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

Am Heart J. 2018 Jul;201:54-62. doi: 10.1016/j.ahj.2018.02.009. Epub 2018 Apr 4.

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.

Trial registration: ClinicalTrials.gov NCT02509156.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / adverse effects*
  • Anthracyclines / therapeutic use
  • Cancer Survivors / statistics & numerical data*
  • Double-Blind Method
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Heart Failure / chemically induced
  • Heart Failure / physiopathology
  • Heart Failure / surgery*
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Middle Aged
  • Neoplasms / drug therapy*
  • Quality of Life*
  • Transplantation, Autologous
  • Treatment Outcome
  • Ventricular Function, Left / physiology*
  • Young Adult

Substances

  • Anthracyclines

Associated data

  • ClinicalTrials.gov/NCT02509156