to TKI treatment. TKI-induced adverse effects are only one of a wide spectrum of reasons for non-adherence to TKI treatment.
Recently several studies have demonstrated the prognostic importance of adhering to imatinib treatment. In a pivotal study of 87 chronic phase CML (CP-CML) patients in CCyR, an adherence rate of > 90% strongly correlated with the 6 year probability of achieving MMR (94.5% vs. 28.4% when adherence rates were ≤ 90%). Non-adherence to imatinib treatment also adversely affects event free survival and is associated with loss of CCyR in patients on long term treatment. These data support the intuitive concept that CML can be effectively treated with the drugs currently available, as long as patients adhere to treatment. Moreover, non-adherence to imatinib treatment has been associated with increased economic burden and healthcare costs. Consequently, TKI adherence is an attractive potential target for intervention.
Non-adherence to medication is an intricate problem that is influenced by the physician, the healthcare system, and economic and social factors. Other medical disciplines have assessed various modes of improving adherence to therapeutic regimens, with varying success. A recent study assessing adherence-related behavior among CML patients, demonstrated that among a multitude of reasons for non-adherence, patient forgetfulness and drug side effects were the most common causes of unintentional and intentional non-adherence, respectively. Several methods of improving adherence among patients with CML were retrospectively assessed by Moon et al. Subjects in the intervention arm were more likely to receive prescriptions for imatinib than those receiving standard care (98.2 ± 0.03% vs. 79.3 ± 0.16%). Although there was no difference in adherence to prescribed treatment between the two groups, the overall compliance, a composite endpoint of the above two outcomes, was markedly improved in the intervention group ((93.0 ± 2.3% vs. 76.2 ± 7.4%, P = 0.001). Recently, Gater et al conceived a conceptual model aimed at improving adherence in CML patients treated with 1st and 2nd generation TKIs, based on a systematic review of the literature. However, there are currently no prospective data evaluating whether adherence in CML can be influenced by active intervention.
Study Hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
盲法说明
The adherence assessed per study protocol was masked to participants and care providers during the preintervention and post intervention phases. At the time of intervention participants were notified once of their adherence as part of the feedback-based intervention
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
- •Patients with chronic phase chronic myeloid leukemia (CP-CML), aged 18 years or older
- •CP-CML defined as: Medical history of cytogenetically confirmed CP-CML defined as the presence of the Philadelphia chromosome on bone marrow aspirates (a minimum of 20 metaphases is required; FISH cannot be used). If Philadelphia chromosome was negative or if cytogenetic results were not available, BCR-ABL-positive CML patients can be included.
- •At least 3 months of TKI treatment (imatinib, dasatinib or nilotinib) before study initiation.
排除标准
- •Current or prior accelerated/blast phase or stem cell transplant
- •Participation in another interventional study
- •Pregnancy
结局指标
主要结局
Clinically relevant change in MEMS-measured adherence
时间窗: From 3 months before intervention, until 3 months after starting the intervention
Improvement in a patient's adherence from less than 90% during the initial 3 month run-in period, to 90% or more during the first 3 months of intervention. Definitions: 1. Adherence above 90% was defined as clinically relevant. 2. Adherence rate = actual calculated dose/prescribed dose. 3. Adherence will be calculated from "medical events monitoring system" (MEMS) data which will be collected continuously throughout the first 7.5 months of the study period. MEMS is an electronic monitoring system designed to compile the dosing histories of ambulatory patients prescribed oral medications
General improvement in MEMS-measured adherence
时间窗: 3 months prior to the intervention, until 3 months after starting the intervention
An absolute improvement of 10% in a patient's adherence, between their adherence during the initial 3 month run-in period and their adherence during the first 3 months of intervention. See Definitions of adherence rate and measurement of adherence in the first primary outcome description.
次要结局
- Mean-difference in MEMS-measured adherence(3 months prior to intervention until 3 months after starting the intervention)
- Mean change in The Basel Assessment of Adherence to Tyrosine Kinase Inhibitors Scale (BAATIS)(1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention)
- Effect of intervention on tyrosine kinase inhibtor related adverse events(3 months prior to intervention until 6 months after starting the intervention)
- Adverse effects of tyrosine kinase inhibitors as a measure of MEMS-measured adherence(3 months prior to intervention until 3 months after starting the intervention)
- Percentage of patients improving in patient self-reported non-adherence(3 months prior to intervention until 6 months after starting the intervention)
- Mean change in the physician visual analogue scale (VAS) of adherence(1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention)
- Mean change in the patient visual analogue scale (VAS) of adherence(1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention)
研究者
pia raanani
Prof. Pia Raanani
Rabin Medical Center