Stem Cell Injection in Cancer Survivors
- Conditions
- Cardiomyopathy Due to Anthracyclines
- Interventions
- Biological: PlaceboBiological: Allo-MSCs
- Registration Number
- NCT02509156
- Brief Summary
The primary purpose of this study is 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).
The secondary purpose of this study is to obtain preliminary evidence for therapeutic efficacy of allo-MSCs delivered by transendocardial injection to cancer survivors with LV dysfunction secondary to AIC.
- Detailed Description
This phase I, randomized, placebo-controlled, trial will evaluate the safety and feasibility of allo-MSCs administered by transendocardial injection in thirty-seven subjects with anthracycline-induced cardiomyopathy (AIC). The first six subjects received allo-MSC therapy (open label) and were assessed for safety and feasibility of the study procedures. Following 1 month data review of each of the six subjects by the National Heart, Lung, and Blood Institute Gene and Cell Therapy Data Safety Monitoring Board; this was followed by a randomized, double-blind clinical trial enrolling thirty-one subjects. These subjects were randomized 1:1 to receive allo-MSCs or placebo. All subjects underwent cardiac catheterization and study product administration using the NOGA Myostar catheter injection system. Subjects are being followed at 1 day, 1 week, 1 month, 6 months, and 12 months post study product injection. All endpoints are assessed at the 6 and 12 month visits which will occur 180 ±30 days and 365 ±30 days, respectively, after the day of study product injection (Day 0). For the purpose of the safety evaluations and endpoint analysis, the Investigators will utilize an "intention-to-treat" study population. In addition, because this phase I study is the first cell therapy study in this population, at 12 months available standard-of-care medical records for cancer surveillance will be reviewed for cancer recurrence.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Buminate solution Allo-MSCs Allo-MSCs Target dose of 100 million allo-MSCs
- Primary Outcome Measures
Name Time Method Subjects Who Receive Less Than 20 Injections During SPI During SPI procedure Number and percent of subjects who receive less than 20 injections during SPI
Subjects Who Did Not Receive the Study Product (Either 100 Million Cells or Placebo) During SPI procedure Number and percent of subjects who did not receive the study product (either 100 million cells or placebo)
Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable Baseline to 12 months Number and percent of subjects who have at least one cardiac MRI endpoint measure that is uninterpretable due to issues related to the device, including, but not limited to, inability to undergo the procedure.
Proportion of Other Significant Clinical Events Baseline to 12 months Proportion of other significant adjudicated clinical events including: non-fatal stroke, non-fatal MI, coronary artery revascularization, ventricular tachycardia/fibrillation, pericardial tamponade, infectious myocarditis, hypersensitivity reaction, neoplasm, and/or other potential deleterious late effects.
Proportion of Major Adverse Cardiac Events (MACE) Baseline to 12 months Proportion of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
Subjects With Events Precluding Their Receipt of Product Randomization to SPI Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product.
Subjects Who Fail to Complete Follow-up Baseline to 12 months Number and percent of subjects who fail to complete follow up
- Secondary Outcome Measures
Name Time Method Change From Baseline in Global Strain (HARP MRI) Baseline to 12 months Change in global circumferential strain as assessed via cardiac MRI
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Baseline to 12 months Change in left ventricular ejection fraction as assessed via cardiac MRI.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) Baseline to 12 months Change in left ventricular end diastolic volume index as measured via cardiac MRI
Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score Baseline to 12 months Change in the quality of life summary score as measured by the Minnesota Living with Heart Failure Questionnaire. Minimum and maximum scores for scale are 0 and 105 respectively. Lower scores indicative of better outcome.
Change From Baseline in Global Strain (HARP MRI)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Regional Strain (HARP MRI) Baseline to 12 months Change in regional longitudinal strain as assessed via cardiac MRI
Change From Baseline in Exercise Tolerance (Six Minute Walk Test) Baseline to 12 months Change in the distance walked (in meters) as measured by the six minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 min). The average distance of the two walk tests will be used for analysis.
Change From Baseline in Left Ventricular Sphericity Index Baseline to 12 months Change in Left Ventricular Sphericity Index as assessed by cardiac MRI. Sphericity index is the ratio of the long and short axis measurements of the left ventricle.
Change From Baseline in Area of Injury Baseline to 12 months Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.
Change From Baseline in Area of Injury-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) Change in the distance walked (in feet) as measured by the six minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 min). The average distance of the two walk tests will be used for analysis. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Left Ventricular Sphericity Index-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Sphericity index is the ratio of the long and short axis measurements of the left ventricle.Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Cumulative Days Alive and Out of Hospital for Heart Failure Baseline to End of 12 Month Visit Window (i.e. 395 days after intervention) Days alive and out of hospital for heart failure during the study evaluation period. Subjects were allotted a visit window extending 30 days past their anticipated 12-month visit (i.e., 395 days).
Change From Baseline in Regional Strain (HARP MRI)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) Baseline to 12 months Change in left ventricular end systolic volume index as assessed via cardiac MRI
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score-Trajectory Assessed as a trajectory (baseline, 6 months, and 12 months) The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.
Minimum and maximum scores for scale are 0 and 105 respectively. Lower scores indicative of better outcome.Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Baseline to 12 months Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw
Trial Locations
- Locations (7)
Stanford University School of Medicine
🇺🇸Stanford, California, United States
University of Miami-Interdiciplinary Stem Cell Institute
🇺🇸Miami, Florida, United States
University of Florida-Department of Medicine
🇺🇸Gainesville, Florida, United States
Indiana Center for Vascular Biology and Medicine
🇺🇸Indianapolis, Indiana, United States
Minneapolis Heart Institute Foundation
🇺🇸Minneapolis, Minnesota, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Texas Heart Institute
🇺🇸Houston, Texas, United States