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| ID | Type | Description | Link |
|---|---|---|---|
| 5UM1HL087318 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allo-MSCs | Experimental | Target dose of 100 million allo-MSCs |
|
| Placebo | Placebo Comparator | Buminate solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allo-MSCs | Biological | 20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Major Adverse Cardiac Events (MACE) | Proportion of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization). | Baseline to 12 months |
| Proportion of Other Significant Clinical Events | 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. | Baseline to 12 months |
| Subjects With Events Precluding Their Receipt of Product | Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product. | Randomization to SPI |
| Subjects Who Receive Less Than 20 Injections During SPI | Number and percent of subjects who receive less than 20 injections during SPI | During SPI procedure |
| Subjects Who Did Not Receive the Study Product (Either 100 Million Cells or Placebo) | Number and percent of subjects who did not receive the study product (either 100 million cells or placebo) | During SPI procedure |
| Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Change in left ventricular ejection fraction as assessed via cardiac MRI. | Baseline to 12 months |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory |
Not provided
Inclusion Criteria
To participate, a subject MUST:
Exclusion Criteria
To participate, a subject MUST NOT HAVE:
A life expectancy <12 months
A CT scan or baseline cardiac MRI showing new tumor or suspicious lymphadenopathy raising concern of malignancy
Presence of obstructive CAD as determined via imaging within 5 years prior to study enrollment provided there have been no symptoms or evidence of CAD since the test
Had a previous myocardial infarction
A history of radiation therapy AND evidence of constrictive physiology and/or evidence of other patterns of non-ischemic cardiomyopathy on cardiac MRI (e.g., amyloidosis, sarcoidosis, hemochromatosis, pure radiation-induced cardiomyopathy, etc.) not consistent with AIC being the dominant etiology of heart failure
Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent.
Aortic stenosis with valve area ≤ 1.5cm2
A history of LV reduction surgery or cardiomyoplasty
Evidence of cardiogenic shock
A history of ischemic or hemorrhagic stroke within 90 days of baseline testing
Liver dysfunction during baseline testing, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal
Diabetes with poorly controlled blood glucose levels (HbA1c > 8.5%)
An underlying autoimmune disorder or current immunosuppressive therapy (e.g., chronic corticosteroid, rheumatologic or immune modulating therapy) or likelihood of use of immunosuppressive therapy during participation in the trial (medications will be considered on a case by case basis)
A baseline eGFR <35 ml/min/1.73m2
A contrast allergy that cannot adequately be managed by premedication
Received gene or cell-based therapy from any source within the previous 12 months
A hematologic abnormality during baseline testing as evidenced by hemoglobin < 9 g/dl; hematocrit < 30%; absolute neutrophil count < 2,000 or total WBC count more than 2 times upper limit of normal; or platelet values < 100,000/ul
Evidence of active systemic infection at time of study product delivery
HIV and/or active HBV or HCV
Coagulopathy (INR > 1.5) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors) (see Section 6.4 re: injection procedure and anticoagulation therapy) Note: Subjects who cannot be withdrawn from anticoagulation will be excluded.
Presence of LV thrombus
Presence of a pacemaker and/or ICD generator with any of the following limitations/conditions:
Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to consent
Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
A history of drug abuse (use of illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
Cognitive or language barriers that prohibit obtaining informed consent or any study elements (interpreter permitted)
Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell based therapies) or device trial
Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation
Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up
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| Name | Affiliation | Role |
|---|---|---|
| Robert Simari, MD | CCTRN Steering Committee Chair | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States | ||
| University of Florida-Department of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20850099 | Background | Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, Williams K, Itescu S, Sanders P, Gronthos S, Zannettino AC, Worthley SG. Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC Cardiovasc Interv. 2010 Sep;3(9):974-83. doi: 10.1016/j.jcin.2010.05.016. | |
| 19121814 | Background | Nazarian S, Halperin HR. How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm. 2009 Jan;6(1):138-43. doi: 10.1016/j.hrthm.2008.10.021. Epub 2008 Oct 22. No abstract available. |
| Label | URL |
|---|---|
| Cardiovascular Cell Therapy Research Network | View source |
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46 subjects consented to participate; 37 completed baseline testing and met eligibility criteria. This includes 6 (open label) and 31 (randomized) subjects. Reasons for failed eligibility (n=9) include elevated LVEF, failure to complete baseline testing, MRI contraindications, and investigator discretion.
Enrollment took place at seven CCTRN centers between September 2016 and October 2018. The main centers are located in Texas, Florida (2 locations), Minnesota, Kentucky, Indiana, and California. Recruitment methods included www.clinicaltrials.gov, cancer survivorship organization websites, and local cancer center physician outreach.
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| ID | Title | Description |
|---|---|---|
| FG000 | Allo-MSCs | Target dose of 100 million allo-MSCs Allo-MSCs: 20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
| FG001 | Placebo | Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Open-Label Lead-In Phase |
| |||||||||||||
| Randomized Phase |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Allo-MSCs | Target dose of 100 million allo-MSCs Allo-MSCs: 20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Major Adverse Cardiac Events (MACE) | Proportion of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization). | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31). | Posted | Number | events | Baseline to 12 months |
|
Events reported are from randomization date to the 12 month endpoint data collection window (i.e 395 days post intervention)
Events were assessed systematically at each study visit during the physical exam assessment. A standard workbook was used to collect event details. Sponsor safety team reviewed events and requested additional documentation as needed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Allo-MSCs | Target dose of 100 million allo-MSCs Allo-MSCs: 20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure acute | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular tachycardia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
Heterogeneous history of cancer; Lengthy time interval (both from cancer diagnosis and AIC diagnosis); Age of cancer records (>15 yrs in some cases); Natural history of AIC in our cohort better than expected on the basis of the literature.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shelly Sayre, M.P.H. Project Manager | University of Texas-Houston School of Public Health | 713-500-9529 | Shelly.L.Sayre@uth.tmc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jun 13, 2017 | Jun 24, 2019 | ICF_001.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 19, 2018 | Jun 16, 2020 | Prot_SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D001943 | Breast Neoplasms |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D012509 | Sarcoma |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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|
| Placebo | Biological | 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure) |
|
|
| Baseline to 12 months |
| Subjects Who Fail to Complete Follow-up | Number and percent of subjects who fail to complete follow up | Baseline to 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.
| Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Global Strain (HARP MRI) | Change in global circumferential strain as assessed via cardiac MRI | Baseline to 12 months |
| Change From Baseline in Global Strain (HARP MRI)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Regional Strain (HARP MRI) | Change in regional longitudinal strain as assessed via cardiac MRI | Baseline to 12 months |
| Change From Baseline in Regional Strain (HARP MRI)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | Change in left ventricular end diastolic volume index as measured via cardiac MRI | Baseline to 12 months |
| Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | Change in left ventricular end systolic volume index as assessed via cardiac MRI | Baseline to 12 months |
| Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Left Ventricular Sphericity Index | 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. | Baseline to 12 months |
| Change From Baseline in Left Ventricular Sphericity Index-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Area of Injury | Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI. | Baseline to 12 months |
| Change From Baseline in Area of Injury-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 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. | Baseline to 12 months |
| Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score | 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. | Baseline to 12 months |
| Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw | Baseline to 12 months |
| Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 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. | Assessed as a trajectory (baseline, 6 months, and 12 months) |
| Cumulative Days Alive and Out of Hospital for Heart Failure | 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). | Baseline to End of 12 Month Visit Window (i.e. 395 days after intervention) |
| Gainesville |
| Florida |
| 32610 |
| United States |
| University of Miami-Interdiciplinary Stem Cell Institute | Miami | Florida | 33101 | United States |
| Indiana Center for Vascular Biology and Medicine | Indianapolis | Indiana | 46202 | United States |
| University of Louisville | Louisville | Kentucky | 40202 | United States |
| Minneapolis Heart Institute Foundation | Minneapolis | Minnesota | 55407 | United States |
| Texas Heart Institute | Houston | Texas | 77030 | United States |
| 29910056 | Background | Bolli R, Hare JM, Henry TD, Lenneman CG, March KL, Miller K, Pepine CJ, Perin EC, Traverse JH, Willerson JT, Yang PC, Gee AP, Lima JA, Moye L, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). 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. |
| National Heart, Lung, and Blood Institute | View source |
| NOT COMPLETED |
|
|
Buminate solution
Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Heart rate | Mean | Standard Deviation | beats per minute |
|
| Systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diabetes | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Smoking (lifetime) | Count of Participants | Participants |
|
| Left ventricular ejection fraction | Mean | Standard Deviation | percentage of blood ejected |
|
| Previous hospitalization for heart failure | Count of Participants | Participants |
|
| Previous emergency department visit for heart failure | Count of Participants | Participants |
|
| Time since AIC diagnosis | Time since anthracycline induced cardiomyopathy diagnosis (years) | Mean | Standard Deviation | years |
|
| New York Heart Association class II | Physicians use the NYHA classification system to place patients in one of four categories based on how much they are limited during physical activity. Class II is characterized by slight limitation of physical activity. The patient is comfortable at rest, however ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). | Count of Participants | Participants |
|
| New York Heart Association class III | Physicians use the NYHA classification system to place patients in one of four categories based on how much they are limited during physical activity. Class III is characterized by marked limitation of physical activity. The patient is comfortable at rest. Less than ordinary activity however, causes fatigue, palpitation, or dyspnea. | Count of Participants | Participants |
|
| Presence of a cardiac device | Presence of a cardiac device (implantable cardioverter defibrillator or pacemaker) | Count of Participants | Participants |
|
| Angina | Count of Participants | Participants |
|
| Sustained ventricular arrhythmia | Count of Participants | Participants |
|
| Leukemia | Count of Participants | Participants |
|
| Breast cancer | Count of Participants | Participants |
|
| Hodgkin's disease | Count of Participants | Participants |
|
| Non-Hodgkin's lymphoma | Count of Participants | Participants |
|
| Sarcomas | Count of Participants | Participants |
|
| Multiple cancers | Count of Participants | Participants |
|
| Doxorubicin | Count of Participants | Participants |
|
| Epirubicin | Count of Participants | Participants |
|
| Daunorubicin | Count of Participants | Participants |
|
| AIC exposure | Limited information due to treatment record availability (>15yrs). Dosing information (mg/m^2) not always available. Data represents a subset of the cohort. | Mean | Standard Deviation | mg/m^2 |
|
| Time from Cancer Diagnosis | Time from earliest diagnosis requiring anthracycline treatment | Mean | Standard Deviation | years |
|
| Time from last anthracycline treatment | Mean | Standard Deviation | years |
|
|
|
| Primary | Proportion of Other Significant Clinical Events | 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. | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31). | Posted | Number | events | Baseline to 12 months |
|
|
|
| Primary | Subjects With Events Precluding Their Receipt of Product | Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product. | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31). | Posted | Count of Participants | Participants | Randomization to SPI |
|
|
|
| Primary | Subjects Who Receive Less Than 20 Injections During SPI | Number and percent of subjects who receive less than 20 injections during SPI | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects who were participating at the time of study product injection (n=30). Note: one placebo patient withdrew after randomization but prior to injection visit. | Posted | Count of Participants | Participants | During SPI procedure |
|
|
|
| Primary | Subjects Who Did Not Receive the Study Product (Either 100 Million Cells or Placebo) | Number and percent of subjects who did not receive the study product (either 100 million cells or placebo) | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects who were participating at the time of study product injection (n=30). Note: one placebo patient withdrew after randomization but prior to injection visit. | Posted | Count of Participants | Participants | During SPI procedure |
|
|
|
| Primary | Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 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. | Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31). Analysis population includes only participants who completed an MRI at 12 months (n=32). | Posted | Count of Participants | Participants | Baseline to 12 months |
|
|
|
| Primary | Subjects Who Fail to Complete Follow-up | Number and percent of subjects who fail to complete follow up | Population for safety and feasibility analysis include open label lead-in participants (n=6) | Posted | Count of Participants | Participants | Baseline to 12 months |
|
|
|
| Secondary | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Change in left ventricular ejection fraction as assessed via cardiac MRI. | Participants who had available analyzable LVEF at baseline and 12 month. | Posted | Mean | Standard Deviation | percentage of end diastolic volume | Baseline to 12 months |
|
|
|
|
| Secondary | Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory | 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. | Participants who had available analyzable LVEF at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | percentage of end diastolic volume | Assessed as a trajectory (baseline, 6 months, and 12 months) |
|
|
|
|
| Secondary | Change From Baseline in Global Strain (HARP MRI) | Change in global circumferential strain as assessed via cardiac MRI | Participants with available analyzable global circumferential strain at baseline and 12 months | Posted | Mean | Standard Deviation | percent | Baseline to 12 months |
|
|
|
|
| Secondary | Change From Baseline in Global Strain (HARP MRI)-Trajectory | 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. | Participants who had available analyzable global strain at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | percent | Assessed as a trajectory (baseline, 6 months, and 12 months) |
|
|
|
|
| Secondary | Change From Baseline in Regional Strain (HARP MRI) | Change in regional longitudinal strain as assessed via cardiac MRI | Participants with available analyzable regional longitudinal strain at baseline and 12 months | Posted | Mean | Standard Deviation | percent | Baseline to 12 months |
|
|
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| Secondary | Change From Baseline in Regional Strain (HARP MRI)-Trajectory | 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. | Participants who had available analyzable regional strain at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | percent | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | Change in left ventricular end diastolic volume index as measured via cardiac MRI | Participants with available analyzable LVEDVI at baseline and 12 months | Posted | Mean | Standard Deviation | ratio- unitless | Baseline to 12 months |
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| Secondary | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 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. | Participants who had available analyzable LVEDVI at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | ratio-unitless | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | Change in left ventricular end systolic volume index as assessed via cardiac MRI | Participants with available analyzable LVESVI at baseline and 12 months | Posted | Mean | Standard Deviation | ratio- unitless | Baseline to 12 months |
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| Secondary | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | 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. | Participants who had available analyzable LVESVI at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | ratio- unitless | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Left Ventricular Sphericity Index | 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. | Participants who had available analyzable LV sphericity index at baseline and 12 month LV. | Posted | Mean | Standard Deviation | ratio- unitless | Baseline to 12 months |
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| Secondary | Change From Baseline in Left Ventricular Sphericity Index-Trajectory | 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. | Participants who had available analyzable sphericity index at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | ratio-unitless | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Area of Injury | Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI. | Participants who had available analyzable scar percent at baseline and 12 month. | Posted | Mean | Standard Deviation | percentage of mass | Baseline to 12 months |
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| Secondary | Change From Baseline in Area of Injury-Trajectory | 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. | Participants who had available analyzable scar percent at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | percentage of mass | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 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. | Participants who had available analyzable walk tests at baseline and 12 month. | Posted | Mean | Standard Deviation | meters | Baseline to 12 months |
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| Secondary | Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | 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. | Participants who had available analyzable six minute walk test data at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | meters | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score | 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. | Participants who had available analyzable MLHFQ summary score at baseline and 12 month. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 12 months |
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| Secondary | Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score-Trajectory | 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. | Participants who had available analyzable MLHFQ data at baseline, 6 month, and 12 month. | Posted | Least Squares Mean | Standard Error | score on a scale | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw | Participants who had available analyzable NT-proBNP results at baseline and 12 month. Log transformation used. p-values were obtained from transformed data. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 12 months |
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| Secondary | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 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. | Participants who had available analyzable NT-proBNP results at baseline, 6 month, and 12 month. Log transformation used for the regression. p-values were obtained from transformed data. | Posted | Least Squares Mean | Standard Error | pg/ml | Assessed as a trajectory (baseline, 6 months, and 12 months) |
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| Secondary | Cumulative Days Alive and Out of Hospital for Heart Failure | 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). | Comparison of the two groups on days alive and out of the hospital for heart failure during the 12 month study evaluation period. Analysis includes all study subjects (including the 6 open label patients). | Posted | Mean | Standard Deviation | days | Baseline to End of 12 Month Visit Window (i.e. 395 days after intervention) |
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| 1 |
| 20 |
| 5 |
| 20 |
| 4 |
| 20 |
| EG001 | Placebo | Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure) | 0 | 17 | 11 | 17 | 4 | 17 |
| Cardiac failure | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Cardiovascular deconditioning | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Arrhythmia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Atrial flutter | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Cardiogenic shock | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Chrohn's disease | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Intestinal stenosis | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Sudden cardiac death | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Drug induced liver injury | Hepatobiliary disorders | MedDRA (19.0) | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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| Post operative wound infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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| Procedural pneumothorax | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Lead dislodgement | Product Issues | MedDRA (19.0) | Systematic Assessment |
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| Device lead damage | Product Issues | MedDRA (19.0) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Glomerular filtration rate decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
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Not provided
Not provided
Not provided
| D001941 |
| Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D018204 | Neoplasms, Connective and Soft Tissue |
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Superiority |