Stem Cell Therapy for Glioblastoma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Bevacizumab

Disqualifiers: Needle biopsy, Brain stem tumors, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using stem cells derived from body fat to help patients with recurrent glioblastoma or astrocytoma, aggressive brain tumors. The goal is to determine if these stem cells can safely reduce tumor growth and resistance to chemotherapy when placed directly in the brain during surgery. Patients with glioblastoma or astrocytoma undergoing surgery for tumor removal might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research continues to determine the safety of using stem cells from body fat to treat recurrent glioblastoma, a type of brain cancer. Surgeons place these stem cells in the surgical area during brain surgery to assess their potential in fighting the tumor.

The current research phase focuses on finding the safest dose and understanding any side effects. As this treatment remains in early testing stages, clear data on its tolerance is not yet available. However, this phase is crucial for identifying major safety concerns before further research can proceed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and chemotherapy, this innovative approach uses allogenic adipose-derived mesenchymal stem cells (AMSCs) to potentially combat the disease. One of the standout features of AMSCs is their ability to home in on tumor sites and modulate the immune response, offering a new mechanism that could enhance tumor targeting and treatment effectiveness. Additionally, the delivery method via an Ommaya reservoir placed during a craniotomy allows for direct administration into the cerebrospinal fluid, potentially increasing the treatment's impact directly at the site of the tumor. Researchers are excited about this novel approach because it might provide a more targeted, less invasive, and potentially more effective treatment option for glioblastoma patients.

What evidence suggests that this treatment might be an effective treatment for glioblastoma?

Research has shown that certain stem cells from donated fat tissue, known as allogenic adipose-derived mesenchymal stem cells (AMSCs), can affect tumor growth and increase cancer cell death in glioblastoma, a type of brain cancer. In lab studies, brain cancer cells showed lower survival rates when exposed to these stem cells, with survival dropping to about 52.3% to 69.4%, depending on the cancer cell type. This trial will explore the effects of AMSCs on patients with glioblastoma, aiming to determine if they might help shrink tumors and slow cancer progression. Although more human studies are needed, these early findings offer promise for treating recurring glioblastoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Alfredo Quinones-Hinojosa, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with recurrent glioblastoma who've had standard treatment and are now undergoing brain surgery. They must have certain normal blood, liver, and kidney functions, understand the study, consent to provide samples for research, not be pregnant or breastfeeding if applicable, and agree to follow-up visits.

Inclusion Criteria

If you are able to become pregnant, a negative pregnancy test taken within the past week is required before registration.

Your hemoglobin level must be at least 9 g/dL in the preceding three weeks before registering.

You are willing to return to the enrolling institution for follow-up assessments during the monitoring phase of the study.

Exclusion Criteria

Radiographic evidence of leptomeningeal disease

My tumor is in the brain stem, midbrain, or thalamus.

I have been treated with bevacizumab before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive AMSCs intratumorally and undergo Ommaya reservoir placement during a craniotomy

Up to 4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI and sample collections

1 year

Every 2 months

Long-term follow-up

Participants are monitored for progression free survival and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogenic Adipose-Derived Mesenchymal Stem Cells

Trial Overview The trial tests allogenic adipose-derived mesenchymal stem cells (AMSCs) delivered into the surgical cavity during craniotomy in patients with recurrent glioblastoma. It aims to find a safe dose that might slow tumor growth and improve survival by affecting residual tumor cells after surgery.

How Is the Trial Designed?

Group I: Treatment (AMSCs) Experimental Treatment 5 Interventions

Patients receive AMSCs IT and undergo Ommaya reservoir placement during a craniotomy on study. Patients also undergo MRI on study and during follow-up, as well as blood sample, tissue sample, and CSF sample collection on study.

Allogenic Adipose-Derived Mesenchymal Stem Cells is already approved in United States for the following indications:

Approved in United States as Allogenic Adipose-Derived Mesenchymal Stem Cells for:

• Research use for various conditions including glioblastoma, astrocytoma, knee osteoarthritis, and acute radiation syndrome

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Human adipose mesenchymal stromal cells (hAMSCs) expressing thymidine kinase (TK) can effectively reduce glioblastoma (GB) tumors to a chronically inhibited state, demonstrating their therapeutic potential in a preclinical model.

The study found that up to 25% of unmodified hAMSCs can be included in the treatment without compromising efficacy, and that tumor debulking prior to cell therapy enhances tumor growth inhibition, suggesting a promising approach for GB treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms. Guerra-Rebollo, M., Nogueira de Moraes, C., Alcoholado, C., et al.[2020]

Engineered human adipose-derived mesenchymal stem cells (hAMSCs-BMP4) effectively targeted glioblastoma cells, reducing their proliferation and migration while promoting differentiation of brain tumor-initiating cells (BTICs), both in vitro and in vivo.

The use of hAMSCs was found to be safe in animal models, and hAMSCs-BMP4 significantly prolonged survival in mice with glioblastoma, suggesting they are a promising treatment option for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells from human fat engineered to secrete BMP4 are nononcogenic, suppress brain cancer, and prolong survival. Li, Q., Wijesekera, O., Salas, SJ., et al.[2021]

Injecting mesenchymal stem cells (MSCs) loaded with paclitaxel (Ptx)-encapsulated nanoparticles significantly improved survival in rats with glioma compared to other treatment methods, indicating effective tumor-targeted therapy.

