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

• ClinicalTrials.gov Identifier: NCT02962661
• Recruitment Status: Recruiting
• First Posted: November 11, 2016
• Last Update Posted: October 8, 2021
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

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 disease	Intervention/treatment	Phase
Cardiomyopathy; Heart Failure	Other: Best Practice; Other: Laboratory Biomarker Analysis; Biological: Mesenchymal Stem Cell Transplantation	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated 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: July 18, 2020
• Estimated Primary Completion Date: July 30, 2023
• Estimated Study Completion Date: July 30, 2023

Arms and Interventions

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: 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 [ Time Frame: Up to 6 months ]
   Statistical analyses of safety will be descriptive.
2. Change in left ventricular ejection fraction (LVEF) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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

Contacts

Contact: Amanda L. Olson, MD; 713-745-1505; alolson@mdanderson.org

Locations

United States, Texas

M D Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Amanda Olson 713-745-3055

Principal Investigator: Amanda Olson

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

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

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02962661
• Other Study ID Numbers: 2015-0835; NCI-2016-01921 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2015-0835 ( Other Identifier: M D Anderson Cancer Center ); P30CA016672 ( U.S. NIH Grant/Contract )
• First Posted: November 11, 2016
• Last Update Posted: October 8, 2021
• Last Verified: September 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:

Heart Failure; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases