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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Treatment (AMSCs)
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.
干预措施: Allogeneic Adipose-derived Mesenchymal Stem Cells (Biological)
Treatment (AMSCs)
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.
干预措施: Biospecimen Collection (Procedure)
Treatment (AMSCs)
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.
干预措施: Craniotomy (Procedure)
Treatment (AMSCs)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (AMSCs)
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.
干预措施: Ommaya Reservoir Tap (Procedure)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to 4 weeks
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.
次要结局
- Incidence of adverse events (AEs)(Up to 1 year)
- Overall survival(From beginning the time of AMSCs application to the date of death, assessed up to 5 years)
- Best response(Up to 5 years)
- Response rate (RR)(Up to 5 years)
- Progression free survival(From time of AMSCs application until the first occurrence of progression or death, assessed up to 5 years)