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

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02962661
• Other study ID #: 2015-0835
• Secondary ID: NCI-2016-0192120
• Status: Recruiting
• Phase: Phase 1
• Start date: July 18, 2020
• Est. completion date: July 30, 2025

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: Amanda Olson, MD
• Phone: 713-745-3055
• Email: alolson[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: July 30, 2025
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Heart Failure
• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

Intervention

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

Drug:
• Mesenchymal Stem Cell Transplantation
Given IV
• Mesenchymal Stem Cell Transplantation
Given transendocardially

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	Statistical analyses of safety will be descriptive.	Up to 6 months
Primary	Change in left ventricular ejection fraction (LVEF)	The comparison will be between the two groups of patients.	Baseline to 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   MD Anderson Cancer Center