Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)
Conditions
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).
Interventions
DRUGLisaftoclax
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.
DRUGChidamide
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.
DRUGrituximab
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (DLTs) (Phase 1b) | During the first treatment cycle (21 days) | DLTs will be assessed during the DLT evaluation period and graded according to NCI CTCAE version 5.0. |
| Maximum tolerated dose (MTD) (Phase 1b) | During the first treatment cycle (21 days) | MTD is defined as the highest dose level at which fewer than one-third of patients experience a DLT during the DLT evaluation period. |
| Recommended phase 2 dose (RP2D) (Phase 1b) | During the first treatment cycle (21 days) | RP2D will be determined based on the overall safety, tolerability, and DLT assessment results. |
| Objective response rate (ORR) | Up to approximately 6 months | ORR is defined as the proportion of patients who achieve complete response or partial response according to Lugano 2014 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | Up to approximately 6 months | CRR is defined as the proportion of patients who achieve complete response according to Lugano 2014 criteria. |
| Duration of response (DOR) | Up to 24 months | DOR is defined as the time from the first documented response to disease progression or death from any cause. |
| Disease-free survival (DFS) | Up to 24 months | DFS is defined as the time from first documented complete response to disease progression or death from any cause. |
| Progression-free survival (PFS) | Up to 24 months | PFS is defined as the time from enrollment to disease progression or death from any cause. |
| Overall survival (OS) | Up to 24 months | OS is defined as the time from enrollment to death from any cause. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Up to 30 days after the last study treatment | 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. |
| Change in Quality of Life | Up to 24 months | Quality of life will be assessed using the EORTC QLQ-C30 or EQ-5D questionnaire. |
Countries
China
Contacts
CONTACTPrincipal Investigator
Outcome results
None listed