A Clinical Trial of P134 Cells in Recurrent Glioblastoma

Официальное название

A Phase I/II Clinical Study to Evaluate the Safety and Efficacy of P134 Cells in the Treatment of Recurrent Glioblastoma

Обзор

This is an open-label, single-arm, dose-escalation and expansion Phase 1/2 clinical trial designed to evaluate the safety, tolerability and efficacy of P134 cells in patients with recurrent glioblastoma, to explore the maximum tolerated dose (MTD)and recommended Phase 2 dose (RP2D), and to characterize the cytokinetic profile of CAR-T cells in the cerebrospinal fluid of patients. Eligible participants are adults diagnosed with recurrent or progressive glioblastoma who are confirmed as grade 4 glioblastoma (IDH wild-type) by histopathology or molecular pathology. P134 cells are CD44/CD133 dual-targeting CAR-T cells developed by the research team led by Academician Jiang Tao and Professor Zhang Wei from the Beijing Neurosurgical Institute and the Department of Neurosurgery, Beijing Tiantan Hospital. This study is spearheaded by Professor Zhang Wei of the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China, with scientific oversight and guidance provided by Academician Jiang Tao of the Chinese Academy of Engineering.

Вмешательства

• Биопрепарат P134 cell injection
  In Phase 1 dose-escalation study, P134 cell dosing and safety are evaluated using an accelerated titration initial dose followed by a "3+3" design. The starting dose is 1 × 10⁸ CAR⁺ T cells, administered intratumorally or intraventricularly via an Ommaya reservoir. Three dose levels are planned: Level 1: 1 × 10⁸ CAR⁺ T cells, Q2W. Level 2: 3 × 10⁸ CAR⁺ T cells, Q2W. Level 3: 5 × 10⁸ CAR⁺ T cells, Q2W. The Level 1 adopts accelerated titration, and the Level 2 and Level 3 adopt the "3+3" design.

Первичные конечные точки

• Dose limiting toxicities (DLTs) [Срок оценки: From the first dose up to Day 28 post-first dose]
• Adverse events (AEs) [Срок оценки: Through study completion, an average of two and a half years]
• Maximum tolerated dose (MTD) [Срок оценки: From the first dose up to Day 28 after the first dose.]

Вторичные конечные точки (8)

• Recommended Phase 2 Dose (RP2D) [Срок оценки: From study enrollment to Day 28 after the last dose of participants in the dose-escalation phase]
• Objective Response Rate (ORR) [Срок оценки: Through study completion, an average of two and a half years]
• Disease Control Rate (DCR) [Срок оценки: Through study completion, an average of two and a half years]
• Progression-Free Survival (PFS) [Срок оценки: Through study completion, an average of two and a half years]
• Duration of Response (DOR) [Срок оценки: Through study completion, an average of two and a half years]
• Time to Response (TTR) [Срок оценки: Through study completion, an average of two and a half years]
• 1-year OS Rate [Срок оценки: From study enrollment up to 12 months after study enrollment]
• Overall Survival [Срок оценки: Through study completion, an average of two and a half years]

Критерии участия

Критерии включения

• Voluntary written informed consent.
• 18-70 years of age (inclusive), male or female.
• Recurrent or progressive glioblastoma, histopathologically or molecularly diagnosed consistent with grade 4 glioblastoma (IDH wild-type) (refer to WHO Classification of Central Nervous System Tumors, 5th Edition, 2021).
• Positive CD44 or CD133 antigen expression in tumor tissue confirmed by IHC, defined as ≥1% of tumor cells showing positive CD44 or CD133 IHC staining, regardless of intensity (applicable only in Phase II dose expansion study).
• At least one measurable lesion meeting RANO 2.0 criteria and having a radiographically assessed measurable lesion ≤ 3 cm in longest diameter
• Patient has received prior radiation therapy and/or temozolomide/bevacizumab.
• The investigator confirmed that the patient was suitable for craniotomy cerebrospinal fluid shunt and accessory (Ommaya reservoir) implantation.

Критерии исключения

• Highly allergic constitution or history of severe allergy, or allergy to related cell products
• Receipt of biologic anti-tumor therapy (including monoclonal or bispecific antibody-targeted therapy, immune checkpoint inhibitor therapy, etc.) within 6 weeks prior to PBMC collection; receipt of radiotherapy or surgery within 4 weeks prior to PBMC collection (excluding placement of vascular access devices; a 1-week washout period is acceptable for diagnostic biopsy surgeries); receipt of chemotherapy, hormone therapy (excluding hormone replacement therapy), or non-specific immunomodulatory therapy (such as interleukins, interferons, thymosin, cyclophosphamide, methotrexate, tumor necrosis factor, etc.) within 2 weeks prior to PBMC collection; receipt of traditional Chinese medicine therapy with a clear anticancer indication within 1 week prior to PBMC collection.
• The adverse reactions caused by previous anti-tumor treatment have not recovered to ≤ Grade 1 as evaluated by NCI CTCAE v6.0 (except alopecia, skin pigmentation, leukoplakia, etc. which are assessed as having no safety risk).
• Tumor metastasis to the brainstem or spinal cord.
• Suffering from other serious neurological diseases other than brain tumors, such as meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, amyotrophic lateral sclerosis, spinal muscular atrophy, nerve paralysis, uncontrolled epilepsy, etc.
• Patients with primary immunodeficiency disease, autoimmune diseases requiring medication (such as Crohn 's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus), or previous history of autoimmune diseases of the nervous system (such as multiple sclerosis, Parkinson' s disease).
• Receiving or requiring long-term use of immunosuppressive agents (except for physiological doses of systemic corticosteroids ≤ 10 mg/day prednisone equivalent, short-term ≤ 7 days corticosteroids for allergies, or topical glucocorticoids).
• Trial participants who have a previous history of allogeneic bone marrow transplantation or organ transplantation, or are awaiting organ transplantation.
• HBsAg positive and HBV DNA positive, HCV Ab positive and HCV RNA positive; Treponema pallidum antibody positive; human immunodeficiency virus (HIV) antibody positive.
• Prior receipt of any gene therapy or cell therapy trial participant.
• Pregnant or lactating women.
• History of malignancy other than glioma within 5 years (except for adequately treated carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer, or stage I cervical cancer, which in the opinion of the investigator carries a minimal risk of recurrence).

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

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07318818 · TSL-B2172-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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