Trial With Mesenchymal Stromal Cells (MSCs) vs Standard of Care in Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT02962661
• Recruitment Status: Not yet recruiting
• First Posted: November 11, 2016
• Last Update Posted: May 9, 2019
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: Texas Medical Center
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

Objectives:

Primary Objective 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 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.

Condition or disease	Intervention/treatment	Phase
Other Forms of Heart Disease	Biological: Intravenous Infusion of Human Mesenchymal Stem Cells (hMSCs); Other: Routine Heart Failure Medical Therapy; Biological: Transendocardial Injections of Mesenchymal Stromal Cells	Phase 1

Study Design

• 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
• Estimated Study Start Date: July 30, 2019
• Estimated Primary Completion Date: July 30, 2023
• Estimated Study Completion Date: July 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intravenous Infusion of MSCs; Participants receive 4 weekly doses of Mesenchymal Stromal Cells (MSCs) administered intravenously at a dose of 2 x 10^6 cells/Kg. Participants treated with routine heart failure medical therapy as prescribed by physician.	Biological: Intravenous Infusion of Human Mesenchymal Stem Cells (hMSCs); Intravenous Infusion of Mesenchymal Stromal Cells (MSCs) Group: 4 weekly doses of MSCs administered intravenously at a dose of 2 x 10^6 cells/Kg.; Other Names: Intravenous Infusion of Mesenchymal Stromal Cells; MSC; Other: Routine Heart Failure Medical Therapy; Participants treated with routine heart failure medical therapy, Ace-inhibitors/Non-Selective beta blockers and when necessary diuretics/Aldosterone Inhibitors per institutionally defined standard of care.
Experimental: Transendocardial Injections of MSCs; Participants receive 15 injections of 0.2 ml Mesenchymal Stromal Cells (MSCs) at a total dose of 15 x 10^7 cells during one operative procedure. Participants treated with routine heart failure medical therapy as prescribed by physician.	Other: Routine Heart Failure Medical Therapy; Participants treated with routine heart failure medical therapy, Ace-inhibitors/Non-Selective beta blockers and when necessary diuretics/Aldosterone Inhibitors per institutionally defined standard of care.; Biological: Transendocardial Injections of Mesenchymal Stromal Cells; Transendocardial Injections of Mesenchymal Stromal Cells (MSCs) Group: 15 injections of 0.2 ml MSCs at a total dose of 15 x 10^7 cells during one operative procedure using the MyoStarTM injection catheter (Biosense Webster, Inc.).; Other Name: MSC
Active Comparator: Standard of Care; Participants treated with routine heart failure medical therapy as prescribed by physician.	Other: Routine Heart Failure Medical Therapy; Participants treated with routine heart failure medical therapy, Ace-inhibitors/Non-Selective beta blockers and when necessary diuretics/Aldosterone Inhibitors per institutionally defined standard of care.

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events of Allogeneic Human Mesenchymal Stem Cells (hMSCs) Administered by Intravenous Infusion and Transendocardial Injection [ Time Frame: 6 months ]
   Adverse events include toxicity and death during 6 months after randomization.

Secondary Outcome Measures :

1. Improvement in Left Ventricular Systolic Function (LVEF) Assessed by Left Ventricular Ejection Fraction [ Time Frame: 3, 6, and 12 months ]
2. Left Ventricular End-Systolic and End-Diastolic Volumes Determined by Contrast-Enhanced 3-D Echography [ Time Frame: 3, 6, and 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 </= 80 years of Age.
3. Documented NYHA class I, II and III.
4. Patients with persistent LV dysfunction 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. eGFR < 50 by Mayo or Cockcroft formula.
7. Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram.
8. Liver function tests > 3 x upper limit of normal.
9. NYHA class IV heart failure.
10. Inotropic dependence.
11. Unstable or life-threatening arrhythmia.
12. Coagulopathy INR > 1.5.
13. Mechanical or Bioprosthetic heart valve.
14. Cardiogenic shock.
15. Breastfeeding and/or pregnant women.
16. Autoimmune disorders on current immunosuppressive therapy.
17. Active infection not responding to appropriate therapy as determined by Study Chair.
18. Trastuzumab treatment within the last 3 months.
19. Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days.
20. AICD firing within the last 30 days.

Contacts and Locations

Contacts

Contact: Amanda L. Olson, MD; 713-745-1505; alolson@mdanderson.org

Locations

United States, Texas

University of Texas MD Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

Contact alolson@mdanderson.org

Sponsors and Collaborators

M.D. Anderson Cancer Center

Texas Medical Center

Investigators

• Principal Investigator: Amanda L. Olson, MD; M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02962661 History of Changes
• Other Study ID Numbers: 2015-0835; NCI-2016-01921 ( Registry Identifier: NCI CTRP )
• First Posted: November 11, 2016
• Last Update Posted: May 9, 2019
• Last Verified: May 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:

Other forms of heart disease; Left ventricular dysfunction; LV; Heart failure secondary to chemotherapy with anthracyclines; Human mesenchymal stem cells; hMSCs; Mesenchymal Stromal Cells; MSCs; Intravenous infusion; Transendocardial injection; Standard of care drugs for heart failure

Additional relevant MeSH terms:

Heart Diseases; Cardiomyopathies; Cardiovascular Diseases