A Study of C-CAR039 (Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma

Официальное название

A Phase 1b/2 Study of a Anti-CD19/CD20 Bispecific CAR-T Therapy (C-CAR039/Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma

Обзор

This is a multicenter, single arm, open-label study. The purpose of the study is to evaluate safety of Prizloncabtagene Autoleucel (Prizlon-cel) and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of Prizlon-cel (Phase 2) in patients with relapsed or refractory large b-cell lymphoma (LBCL).

Подробное описание

The purpose of the study is to evaluate the safety and efficacy of Prizlon-cel. It includes two phases, Phase 1b and Phase 2. In Phase 1b study, RP2D will be determined. The selected dose will be further evaluated in the Phase 2 study. The study includes the following sequential procedures: Screening, Apheresis and CAR-T manufacturing, Baseline, Lymphodepletion, CAR-T infusion, DLT period (Phase 1b) and Follow-up Visit. Subjects will be followed for at least 2 years after Prizlon-cel infusion, with up to 15 years long-term follow-up on a separate study.

Вмешательства

• Биопрепарат Prizloncabtagene autoleucel
  Prizlon-cel is a novel 2nd generation 4-1BB bispecific chimeric antigen receptor T-cell (CAR-T) targeting both CD19 and CD20 antigens

Первичные конечные точки

• Phase 1b: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Up to 90 days after C-CAR039 infusion]
• Phase 1b: Recommended Phase 2 Dose (R2PD) [Срок оценки: Up to 3 months after C-CAR039 infusion]
• Phase 2: Overall Response Rate (ORR) at 3 months [Срок оценки: Up to 3 months after C-CAR039 infusion]

Вторичные конечные точки (12)

• Phase 1b: Incidence and Severity of Adverse Events (AEs) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Phase 1b: ORR at 3 months [Срок оценки: Up to 3 months after C-CAR039 infusion]
• Phase 2: Incidence and Severity of Adverse Events (AEs) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• ORR [Срок оценки: Up to 2 years after C-CAR039 infusion]
• ORR at 6 months [Срок оценки: Up to 6 months after C-CAR039 infusion]
• Duration of response (DOR) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Time to response (TTR) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Progression-free survival (PFS) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Overall survival (OS) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Maximal plasma concentration (Cmax) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Time to reach the maximal plasma concentration (Tmax) [Срок оценки: Up to 2 years after C-CAR039 infusion]
• Area under the curve within 28 days (AUC0-28d) [Срок оценки: Up to 28 days after C-CAR039 infusion]

Критерии участия

Критерии включения

• ≥ 18 years of age
• Histologically confirmed CD19 or CD20 positive B-cell non-Hodgkin lymphoma, including the following neoplasms as defined by the 2016 WHO classification of lymphoid neoplasms:

• Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS)
• Primary mediastinal large B-cell lymphoma (PMBCL)
• Transformed follicular lymphoma (tFL)
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH)
• High-grade B-cell lymphoma, NOS (HGBL, NOS)
• Follicular lymphoma grade 3B (FL3B)
• Relapsed or refractory disease after ≥ 2 lines of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
• At least one measurable lesion per the Lugano 2014 Classification
• Adequate organ and marrow function

Критерии исключения

• Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or ASCT within 12 weeks prior to apheresis
• Suspected or confirmed central nervous system involvement
• Stroke or convulsion history within 6 months of signing informed consent form (ICF)
• Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment
• Uncontrolled active infection
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis C virus (HCV) antibody with positive HCV RNA in peripheral blood; positive human immunodeficiency virus (HIV) antibody; positive syphilis test
• Severe heart, liver, renal or metabolism disease
• Inadequate wash-out time for previous anti-tumor treatments prior to apheresis
• Prior CAR-T therapy

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 · 15 центров

• Beijing Cancer Hospital — Пекин
• Beijing GoBroad Hospital — Пекин
• Peking University Third Hospital — Пекин
• Chongqing University Cancer Hospital — Чунцин
• Guangdong Provincial People's Hospital — Гуанчжоу
• Zhujiang Hospital of Southern Medical University — Гуанчжоу
• The First Affiliated Hospital Zhejiang University School of Medicine — Ханчжоу
• Cancer Hospital of Shandong First Medical University — Цзинань
• … и ещё 7 центров

Идентификаторы

NCT: NCT05800977 · 0702-032

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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