Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02962661
Recruitment Status : Recruiting
First Posted : November 11, 2016
Last Update Posted : August 25, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Layout table for study information
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

Resource links provided by the National Library of Medicine


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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02962661


Contacts
Layout table for location contacts
Contact: Amanda L. Olson, MD 713-745-1505 alolson@mdanderson.org

Locations
Layout table for location information
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
Layout table for investigator information
Principal Investigator: Amanda Olson M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
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    Key Record Dates
Last Update Posted: August 25, 2020
Last Verified: August 2020

Layout table for additional information
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:
Layout table for MeSH terms
Heart Failure
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases