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MDSNCT04110925

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

A study testing Genetic Mutations, Inflammatory and lipid markers and Computed Tomography (CT) of the heart in people with MDS and Cardiovascular Diseases, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
MDS, Cardiovascular Diseases, Inflammation
What is being tested?
Genetic Mutations, Inflammatory and lipid markers and Computed Tomography (CT) of the heart
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
1 siteCanada
Study dates
Sep 2019to Sep 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Rena Buckstein, MD contact

416-480-5847

rena.buckstein@sunnybrook.ca

Canada1 site

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular Disease in Patients With Myelodysplasia

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.

Read the 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.

Being tested
Genetic Mutations, Inflammatory and lipid markers, Computed Tomography (CT) of the heart
Keywords
CT imaging, next generation sequencing, myelodysplastic syndrome
Medical subject headings
Cardiovascular Diseases, Inflammation, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Genetic MutationsGenetic

    DNA sequencing for mutations to be obtained by bloodwork within 6 months of diagnosis, or by accessing diagnostic bone marrow aspirate slides.

  • Inflammatory and lipid markersOther

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

  • Computed Tomography (CT) of the heartOther

    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.

Study groups in NCT04110925
Study groupRoleWhat they receive
MDS patientsOtherAll Canadian MDS patients on the MDS-database to be included.
Receives: Genetic: Genetic Mutations; Other: Inflammatory and lipid markers; Other: Computed Tomography (CT) of the heart

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides

    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.

    Measured: 2 years

  2. Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT

    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

    Measured: 2 years

  3. Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD

    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.

    Measured: 2 years

Secondary outcomes (2)

  1. Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring

    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

    Measured: 2 years

  2. Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD

    Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2019
  2. Study startSep 2019 (estimated)
  3. Primary completionSep 2021 (estimated)
  4. Study completionSep 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04110925
Sponsor's protocol ID
MDS CVD
Status last verified
Sep 2019
First submitted
23 Aug 2019
Last updated
1 Oct 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Stahl M, Zeidan AM. Management of lower-risk myelodysplastic syndromes without del5q: current approach and future trends. Expert Rev Hematol. 2017 Apr;10(4):345-364. doi: 10.1080/17474086.2017.1297704. Epub 2017 Mar 9.

    PubMed 28277851

  • Brunner AM, Blonquist TM, Hobbs GS, Amrein PC, Neuberg DS, Steensma DP, Abel GA, Fathi AT. Risk and timing of cardiovascular death among patients with myelodysplastic syndromes. Blood Adv. 2017 Oct 18;1(23):2032-2040. doi: 10.1182/bloodadvances.2017010165. eCollection 2017 Oct 24.

    PubMed 29296849

  • Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12.

    PubMed 24030381

  • Elbaek MV, Sorensen AL, Hasselbalch HC. Cardiovascular disease in chronic myelomonocytic leukemia: do monocytosis and chronic inflammation predispose to accelerated atherosclerosis? Ann Hematol. 2019 Jan;98(1):101-109. doi: 10.1007/s00277-018-3489-0. Epub 2018 Sep 4.

    PubMed 30182347

  • Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, McConkey M, Gupta N, Gabriel S, Ardissino D, Baber U, Mehran R, Fuster V, Danesh J, Frossard P, Saleheen D, Melander O, Sukhova GK, Neuberg D, Libby P, Kathiresan S, Ebert BL. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017 Jul 13;377(2):111-121. doi: 10.1056/NEJMoa1701719. Epub 2017 Jun 21.

    PubMed 28636844

  • Okwuosa TM, Greenland P, Ning H, Liu K, Bild DE, Burke GL, Eng J, Lloyd-Jones DM. Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) potential implications for coronary risk assessment. J Am Coll Cardiol. 2011 May 3;57(18):1838-45. doi: 10.1016/j.jacc.2010.11.053.

    PubMed 21527159

Questions about this trial

What is this clinical trial studying?

A study testing Genetic Mutations, Inflammatory and lipid markers and Computed Tomography (CT) of the heart in people with MDS and Cardiovascular Diseases, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Rena Buckstein, MD (416-480-5847, rena.buckstein@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04110925, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2019.

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