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.

PRIMARY OBJECTIVE:

I. To establish the maximum tolerated dose (MTD) of locally delivered adipose-derived mesenchymal stem cells (AMSCs) in patients with recurrent glioblastoma (GBM).

SECONDARY OBJECTIVES:

I. To assess the safety and toxicity profile of locally delivered AMSCs in patients with recurrent GBM.

II. To assess overall survival (OS) in recurrent GBM patients treated with locally delivered AMSCs.

III. To assess progression free survival (PFS) in recurrent GBM patients treated with locally delivered AMSCs.

CORRELATIVE OBJECTIVES:

I. To explore the systemic immune response after application of AMSCs through cytokine analysis on peripheral blood samples.

II. To explore the local changes on the brain parenchyma by analyzing tissue at recurrence.

III. To explore the presence of AMSCs on brain tissue at recurrence.

OUTLINE: This is a dose-escalation study.

Patients receive AMSCs intratumorally (IT) and undergo Ommaya reservoir placement during a craniotomy on study. Patients also undergo magnetic resonance imaging (MRI) on study and during follow-up, as well as blood sample, tissue sample and cerebrospinal fluid (CSF) sample collection on study.

After completion of study treatment patients are followed up every 2 months for 1 year.

Inclusion Criteria:

• Participants >= 18 years
• Karnofsky Performance Scale (KPS) >= 60
• Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
• Patients with a previous histological diagnosis of glioblastoma multiforme, isocitrate dehydrogenase (IDH) wildtype (WT) or astrocytoma, IDH-mutant World Health Organization (WHO) grade IV according to the 2021 WHO classification of tumors of the central nervous system , who are candidates to- and will undergo a redo craniotomy for excision of recurrent tumor
• There is measurable disease according to the immunotherapy response assessment in neuro-oncology (iRANO) criteria
• Serum creatinine and urea <= 2 times the upper limit of normal (=< 3 weeks prior to registration)
• Alanine transaminase (ALT), aspartate transferase (AST) and alkaline phosphatase =< 3 times the upper limit of normal, and bilirubin =< 2.5 mg/dL (=< 3 weeks prior to registration)
• Prothrombin time =< 1.5 times upper limit of normal (=< 3 weeks prior to registration)
• International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 times the upper limit of normal (=< 3 weeks prior to registration)
• Hemoglobin >= 9 g/dL (=< 3 weeks prior to registration)
• Platelets >= 100 x 10^9/L (=< 3 weeks prior to registration)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (=< 3 weeks prior to registration)
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Patient or legally authorized representative (LAR) is able to fully understand and provide written and verbal consent for the protocol
• Willingness to provide mandatory blood specimens for correlative research
• Willingness to provide mandatory tissue specimens for correlative research
• Willingness to undergo Ommaya reservoir placement and provide cerebrospinal fluid (CSF) samples for correlative research

Exclusion Criteria:

• Patients who are undergoing needle biopsy only or non-eligible for a surgical intervention
• Tumors located solely in the brain stem, midbrain, or thalamus without inclusion/involvement of surrounding brain matter
• Previous treatment with bevacizumab
• Radiographic evidence of leptomeningeal disease