A Phase I Study Of Allogeneic Mesenchymal Stem Cell Therapy In Patients With Heart Failure Secondary To Anthracycline-Induced Cardiomyopathy: The Cctrn Stem Cell Injection In Cancer Survivors (Seneca) Trial

Background Anthracycline-induced cardiomyopathy (AIC) can be irreversible with a poor prognosis, and disproportionately affects women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure treatment. Allo-MSCs are known to favorably affect fibrosis, apoptosis, and inflammation, which are key features of AIC. Methods This phase I study evaluated 37 adult cancer survivors (68% female) with left ventricular dysfunction secondary to chronic AIC. The study included a six-subject open-label, lead-in phase followed by 31 subjects randomized 1:1 to receive 1 × 108 allo-MSCs or vehicle via 20 transendocardial injections. Subjects were followed for 1 year to assess safety and feasibility (Fisher\u0027s test). Secondary efficacy measures included cardiac function/structure measured by magnetic resonance imaging (MRI), functional capacity, quality of life (MLHFQ), and biomarkers. These were assessed by ANCOVA adjusting for baseline values. Results Ninety-seven percent of subjects underwent successful study product injections, all allo-MSC-assigned subjects received the target dose. Follow-up visits were well attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-MRI compatible devices, MRI endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes including major adverse cardiac events, other significant adverse events, and days alive and out of the hospital. Ten of the 13 efficacy measures numerically favored the allo-MSC group including a lower MLHFQ score (p = .048). Conclusion In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible and MRI was successfully performed in the majority of patients with devices. This study provides crucial information for designing Phase II trials aimed at assessing efficacy of cell therapy in patients with AIC.