Allogenic Adipose-Derived Mesenchymal Stem Cells for the Treatment of Recurrent Glioblastoma or Recurrent Astrocytoma in Patients Undergoing Craniotomy

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Allogeneic Adipose-derived Mesenchymal Stem Cells
  Receive IT
• Процедура Biospecimen Collection
  Undergo blood and tissue sample collection
• Процедура Craniotomy
  Undergo craniotomy
• Процедура Magnetic Resonance Imaging
  Undergo MRI
• Процедура Ommaya Reservoir Tap
  Undergo Ommaya reservoir placement for collection of CSF

Первичные конечные точки

• Maximum tolerated dose (MTD) [Срок оценки: Up to 4 weeks]

Вторичные конечные точки (5)

• Incidence of adverse events (AEs) [Срок оценки: Up to 1 year]
• Best response [Срок оценки: Up to 5 years]
• Response rate (RR) [Срок оценки: Up to 5 years]
• Progression free survival [Срок оценки: From time of AMSCs application until the first occurrence of progression or death, assessed up to 5 years]
• Overall survival [Срок оценки: From beginning the time of AMSCs application to the date of death, assessed up to 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Mayo Clinic in Florida — Jacksonville

Идентификаторы

NCT: NCT05789394 · MC220704 · 21-004561

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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