Phase I Study of Intraventricular Infusion of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) in Subjects With Recurrent or Refractory Glioblastoma
UNC Lineberger Comprehensive Cancer Center
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.
Description
This is a phase 1, single center, open-label study aims to determine the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells targeting the B7-H3 antigen administered via intraventricular infusion to adult subjects with relapsed or refractory glioblastoma (GBM). Subjects with GBM who meet procurement eligibility criteria will have cells collected following their initial surgical resection to manufacture CAR.B7-H3T cells, preferably prior to initiation of adjuvant chemoradiation. At the time that the subjects have confirmed refractory or recurrent GBM, CAR.B7-H3T cell…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
INCLUSION CRITERIA 1. Karnofsky score of \> 60% 2. 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. 3. Must have undergone at least 4005 cGy of radiation with concurrent temozolomide. 4. No current or previous exposure to antiangiogenic agents, such as bevacizumab. 5. Female subjects o…
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).
Location
- Lineberger Comprehensive Cancer CenterChapel Hill, North Carolina