Safety and Efficacy Study of BAFF-R CAR-T Cells in Adult Subjects With CD19-Negative Relapsed or Refractory B-Cell Lymphoma

Официальное название

A Prospective, Open-label and Single-arm Study of BAFF-R CAR-T Cells in Adult Subjects With CD19-Negative Relapsed or Refractory B-Cell Lymphoma

Обзор

The purpose of this study is to evaluate the safety and tolerability of BAFF-R CAR-T Cells in Adult Subjects with CD19-Negative relapsed or refractory B-Cell Lymphoma.

Подробное описание

This is a prospective open-label, single-arm clinical study to evaluate the safety, tolerability of BAFF-R CAR-T cells in adult subjects with CD19-negative relapsed or refractory B-Cell Lymphoma. The study plans to explore across three dose levels (1.00 × 10\^6, 3.00 × 10\^6, 9.00 × 10\^6 CAR+ T cells/kg), and 6.00×10\^8 CAR+T cells as maximum dose, aiming to evaluate the safety, tolerability of BAFF-R CAR-T cells in CD19-negative relapsed or refractory B-Cell Lymphoma, explore Maximum Tolerated Dose (MTD) and determine the recommended dose for Phase II. Besides, efficacy, pharmacokinetics and persistence profile of CAR-T cells are also study objectives.

Вмешательства

• Биопрепарат BAFF-R CAR-T cells
  BAFF-R CAR-T cells, single intravenous infusion

Первичные конечные точки

• Incidence of dose-limiting toxicity (DLT) [Срок оценки: 1 month after injection]
• AE/SAE [Срок оценки: 1 month, 3 months, 6 months, 12 months after injection]

Вторичные конечные точки (4)

• Objective response rate (ORR) [Срок оценки: 1 month, 3 months, 6 months, 9 months, 12 months after injection]
• Overall survival (OS) [Срок оценки: 1 month, 3 months, 6 months, 9 months, 12 months after injection]
• Duration of response (DOR) [Срок оценки: 1 month, 3 months, 6 months, 9 months, 12 months after injection]
• Progression-free survival (PFS) [Срок оценки: 1 month, 3 months, 6 months, 9 months, 12 months after injection]

Критерии участия

Критерии включения

• 1\. Subjects voluntarily participate in clinical research and sign informed consent.
• 2\. Subjects with CD19-negative relapsed or refractory B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation).
• 3\. Expected survival ≥ 3 months.
• 4\. BAFF-R expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry.
• 5\. ECOG score ≤ 2.
• 6\. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values:
• Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m²
• Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included.
• Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation >95% on room air.
• 7\. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA).
• 8\. Adequate bone-marrow reserve without blood transfusion as defined by:
• Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L.
• Absolute lymphocyte count (ALC) ≥ 0.1 x 10\^9/L.
• Platelets ≥ 50 x 10\^9/L.
• Hemoglobin >80g/L.
• 9\. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy.

Критерии исключения

• 1\. Women who are pregnant or breastfeeding, or planned pregnancy within 6 months.
• 2\. Infectious disease(HIV, Active Tuberculosis ect.).
• 3\. Active infection: hepatitis B, hepatitis C.
• 4\. Abnormal vital signs or refuse to receive examination.
• 5\. Subjects with psychiatric or psychological disorders are unable to complete treatment or efficacy assessment.
• 6\. History of severe hypersensitivity or known hypersensitivity to IL-2.
• 7\. Systemic or local severe infection requiring antimicrobial therapy.
• 8\. Significant dysfunction of vital organs (heart, lung, brain, kidney, etc.), or in the investigator's judgment, subjects are unable to be enrolled with any other condition.

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

• Suzhou Hongci Hematology Hospital — Сучжоу

Идентификаторы

NCT: NCT07369492 · TH-RD09-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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