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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Cardiomyopathy
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Best Practice; Drug: Mesenchymal Stem Cell Transplantation; Drug: Mesenchymal Stem Cell Transplantation

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.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amanda Olson, MD; Phone Number: 713-745-3055; Email: alolson@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Principal Investigator: Amanda Olson, MD
      • Contact: Amanda Olson, MD; Phone Number: 713-745-3055; Email: alolson@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Age >/= 18 and </= 80 years of Age.
3. Documented NYHA class I, II and III.
4. For patients who have received trastuzumab: Persistent LV dysfunction must be present 90 days after discontinuation of trastuzumab.
5. Able to perform 6 minute walk test.
6. Been treated with appropriate maximal medical therapy for heart failure.
7. Patient or legally authorized representative able to sign informed consent.

Exclusion Criteria:

1. Evidence of Ischemic Heart Disease as determined by study cardiologist.
2. Significant Valvular Disease. (AS with AVA <1.5 and severe AR and MR)
3. History of Familial Cardiomyopathy.
4. Recent documented myocarditis within 2 months of enrollment.
5. History of Infiltrative cardiomyopathy or restrictive cardiomyopathy.
6. Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram.
7. Liver function tests > 3 x upper limit of normal.
8. NYHA class IV heart failure.
9. Inotropic dependence.
10. Unstable or life-threatening arrhythmia.
11. For patients not on anticoagulants, INR>1.5
12. Mechanical or Bioprosthetic heart valve.
13. Cardiogenic shock.
14. Breastfeeding and/or pregnant women.
15. Autoimmune disorders on current immunosuppressive therapy.
16. Active infection not responding to appropriate therapy as determined by Study Chair.
17. Trastuzumab treatment within the last 3 months.
18. Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days.
19. AICD firing within the last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / 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: Laboratory Biomarker Analysis; Correlative studies; Other: Best Practice; Given standard of care; Other Names: standard of care; standard therapy; Drug: Mesenchymal Stem Cell Transplantation; Given IV; Drug: Mesenchymal Stem Cell Transplantation; Given transendocardially
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: Laboratory Biomarker Analysis; Correlative studies; Other: Best Practice; Given standard of care; Other Names: standard of care; standard therapy; Drug: Mesenchymal Stem Cell Transplantation; Given IV; Drug: Mesenchymal Stem Cell Transplantation; Given transendocardially
Active Comparator: Arm III (standard of care); Patients receive standard of care treatment for heart failure.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Best Practice; Given standard of care; Other Names: standard of care; standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Statistical analyses of safety will be descriptive.	Up to 6 months
Change in left ventricular ejection fraction (LVEF)	The comparison will be between the two groups of patients.	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 6 months
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.	Up to 6 months
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.	Up to 6 months
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.	Up to 6 months
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.	Up to 6 months
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.	Up to 6 months
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.	Up to 6 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amanda Olson, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2020
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: November 8, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (Estimated): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Neoplasms; Cardiomyopathies
• Other Study ID Numbers: 2015-0835 (Other Identifier: M D Anderson Cancer Center); NCI-2016-01921 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• 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