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Effects of IL-1 Beta Inhibition on Vascular Inflammation in TET2 Clonal Hematopoiesis

RecruitingPhase 2Ages 18 Years - anyAllMassachusetts General Hospital
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In plain words

What the trial is, and whether it could suit you

The primary goal of this clinical trial is to test the hypothesis that the drug canakinumab (anti-IL-1B monoclonal antibody) decreases vascular inflammation when used by people with a history of coronary artery disease, including those with and without TET2 mutations.

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
Inclusion Criteria: * 18 years or older * Coronary artery disease, defined as prior heart attack, coronary stent procedure \>180 days before baseline imaging, or advanced subclinical coronary atherosclerosis (coronary artery calcium score ≥300 Agatston units, CAD-RADS 3 or greater atherosclerosis on coronary CT angiography, or qualitatively severe coronary artery calcification identified on non-gated CT imaging) * Presence of either TET2 mutations or no myeloid driver mutations on prior sequencing * TET2-mutant myelodysplastic syndrome (MDS) or dysplastic-type chronic myelomonocytic leukemia (CMML) participants only must meet all of the following criteria: * Very low, low, or moderate-low risk for disease progression according to IPSS-M (score ≤0) * Peripheral blood blasts \<2% and bone marrow blasts \<5% * WBC \<13 ×10⁹/L * ANC ≥1.0 ×10⁹/L * Hemoglobin ≥10 g/dL * Platelet count ≥50 ×10⁹/L * No clinically significant transfusion requirement attributable to MDS/CMML, defined as receipt of \<2 units of RBCs and no platelet transfusions during the 8 weeks preceding screening (excluding transfusions for acute bleeding, surgery, or another transient intercurrent condition) * In the judgment of the treating oncologist, clinically stable disease for which disease-modifying therapy is not anticipated to be required within the subsequent 24 months Exclusion Criteria: * placement of a drug-eluting stent in a proximal coronary arterial segment \<180 days before baseline imaging * prior coronary artery bypass grafting * pregnancy or breastfeeding * history of blood malignancy or current solid-tumor malignancy * history of organ or stem cell transplantation * current treatment with prescription, systemic (oral, IV \[intravenous\], or IM \[intramuscular\]) steroids or anti-inflammatory/immune suppressant medical therapies (including colchicine but excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases, post-transplant care, asthma, or pain * use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \>7 days within the past 1 month * use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months * known allergy to dextran's and/or DTPA and/or radiometals and/or severe allergy to iodinated contrast media * estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2 * contraindications to nitroglycerin known narrow angle glaucoma, or known severe aortic stenosis * use of phosphodiesterase type 5 inhibitor AND refusal to abstain from use of these medications within the 5 days prior to scheduled CCTA scan * significant radiation exposure (40msV) received within the past 12 months * concurrent enrollment in another research study judged by the investigators to interfere with the current study * known active or recurrent hepatic disease (including cirrhosis or ALT/AST levels \>3 times the upper limit oof or total bilirubin \>2 times the upper limits of normal) * history or evidence of tuberculosis (TB) (active or latent) infection or risk factor for TB * active bacterial, fungal or viral infection at the time of enrollment or history of recurrent infections * suspected or proven immunocompromised state * live vaccinations within 3 months prior to randomization visit or live vaccinations planned during the trial
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What it tests

  • CANAKINUMAB (ILARIS®)
  • Saline (NaCl 0,9 %) (placebo)
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Where

1 site
Massachusetts General Hospital
Boston, United States
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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