CAR-T Cell Efficacy With Molecular Imaging in Multiple Myeloma

Официальное название

Visualizing CAR-T Cell Therapy in Multiple Myeloma Using a BCMA-Targeted PET Probe

Обзор

⁶⁸Ga-NOTA-BCMA is a novel, targeted PET tracer under clinical investigation. It is designed to provide a non-invasive method for monitoring the biodistribution and persistence of BCMA CAR-T cells in patients. Preclinical data robustly support its specific binding, favorable pharmacokinetics, and excellent safety profile, warranting its advancement into clinical studies.

Подробное описание

⁶⁸Ga-NOTA-BCMA is an investigational PET radiopharmaceutical designed for targeted in vivo tracking of BCMA-directed CAR-T cells. Its molecular design incorporates a BCMA-derived peptide, specific for the CAR's scFv, conjugated to the ⁶⁸Ga-chelator NOTA. Preclinical data confirm high target affinity, rapid renal clearance (t₁/₂α=3.30 min, t₁/₂β=33.27 min), and an excellent safety profile with no drug-related toxicities in murine models. The agent is administered as a single IV bolus (4 mCi/80 μg) and must be used within 4 hours of GMP-compliant, on-site radiolabeling.

Вмешательства

• Другое BCMA-Targeting CAR-T Cell Therapy
  Patient T-cells are harvested and genetically engineered to express chimeric antigen receptors (CARs) targeting B-cell maturation antigen (BCMA). These modified CAR-T cells specifically recognize and eliminate multiple myeloma cells expressing BCMA. Following reinfusion, the CAR-T cells undergo antigen-stimulated proliferation, establishing sustained antitumor immune activity.
• Устройство PET/CT Imaging
  A low-dose PET/CT scan will be performed 60 minutes post-administration of the agent. Low-dose CT is only utilized for anatomic localization and PET attenuation correction, and the radiation dose involved is substantially lower than that of conventional CT.

Первичные конечные точки

• Biodistribution of 68Ga-NOTA-BCMA [Срок оценки: Baseline (pre-CAR-T), and at Day 6±2, Day 11±2, Day 21±2 post-CAR-T infusion (Scan at 60 minutes post-injection). For the first 3 subjects, additional scans at 30 and 120 minutes post-injection will be performed at baseline.]
• Pharmacokinetic assessment of 68Ga-NOTA-BCMA: measurement of elimination half-life (t1/2) [Срок оценки: Baseline: pre-injection, and at 2, 5, 10, 15, 30, 60, 90, 120 minutes post-injection of 68Ga-NOTA-BCMA. (May be omitted for subsequent subjects based on results from the first 5 subjects).]

Вторичные конечные точки (3)

• CAR-T Cell Expansion and Persistence [Срок оценки: Day 6±2 and Day 11±2 post-CAR-T infusion.]
• Safety and Tolerability of 68Ga-NOTA-BCMA [Срок оценки: Vital signs: pre-injection and 2 hours (±1h) post-injection of 68Ga-NOTA-BCMA. Other safety assessments: throughout the study, with a follow-up at Day 28±2 after the last tracer dose.]
• CAR-T Cell Immunophenotyping [Срок оценки: Day 6±2 and Day 11±2 post-CAR-T infusion.]

Критерии участия

Критерии включения

• \*\*Inclusion Criteria\*\*

• Subjects must voluntarily sign the informed consent form and be able to complete the trial per the protocol requirements.
• Age 18 years or older, regardless of gender.
• Diagnosed with multiple myeloma and scheduled to receive anti-BCMA CAR-T cell therapy.
• ECOG performance status of 0-2; with a life expectancy of not less than 3 months.
• Female subjects of childbearing potential must have a negative serum pregnancy test prior to enrollment.
• For female subjects of childbearing potential or male subjects with partners of childbearing potential, agreement to remain abstinent or use one or more forms of contraception with a failure rate of <1% per year during the study period and for at least one year after the study completion.

Критерии исключения

• \*\*Exclusion Criteria\*\*

• Participation in another interventional clinical trial, concurrently or within 28 days prior to the first dose in this study. Participation in non-interventional trials is permitted.
• History of hypersensitivity to any component of the imaging agent or antibodies, or a known allergic predisposition.
• Inability to undergo PET/CT imaging, such as due to claustrophobia or emotional instability.
• Current use of anticoagulant therapy or anticipated requirement for such therapy during the study period.
• Known allergic or hypersensitivity reactions to biological products or any excipient of the 68Ga-NOTA-BCMA molecular probe.
• Active hepatitis B or C infection, or seropositivity for human immunodeficiency virus (HIV) antibody or Treponema pallidum antibody.
• Pregnancy, lactation, or intention to become pregnant during the trial period.
• Any other condition deemed by the investigator to render the subject unsuitable for trial participation.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07280793 · XYFY2025-KL519-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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