Mesenchymal Stem Cell Transplantation for Heart Failure

Overseen By Amanda Olson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressives, Anticoagulants

Disqualifiers: Ischemic heart disease, Valvular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should have been treated with appropriate maximal medical therapy for heart failure, which suggests you may need to continue your current heart failure medications.

What data supports the effectiveness of the treatment Mesenchymal Stem Cell Transplantation for Heart Failure?

Research shows that mesenchymal stem cells (MSCs) can help repair the heart by turning into heart cells and releasing substances that promote healing and reduce inflammation. Clinical trials have suggested that MSC therapy is safe and has potential benefits for heart failure patients. ^{1 2 3 4 5}

Is mesenchymal stem cell therapy safe for heart failure patients?

Research suggests that mesenchymal stem cell therapy appears to be safe for patients with heart conditions like heart failure, as studies found no link between the therapy and immediate harmful effects. However, more detailed studies are needed to fully understand the long-term safety. ^{6 7 8 9 10}

How is Mesenchymal Stem Cell Transplantation different from other heart failure treatments?

Mesenchymal Stem Cell Transplantation is unique because it uses stem cells that can transform into heart and blood vessel cells, helping repair heart damage. Unlike traditional treatments, it also releases growth factors that encourage local cell growth and reduce inflammation, offering a regenerative approach to heart failure. ^{1 5 11 12 13}

What is the purpose of this trial?

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.

Research Team

Amanda Olson

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults aged 18-80 with heart failure due to cardiomyopathy caused by anthracyclines used in cancer treatment. Participants must have a left ventricular ejection fraction (LVEF) of 40% or less, be classified as NYHA class I, II, or III, and able to walk for six minutes. Excluded are those with ischemic heart disease, severe valve disease, familial cardiomyopathy, liver issues, the most severe heart failure (NYHA class IV), certain blood clotting and valve conditions.

Inclusion Criteria

I can walk for 6 minutes without assistance.

I have received the highest standard of treatment for heart failure.

My heart's pumping ability is reduced due to cancer treatment.

Exclusion Criteria

You have a mechanical or bioprosthetic heart valve.

I have had myocarditis in the last 2 months.

Your liver function tests show more than three times the normal levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive hMSCs intravenously or transendocardially and standard of care treatment for heart failure

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Treatment Details

Interventions

• Mesenchymal Stem Cell Transplantation

Trial Overview The study tests whether mesenchymal stem cells from donor bone marrow can control symptoms and improve heart function in patients with anthracycline-induced cardiomyopathy. It's a phase I pilot trial that randomly assigns participants to receive either these stem cells or follow best practice care without them.

Participant Groups

Group I: Arm II (hMSCs transendocardially) Experimental Treatment 3 Interventions

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.

Group II: Arm I (hMSCs IV) Experimental Treatment 3 Interventions

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.

Group III: Arm III (standard of care) Active Control 2 Interventions

Patients receive standard of care treatment for heart failure.

Mesenchymal Stem Cell Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Mesenchymal Stem Cell Transplantation for:

• Heart Failure
• Cardiomyopathy caused by Anthracyclines

Approved in European Union as Mesenchymal Stem Cell Transplantation for:

• Heart Failure
• Ischemic Cardiomyopathy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Mesenchymal stem cells (MSC) show promise as a therapeutic option for heart failure due to their ability to differentiate into heart-related cells and their paracrine effects that promote cardiac repair.

Current clinical trials are underway to assess the safety and efficacy of using autologous MSC in treating heart failure, building on encouraging results from previous in vitro and in vivo studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells for the treatment of heart failure. Ohnishi, S., Ohgushi, H., Kitamura, S., et al.[2018]

Intravenous administration of ischemia-tolerant mesenchymal stem cells (itMSCs) in patients with nonischemic cardiomyopathy was found to be safe, with no major differences in serious adverse events compared to placebo.

itMSC therapy led to significant improvements in patients' functional capacity, as evidenced by increased 6-minute walk distance and better health status scores, suggesting potential benefits in managing heart failure symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial. Butler, J., Epstein, SE., Greene, SJ., et al.[2022]

Mesenchymal stem cells (MSC) show promise in treating heart failure due to their ability to regenerate cardiac tissue by differentiating into heart cells and releasing beneficial factors that promote blood vessel growth and prevent cell death.

Current clinical trials are underway to assess the safety and effectiveness of using autologous MSC (stem cells derived from the patient's own body) as a new therapeutic strategy for heart failure, which could provide alternatives to more invasive treatments like mechanical support and heart transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Regenerative medicine for heart failure]. Nagaya, N., Kitamura, S.[2018]

Bone marrow-derived mesenchymal stem cell (MSC) therapy shows promise for treating heart failure, with over 40 clinical trials indicating its feasibility and safety, although results are still preliminary.

Key future directions for MSC therapy include improving cell delivery methods to enhance engraftment, understanding the mechanisms of therapeutic effects, and validating the use of allogeneic MSCs to broaden treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow-derived mesenchymal stem cells for the treatment of heart failure. Narita, T., Suzuki, K.[2022]

In a study involving 13 patients with end-stage heart failure due to various causes, autologous bone marrow stem cell transplantation led to functional improvements in the heart and enhanced quality of life, with follow-up periods ranging from 6 months to 2 years.

