Lisaftoclax Plus Chidamide and Rituximab in Relapsed or Refractory Diffuse Large B-cell Lymphoma

Официальное название

A Phase Ib/IIa Clinical Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Lisaftoclax in Combination With Chidamide and Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Patients（CLARITY Trial）

Обзор

This is a phase 1b/2a, open-label trial to evaluate the safety, pharmacokinetics, and preliminary efficacy of lisaftoclax in combination with chidamide and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

Вмешательства

• Препарат Lisaftoclax
  Lisaftoclax will be administered orally once daily on Days 1-14 of each 21-day cycle for up to 6 cycles. During Cycle 1, a daily dose ramp-up schedule will be used. In the 600 mg cohort, participants will receive 200 mg on Day 1, 400 mg on Day 2, and 600 mg on Day 3, followed by 600 mg once daily on Days 4-14. In the 800 mg cohort, participants will receive 200 mg on Day 1, 400 mg on Day 2, 600 mg on Day 3, and 800 mg on Day 4, followed by 800 mg once daily on Days 5-14. From Cycles 2-6, partici
• Препарат Chidamide
  Chidamide will be administered orally at a dose of 20 mg on Days 1, 4, 8, and 11 of each 21-day cycle for up to 6 cycles.
• Препарат rituximab
  Rituximab will be administered intravenously at a dose of 375 mg/m² on Day 1 of each 21-day cycle for up to 6 cycles.

Первичные конечные точки

• Dose-limiting toxicities (DLTs) (Phase 1b) [Срок оценки: During the first treatment cycle (21 days)]
• Maximum tolerated dose (MTD) (Phase 1b) [Срок оценки: During the first treatment cycle (21 days)]
• Recommended phase 2 dose (RP2D) (Phase 1b) [Срок оценки: During the first treatment cycle (21 days)]
• Objective response rate (ORR) [Срок оценки: Up to approximately 6 months]

Вторичные конечные точки (7)

• Complete response rate (CRR) [Срок оценки: Up to approximately 6 months]
• Duration of response (DOR) [Срок оценки: Up to 24 months]
• Disease-free survival (DFS) [Срок оценки: Up to 24 months]
• Progression-free survival (PFS) [Срок оценки: Up to 24 months]
• Overall survival (OS) [Срок оценки: Up to 24 months]
• Incidence of adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Up to 30 days after the last study treatment]
• Change in Quality of Life [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• Age ≥18 years.
• Histologically confirmed diffuse large B-cell lymphoma (DLBCL) according to the 2016 WHO classification with BCL-2 positivity by immunohistochemistry (defined as BCL-2 expression ≥30%).
• Relapsed or refractory DLBCL after prior treatment with an anthracycline-containing regimen and an anti-CD20 antibody-containing regimen.
• Received at least one prior line of therapy and considered ineligible for autologous stem cell transplantation (ASCT).
• Estimated life expectancy ≥3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• At least one measurable or evaluable lesion according to the Lugano 2014 lymphoma response criteria.
• Adequate bone marrow, hepatic, and renal function.
• Ability to understand and willingness to voluntarily sign a written informed consent form.

Критерии исключения

• Central nervous system (CNS) involvement by lymphoma, primary CNS lymphoma, or leukemic phase lymphoma.
• Prior intolerance to BCL-2 inhibitors and chidamide, or disease refractory to or relapsed after treatment with both agents.
• Known hypersensitivity to any component of the study drugs or their analogs.
• Prior allogeneic hematopoietic stem cell transplantation within 6 months before the first dose, active graft-versus-host disease (GvHD), or requirement for immunosuppressive therapy within 28 days prior to study treatment.
• Clinically significant active cardiovascular disease.
• Uncontrolled or clinically unstable infection requiring parenteral antibacterial, antiviral, or antifungal therapy within 7 days before the first dose of study treatment.
• Pregnant or breastfeeding women.
• Active human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS).
• Malabsorption syndrome or other conditions that may interfere with enteral administration or absorption of study drugs.
• Any other medical, psychiatric, or social condition that, in the investigator's judgment, would make the subject inappropriate for participation in this study.

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

• Sun yat-sen university cancer center — Гуанчжоу

Идентификаторы

NCT: NCT07601607 · B2026-253

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