Study design and participants
abnormal renal (, tumor
ADVERSE EVENTS, TUMOR, RECRUITMENT, COMPLICATIONS
This investigation was an open-label, non-randomized, single-arm phase I clinical trial with a 3 + 3 dose escalation design, which was approved by the institutional review board of the Shohada Tajrish hospital and the ethics committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.REC.1396.224). This clinical trial was also registered at the Iranian Registry of Clinical Trials (IRCT20200502047277N2). In the present study, all patients who were referred to the neurosurgery department of Shohada Tajrish hospital due to recurrent GBM between October 2020 to March 2021 were screened for eligibility. Before enrollment, patients were fully informed regarding the experimental nature of the study intervention, all potential outcomes, and possible complications or intervention-related adverse events (AEs). After that, written informed consent, including all the study procedures was obtained from all patients. To improve the reporting quality, this clinical trial followed Consolidated Standards of Reporting Trials (CONSORT) guidelines.The inclusion criteria were age ≥ 18 years, Karnofsky performance scale ≥ 70, previous diagnosis of GBM based on histopathological examination of the tumor specimen, recurrent GBM with clinical and radiological evidence highly suggestive of true progression (exclusion of pseudoprogression as mentioned later in this section), complete course of standard treatment for GBM previously, including standard chemoradiotherapy regimen with or without surgical resection, and tumor location accessible for stereotactic cell injection. Exclusion criteria were surgical resection for recurrent GBM, inaccessible tumor location (e.g., brainstem), high suspicion of pseudoprogression (mentioned later in this section), abnormal renal (serum creatinine > 1.5 mg/dL), hepatic (serum bilirubin > 1.5 mg/dL or serum transaminases level > 3 x upper limit of normal), immunologic (known immunosuppression or white blood cell < 3 × 10Moreover, in order to exclude cases with pseudoprogression, the clinical and radiological characteristics of the patient were taken into account. Regarding this, any case with increased contrast-enhanced tumor (CET) volume, who also had clinical deterioration, increased steroid intake, and mutation status associated with poor prognosis, was included in this study. However, in case of unremarkable clinical status and absence of mutations associated with poor prognosis, further imaging studies were utilized. In this study, radiological evidence suggestive of true progression was considered as apparent diffusion coefficient ratio < 1.5 on diffusion MR imaging, relative cerebral blood volume < 3.0 on perfusion MR imaging, or choline/N-acetylaspartate > 2 on magnetic resonance spectroscopy.After recruitment, all patients were assigned to the single study arm and no blinding was performed given the goal of the trial, which was safety evaluation. This investigation was performed according to the Declaration of Helsinki and good clinical practice guidelines. All procedures for the preparation of stem cell vectors in this study, such as cell culture and vector transduction, were performed in a good manufacturing practice (GMP)- and clinical-grade clean room, which was specifically designed to produce cellular therapy products. Moreover, all the materials used during the vector preparation process were GMP-grade in order to prevent potential contamination. Quality control at the end of the production process was performed and ADSC vectors were controlled for any potential contamination before their use.