Back to resultsDonor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines
Primary Purpose
Cardiomyopathy, Heart Failure, Hematopoietic and Lymphoid Cell Neoplasm
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Best Practice
Laboratory Biomarker Analysis
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cell Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Cardiomyopathy
Eligibility Criteria
Inclusion Criteria:
- Patients with LVEF </= 40% documented from treatment with anthracyclines for any malignancy at any dose at any time without evidence of other causes of cardiomyopathy.
- Age >/= 18 and </= 80 years of Age.
- Documented NYHA class I, II and III.
- For patients who have received trastuzumab: Persistent LV dysfunction must be present 90 days after discontinuation of trastuzumab.
- Able to perform 6 minute walk test.
- Been treated with appropriate maximal medical therapy for heart failure.
- Patient or legally authorized representative able to sign informed consent.
Exclusion Criteria:
- Evidence of Ischemic Heart Disease as determined by study cardiologist.
- Significant Valvular Disease. (AS with AVA <1.5 and severe AR and MR)
- History of Familial Cardiomyopathy.
- Recent documented myocarditis within 2 months of enrollment.
- History of Infiltrative cardiomyopathy or restrictive cardiomyopathy.
- Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram.
- Liver function tests > 3 x upper limit of normal.
- NYHA class IV heart failure.
- Inotropic dependence.
- Unstable or life-threatening arrhythmia.
- For patients not on anticoagulants, INR>1.5
- Mechanical or Bioprosthetic heart valve.
- Cardiogenic shock.
- Breastfeeding and/or pregnant women.
- Autoimmune disorders on current immunosuppressive therapy.
- Active infection not responding to appropriate therapy as determined by Study Chair.
- Trastuzumab treatment within the last 3 months.
- Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days.
- AICD firing within the last 30 days.
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Arm I (hMSCs IV)
Arm II (hMSCs transendocardially)
Arm III (standard of care)
Arm Description
Patients receive hMSCs IV over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
Patients receive standard of care treatment for heart failure.
Outcomes
Primary Outcome Measures
Incidence of adverse events
Statistical analyses of safety will be descriptive.
Change in left ventricular ejection fraction (LVEF)
The comparison will be between the two groups of patients.
Secondary Outcome Measures
Change in improvement of left ventricular (LV) systolic function as assessed by LVEF
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
LV end-systolic and end-diastolic volumes as determined by contrast-enhanced 2-dimensional(D)/3D echography
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Cardiac death
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Re-hospitalization after heart failure
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Aborted death from an automatic implantable cardioverter defibrillator (AICD) firing
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Nonfatal myocardial infarction
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Revascularization
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Full Information
NCT ID
NCT02962661
First Posted
November 8, 2016
Last Updated
October 20, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02962661
Brief Title
Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines
Official Title
Randomized 3-Arm Trial With Standard of Care Alone vs Either Intravenous Infusion or Transendocardial Injection of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) Plus Standard of Care in Patients With Anthracycline-Associated Cardiomyopathy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 18, 2020 (Actual)
Primary Completion Date
July 30, 2025 (Anticipated)
Study Completion Date
July 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This randomized pilot phase I trial studies the side effects of donor bone marrow derived mesenchymal stem cells in controlling heart failure in patients with cardiomyopathy caused by anthracyclines. Donor bone marrow derived mesenchymal stem cells may help to control symptoms of heart failure and improve heart function.
Detailed Description
PRIMARY OBJECTIVE:
I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion and transendocardial injection in patients with left ventricular (LV) dysfunction and heart failure secondary to chemotherapy with anthracyclines.
SECONDARY OBJECTIVE:
I. To demonstrate the efficacy of allogeneic hMSCs administered by intravenous infusion and transendocardial injection in patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] < 40%) and heart failure secondary to treatment with anthracyclines.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive hMSCs intravenously (IV) over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive standard of care treatment for heart failure.
After completion of study treatment, patients are followed up periodically.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiomyopathy, Heart Failure, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I (hMSCs IV)
Arm Type
Experimental
Arm Description
Patients receive hMSCs IV over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (hMSCs transendocardially)
Arm Type
Experimental
Arm Description
Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm III (standard of care)
Arm Type
Active Comparator
Arm Description
Patients receive standard of care treatment for heart failure.
Intervention Type
Other
Intervention Name(s)
Best Practice
Other Intervention Name(s)
standard of care, standard therapy
Intervention Description
Given standard of care
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Mesenchymal Stem Cell Transplantation
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mesenchymal Stem Cell Transplantation
Intervention Description
Given transendocardially
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Statistical analyses of safety will be descriptive.
Time Frame
Up to 6 months
Title
Change in left ventricular ejection fraction (LVEF)
Description
The comparison will be between the two groups of patients.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Change in improvement of left ventricular (LV) systolic function as assessed by LVEF
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Baseline up to 6 months
Title
LV end-systolic and end-diastolic volumes as determined by contrast-enhanced 2-dimensional(D)/3D echography
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Cardiac death
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Re-hospitalization after heart failure
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Aborted death from an automatic implantable cardioverter defibrillator (AICD) firing
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Nonfatal myocardial infarction
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Revascularization
Description
As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p < .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with LVEF </= 40% documented from treatment with anthracyclines for any malignancy at any dose at any time without evidence of other causes of cardiomyopathy.
Age >/= 18 and </= 80 years of Age.
Documented NYHA class I, II and III.
For patients who have received trastuzumab: Persistent LV dysfunction must be present 90 days after discontinuation of trastuzumab.
Able to perform 6 minute walk test.
Been treated with appropriate maximal medical therapy for heart failure.
Patient or legally authorized representative able to sign informed consent.
Exclusion Criteria:
Evidence of Ischemic Heart Disease as determined by study cardiologist.
Significant Valvular Disease. (AS with AVA <1.5 and severe AR and MR)
History of Familial Cardiomyopathy.
Recent documented myocarditis within 2 months of enrollment.
History of Infiltrative cardiomyopathy or restrictive cardiomyopathy.
Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram.
Liver function tests > 3 x upper limit of normal.
NYHA class IV heart failure.
Inotropic dependence.
Unstable or life-threatening arrhythmia.
For patients not on anticoagulants, INR>1.5
Mechanical or Bioprosthetic heart valve.
Cardiogenic shock.
Breastfeeding and/or pregnant women.
Autoimmune disorders on current immunosuppressive therapy.
Active infection not responding to appropriate therapy as determined by Study Chair.
Trastuzumab treatment within the last 3 months.
Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days.
AICD firing within the last 30 days.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Olson, MD
Phone
713-745-3055
Email
alolson@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Olson, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Olson, MD
Phone
713-745-3055
Email
alolson@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Amanda Olson, MD
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center
Learn more about this trial
Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines
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