Back to resultsAllogenic Adipose-Derived Mesenchymal Stem Cells for the Treatment of Recurrent Glioblastoma in Patients Undergoing Craniotomy
Primary Purpose
Recurrent Glioblastoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Adipose-derived Mesenchymal Stem Cells
Biospecimen Collection
Craniotomy
Magnetic Resonance Imaging
Ommaya Reservoir Tap
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Glioblastoma
Eligibility Criteria
Inclusion Criteria: Participants >= 18 years < 65 years of age 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 GBM that show recurrence at the same location, who are candidates to- and will undergo a redo craniotomy for excision of recurrent tumor Patients have undergone previous standard of care as outlined by Stupp et al. (2004) which include maximal safe resection followed by concomitant radiation therapy and chemotherapy with oral temozolomide 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 in the brain stem, midbrain, or thalamus Previous treatment with bevacizumab Radiographic evidence of leptomeningeal disease
Sites / Locations
- Mayo Clinic in FloridaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (AMSCs)
Arm Description
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 and CSF sample collection on study.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Overall survival
The quality of survival will be measured by performance status. The data on time-related variables will be summarized descriptively.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05789394
Brief Title
Allogenic Adipose-Derived Mesenchymal Stem Cells for the Treatment of Recurrent Glioblastoma in Patients Undergoing Craniotomy
Official Title
Phase 1, Dose Escalation, Non-Randomized, Open Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells (AMSCs) for Recurrent Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2023 (Actual)
Primary Completion Date
July 24, 2024 (Anticipated)
Study Completion Date
July 24, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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 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 GBM 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 GBM during a craniotomy could improve the long-term outcomes of these patients by decreasing the progression rate and invasiveness of malignant cells.
Detailed Description
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 and cerebrospinal fluid (CSF) sample collection on study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (AMSCs)
Arm Type
Experimental
Arm Description
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 and CSF sample collection on study.
Intervention Type
Biological
Intervention Name(s)
Allogeneic Adipose-derived Mesenchymal Stem Cells
Other Intervention Name(s)
Allogeneic Adipose-derived MSCs, Allogeneic Adipose-derived Stem/Stromal Cells, Allogeneic Mesenchymal Stem/Stromal Cells
Intervention Description
Receive IT
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood sample collection
Intervention Type
Procedure
Intervention Name(s)
Craniotomy
Other Intervention Name(s)
incision of the skull, Open Craniotomy
Intervention Description
Undergo craniotomy
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Procedure
Intervention Name(s)
Ommaya Reservoir Tap
Other Intervention Name(s)
Ommaya Reservoir Access
Intervention Description
Undergo Ommaya reservoir placement for collection of CSF
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
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.
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
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.
Time Frame
Up to 1 year
Title
Best response
Description
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.
Time Frame
Up to 5 years
Title
Response rate (RR)
Description
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.
Time Frame
Up to 5 years
Title
Progression free survival
Description
The quality of survival will be measured by performance status. The data on time-related variables will be summarized descriptively.
Time Frame
From time of AMSCs application until the first occurrence of progression or death, assessed up to 5 years
Title
Overall survival
Description
The quality of survival will be measured by performance status. The data on time-related variables will be summarized descriptively.
Time Frame
From beginning the time of AMSCs application to the date of death, assessed up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants >= 18 years < 65 years of age
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 GBM that show recurrence at the same location, who are candidates to- and will undergo a redo craniotomy for excision of recurrent tumor
Patients have undergone previous standard of care as outlined by Stupp et al. (2004) which include maximal safe resection followed by concomitant radiation therapy and chemotherapy with oral temozolomide
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 in the brain stem, midbrain, or thalamus
Previous treatment with bevacizumab
Radiographic evidence of leptomeningeal disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfredo Quinones-Hinojosa
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Alfredo Quinones-Hinojosa, M.D.
12. IPD Sharing Statement
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Allogenic Adipose-Derived Mesenchymal Stem Cells for the Treatment of Recurrent Glioblastoma in Patients Undergoing Craniotomy
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