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

NCT ID: NCT05366179

Last Updated: 2025-10-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-02
• Study Completion Date: 2030-05-30

Brief 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.

Detailed 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 cells will be manufactured for subjects who likely to be eligible for cell infusion.

Eligible subjects will receive up to 3 weekly infusions of CAR.B7-H3 cells. To receive the additional cycles of CAR.B7-H3 cells, all treatment-related toxicities must have resolved to grade < 3, the subject must not have experienced a dose limiting toxicity (DLT) and the subject must not have progressive disease that has been confirmed by magnetic resonance imaging per Immunotherapy response assessment in neuro-oncology criteria.

The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided on based on the maximum tolerated dose (MTD) and additional factors such as the feasibility of administering infusions.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

CAR.B7-H3 T cells:

Subjects with refractory or recurrent glioblastoma multiforme, have cells collected following their initial surgical resection to manufacture CAR.B7-H3 T cells, preferably before initiation of adjuvant chemoradiation.

Group Type: EXPERIMENTAL

CAR.B7-H3T cells infusion

Intervention Type: DRUG

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).

Interventions

CAR.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).

Intervention Type: DRUG

Eligibility Criteria

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 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.

6. 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.

7. The subject is willing and able to comply with study procedures based on the judgment of the investigator.

Exclusion Criteria

1. Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).

2. 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.

3. 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.

4. Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.

5. Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.

6. Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord.

7. Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yasmeen Rauf, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Catherine Cheng

Role: CONTACT

UNCImmunotherapy@med.unc.edu

919-445-4208

Caroline Babinec

Role: CONTACT

UNCImmunotherapy@med.unc.edu

919-962-7426

Facility Contacts

Sierra Thomas

Role: primary

UNCImmunotherapy@med.unc.edu

919-445-4208

Chelsea Baker

Role: backup

UNCImmunotherapy@med.unc.edu

+1 919-962-8491

Related Links

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

LCCC2059-ATL

Identifier Type: -

Identifier Source: org_study_id