Cardiomyopathy, Heart Failure, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Conditions
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.
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.
Interventions
OTHERBest Practice
Given standard of care
OTHERLaboratory Biomarker Analysis
Correlative studies
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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 \</= 90 years of age. English and non-English speaking patients are eligible. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Up to 6 months | Statistical analyses of safety will be descriptive. |
| Change in left ventricular ejection fraction (LVEF) | Baseline to 6 months | The comparison will be between the two groups of patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
Primary ContactAmanda Olson, MD
Outcome results
None listed