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.
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
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
Single group
Allogeneic Adipose-derived Mesenchymal Stem Cells
Biological/VaccineReceive IT
Biospecimen Collection
Procedure/SurgeryUndergo blood and tissue sample collection
Craniotomy
Procedure/SurgeryUndergo craniotomy
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Ommaya Reservoir Tap
Procedure/SurgeryUndergo Ommaya reservoir placement for collection of CSF
Maximum tolerated dose (MTD)
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients). Will use the standard cohort 3+3 design.
Incidence of adverse events (AEs)
All patients who have received any treatment will be considered evaluable for assessing adverse event rates. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Will follow the Common Terminology Criteria for Adverse Events version 5.0 to record and grade (1-5) any potential AEs.
Best response
Best response per patient is defined to be the best objective status recorded from treatment application until disease progression or death (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Best response assignment will depend on the achievement of both measurement and confirmation criteria.
Response rate (RR)
RR is defined as the number of patients who have achieved complete response or partial response per immunotherapy response assessment for neuro-oncology for recurrent glioblastoma after application of allogeneic adipose-derived mesenchymal stem cells (AMSCs) divided by total number of evaluable patients. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.
Progression free survival
The quality of survival will be measured by performance status. The data on time-related variables will be summarized descriptively.
Click on the lead sponsor to view all of their trials.
