Elsevier

American Heart Journal

Volume 201, July 2018, Pages 54-62
American Heart Journal

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

https://doi.org/10.1016/j.ahj.2018.02.009Get rights and content

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.

Section snippets

Study design

SENECA is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allo-MSCs by the transendocardial route in subjects with LV dysfunction secondary to AIC (clinicaltrials.gov Identifier: NCT02509156). This first-in-human trial, funded by the National Heart, Lung, and Blood Institute (NHLBI) and sponsored by the Cardiovascular Cell Therapy Research Network (CCTRN), will also collect preliminary evidence for the therapeutic efficacy of

Discussion

SENECA is the first clinical trial to utilize direct cardiac injection of cells for the treatment of AIC – an incurable and often fatal syndrome that disproportionately affects women and young adults, and for which no effective treatment currently exists.5., 7. This first-in-human study has the potential to herald a novel approach to the management of AIC.

Despite attempts at improving therapy, the prognosis of AIC is grim, worse than that of ischemic or idiopathic cardiomyopathy.5., 7.

Sources of Funding

This work is supported by National Institutes of Health, Bethesda, MD: 5 UM1 HL087318.

Disclosures

All investigators received funding from the NIH National Heart, Lung, and Blood Institute (NHLBI) for conduct of the Cardiovascular Cell Therapy Research Network (CCTRN). Additional disclosures: Hare has a relationship with Vestion Inc that includes equity, board membership, and consulting.

Acknowledgments

We thank the NHLBI-sponsored Protocol Review Committee and Gene and Cell Therapy DSMB for helpful guidance. Dr. Ebert is a staff member of the NHLBI, the source of funding for the SENECA Trial. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, National Institutes of Health, or the United States Department of Health and Human Services.

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