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

Trial Summary

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.

What data supports the effectiveness of this treatment for glioblastoma?

Research shows that adipose-derived mesenchymal stem cells (hAMSCs) can be engineered to deliver therapeutic agents like BMP4 and oncolytic viruses to glioblastoma cells, leading to tumor suppression and increased survival in experimental models. These stem cells have a natural ability to target tumor cells, making them promising for glioblastoma treatment. ^{1 2 3 4 5}

Is stem cell therapy using adipose-derived mesenchymal stem cells generally safe for humans?

Adipose-derived mesenchymal stem cell therapy has shown a favorable safety profile in clinical trials, with few serious adverse events reported. Some studies noted the development of antibodies in patients, but the consequences are unknown, and one case of cancer recurrence was reported. Overall, the therapy appears safe, but more detailed safety assessments are needed in future studies. ^{1 6 7 8 9}

How is the treatment with Allogenic Adipose-Derived Mesenchymal Stem Cells unique for glioblastoma?

This treatment uses stem cells derived from fat tissue that can naturally find and target brain tumors, acting as carriers for therapeutic agents like viruses or proteins that suppress tumor growth. Unlike traditional treatments, these stem cells can cross the blood-brain barrier and deliver treatment directly to the tumor site, potentially improving effectiveness and reducing side effects. ^{1 2 4 5 10}

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of allogenic adipose-derived mesenchymal stem cells (AMSCs) in treating patients with glioblastoma or astrocytoma that has come back (recurrent) who are undergoing brain surgery (craniotomy). Glioblastoma is the most common and most aggressive form of primary and malignant tumor of the brain. Currently, the standard of care for this disease includes surgical resection, followed by radiation with chemotherapy and tumor treating fields. Despite this aggressive therapy, the survival after finishing treatment remains low and the disease often reoccurs. Unfortunately, the available therapy options for recurrent glioblastoma are minimal and do not have a great effect on survival. AMSCs are found in body fat and when separated from the fat, are delivered into the surgical cavity at the time of surgery. When in direct contact with tumor cells, AMSCs affect tumor growth, residual tumor cell death, and chemotherapy resistance. 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 by decreasing the progression rate and invasiveness of malignant cells.

Research Team

Alfredo Quinones-Hinojosa, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Mesenchymal stem cells from human fat engineered to secrete BMP4 are nononcogenic, suppress brain cancer, and prolong survival. [2021]

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

Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma. [2021]

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

Glioblastoma therapy with cytotoxic mesenchymal stromal cells optimized by bioluminescence imaging of tumor and therapeutic cell response. [2021]

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

Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells loaded with paclitaxel-poly(lactic-co-glycolic acid) nanoparticles for glioma-targeting therapy. [2022]

6. England 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. [2022]

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

Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. [2022]

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. [2022]

10. Netherlands 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. [2022]