RecruitingPhase 1NCT05366179

Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc

Phase I Study of Intraventricular Infusion of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) in Subjects With Recurrent or Refractory Glioblastoma

Sponsor

UNC Lineberger Comprehensive Cancer Center

Enrollment

36 participants

Start Date

Sep 2, 2022

Study Type

INTERVENTIONAL

Conditions

Glioblastoma Multiforme

Summary

The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for glioblastoma.

Eligibility

Min Age: 18 Years

Inclusion Criteria7

Karnofsky score of \> 60%
Diagnosis or recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021) based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis.
Must have undergone at least 4005 cGy of radiation with concurrent temozolomide.
No current or previous exposure to antiangiogenic agents, such as bevacizumab.
Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation.
Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the cell infusion therapy. If a male subject receives multiple infusions, they must remain on contraception throughout the duration and 3 months after the last cell infusion therapy.
The subject is willing and able to comply with study procedures based on the judgment of the investigator.

Exclusion Criteria7

Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).
Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load.
Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.
Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.
Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord.
Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.

Interventions

DRUGCAR.B7-H3T cells infusion

The Chimeric Antigen Receptors (CAR).B7-H3T cells will be administered via intraventricular infusion up to 3 weekly infusions. A suspension of T cells infusion is given, over 5-10 minutes, via a Rickham catheter and will be followed by a normal-saline flush. Dose escalation will be performed considering the dose limiting toxicities (DLTs) listed in the protocol. Six doses will be explored. The starting dose will be 2 × 10\^6 transduced cells/infusion (Dose Level (DL) 1) and will enroll at least 3 subjects. If there are no dose DLTs within 4 weeks of the third cellular product administration in the first 3 subjects, then the next cohort will evaluate 5 × 10\^6 transduced cells/infusion (DL2).