Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial

• Published in: The American heart journal Vol. 201; pp. 54 - 62
• Main Authors: Bolli, Roberto, Hare, Joshua M., Henry, Timothy D., Lenneman, Carrie G., March, Keith L., Miller, Kathy, Pepine, Carl J., Perin, Emerson C., Traverse, Jay H., Willerson, James T., Yang, Phillip C., Gee, Adrian P., Lima, João A., Moyé, Lem, Vojvodic, Rachel W., Sayre, Shelly L., Bettencourt, Judy, Cohen, Michelle, Ebert, Ray F., Simari, Robert D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Anthracycline; Anthracyclines - adverse effects; Anthracyclines - therapeutic use; Biomarkers; Biopsy; Breast cancer; Cancer; Cancer Survivors - statistics & numerical data; Cancer therapies; Cardiac arrhythmia; Cardiomyopathy; Clinical trials; Consent; Double-Blind Method; Drug dosages; Feasibility Studies; Female; Fibrosis; Follow-Up Studies; Heart; Heart diseases; Heart failure; Heart Failure - chemically induced; Heart Failure - physiopathology; Heart Failure - surgery; Humans; Injection; Ischemia; Laboratories; Magnetic resonance imaging; Male; Medical imaging; Mesenchymal Stem Cell Transplantation - methods; Mesenchyme; Middle Aged; Myocardium; Neoplasms - drug therapy; NMR; Nuclear magnetic resonance; Participation; Population studies; Quality of Life; Randomization; Stem cells; Stromal cells; Therapy; Transplantation, Autologous; Treatment Outcome; Ventricle; Ventricular Function, Left - physiology; Womens health; Young Adult
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2018.02.009

SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome.