Stem Cell Injection in Cancer Survivors (SENECA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02509156

Recruitment Status : Completed

First Posted : July 27, 2015

Results First Posted : November 5, 2020

Last Update Posted : November 5, 2020

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

Barry R Davis, The University of Texas Health Science Center, Houston

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Cardiomyopathy Due to Anthracyclines
Interventions	Biological: Allo-MSCs Biological: Placebo
Enrollment	46

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Period Title: Open-Label Lead-In Phase
Started	6	0
Completed	6	0
Not Completed	0	0
Period Title: Randomized Phase
Started	14 ^[1]	17
Completed	12	16
Not Completed	2	1
Reason Not Completed
Death	1	0
Withdrawal by Subject	1	1
[1] Includes randomized participants only

Baseline Characteristics

Arm/Group Title		Allo-MSCs	Placebo	Total
Arm/Group Description		Target dose of 100 million allo-MSC...	Buminate solution ...	Total of all reporting groups
Arm/Group Description		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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)	Total of all reporting groups
Overall Number of Baseline Participants		14	17	31
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	14 participants	17 participants	31 participants
		54.7 (12.8)	58.2 (11.2)	56.6 (11.8)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
	Female	8 57.1%	13 76.5%	21 67.7%
	Male	6 42.9%	4 23.5%	10 32.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
	Hispanic or Latino	1 7.1%	3 17.6%	4 12.9%
	Not Hispanic or Latino	12 85.7%	13 76.5%	25 80.6%
	Unknown or Not Reported	1 7.1%	1 5.9%	2 6.5%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 28.6%	3 17.6%	7 22.6%
	White	8 57.1%	13 76.5%	21 67.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 14.3%	1 5.9%	3 9.7%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	14 participants	17 participants	31 participants
United States		14	17	31
Body Mass Index Mean (Standard Deviation) Unit of measure: Kg/m^2
	Number Analyzed	14 participants	17 participants	31 participants
		30.2 (9)	30.4 (6.5)	30.3 (7.6)
Heart rate Mean (Standard Deviation) Unit of measure: Beats per minute
	Number Analyzed	14 participants	17 participants	31 participants
		74.4 (9)	76.1 (11.2)	75.4 (10.1)
Systolic blood pressure Mean (Standard Deviation) Unit of measure: mmHg
	Number Analyzed	14 participants	17 participants	31 participants
		118.6 (21.6)	115.4 (11.0)	116.8 (16.4)
Diastolic blood pressure Mean (Standard Deviation) Unit of measure: mmHg
	Number Analyzed	14 participants	17 participants	31 participants
		68.9 (18.6)	67.1 (11.2)	67.9 (14.7)
Diabetes Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		3 21.4%	5 29.4%	8 25.8%
Hypertension Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		6 42.9%	10 58.8%	16 51.6%
Smoking (lifetime) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		5 35.7%	3 17.6%	8 25.8%
Left ventricular ejection fraction Mean (Standard Deviation) Unit of measure: Percentage of blood ejected
	Number Analyzed	14 participants	17 participants	31 participants
		33.7 (3.4)	32.5 (6.5)	33.0 (5.3)
Previous hospitalization for heart failure Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		7 50.0%	8 47.1%	15 48.4%
Previous emergency department visit for heart failure Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		4 28.6%	3 17.6%	7 22.6%
Time since AIC diagnosis ^[1] Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	14 participants	17 participants	31 participants
		6.1 (5.9)	8.7 (5.0)	7.5 (5.5)
		[1] Measure Description: Time since anthracycline induced cardiomyopathy diagnosis (years)
New York Heart Association class II ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		13 92.9%	13 76.5%	26 83.9%
		[1] Measure Description: 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).
New York Heart Association class III ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		1 7.1%	4 23.5%	5 16.1%
		[1] Measure Description: 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.
Presence of a cardiac device ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		6 42.9%	12 70.6%	18 58.1%
		[1] Measure Description: Presence of a cardiac device (implantable cardioverter defibrillator or pacemaker)
Angina Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		3 21.4%	5 29.4%	8 25.8%
Sustained ventricular arrhythmia Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		5 35.7%	7 41.2%	12 38.7%
Leukemia Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		3 21.4%	0 0.0%	3 9.7%
Breast cancer Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		6 42.9%	9 52.9%	15 48.4%
Hodgkin's disease Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		0 0.0%	1 5.9%	1 3.2%
Non-Hodgkin's lymphoma Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		1 7.1%	5 29.4%	6 19.4%
Sarcomas Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		1 7.1%	0 0.0%	1 3.2%
Multiple cancers Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		3 21.4%	2 11.8%	5 16.1%
Doxorubicin Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		11 78.6%	17 100.0%	28 90.3%
Epirubicin Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		1 7.1%	0 0.0%	1 3.2%
Daunorubicin Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	14 participants	17 participants	31 participants
		2 14.3%	0 0.0%	2 6.5%
AIC exposure ^[1] Mean (Standard Deviation) Unit of measure: Mg/m^2
	Number Analyzed	10 participants	10 participants	20 participants
		353.0 (351.3)	339.5 (113.6)	346.2 (254.2)
		[1] Measure Analysis Population Description: Limited information due to treatment record availability (>15yrs). Dosing information (mg/m^2) not always available. Data represents a subset of the cohort.
Time from Cancer Diagnosis ^[1] Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	14 participants	17 participants	31 participants
		16.4 (9.5)	18.8 (8.5)	17.7 (8.9)
		[1] Measure Description: Time from earliest diagnosis requiring anthracycline treatment
Time from last anthracycline treatment Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	14 participants	17 participants	31 participants
		13.3 (9.3)	16.8 (7.6)	15.2 (8.4)

Outcome Measures

1.Primary Outcome


Title	Proportion of Major Adverse Cardiac Events (MACE)
Description	Proportion of adjudicated events including death, hospitalization for ...
Description	Proportion of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31).


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	17
Measure Type: Number Unit of Measure: events
	3	6

2.Primary Outcome


Title	Proportion of Other Significant Clinical Events
Description	Proportion of other significant adjudicated clinical events including:...
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31).


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	17
Measure Type: Number Unit of Measure: events
	0	1

3.Primary Outcome


Title	Subjects With Events Precluding Their Receipt of Product
Description	Number and percent of subjects with events between randomization and s...
Description	Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product.
Time Frame	Randomization to SPI

Outcome Measure Data

Analysis Population Description

Population for safety and feasibility measures include open label lead-in participants (n=6) as well as randomized subjects (n=31).


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	17
Measure Type: Count of Participants Unit of Measure: Participants
	0 0.0%	1 5.9%

4.Primary Outcome


Title	Subjects Who Receive Less Than 20 Injections During SPI
Description	Number and percent of subjects who receive less than 20 injections dur...
Description	Number and percent of subjects who receive less than 20 injections during SPI
Time Frame	During SPI procedure

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	16
Measure Type: Count of Participants Unit of Measure: Participants
	1 5.0%	0 0.0%

5.Primary Outcome


Title	Subjects Who Did Not Receive the Study Product (Either 100 Million Cells or Placebo)
Description	Number and percent of subjects who did not receive the study product (...
Description	Number and percent of subjects who did not receive the study product (either 100 million cells or placebo)
Time Frame	During SPI procedure

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	16
Measure Type: Count of Participants Unit of Measure: Participants
	0 0.0%	0 0.0%

6.Primary Outcome


Title	Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable
Description	Number and percent of subjects who have at least one cardiac MRI endpo...
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

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).


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	18	14
Measure Type: Count of Participants Unit of Measure: Participants
	1 5.6%	4 28.6%

7.Primary Outcome


Title	Subjects Who Fail to Complete Follow-up
Description	Number and percent of subjects who fail to complete follow up
Description	Number and percent of subjects who fail to complete follow up
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Population for safety and feasibility analysis include open label lead-in participants (n=6)


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	17
Measure Type: Count of Participants Unit of Measure: Participants
	2 10.0%	1 5.9%

8.Secondary Outcome


Title	Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Description	Change in left ventricular ejection fraction as assessed via cardiac M...
Description	Change in left ventricular ejection fraction as assessed via cardiac MRI.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable LVEF at baseline and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: percentage of end diastolic volume
	3.47 (6.00)	2.68 (6.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.746
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	The change in LVEF was compared using ANCOVA analyses adjusting for baseline values.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% -4.52 to 6.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.57
	Estimation Comments	Confidence intervals based on t-test

9.Secondary Outcome


Title	Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable LVEF at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Least Squares Mean (Standard Error) Unit of Measure: percentage of end diastolic volume
	1.81 (0.86)	1.33 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.024
	Comments	No adjustments for multiplicity were made in this Phase I trial
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	1.53
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.63
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate of the slope of time.

10.Secondary Outcome


Title	Change From Baseline in Global Strain (HARP MRI)
Description	Change in global circumferential strain as assessed via cardiac MRI
Description	Change in global circumferential strain as assessed via cardiac MRI
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants with available analyzable global circumferential strain at baseline and 12 months


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	11	13
Mean (Standard Deviation) Unit of Measure: percent
	-0.83 (1.70)	-0.12 (2.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in global strain was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.328
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95% -2.68 to 1.26
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.94
	Estimation Comments	Confidence intervals based on t-test

11.Secondary Outcome


Title	Change From Baseline in Global Strain (HARP MRI)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable global strain at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	11	13
Least Squares Mean (Standard Error) Unit of Measure: percent
	-0.49 (0.24)	-0.04 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.261
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-0.26
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.23
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

12.Secondary Outcome


Title	Change From Baseline in Regional Strain (HARP MRI)
Description	Change in regional longitudinal strain as assessed via cardiac MRI
Description	Change in regional longitudinal strain as assessed via cardiac MRI
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants with available analyzable regional longitudinal strain at baseline and 12 months


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: percent
	-1.20 (3.34)	0.38 (3.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in regional strain was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.071
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.58
	Confidence Interval	(2-Sided) 95% -4.51 to 1.35
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.41
	Estimation Comments	Confidence intervals based on t-test

13.Secondary Outcome


Title	Change From Baseline in Regional Strain (HARP MRI)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable regional strain at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Least Squares Mean (Standard Error) Unit of Measure: percent
	-0.58 (0.42)	0.21 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.689
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.35
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

14.Secondary Outcome


Title	Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)
Description	Change in left ventricular end diastolic volume index as measured via ...
Description	Change in left ventricular end diastolic volume index as measured via cardiac MRI
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants with available analyzable LVEDVI at baseline and 12 months


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: ratio- unitless
	-2.30 (16.97)	-3.36 (15.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in LVEDVI was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.935
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95% -12.33 to 14.45
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.46
	Estimation Comments	Confidence intervals based on t-test

15.Secondary Outcome


Title	Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable LVEDVI at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Least Squares Mean (Standard Error) Unit of Measure: ratio-unitless
	-0.94 (2.38)	-1.98 (1.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.325
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-1.56
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.55
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

16.Secondary Outcome


Title	Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)
Description	Change in left ventricular end systolic volume index as assessed via c...
Description	Change in left ventricular end systolic volume index as assessed via cardiac MRI
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants with available analyzable LVESVI at baseline and 12 months


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: ratio- unitless
	-3.62 (15.66)	-4.28 (14.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in LVESVI was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.919
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% -11.75 to 13.08
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.99
	Estimation Comments	Confidence intervals based on t-test

17.Secondary Outcome


Title	Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable LVESVI at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Least Squares Mean (Standard Error) Unit of Measure: ratio- unitless
	-2.05 (2.14)	-2.34 (1.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.183
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-1.99
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.45
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope.

18.Secondary Outcome


Title	Change From Baseline in Left Ventricular Sphericity Index
Description	Change in Left Ventricular Sphericity Index as assessed by cardiac MRI...
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable LV sphericity index at baseline and 12 month LV.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: ratio- unitless
	0.01 (0.08)	-0.07 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in LV sphericity index was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.124
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.077
	Confidence Interval	(2-Sided) 95% 0.003 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.035
	Estimation Comments	Confidence intervals based on t-test

19.Secondary Outcome


Title	Change From Baseline in Left Ventricular Sphericity Index-Trajectory
Description	The change in this measu...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable sphericity index at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	13
Least Squares Mean (Standard Error) Unit of Measure: ratio-unitless
	0.005 (0.013)	-0.037 (0.012)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. A time by treatment interaction was assessed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Other Statistical Analysis		There was a significant treatment and time interaction (p=0.024), so we report a slope for each treatment arm.

20.Secondary Outcome


Title	Change From Baseline in Area of Injury
Description	Change in the scar percent (scar mass normalized to left ventricular m...
Description	Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable scar percent at baseline and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	11	10
Mean (Standard Deviation) Unit of Measure: percentage of mass
	-1.06 (2.44)	-0.41 (2.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in scar percent was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.993
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95% -3.05 to 1.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.14
	Estimation Comments	Confidence intervals based on t-test

21.Secondary Outcome


Title	Change From Baseline in Area of Injury-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable scar percent at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	11	10
Least Squares Mean (Standard Error) Unit of Measure: percentage of mass
	-0.56 (0.41)	-0.27 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.151
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-0.44
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

22.Secondary Outcome


Title	Change From Baseline in Exercise Tolerance (Six Minute Walk Test)
Description	Change in the distance walked (in meters) as measured by the six minut...
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable walk tests at baseline and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	15
Mean (Standard Deviation) Unit of Measure: meters
	34.96 (61.62)	-3.07 (42.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in distance walked was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.056
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	38.03
	Confidence Interval	(2-Sided) 95% -5.84 to 81.89
	Parameter Dispersion	Type: Standard Error of the Mean Value: 20.96
	Estimation Comments	Confidence intervals based on t-test

23.Secondary Outcome


Title	Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory
Description	Change in the distance walked (in feet) as measured by the six minute ...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable six minute walk test data at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	15
Least Squares Mean (Standard Error) Unit of Measure: meters
	9.81 (7.53)	-3.43 (5.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.583
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	2.82
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.06
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

24.Secondary Outcome


Title	Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score
Description	Change in the quality of life summary score as measured by the Minneso...
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable MLHFQ summary score at baseline and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	14
Mean (Standard Deviation) Unit of Measure: score on a scale
	-25.45 (25.65)	-12.63 (14.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in MLHFQ summary score was compared using ANCOVA analyses adjusting for baseline values.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.048
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.82
	Confidence Interval	(2-Sided) 95% -30.49 to 4.84
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.37
	Estimation Comments	Confidence intervals based on t-test

25.Secondary Outcome


Title	Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score-Trajectory
Description	The change in this measu...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable MLHFQ data at baseline, 6 month, and 12 month.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	14
Least Squares Mean (Standard Error) Unit of Measure: score on a scale
	-10.15 (2.94)	-6.05 (1.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0002
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-8.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.86
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope.

26.Secondary Outcome


Title	Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
Description	Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as meas...
Description	Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Participants who had available analyzable NT-proBNP results at baseline and 12 month. Log transformation used. p-values were obtained from transformed data.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	15
Mean (Standard Deviation) Unit of Measure: pg/ml
	-392.58 (953.71)	-76.76 (410.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	The change in NT-proBNP was compared using ANCOVA analyses adjusting for baseline values. Data log transformed. p-values were obtained from transformed data.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.199
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-315.80
	Confidence Interval	(2-Sided) 95% -947.50 to 315.80
	Parameter Dispersion	Type: Standard Error of the Mean Value: 295
	Estimation Comments	Confidence intervals based on t-test

27.Secondary Outcome


Title	Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory
Description	The change in this measure over time is assessed using a repeated meas...
Description	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.
Time Frame	Assessed as a trajectory (baseline, 6 months, and 12 months)

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	12	15
Least Squares Mean (Standard Error) Unit of Measure: pg/ml
	-184.18 (113.16)	-58.58 (49.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allo-MSCs, Placebo
	Comments	Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the treatment groups. If there was no significant interaction, only one trajectory (slope) was reported. Log transformation used for the regression. p-values were obtained from transformed data.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.229
	Comments	No adjustments for multiplicity were made in this Phase I trial.
	Method	Repeated Measures Linear Regression
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	slope of time
	Estimated Value	-23.391
	Parameter Dispersion	Type: Standard Error of the Mean Value: 202.080
	Estimation Comments	"Standard error of the mean" is the standard error of the estimate over time of the slope

28.Secondary Outcome


Title	Cumulative Days Alive and Out of Hospital for Heart Failure
Description	Days alive and out of hospital for heart failure during the study eval...
Description	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).
Time Frame	Baseline to End of 12 Month Visit Window (i.e. 395 days after intervention)

Outcome Measure Data

Analysis Population Description

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).


Arm/Group Title	Allo-MSCs	Placebo
Arm/Group Description:	Target dose of 100 million allo-MSC...	Buminate solution ...
Arm/Group Description:	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)	Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Overall Number of Participants Analyzed	20	16
Mean (Standard Deviation) Unit of Measure: days
	368 (25.8)	363 (31.9)

Adverse Events

Time Frame	Events reported are from randomization date to the 12 month endpoint data collection window (i.e 395 days post intervention)
Adverse Event Reporting Description	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.

Arm/Group Title	Allo-MSCs		Placebo
Arm/Group Description	Target dose of 100 million allo-MSC...		Buminate solution ...
Arm/Group Description	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)		Buminate solution Placebo: 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
All-Cause Mortality
	Allo-MSCs		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/20 (5.00%)		0/17 (0.00%)
Serious Adverse Events Serious Adverse Events
	Allo-MSCs		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/20 (25.00%)		11/17 (64.71%)
Cardiac disorders
Cardiac failure acute ^† 1	2/20 (10.00%)	2	2/17 (11.76%)	3
Cardiac failure ^† 1	1/20 (5.00%)	1	2/17 (11.76%)	3
Atrial fibrillation ^† 1	1/20 (5.00%)	1	1/17 (5.88%)	1
Ventricular tachycardia ^† 1	1/20 (5.00%)	1	1/17 (5.88%)	1
Cardiovascular deconditioning ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Arrhythmia ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Atrial flutter ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Cardiogenic shock ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Pericardial effusion ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Gastrointestinal disorders
Chrohn's disease ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Intestinal stenosis ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
General disorders
Sudden cardiac death ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Hepatobiliary disorders
Drug induced liver injury ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Infections and infestations
Appendicitis ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Post operative wound infection ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Injury, poisoning and procedural complications
Procedural pneumothorax ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Fall ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Hyponatraemia ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Nervous system disorders
Transient ischaemic attack ^† 1	1/20 (5.00%)	1	0/17 (0.00%)	0
Syncope ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Product Issues
Lead dislodgement ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Device lead damage ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Renal and urinary disorders
Acute kidney injury ^† 1	1/20 (5.00%)	1	1/17 (5.88%)	1
Reproductive system and breast disorders
Menorrhagia ^† 1	0/20 (0.00%)	0	1/17 (5.88%)	1
Vascular disorders
Hypotension ^† 1	1/20 (5.00%)	1	1/17 (5.88%)	1
1 Term from vocabulary, MedDRA (19.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Allo-MSCs		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/20 (20.00%)		4/17 (23.53%)
Cardiac disorders
Ventricular tachycardia ^† 1	0/20 (0.00%)	0	4/17 (23.53%)	4
Pericardial effusion ^† 1	2/20 (10.00%)	2	0/17 (0.00%)	0
Investigations
Glomerular filtration rate decreased ^† 1	2/20 (10.00%)	2	0/17 (0.00%)	0
1 Term from vocabulary, MedDRA (19.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Shelly Sayre, M.P.H. Project Manager
Organization:	University of Texas-Houston School of Public Health
Phone:	713-500-9529
EMail:	Shelly.L.Sayre@uth.tmc.edu

Publications:

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.

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. Review.

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, Moyé 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.

Layout table for additonal information

Responsible Party:	Barry R Davis, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT02509156
Other Study ID Numbers:	HSC-SPH-15-0443 5UM1HL087318 ( U.S. NIH Grant/Contract )
First Submitted:	July 23, 2015
First Posted:	July 27, 2015
Results First Submitted:	September 15, 2020
Results First Posted:	November 5, 2020
Last Update Posted:	November 5, 2020

To Top