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
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Change in left ventricular ejection fraction (LVEF)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Patients with LVEF \/= 18 and \
排除标准
- •Evidence of Ischemic Heart Disease as determined by study cardiologist.
- •Significant Valvular Disease. (AS with AVA <1.5 and severe AR and MR)
- •History of Familial Cardiomyopathy.
- •Recent documented myocarditis within 2 months of enrollment.
- •History of Infiltrative cardiomyopathy or restrictive cardiomyopathy.
- •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.
- •For patients not on anticoagulants, 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.
研究组 & 干预措施
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.
干预措施: Best Practice (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (standard of care)
Patients receive standard of care treatment for heart failure.
干预措施: Best Practice (Other)
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.
干预措施: Best Practice (Other)
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.
干预措施: Mesenchymal Stem Cell Transplantation (Drug)
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.
干预措施: Mesenchymal Stem Cell Transplantation (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (standard of care)
Patients receive standard of care treatment for heart failure.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Change in left ventricular ejection fraction (LVEF)
时间窗: Baseline to 6 months
The comparison will be between the two groups of patients.
Incidence of adverse events
时间窗: Up to 6 months
Statistical analyses of safety will be descriptive.
次要结局
- Cardiac death(Up to 6 months)
- Change in improvement of left ventricular (LV) systolic function as assessed by LVEF(Baseline up to 6 months)
- Re-hospitalization after heart failure(Up to 6 months)
- LV end-systolic and end-diastolic volumes as determined by contrast-enhanced 2-dimensional(D)/3D echography(Up to 6 months)
- Aborted death from an automatic implantable cardioverter defibrillator (AICD) firing(Up to 6 months)
- Nonfatal myocardial infarction(Up to 6 months)
- Revascularization(Up to 6 months)