Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia

NCT01805843 | Completed DMC

• 1 other identifier: 24-311 ex 10/11
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Chronic Myeloid Leukemia

Keywords

Pulmonary hypertension; chronic myeloid leukemia; dasatinib; nilotinib

Outcome Measures

Primary Outcomes (1)

• systolic pulmonary arterial pressure during exercise (50W)

  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.

  at baseline

Secondary Outcomes (3)

• peak VO2

  At baseline

• change of pulmonary arterial pressure

  between baseline and after 6 months

• Pulmonary vascular resistance

  at baseline

Study Arms (1)

chronic meloid leukemia

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

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

Interventions

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

chronic meloid leukemia

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

patients with chronic myeloid leukemia under second-line therapy with dasatinib or nilotinib,

You may qualify if:

• patients with chronic myeloid leukemia under second-line therapy with dasatinib or nilotinib
• written informed consent

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz, Division of Pulmonology

Graz, 8036, Austria

Location

Biospecimen

Retention: SAMPLES WITH DNA

Samples with DNA will be retained for later examinations at the Biobank, in case that the patient agrees (extra patient information). The blood samples are taken only during routine tests.

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hypertension, Pulmonary

Interventions

Caves

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health

Study Officials

• Horst Olschewski, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: March 6, 2013
• Study Start: July 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 9, 2015

Record last verified: 2015-09

Locations

AU (1)