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

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）

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).

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.