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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Number of participants with adverse event [Срок оценки: Up to 10 weeks]
• Cytokine Release Syndrome [Срок оценки: Up to 10 weeks]
• Neurotoxicity [Срок оценки: Up to 10 weeks]

Вторичные конечные точки (5)

• Identification of Recommended phase 2 dose (RP2D) [Срок оценки: Up to 4 weeks]
• Objective Response Rate (ORR) [Срок оценки: Up to 4 weeks]
• Progression Free Survival (PFS) [Срок оценки: Up to 12 months]
• Overall Survival (OS) [Срок оценки: Up to 5 years]
• Duration of Response (DOR) [Срок оценки: Up to 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Lineberger Comprehensive Cancer Center — Chapel Hill

Идентификаторы

NCT: NCT05366179 · LCCC2059-ATL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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