The MSCs maintained their migration and differentiation abilities while enhancing the sustained release of the drug, demonstrating a safe and effective mechanism for delivering chemotherapy directly to tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells loaded with paclitaxel-poly(lactic-co-glycolic acid) nanoparticles for glioma-targeting therapy. Wang, X., Gao, J., Ouyang, X., et al.[2022]

A systematic review of 70 studies involving over 1,400 patients treated with adipose-derived cell therapy indicated a generally favorable safety profile, with only one reported case of breast cancer recurrence among 121 patients.

Concerns remain regarding thromboembolic events, as one case of pulmonary thromboembolism and instances of myocardial and cerebral infarctions were noted, highlighting the need for improved safety assessment methods in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events. Toyserkani, NM., Jørgensen, MG., Tabatabaeifar, S., et al.[2022]

Glioblastoma, a highly aggressive brain tumor, has a poor prognosis with an average survival of only 14.6 months, largely due to its ability to evade the immune system and promote tumor growth through immunosuppressive factors.

Mesenchymal stem cells (MSCs) show promise as a therapeutic approach for glioblastoma due to their ability to migrate to tumor sites, modulate the immune response, and potentially deliver treatments across the blood-brain barrier, making them effective 'Trojan horses' in brain cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammatory Mediators in Glioma Microenvironment Play a Dual Role in Gliomagenesis and Mesenchymal Stem Cell Homing: Implication for Cellular Therapy. Al-Kharboosh, R., ReFaey, K., Lara-Velazquez, M., et al.[2022]

Human adipose tissue-derived mesenchymal stem cells (hAdMSCs) were found to be safe for intravenous administration, as no toxicity or side effects were observed in immunodeficient mice even at high doses over a 13-week period.

In a clinical trial involving 8 patients with spinal cord injuries, the administration of hAdMSCs did not result in any serious adverse events during a 3-month follow-up, indicating their potential for safe therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Ra, JC., Shin, IS., Kim, SH., et al.[2022]

This first-in-human phase I clinical trial demonstrated that suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying the HSV-TK gene is safe and well tolerated in patients with recurrent glioblastoma multiforme (GBM).

Although 91.7% of patients experienced tumor progression, the median overall survival was 16 months, with some patients showing partial response and stable disease, indicating potential for further investigation into the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cell gene delivery vehicles in recurrent glioblastoma multiforme: a first-in-human, dose-escalation, phase I clinical trial. Oraee-Yazdani, S., Tavanaei, R., Rostami, F., et al.[2023]

Genetically modified adipose tissue-derived mesenchymal stromal cells (hAMSCs) effectively target and reduce glioblastoma tumors in SCID mice, showing a significant reduction in tumor size by a factor of 10,000 after treatment with ganciclovir (GCV) over 49 days.

The mechanism of action involves hAMSCs homing to tumor blood vessels and differentiating into endothelial cells, suggesting they can be used as vehicles for localized therapy in glioblastoma treatment, especially after surgical removal of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma therapy with cytotoxic mesenchymal stromal cells optimized by bioluminescence imaging of tumor and therapeutic cell response. Alieva, M., Bagó, JR., Aguilar, E., et al.[2021]

Adipose-derived stem cells (ADSCs) can effectively deliver the myxoma virus to glioblastoma cells, leading to significant cell death in the tumor while maintaining ADSC viability.

In vivo studies showed that injecting myxoma virus-infected ADSCs into the brain resulted in increased survival rates for glioblastoma-bearing mice, suggesting a novel therapeutic strategy for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma. Josiah, DT., Zhu, D., Dreher, F., et al.[2021]

The secretome of human adipose-derived stem cells (hADSC) did not enhance the cancer stem cell features or drug resistance in human glioblastoma (GBM) cells, indicating a level of safety for potential cancer therapies.

While hADSC conditioned medium did not affect the proliferation or drug response of GBM cells, it significantly increased their migration capacity, suggesting that interactions between hADSCs and tumor cells could influence tumor behavior in the microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Onzi, GR., Ledur, PF., Hainzenreder, LD., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05789394

Study Details | NCT05789394 | Allogenic Adipose-Derived ... The use of AMSCs delivered locally into the surgical cavity of recurrent glioblastoma during a craniotomy could improve the long-term outcomes of these patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10923529/

A Clinical Trial Protocol - PubMed Central - NIH The objective was to assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39959387/

A Clinical Trial Protocol Expected outcomes: This study will explore the maximum tolerated dose of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM.

4. trialx.com trialx.com/clinical-trials/listings/236390/allogenic-adipose-derived-mesenchymal-stem-cells-for-the-treatment-of-recurrent-glioblastoma-or-recurrent-astrocytoma-in-patients-undergoing-craniotomy/?&radius=50

Allogenic Adipose-Derived Mesenchymal Stem Cells for ... The use of AMSCs delivered locally into the surgical cavity of recurrent glioblastoma during a craniotomy could improve the long-term outcomes ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0304419X21000792

Mesenchymal stem cells in glioblastoma therapy and ... Survival of glioma cells co-cultured with MSCs was reduced to 69.4% in case of ΔGli36 line, and 52.3% to 56.6% in patient-derived glioma cells, compared to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38464470/

A Clinical Trial Protocol - PubMed - NIH This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM.

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05789394

Allogenic Adipose-Derived Mesenchymal Stem Cells for ... ... Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol. ... Download Trial Data ...