Clinical trial NCT02962661: Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cardiomyopathy
Heart Failure
Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-11-11
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 6 months
measure: Change in left ventricular ejection fraction (LVEF)
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change in improvement of left ventricular (LV) systolic function as assessed by LVEF
timeFrame: Baseline up to 6 months
measure: LV end-systolic and end-diastolic volumes as determined by contrast-enhanced 2-dimensional(D)/3D echography
timeFrame: Up to 6 months
measure: Cardiac death
timeFrame: Up to 6 months
measure: Re-hospitalization after heart failure
timeFrame: Up to 6 months
measure: Aborted death from an automatic implantable cardioverter defibrillator (AICD) firing
timeFrame: Up to 6 months
measure: Nonfatal myocardial infarction
timeFrame: Up to 6 months
measure: Revascularization
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Amanda Olson, MD
role: PRINCIPAL_INVESTIGATOR
References: