Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia
Pulmonary Vascular Changes in Patients With Chronic Myeloid Leukemia With Second-line Therapy Dasatinib vs. Nilotinib
Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder characterized by a translocation between chromosome 9 and 22, leading to a pathogenic tyrosine kinase signal transduction protein. CML can be treated with tyrosine kinase inhibitors (TKIs), which inhibit BCR/ABL kinase, such as imatinib. In about 20% of CML patients who are treated by imatinib, a complete cytogenetic response cannot be achieved. The other two novel TKIs (dasatinib and nilotinib), achieve higher rates of complete cytogenetic response and they are proposed as second-line therapy for imatinib-resistant patients or for those who do not tolerate imatinib. Dasatinib inhibits BCR/ABL kinase in about >300 times in vitro in more than imatinib and also inhibits several other kinases, including the Src family. Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. Imatinib and nilotinib do not inhibit the Src.
Incident cases of precapillary PH have been reported in patients who have CML treated with the dasatinib. Improvements were usually observed after withdrawal of dasatinib.
This study is designed to identify incident cases of dasatinib-associated PH and describe pulmonary vascular changes induced by dasatinib. As comparison population will be patients who receive another second-line TKI (nilotinib).
調査の概要
詳細な説明
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Graz、オーストリア、8036
- Medical University of Graz, Division of Pulmonology
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- patients with chronic myeloid leukemia under second-line therapy with dasatinib or nilotinib
- written informed consent
Exclusion Criteria:
- Manifest pulmonary hypertension
- significant pulmonary disease
- Left-sided heart failure or diastolic compliance dysfunction +
- Hemodynamic relevant valvular disease
- Systemic arterial hypertension (at rest systolic >150 mmHg, diastolic > 90 mmHg, during exercise > 220 mmHg)
- Severe anemia
- Uncontrolled supraventricular and ventricular arrhythmias
- Myocardial infarction (within the last 12 months)
- Pulmonary embolism (within the last 12 months)
- Recent therapy changes (within the last 12 months)
- Recent major surgeries (within the last 12 months)
- For exercise tests: musculoskeletal diseases which may unable the exercise tests.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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chronic meloid leukemia
echo, exercise echo, and if indicated, right heart catheter
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routine echocardiography and special measurements of the right heart are performed at rest and during exercise
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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systolic pulmonary arterial pressure during exercise (50W)
時間枠：at baseline
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In patients who undergo stressechocardiography: systolic pulmonary arterial pressure (SPAP) at 50W will be measured and the comparison between patients under dasatinib and nilotinib therapy will be performed.
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at baseline
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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peak VO2
時間枠：At baseline
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Mean PAP at rest, mPAP at 50W, peak VO2, 6 minute walk distance (6MWD), N terminal pro brain natriuretic peptide (NT-proBNP) at "dasatinib" vs."nilotinib" patients. Changes of SPAP at 50 W, pulmonary vascular resistance (PVR) at rest, changes of mPAP at rest and at 50W, peak VO2, 6 MWD, NT-pro BNP- in patients with dasatinib and nilotinib between the baseline and 6 months after. |
At baseline
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change of pulmonary arterial pressure
時間枠：between baseline and after 6 months
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Changes of SPAP at 50 W, pulmonary vascular resistance (PVR) at rest, changes of mPAP at rest and at 50W, peak VO2, 6 MWD, NT-pro BNP- in patients with dasatinib and nilotinib between the baseline and 6 months after.
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between baseline and after 6 months
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Pulmonary vascular resistance
時間枠：at baseline
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In patients who undergo a RHC: pulmonary vascular resistance (PVR) at rest will be measured and the comparison of patients with dasatinib and nilotinib therapy will be performed.
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at baseline
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協力者と研究者
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。