Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT01805843|
Recruitment Status : Completed
First Posted : March 6, 2013
Last Update Posted : September 9, 2015
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).
|Condition or disease||Intervention/treatment|
|Chronic Myeloid Leukemia||Other: Echo, exercise echo, and if indicated, right heart catheter|
|Study Type :||Observational|
|Actual Enrollment :||16 participants|
|Official Title:||Pulmonary Vascular Changes in Patients With Chronic Myeloid Leukemia With Second-line Therapy Dasatinib vs. Nilotinib|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||June 2015|
chronic meloid leukemia
echo, exercise echo, and if indicated, right heart catheter
Other: Echo, exercise echo, and if indicated, right heart catheter
routine echocardiography and special measurements of the right heart are performed at rest and during exercise
- systolic pulmonary arterial pressure during exercise (50W) [ Time Frame: at baseline ]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.
- peak VO2 [ Time Frame: At baseline ]
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.
- change of pulmonary arterial pressure [ Time Frame: between baseline and after 6 months ]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.
- Pulmonary vascular resistance [ Time Frame: at baseline ]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.
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01805843
|Medical University of Graz, Division of Pulmonology|
|Graz, Austria, 8036|
|Principal Investigator:||Horst Olschewski, MD||Medical University of Graz|