Intracavitary Administration of 15.GPC3-CAR T Cells for the Treatment of Patients with GPC3-Positive Recurrent Glioblastoma who are Undergoing Repeat Resection, GO-CART Trial

Status: active

This phase I trial studies the side effects and best dose of 15.GPC3-chimeric antigen receptor (CAR) T cells given in the tumor area (intracavitary administration) in treating patients with glioblastoma (GBM) that is GPC-3 positive and that has come back after a period of improvement (recurrent) who are undergoing repeat surgical removal (resection). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s tumor cells is added to the T cells in the laboratory. The special receptor is called a CAR. The 15.GPC3-CAR T cells in this study recognize GC33, which is the protein found on GPC-3 positive GBM, and are given via intracavitary administration during the repeat resection. They are made more effective through the addition of a gene that includes interleukin-15, which is a protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumor cells better. Giving 15.GPC3-CAR T cells via intracavitary administration may be safe, tolerable, and/or effective in treating patients with GPC3-positive recurrent GBM who are undergoing repeat resection.

Inclusion Criteria

PROCUREMENT: GPC3-positive recurrent GBM with previous resection (as determined by immunohistochemistry with an extent score of >= grade 2 [> 25% positive tumor cells] and an intensity score of >= 2 [scale 0-4]) who are planned for further resection * GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Baylor College of Medicine, Department of Pathology for all patients to meet procurement eligibility. All patients will send at least 5 unstained slides
PROCUREMENT: Age ≥ 18 years
PROCUREMENT: Karnofsky score ≥ 60%
PROCUREMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
TREATMENT: Diagnosis of GPC3-positive recurrent glioblastoma with previous resection planned for repeat resection
TREATMENT: Age ≥ 18 years
TREATMENT: Diagnosis of recurrent glioblastoma with previous resection and plans for repeat resection
TREATMENT: Karnofsky score ≥ 60%
TREATMENT: Stable neurologic exam for 7 days prior to enrollment
TREATMENT: Stable or decreasing dose of steroids over past 7 days prior to surgery and administration of therapy (max allowable dose is 0.1mg/kg dexamethasone or equivalent per day)
TREATMENT: Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
TREATMENT: Total bilirubin < 3 times upper limit of normal (ULN) for age
TREATMENT: International normalized ratio (INR) ≤ 1.7
TREATMENT: Absolute neutrophil count > 500/µl
TREATMENT: Platelet count > 100,000/µl (can be transfused but must be achieved prior to enrollment)
TREATMENT: Hemoglobin (Hgb) ≥ 7.0 g/dl (can be transfused)
TREATMENT: Pulse oximetry > 90% on room air
TREATMENT: Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
TREATMENT: Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion
TREATMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria

PROCUREMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
PROCUREMENT: History of organ transplantation
PROCUREMENT: Known HIV positivity
PROCUREMENT: Active bacterial, fungal or viral infection (except hepatitis B or hepatitis C virus infections)
TREATMENT: Pregnancy or lactation
TREATMENT: Uncontrolled infection
TREATMENT: Known HIV positivity
TREATMENT: Active bacterial, fungal or viral infection
TREATMENT: History of organ transplantation
TREATMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

PRIMARY OBJECTIVE:

I. To determine the safety of escalating doses of intracavitary administration of autologous anti-glypican-3 CAR-IL-15-iC9-expressing T-lymphocytes (15.GPC3-CAR T cells) in patients undergoing repeat resection of GPC3-positive recurrent GBM.

SECONDARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of intracavitary 15.GPC3-CAR T cells in treating patients with GPC3-positive recurrent GBM.

II. To assess the anti-tumor effect of intracavitary 15.GPC3-CAR T cells in patients with GPC3-positive recurrent GBM.

EXPLORATORY OBJECTIVE:

I. To assess the in vivo persistence, phenotype and functional activity of 15.GPC3-CAR T cells following intracavitary administration in patients with GPC3-positive recurrent GBM.

OUTLINE: This is a dose-escalation study.

Patients undergo blood sample collection at baseline for production of 15.GPC3-CAR T cells. As soon as four to six weeks later, patients undergo standard of care surgical resection plus Ommaya reservoir placement and receive 15.GPC3-CAR T cells via intracavitary administration during week 0 in the absence of unacceptable toxicity. Additionally, patients undergo blood and cerebrospinal fluid (CSF) sample collection and magnetic resonance imaging (MRI) throughout the study. Patients also undergo tumor biopsy on study.

After completion of study treatment, patients are followed up at 1, 2, 3, 4, and 8 weeks, 3, 6, 9, and 12 months, every 6 months for 4 years, and then annually for up to 15 years total.

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Intracavitary Administration of 15.GPC3-CAR T Cells for the Treatment of Patients with GPC3-Positive Recurrent Glioblastoma who are Undergoing Repeat Resection, GO-CART Trial

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Intracavitary Administration of 15.GPC3-CAR T Cells for the Treatment of Patients with GPC3-Positive Recurrent Glioblastoma who are Undergoing Repeat Resection, GO-CART Trial

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