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

Heart Failure Clinical Trial

Official title:

Intravenous Administration of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) in Patients With Recent Onset Anthracycline-Associated Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02408432
• Other study ID #: 2014-0519
• Secondary ID: NCI-2015-0096920
• Status: Completed
• Phase: Phase 1
• Start date: January 11, 2016
• Est. completion date: December 8, 2021

Study information

• Verified date: May 2022
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 8, 2021
• Est. primary completion date: December 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Heart Failure

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Standard of Care
Undergo mesenchymal stem cell infusion

Drug:
• Mesenchymal Stem Cell Transplantation
Undergo mesenchymal stem cell infusion

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 6 months
Secondary	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.	Baseline up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Baseline to up to 6 months
Secondary	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.	Up to 6 months
Secondary	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.	Up to 12 months

External Links

•   MD Anderson Cancer Center Website