NCT01805843

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 16 (actual)
• Sponsor: Medical University of Graz · Academic / Other
• Sex: All
• Age: 18 Years – 95 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

Doppler echocardiography at rest will be performed in each patient. Patients without exercise capacity limitation an exercise test (Doppler echocardiography with spiroergometry) will be performed. Patients who show elevated SPAP at rest or during exercise (in this study SPAP ≥ 40 mmHg) or with reduced exercise capacity (peak VO2 \< 75%) a right heart catheterization (RHC) will be suggested. Additionally for the evaluation of exercise capacity a 6 MWD will be performed. This work- up of patients allows clinical and hemodynamic evaluation.

Conditions

• Chronic Myeloid Leukemia

Interventions

Type	Name	Description
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

Timeline

• Start date: 2012-07-01
• Primary completion: 2015-06-01
• Completion: 2015-06-01
• First posted: 2013-03-06
• Last updated: 2015-09-09

Locations

1 site across 1 country: Austria