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NCT Number: NCT01805843

Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia

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).

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Key information

Conditions

Chronic Myeloid Leukemia Bone Marrow Diseases Cardiovascular Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Hypertension Hypertension, Pulmonary Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Lung Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Vascular Diseases

Age range

18 year–95 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Medical University of Graz, Division of Pulmonology

Graz, 8036, Austria

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Echo, exercise echo, and if indicated, right heart catheter

Other

routine echocardiography and special measurements of the right heart are performed at rest and during exercise

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Medical University of Graz

Other

Registry information

Official study title

Pulmonary Vascular Changes in Patients With Chronic Myeloid Leukemia With Second-line Therapy Dasatinib vs. Nilotinib

Important dates

Study start
2012
Primary completion
2015
Study completion
2015
First posted
Mar 6, 2013
Registry last updated
Sep 9, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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