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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of mesenchymal stem cells, sourced from donor bone marrow, in managing heart failure in individuals whose hearts have been weakened by anthracycline treatments (a type of chemotherapy). Participants will receive either stem cells injected directly into the heart, through an IV, or will continue with standard heart failure treatment to determine which method is most effective. Prospective participants should have heart failure symptoms with reduced heart function due to past cancer treatments involving anthracyclines and should be managing their condition with regular heart failure treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using mesenchymal stem cells (MSCs) to treat heart failure is generally safe. When administered through an IV, studies have found no serious side effects, though some people might experience mild reactions like a fever. This suggests the treatment is relatively safe.

When MSCs are delivered directly into the heart, safety remains promising. Studies indicate that various delivery methods are safe for heart failure, though some might be more effective than others.

Since this trial is in the early stages, it focuses on testing safety. Early trials like this are crucial for understanding any possible side effects, so participation helps researchers learn more about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mesenchymal Stem Cell Transplantation is unique because it introduces stem cells directly into the heart to potentially repair damaged tissue, which is a novel approach compared to standard heart failure treatments that primarily manage symptoms. Researchers are excited about this treatment because it offers a regenerative solution, aiming to improve heart function and patient outcomes rather than just slowing disease progression. Additionally, the treatment can be administered in two innovative ways: transendocardially, delivering cells directly into the heart muscle, or intravenously, providing a less invasive option while still aiming for effective results. These approaches could revolutionize how heart failure is treated by addressing the root cause of the damage.

What evidence suggests that mesenchymal stem cell transplantation might be an effective treatment for heart failure?

Research has shown that mesenchymal stem cells (MSCs) can benefit people with heart failure. In this trial, participants will receive MSCs either intravenously or transendocardially, or they will receive standard care treatment. Studies have found that injecting MSCs into the bloodstream or directly into the heart muscle might reduce the risk of death and improve health for those with heart problems due to poor blood flow or heart muscle issues. While MSC treatment has been safe and has improved the quality of life for some patients, it has not always led to significant improvements in heart pumping function. More research is needed to confirm these early results, but MSCs show promise in managing heart failure symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

Amanda Olson

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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 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 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]

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]

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]

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]

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]

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]

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