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).

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)
• Intervention / Treatment: Drug: Lisaftoclax; Drug: Chidamide; Drug: rituximab

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Principal investigator; Phone Number: 0086-20-87342823; Email: caiqq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
      • Contact: Principal investigator; Phone Number: 0086-20-87342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lisaftoclax in combination with chidamide and rituximab; Patients will receive lisaftoclax orally once daily on Days 1-14 of each 21-day cycle for up to 6 cycles, with daily dose ramp-up during Cycle 1. Chidamide will be administered orally at 20 mg on Days 1, 4, 8, and 11 of each cycle, and rituximab will be administered intravenously at 375 mg/m² on Day 1 of each cycle.

Drug: 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, participants will receive lisaftoclax at the target dose (600 mg or 800 mg) once daily on Days 1-14.; Drug: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (DLTs) (Phase 1b)	DLTs will be assessed during the DLT evaluation period and graded according to NCI CTCAE version 5.0.	During the first treatment cycle (21 days)
Maximum tolerated dose (MTD) (Phase 1b)	MTD is defined as the highest dose level at which fewer than one-third of patients experience a DLT during the DLT evaluation period.	During the first treatment cycle (21 days)
Recommended phase 2 dose (RP2D) (Phase 1b)	RP2D will be determined based on the overall safety, tolerability, and DLT assessment results.	During the first treatment cycle (21 days)
Objective response rate (ORR)	ORR is defined as the proportion of patients who achieve complete response or partial response according to Lugano 2014 criteria.	Up to approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	CRR is defined as the proportion of patients who achieve complete response according to Lugano 2014 criteria.	Up to approximately 6 months
Duration of response (DOR)	DOR is defined as the time from the first documented response to disease progression or death from any cause.	Up to 24 months
Disease-free survival (DFS)	DFS is defined as the time from first documented complete response to disease progression or death from any cause.	Up to 24 months
Progression-free survival (PFS)	PFS is defined as the time from enrollment to disease progression or death from any cause.	Up to 24 months
Overall survival (OS)	OS is defined as the time from enrollment to death from any cause.	Up to 24 months
Incidence of adverse events (AEs) and serious adverse events (SAEs)	The incidence and severity of adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	Up to 30 days after the last study treatment
Change in Quality of Life	Quality of life will be assessed using the EORTC QLQ-C30 or EQ-5D questionnaire.	Up to 24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: May 16, 2026
• First Submitted That Met QC Criteria: May 16, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Lisaftoclax
• Other Study ID Numbers: B2026-253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No