Clinical trial NCT02408432: Bone Marrow Derived Mesenchymal Stem Cells in Improving Heart Function in Patients With Heart Failure Caused by Anthracyclines
Official title: Intravenous Administration of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) in Patients With Recent Onset Anthracycline-Associated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiomyopathy
Heart Failure
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-04-03
Enrollment: 7
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 and best method of delivery of bone marrow derived mesenchymal stem cells (MSCs) in improving heart function in patients with heart failure caused by anthracyclines (a type of chemotherapy drug used in cancer treatment). MSCs are a type of stem cell that can be removed from bone marrow and grown into many different cell types that can be used to treat cancer and other diseases, such as heart failure. Bone marrow derived MSCs may promote heart muscle cells repair and lead to reverse remodeling and ultimately improve heart function and decrease morbidity and mortality from progression to advanced heart failure.

Detailed description: PRIMARY OBJECTIVE:

I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion 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 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 2 treatment arms.

ARM I: Patients receive allogeneic hMSCs intravenously (IV) over 10-20 minutes once weekly for 4 weeks and standard of care drugs for heart failure.

ARM II: Patients receive only standard of care drugs for heart failure.

After completion of study treatment, patients are followed up monthly for 6 months and then at 12 months.

Eligibility criteria: Inclusion Criteria:

* Patients with LVEF =\< 40% from treatment with anthracyclines for all malignancies at any dose at any time without evidence of other causes of cardiomyopathy
* Documented New York Heart Association (NYHA) class I, II and III
* Been treated with appropriate maximal medical therapy for heart failure
* Able to perform 6 minute walk test
* Patient or legally authorized representative able to sign informed consent
* Patients with persistent LV dysfunction 90 days after discontinuation of trastuzumab

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 consent
* History of infiltrative cardiomyopathy or restrictive cardiomyopathy
* Epidermal growth factor receptor (eGFR) \< 50 by Mayo or Cockcroft formula
* 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
* Breast feeding 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

Primary outcomes:
measure: Incidence of adverse events of intravenous injection of human mesenchymal stem cells (hMSCs) in patients with recent onset left ventricular systolic dysfunction from anthracyclines
timeFrame: Up to 6 months
Secondary outcomes:
measure: Change in improvement in left ventricular systolic function by 7 points
timeFrame: Baseline up to 6 months
measure: Development of acute heart failure decompensation
timeFrame: Up to 6 months
measure: Emergency center visits for heart failure
timeFrame: Up to 6 months
measure: Need for new pacemaker/automatic implantable cardioverter defibrillator
timeFrame: Up to 6 months
measure: New onset arrhythmias
timeFrame: Up to 6 months
measure: Sudden cardiac death
timeFrame: Up to 6 months
measure: Acute pulmonary edema
timeFrame: Up to 6 months
measure: Asymptomatic decrease in left ventricular ejection fraction (LVEF) of > 10%
timeFrame: Baseline to up to 6 months
measure: Heart failure admission
timeFrame: Up to 6 months
measure: Progression free survival
timeFrame: Up to 12 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
role: PRINCIPAL_INVESTIGATOR
References: