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Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular (CVD) Disease in Patients With Myelodysplasia

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ClinicalTrials.gov Identifier: NCT04110925
Recruitment Status : Not yet recruiting
First Posted : October 1, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborators:
Ontario Molecular Pathology Research Network
Queen's University
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Brief Summary:
This study evaluates the relationship between myelodysplastic syndromes (MDS) and cardiovascular disease. MDS patients will be evaluated for the presence of mutations and whether they are associated with an increased risk of heart disease (CVD) and inflammation compared to healthy adults. Patients without symptoms of CVD will receive CT scans to assess for hidden disease and if that is related to their mutations.

Condition or disease Intervention/treatment Phase
MDS Cardiovascular Diseases Inflammation Genetic: Genetic Mutations Other: Inflammatory and lipid markers Other: Computed Tomography (CT) of the heart Not Applicable

Detailed Description:
Myelodysplastic syndromes (MDS) are a type of blood cancer that can cause infection or bleeding because they prevent the formation of blood components and may lead to leukemia and death. MDS can arise from changes (or mutations) to a patient's DNA. MDS patients have increased risk of heart disease compared to healthy adults. The investigators will look for links between mutations in MDS patients and increased risk of heart disease. They will also use "CT imaging" to see if MDS patients have asymptomatic artery disease but may lead to heart disease in the future and if that is related to their mutations. The researcher will try to link mutations in MDS patients to markers of inflammation and to the amount of artery disease on CT imaging to look for patterns. The goal is to find certain mutations that are associated with inflammation and heart disease. This may ultimately allow hematologists to test MDS patients with these mutations for heart disease and/or treat them early so they have a better and longer life.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular Disease in Patients With Myelodysplasia
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
MDS patients
All Canadian MDS patients on the MDS-database to be included.
Genetic: Genetic Mutations
DNA sequencing for mutations to be obtained by bloodwork within 6 months of diagnosis, or by accessing diagnostic bone marrow aspirate slides.

Other: Inflammatory and lipid markers
Bloodwork to be done for lipid profile, c-reactive protein (CRP), and multiplex chemokine/cytokine analysis.

Other: Computed Tomography (CT) of the heart
Sunnybrook Patients with no history of cardiovascular disease [ex: past/present coronary artery disease (CAD), peripheral vascular disease (PVD), angina, myocardial infarction (MI), stroke, transient ischemic attack (TIA), or stents], not pregnant, and able to undergo CT will receive a CT of the heart to look for and quantify any occult coronary artery disease.




Primary Outcome Measures :
  1. Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides [ Time Frame: 2 years ]
    Screen for Presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes.

  2. Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT [ Time Frame: 2 years ]

    Patients at Sunnybrook hospital with no pre-existing history of CAD who receive CT of the heart and found to harbour occult CAD by means of coronary calcium scoring:

    1. zero calcium (No CAD)
    2. 1-400: mild-moderate calcification
    3. >400: severe calcification

  3. Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD [ Time Frame: 2 years ]
    Comparing the presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes between patients with pre-existing/occult CAD and those without.


Secondary Outcome Measures :
  1. Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring [ Time Frame: 2 years ]

    The investigators will track any interventions in patients without a prior history of CAD who who are discovered to have occult CAD by coronary CT. This includes number of patients who were recommended:

    1. medical management of CAD
    2. Referral to clinical cardiologist
    3. Invasive angiography

  2. Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD [ Time Frame: 2 years ]
    Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of: myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), Chronic myelomonocytic leukemia leukemia (CMML), or low-blast acute myeloid leukemia (AML, blasts 20-29%) less than 24 months ago
  • Alive and registered in the MDS-Canada (MDS-CAN) database
  • Known comorbidity history and known history of cardiovascular disease
  • Able to provide peripheral blood sample for cytokine analysis
  • Able top provide samples for next generation sequencing (NGS) - if diagnosis 0-6 months ago: peripheral blood; if diagnosis 6-24 months ago: diagnostic bone marrow aspirate slides or peripheral blood

Exclusion Criteria:

  • MDS/MPN patients other than CMML due to higher prevalence of Janus Kinase 2 (JAK2) mutation (a known risk factor for CVD)
  • Disease progression without available diagnostic bone marrow slides for NGS

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04110925


Contacts
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Contact: Rena Buckstein, MD 416-480-5847 rena.buckstein@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Ontario Molecular Pathology Research Network
Queen's University
Investigators
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Principal Investigator: Rashmi S Goswani, MD Sunnybrook Health Sciences Centre

Publications:

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04110925     History of Changes
Other Study ID Numbers: MDS CVD
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sunnybrook Health Sciences Centre:
CT imaging
next generation sequencing
myelodysplastic syndrome
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Inflammation
Cardiovascular Diseases
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms