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

Cardiovascular Cell Therapy Research Network (CCTRN)

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: 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). Background: 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. Methods: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalAmerican Heart Journal
Volume201
DOIs
StatePublished - Jul 1 2018
Externally publishedYes

Fingerprint

Cardiomyopathies
Anthracyclines
Survivors
Mesenchymal Stromal Cells
Stem Cells
Injections
Heart Failure
Neoplasms
Exercise Tolerance
Cell- and Tissue-Based Therapy
Left Ventricular Function
Stroke Volume
Cicatrix
Myocardium
Fibrosis
Therapeutics
Biomarkers
Placebos
Quality of Life
Clinical Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. / Cardiovascular Cell Therapy Research Network (CCTRN).

In: American Heart Journal, Vol. 201, 01.07.2018, p. 54-62.

Research output: Contribution to journalArticle

Cardiovascular Cell Therapy Research Network (CCTRN). / Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. In: American Heart Journal. 2018 ; Vol. 201. pp. 54-62.
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abstract = "Objectives: 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). Background: 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. Methods: 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). Conclusions: 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.",
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AU - Cardiovascular Cell Therapy Research Network (CCTRN)

AU - Bolli, Roberto

AU - Hare, Joshua

AU - Henry, Timothy D.

AU - Lenneman, Carrie G.

AU - March, Keith L.

AU - Miller, Kathy

AU - Pepine, Carl J.

AU - Perin, Emerson C.

AU - Traverse, Jay H.

AU - Willerson, James T.

AU - Yang, Phillip C.

AU - Gee, Adrian P.

AU - Lima, João A.

AU - Moyé, Lem

AU - Vojvodic, Rachel W.

AU - Sayre, Shelly L.

AU - Bettencourt, Judy

AU - Cohen, Michelle

AU - Ebert, Ray F.

AU - Simari, Robert D.

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N2 - Objectives: 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). Background: 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. Methods: 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). Conclusions: 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.

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