Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma

Study Overview
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Brief Summary
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The purpose of this study is to examine the use of activated T cells (ATCs) to assess the safety and tolerability of autologous activated T cells, as measured by the number of Grade 3 or higher toxicities, the number of serious adverse events, and treatment-related toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 5, to find the maximum tolerated dose. The secondary objectives include evaluating the rate of overall survival, rate of progression-free survival, health-related quality of life parameters, overall response rate, immune response, and tumor stem cell antigen expression.

Official Title
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A Phase I Trial of Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Biological: Activated T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent glioblastoma HLA-A1 and HLA-A2 positive Complete resection of tumor Exclusion Criteria: Clinically significant pulmonary, cardiac or other systemic disease Presence of an acute infection requiring active treatment with antibiotics/antivirals; prophylactic administration is allowed. Known human immunodeficiency virus positivity or acquired immunodeficiency syndrome related illness or other serious medical condition. Known history of Hepatitis B or Hepatitis C Allergy to Dimethyl sulfoxide (DMSO) Allergy to gentamicin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Activated T cells<br> | Biological: Activated T cells<br>* Activated T cells (ATC) administered intravenously at one timepoint<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Grade 3 or higher toxicities, number of serious adverse events, and the number of treatment-related toxicities to find the maximum tolerated dose | Recorded and graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAEs) Version 5 | From start of study treatment until End of Study, an average of 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | From date of enrollment to date of death of any cause or withdrawal of consent, whichever came first. Assessed up to 3 years. | 
| Progression-Free Survival (PFS) |  | From start of study treatment, until confirmation of disease progression or withdrawal of consent, whichever came first. Assessed up to 3 years. | 
| Health-related quality of life parameters | Measured by change in the Functional Assessment of Cancer Therapy - Brain (FACT-Br) survey score. The FACT-Br total score has a range of 0-200 and higher scores indicate better quality of life | From baseline visit to End of Study, an average of 2 months | 
| Overall Response Rate (ORR) | Percentage of patients showing either partial response or complete response, in patients with subtotal resection, will be measured using Magnetic Resonance Imaging (MRI) and Immunotherapy Response Assessment in Neuro-Oncology (iRANO) Response Criteria | From pre-study Brain MRI through study completion or withdrawal of consent, whichever came first. Assessed up to 3 years. | 
| Immune Response | Assessed by cytotoxic T cell activity in vitro pre- vs post-infusion. | At Visit 1, Post-immunotherapy infusion follow-up Day 14, and Survival follow-up Month 2 | 
| Tumor stem cell antigen expression | Assessed by quantitative PCR for expression of CD133, housekeeping genes, and tumor associated antigens (including HER2, TRP-2, gp100, MAGE-1, IL13Rα2, AIM-2). | At Baseline visit and at time of recurrence. Assessed up to 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioma, brain tumor, glioblastoma, neurosurgery, surgical resection, Complete resection of tumor, extent of resection, maximal safe resection, neuropathology, astrocytoma, ependymoma