Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT02962661
Collaborator
National Cancer Institute (NCI) (NIH)
72
Enrollment
1
Location
3
Arms
36.4
Anticipated Duration (Months)
2
Patients Per Site Per Month

Study Details

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Other: Best Practice
  • Other: Laboratory Biomarker Analysis
  • Biological: Mesenchymal Stem Cell Transplantation
  • Biological: Mesenchymal Stem Cell Transplantation
Phase 1

Detailed Description

PRIMARY OBJECTIVE:
  1. 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:
  1. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
72 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 18, 2020
Anticipated Primary Completion Date :
Jul 30, 2023
Anticipated Study Completion Date :
Jul 30, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I (hMSCs IV)

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.

Other: Best Practice
Given standard of care
Other Names:
  • standard of care
  • standard therapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Biological: Mesenchymal Stem Cell Transplantation
    intravenous infusion (IV)

    Experimental: Arm II (hMSCs transendocardially)

    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.

    Other: Best Practice
    Given standard of care
    Other Names:
  • standard of care
  • standard therapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Biological: Mesenchymal Stem Cell Transplantation
    transendocardially (injection)

    Active Comparator: Arm III (standard of care)

    Patients receive standard of care treatment for heart failure.

    Other: Best Practice
    Given standard of care
    Other Names:
  • standard of care
  • standard therapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse events [Up to 6 months]

      Statistical analyses of safety will be descriptive.

    2. Change in left ventricular ejection fraction (LVEF) [Baseline to 6 months]

      The comparison will be between the two groups of patients.

    Secondary Outcome Measures

    1. Change in improvement of left ventricular (LV) systolic function as assessed by LVEF [Baseline up to 6 months]

      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.

    2. LV end-systolic and end-diastolic volumes as determined by contrast-enhanced 2-dimensional(D)/3D echography [Up to 6 months]

      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.

    3. Cardiac death [Up to 6 months]

      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.

    4. Re-hospitalization after heart failure [Up to 6 months]

      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.

    5. Aborted death from an automatic implantable cardioverter defibrillator (AICD) firing [Up to 6 months]

      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.

    6. Nonfatal myocardial infarction [Up to 6 months]

      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.

    7. Revascularization [Up to 6 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • Documented New York Heart Association (NYHA) class I, II and III

    • Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab

    • Able to perform a 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; (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 enrollment

    • History of infiltrative cardiomyopathy or restrictive cardiomyopathy

    • Estimated glomerular filtration rate (eGFR) < 50 by Mayo or Cockcroft formula.

    • 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

    • Coagulopathy international normalized ratio (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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1M D Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Amanda Olson, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02962661
    Other Study ID Numbers:
    • 2015-0835
    • NCI-2016-01921
    • 2015-0835
    • P30CA016672
    First Posted:
    Nov 11, 2016
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 1, 2021
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021