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

NCT07601607 | Not Yet Recruiting Phase 1

• 1 other identifier: B2026-253
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Complete response rate (CRR)

  Up to approximately 6 months

• Duration of response (DOR)

  Up to 24 months

• Disease-free survival (DFS)

  Up to 24 months

• Progression-free survival (PFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

Study Arms (1)

Lisaftoclax in combination with chidamide and rituximab

EXPERIMENTAL

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; Drug: Chidamide; Drug: rituximab

Interventions

Lisaftoclax DRUG

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.

Lisaftoclax in combination with chidamide and rituximab

Chidamide DRUG

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.

Lisaftoclax in combination with chidamide and rituximab

rituximab DRUG

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.

Lisaftoclax in combination with chidamide and rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun yat-sen university cancer center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse

Interventions

Lisaftoclax; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Principal Investigator

CONTACT

0086-20-87342823; caiqq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician

Study Record Dates

• First Submitted: May 16, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)