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Bone Marrow Derived Mesenchymal Stem Cells in Improving Heart Function in Patients With Heart Failure Caused by Anthracyclines

Primary Purpose

Cardiomyopathy, Heart Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Standard of Care
Mesenchymal Stem Cell Transplantation
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiomyopathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with LVEF =< 40% from treatment with anthracyclines for all malignancies at any dose at any time without evidence of other causes of cardiomyopathy
  • Documented New York Heart Association (NYHA) class I, II and III
  • Been treated with appropriate maximal medical therapy for heart failure
  • Able to perform 6 minute walk test
  • Patient or legally authorized representative able to sign informed consent
  • Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab

Exclusion Criteria:

  • Evidence of ischemic heart disease as determined by study cardiologist
  • Significant valvular disease; (aortic stenosis [AS] with aortic valve area [AVA] < 1.5 and severe aortic regurgitation [AR] and mitral regurgitation [MR])
  • History of familial cardiomyopathy
  • Recent documented myocarditis within 2 months of consent
  • History of infiltrative cardiomyopathy or restrictive cardiomyopathy
  • Epidermal growth factor receptor (eGFR) < 50 by Mayo or Cockcroft formula
  • Liver function tests > 3 x upper limit of normal
  • NYHA class IV heart failure
  • Inotropic dependence
  • Unstable or life-threatening arrhythmia
  • Coagulopathy international normalized ratio (INR) > 1.5
  • Mechanical or bioprosthetic heart valve
  • Cardiogenic shock
  • Breast feeding 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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (hMSCs)

Arm II (standard of care drugs)

Arm Description

Patients receive allogeneic hMSCs IV over 10-20 minutes once weekly for 4 weeks and standard of care drugs for heart failure.

Patients receive only standard of care drugs for heart failure.

Outcomes

Primary Outcome Measures

Incidence of adverse events of intravenous injection of human mesenchymal stem cells (hMSCs) in patients with recent onset left ventricular systolic dysfunction from anthracyclines
Statistical analyses of safety will be descriptive. In particular, will provide a table of adverse events.

Secondary Outcome Measures

Change in improvement in left ventricular systolic function by 7 points
Change from baseline left ventricular ejection fraction (LVEF) at 6 months after randomization, expressed as a percentage. The comparison will be between the two groups of patients.
Development of acute heart failure decompensation
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Emergency center visits for 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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Need for new pacemaker/automatic implantable cardioverter defibrillator
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
New onset arrhythmias
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Sudden 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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Acute pulmonary edema
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Asymptomatic decrease in left ventricular ejection fraction (LVEF) of > 10%
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Heart failure admission
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Progression free survival
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.

Full Information

First Posted
March 31, 2015
Last Updated
May 11, 2022
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02408432
Brief Title
Bone Marrow Derived Mesenchymal Stem Cells in Improving Heart Function in Patients With Heart Failure Caused by Anthracyclines
Official Title
Intravenous Administration of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) in Patients With Recent Onset Anthracycline-Associated Cardiomyopathy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 11, 2016 (Actual)
Primary Completion Date
December 8, 2021 (Actual)
Study Completion Date
December 8, 2021 (Actual)

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
This randomized pilot phase I trial studies the side effects and best method of delivery of bone marrow derived mesenchymal stem cells (MSCs) in improving heart function in patients with heart failure caused by anthracyclines (a type of chemotherapy drug used in cancer treatment). MSCs are a type of stem cell that can be removed from bone marrow and grown into many different cell types that can be used to treat cancer and other diseases, such as heart failure. Bone marrow derived MSCs may promote heart muscle cells repair and lead to reverse remodeling and ultimately improve heart function and decrease morbidity and mortality from progression to advanced heart failure.
Detailed Description
PRIMARY OBJECTIVE: I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion 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 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 2 treatment arms. ARM I: Patients receive allogeneic hMSCs intravenously (IV) over 10-20 minutes once weekly for 4 weeks and standard of care drugs for heart failure. ARM II: Patients receive only standard of care drugs for heart failure. After completion of study treatment, patients are followed up monthly for 6 months and then at 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiomyopathy, Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (hMSCs)
Arm Type
Experimental
Arm Description
Patients receive allogeneic hMSCs IV over 10-20 minutes once weekly for 4 weeks and standard of care drugs for heart failure.
Arm Title
Arm II (standard of care drugs)
Arm Type
Active Comparator
Arm Description
Patients receive only standard of care drugs for heart failure.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Undergo mesenchymal stem cell infusion
Intervention Type
Drug
Intervention Name(s)
Mesenchymal Stem Cell Transplantation
Intervention Description
Undergo mesenchymal stem cell infusion
Primary Outcome Measure Information:
Title
Incidence of adverse events of intravenous injection of human mesenchymal stem cells (hMSCs) in patients with recent onset left ventricular systolic dysfunction from anthracyclines
Description
Statistical analyses of safety will be descriptive. In particular, will provide a table of adverse events.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Change in improvement in left ventricular systolic function by 7 points
Description
Change from baseline left ventricular ejection fraction (LVEF) at 6 months after randomization, expressed as a percentage. The comparison will be between the two groups of patients.
Time Frame
Baseline up to 6 months
Title
Development of acute heart failure decompensation
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Emergency center visits for 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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Need for new pacemaker/automatic implantable cardioverter defibrillator
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
New onset arrhythmias
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Sudden 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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Acute pulmonary edema
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Asymptomatic decrease in left ventricular ejection fraction (LVEF) of > 10%
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Baseline to up to 6 months
Title
Heart failure admission
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 6 months
Title
Progression free survival
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 investigational and control groups. These intervals and the associate p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.
Time Frame
Up to 12 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% from treatment with anthracyclines for all malignancies at any dose at any time without evidence of other causes of cardiomyopathy Documented New York Heart Association (NYHA) class I, II and III Been treated with appropriate maximal medical therapy for heart failure Able to perform 6 minute walk test Patient or legally authorized representative able to sign informed consent Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab Exclusion Criteria: Evidence of ischemic heart disease as determined by study cardiologist Significant valvular disease; (aortic stenosis [AS] with aortic valve area [AVA] < 1.5 and severe aortic regurgitation [AR] and mitral regurgitation [MR]) History of familial cardiomyopathy Recent documented myocarditis within 2 months of consent History of infiltrative cardiomyopathy or restrictive cardiomyopathy Epidermal growth factor receptor (eGFR) < 50 by Mayo or Cockcroft formula Liver function tests > 3 x upper limit of normal NYHA class IV heart failure Inotropic dependence Unstable or life-threatening arrhythmia Coagulopathy international normalized ratio (INR) > 1.5 Mechanical or bioprosthetic heart valve Cardiogenic shock Breast feeding 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Olson
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

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

Bone Marrow Derived Mesenchymal Stem Cells in Improving Heart Function in Patients With Heart Failure Caused by Anthracyclines

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