Cardiovascular Cell Therapy Research Network (CCTRN) A Phase I, First-in-Human, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Allogeneic Mesenchymal Stem Cells in Cancer Survivors With Anthracycline-Induced Cardiomyopathy (SENECA)
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August 2016-November 2019
Dataset(s) Last Updated
November 14, 2022
Clinical Trial URLs
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Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
To examine the safety and feasibility of delivering allogeneic human mesenchymal stem cells (allo-MSCs) by transendocardial injection to cancer survivors with left ventricular (LV) dysfunction secondary to anthracycline-induced cardiomyopathy (AIC).
Anthracycline-based chemotherapies are effective in treating various forms of cancer. The risk of anthracycline-induced cardiomyopathy (AIC) has been primarily related to the lifetime cumulative dose and every exposure to an anthracycline carried some risk of inducing cardiac dysfunction. Historically, AIC has been irreversible with poor prognosis and most prevalent in young persons and females. Previous studies have determined that patients with AIC have approximately 3.5-higher relative risk of death within 5 years compared to ischemic or nonischemic cardiomyopathy. There is currently no effective treatment for AIC.
There are several shared pathological features between AIC and heart failure (HF). A promising approach to treatment of HF is the administration of bone marrow–derived mesenchymal stromal cells (MSCs). The SENECA trial was the first-in-human study of allo-MSCs in patients with LV dysfunction secondary to AIC.
Male and female cancer survivors aged 18 to 79 years, with a diagnosis of AIC, were recruited for the SENECA trial. Inclusion criteria included: initial diagnosis of AIC at least 6 months prior to consent; left ventricular ejection fraction (LVEF) ≤45%; receiving stable, optimally tolerated therapy with beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and/or aldosterone antagonists unless contraindicated; no evidence of ischemic heart disease; cancer-free for at least 2 years with a low likelihood of recurrence (a 5-year risk of recurrence estimated at ≤30%).
Participants were excluded for any condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
The primary objectives of SENECA were the safety of allo-MSC administration, the feasibility of delivering the cells to the subjects, and collecting outcome measures. The secondary objectives were to determine the effects of allo-MSC administration on LV function and functional status from baseline to 6 months and from baseline to 12 months after treatment.
The trial was initiated with a 6-subject, open-label lead-in phase. Between September 2016 and December 2016, 6 candidates consented to participate and received 20 transendocardial, electromechanically-guided injections of allo-MSCs. A complete safety report of the 6 subjects was provided for review by the data safety monitoring board and FDA. Subsequently, the study was allowed to proceed to the randomization phase.
Baseline evaluations to determine eligibility included: cardiac magnetic resonance imaging (CMR), 6-min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ), and a comprehensive laboratory panel that included N-terminal pro-brain natriuretic peptide (NT-proBNP).
Between March 2017 and October 2018, 31 eligible subjects were randomized 1:1. There were 14 subjects enrolled in the treatment arm and 17 subjects in the placebo arm. Participants received either 1 × 108 allo-MSCs in 8 ml of Buminate 5% solution or a placebo (8 ml of cell-free Buminate solution) delivered via 20 transendocardial injections (0.4 ml each).
All subjects were followed for 1 year, with evaluations at: day 0 (day of injection), day 1, day 7, day 30, day 180, and day 365. A physical examination, electrocardiogram, and laboratory evaluations were conducted at each visit, along with the assessment of adverse events and review of medications. In addition, at 6 months and 1 year, subjects performed the following tests: 6MWT, MLHFQ, and CMR. Serum samples were collected at baseline and 1, 6, and 12 months after treatment to determine whether there were any significant changes in panel reactive antibody (PRA).
The SENECA trial demonstrated that allo-MSCs are well-tolerated and that transendocardial injections of allo-MSCs are feasible in patients with AIC. Although the SENECA trial was not designed to test efficacy, a subset of participants was included in secondary endpoint analysis. The only statistically significant differences observed were with the MLHFQ and 6MWT assessments which favored the intervention. Larger studies will be required to determine the efficacy of allo-MSCs treatment.
Bolli R, Hare JM, Henry TD, et al. Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. Am Heart J. 2018;201:54-62. doi:10.1016/j.ahj.2018.02.009
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Resources AvailableStudy Datasets Only
- Data Dictionary (PDF - 248.1 KB)
- SENECA Case Report Forms (PDF - 1.6 MB)
- SENECA Manual of Procedures (PDF - 1.4 MB)
- SENECA Protocol (PDF - 8.8 MB)
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