Clinical Study of U01（ssCART-19） in Patients With B-Cell Lymphoma

Официальное название

A Single-arm, Open-label Clinical Study Evaluating the Efficacy and Safety of U01 (ssCART-19) in Patients With Relapsed or Refractory B-cell Lymphoma.

Обзор

This is a single-arm, open-label clinical study evaluating the efficacy and safety of U01 (ssCART-19) in patients with relapsed or refractory B-cell lymphoma.

Подробное описание

The primary objective of this study is to evaluate the efficacy and safety of CD19-targeted CAR-T cells engineered with an IL-6 silencing element in patients with relapsed or refractory B-cell lymphoma.

Вмешательства

• Препарат ssCART-19
  Lymphodepletion preconditioning is required prior to CAR-T cell therapy. Lymphodepletion will be performed using a regimen of cyclophosphamide (250-500 mg/m²) and fludarabine (25-30 mg/m²), each administered for 3 consecutive days.

Первичные конечные точки

• Incidence of Adverse events after U01 CAR-T cells infusion [Safety and Tolerability] [Срок оценки: 28 days post administration of ssCART-19]
• Objective Response Rate (ORR), as assessed by Investigators [Срок оценки: 2 years post CAR T cell infusion]
• Duration of response (DOR) [Срок оценки: 2 years post CAR T cell infusion]
• Overall survival (OS) [Срок оценки: 2 years post CAR T cell infusion]
• Progression-free survival (PFS) [Срок оценки: 2 years post CAR T cell infusion]

Вторичные конечные точки (4)

• Pharmacokinetics of ssCART-19 [Срок оценки: 2 years post CAR T cell infusion]
• Pharmacokinetics of ssCART-19 [Срок оценки: 2 years post CAR T cell infusion]
• Pharmacokinetics of ssCART-19 [Срок оценки: 2 years post CAR T cell infusion]
• Pharmacodynamics of ssCART-19 [Срок оценки: 2 years post CAR T cell infusion]

Критерии участия

Критерии включения

• Voluntary written informed consent obtained from the participant (or legal guardian) with good compliance expected throughout the study.
• All of the following conditions must be met:

• Age 2-75 years at informed consent; both sexes eligible. For minors (≤18 years), consent must be provided by a parent/legal guardian; minors able to sign must co-sign with their guardian.
• Histologically confirmed B-cell lymphoma per the 2024 v3 NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas.
• Prior therapy requirements:

• Failure to achieve PR after first-line therapy, OR relapse within 12 months after first-line therapy; or Relapsed/refractory after second-line therapy (one standard chemo-regimen + one salvage regimen).

Prior regimens must have included anti-CD20 monoclonal antibody (unless documented CD20-negative tumor) and an anthracycline-containing regimen. In addition, at least one of the following must apply:

i. Ineligible for autologous hematopoietic stem-cell transplantation (ASCT); ii. Refusal of ASCT; iii. Relapse after ASCT. d) Disease status at screening:

• Relapse: progression after prior PR or CR.

• Refractory: i. PD during/after last therapy, or best response ≤SD lasting <6 months; OR ii. Relapse or progression after ASCT (biopsy-proven), including relapse/PD ≤12 months post-ASCT or lack of response (SD/PD) to salvage therapy after ASCT.
• Tumor tissue (archival or fresh) positive for CD19 by IHC; pathology report within 6 months preferred.
• ≥1 measurable lesion per Lugano 2014 response criteria.
• ECOG performance status 0-3.
• Adequate marrow reserve: ALC ≥0.3 × 10⁹/L; PLT ≥30 × 10⁹/L (transfusion permitted).
• Adequate organ function:

• AST ≤3×ULN (≤5×ULN if tumor-related); ALT ≤3×ULN (≤5×ULN if tumor-related);• Total bilirubin ≤2×ULN (≤3×ULN with direct bilirubin ≤1.5×ULN for Gilbert's syndrome);• Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault);• Pulmonary: ≤Grade 1 dyspnea and SpO₂ >91 % on room air;• LVEF ≥50 % by echocardiography;• INR ≤1.5×ULN and APTT ≤1.5×ULN.
• Women of child-bearing potential: negative serum/urine pregnancy test within 7 days before CAR-T infusion. All participants with reproductive potential must use effective contraception from screening through ≥12 months after CAR-T infusion.
• Adequate venous access for leukapheresis or repeated phlebotomy, with no contraindications to leukapheresis.
• Estimated life expectancy >3 months.

Критерии исключения

• Concurrent malignancy other than the study indication, except for carcinoma in situ or any malignancy with a disease-free interval ≥3 years.
• Presence of any of the following:• Positive HBe-Ab and/or HBc-Ab with HBV-DNA above the lower limit of quantification;• Positive HCV-Ab with HCV-RNA above the lower limit of quantification;• Positive Treponema pallidum antibody (TP-Ab);• Positive HIV antibody.
• Active bacterial, fungal, viral, mycoplasmal, or other infection deemed uncontrollable by the investigator.
• History or current clinically significant CNS disorder unrelated to lymphoma-e.g., seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any CNS autoimmune disease-that the investigator considers uncontrolled.
• Within 12 months before informed consent: percutaneous coronary intervention (angioplasty or stent placement), NYHA Class III-IV congestive heart failure, myocardial infarction, unstable angina, or other clinically significant cardiac history judged by the investigator; or QTc >480 ms (Fridericia correction) or LVEF <50 % by echocardiography at screening.
• Known primary immunodeficiency.
• History of severe immediate hypersensitivity to any study drug.
• Receipt of any live vaccine within 6 weeks before screening.
• Pregnant or breastfeeding women.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Participation in any other interventional clinical trial within 30 days before signing informed consent.
• Any condition that, in the investigator's opinion, renders the subject unsuitable for study 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

Китай · 1 центр

• Tongji Hospital of Tongji University — Шанхай

Идентификаторы

NCT: NCT07093073 · U01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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