The stem cells were administered through different methods (intracoronary, direct myocardial injection, and intrapulmonary), and the results suggest that stem cells may effectively replace damaged heart cells and promote healing through their paracrine effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell therapy for cardiovascular disorders - our clinical experience. Jayakrishnan, AG., Madhusankar, N., Rao, YY., et al.[2020]

A systematic review of 23 clinical trials involving mesenchymal stem cells (MSCs) for treating acute myocardial infarction (AMI) and ischemic heart failure (IHF) found no association between MSC therapy and acute adverse events, indicating a favorable safety profile.

Patients receiving MSCs showed a significant improvement in left ventricular ejection fraction (LVEF), suggesting enhanced heart function, although there was no significant difference in mortality rates, highlighting the need for further research to clarify the overall benefits and risks of MSC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis. Lalu, MM., Mazzarello, S., Zlepnig, J., et al.[2019]

Stem cell transplantation, when added to standard medication, significantly improves heart function in chronic heart failure patients, as indicated by a greater reduction in left ventricular end-diastolic volume (LVEDV) compared to standard treatment alone.

Patients receiving stem cell therapy also experience a lower risk of cardiac events, suggesting that this approach not only enhances heart remodeling but also improves overall safety in managing chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A meta-analysis on the efficacy of stem cells transplantation therapy on the prevention of cardiac remodeling and main adverse cardiovascular event in patients with chronic heart failure]. He, W., Wang, G., Quan, XQ., et al.[2013]

In a study of eight patients with severe ischemic cardiomyopathy who were not candidates for revascularization, long-term follow-up over 5 years showed that six patients remained alive, indicating a potential benefit of autologous bone marrow transplantation in this high-risk group.

While there were two deaths related to complications, the majority of patients did not experience significant changes in heart function, suggesting that while the treatment may not improve heart function, it could provide a degree of safety and stability in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracoronary administration of autologous bone marrow mononuclear cells in patients with chronic ischemic symptomatic cardiomyopathy: 5 years follow-up. Blatt, A., Minha, S., Moravsky, G., et al.[2011]

In a study of 8 patients with symptomatic heart failure who received mesenchymal stem cell (MSC) therapy, there were no significant improvements in heart function or biomarkers like BNP and LVEF after 2 months, indicating limited short-term efficacy.

Despite the lack of serious adverse events related to the MSC treatment, the long-term follow-up revealed that 3 patients died from unrelated causes, and 3 others were hospitalized for heart failure exacerbations, suggesting the need for further research on the long-term safety and effectiveness of MSC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Results of Intracardiac Mesenchymal Stem Cell Transplantation in Patients With Cardiomyopathy. Yagyu, T., Yasuda, S., Nagaya, N., et al.[2020]

Mesenchymal stem cell (MSC) treatment in heart failure patients showed a significant reduction in readmission rates by 34% and an improvement in exercise capacity, as measured by a 40.44 m increase in the 6-minute walk test, based on a meta-analysis of nine studies involving 612 patients.

MSC therapy also led to a notable improvement in left ventricular ejection fraction (LVEF) by more than 5.25% and a reduction in New York Heart Association (NYHA) class, indicating better heart function and overall prognosis for heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of mesenchymal stem cell therapy in systolic heart failure: a systematic review and meta-analysis. Fan, M., Huang, Y., Chen, Z., et al.[2020]

Transplantation of mesenchymal stem cells (MSCs) in a rat model of dilated cardiomyopathy (DCM) significantly improved cardiac function, evidenced by increased capillary density and reduced left ventricular pressure, indicating enhanced heart performance.

The therapeutic effects of MSCs may be due to their ability to differentiate into heart and blood vessel cells, as well as their secretion of beneficial factors that promote blood vessel growth and prevent cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Nagaya, N., Kangawa, K., Itoh, T., et al.[2016]

Cardiac mesenchymal stem cells can improve heart function when administered to damaged heart tissue, primarily through the release of beneficial factors rather than becoming heart cells themselves.

However, there are concerns about potential negative effects, such as unwanted differentiation into other cell types and risks of genetic instability, which highlight the need for careful management in their clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities and challenges for mesenchymal stem cell-mediated heart repair. Atsma, DE., Fibbe, WE., Rabelink, TJ.[2018]

Transplantation of mesenchymal stem cells (MSCs) has shown promising clinical outcomes in cardiovascular diseases, including reduced heart remodeling and improved heart cell survival, based on various trials.

Innovative preconditioning methods and novel approaches, such as genetically modified MSCs and MSC-derived exosomes, are being explored to enhance the effectiveness of MSC therapy in treating heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Conditioning Methods and Novel Approaches with Mesenchymal Stem Cells Therapy in Cardiovascular Disease. Matta, A., Nader, V., Lebrin, M., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells for the treatment of heart failure. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Regenerative medicine for heart failure]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Bone marrow-derived mesenchymal stem cells for the treatment of heart failure. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Stem cell therapy for cardiovascular disorders - our clinical experience. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[A meta-analysis on the efficacy of stem cells transplantation therapy on the prevention of cardiac remodeling and main adverse cardiovascular event in patients with chronic heart failure]. [2013]

8. Israel pubmed.ncbi.nlm.nih.gov

Intracoronary administration of autologous bone marrow mononuclear cells in patients with chronic ischemic symptomatic cardiomyopathy: 5 years follow-up. [2011]

9. Japan pubmed.ncbi.nlm.nih.gov

Long-Term Results of Intracardiac Mesenchymal Stem Cell Transplantation in Patients With Cardiomyopathy. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy of mesenchymal stem cell therapy in systolic heart failure: a systematic review and meta-analysis. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Opportunities and challenges for mesenchymal stem cell-mediated heart repair. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Pre-Conditioning Methods and Novel Approaches with Mesenchymal Stem Cells Therapy in Cardiovascular Disease. [2022]