Refractory Diffuse Large B-cell Lymphoma, Relapsed Diffuse Large B-cell Lymphoma
Conditions
Brief summary
The goal of this clinical trial was to evaluate whether zanubrutinib can effectively treat adults with CD79B-mutant relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Participants received zanubrutinib as monotherapy, underwent regular disease assessments to evaluate treatment response, and were monitored for safety and side effects throughout the study.
Interventions
DRUGZanubrutinib
Administered orally as capsules at a dose of 160 mg twice daily on a continuous dosing schedule.
Sponsors
BeiGene
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
1. Participants had histologically confirmed diffuse large B-cell lymphoma, based on the World Health Organization 2008 classification of tumors of hematopoietic and lymphoid tissue. 2. Participants had a positive CD79B gene mutation, as confirmed by a central laboratory. 3. Participants had previously received at least one line of adequate systemic therapy for diffuse large B-cell lymphoma, defined as anti-CD20 antibody-based chemoimmunotherapy administered for at least two consecutive cycles, unless disease progression occurred before completion of Cycle 2. 4. Participants had relapsed or refractory disease prior to study entry, defined as either: 1. Recurrent disease after achieving disease remission, defined as a complete response or partial response, at the completion of the most recent treatment regimen; or 2. Stable disease or progressive disease at the completion of the most recent treatment regimen. 5. Participants were ineligible for high-dose therapy and stem cell transplantation, defined as meeting at least one of the following criteria: a. Presence of significant organ dysfunction, such as: 1. Left ventricular ejection fraction less than 50 percent as measured by echocardiogram or multiple gated acquisition scan; 2. Diffusing capacity of the lung for carbon monoxide less than 60 percent of the predicted value as measured by pulmonary function testing; or 3. Creatinine clearance less than 70 milliliters per minute as demonstrated by nuclear medicine scan or 24-hour urine collection; or comorbid conditions that precluded the use of high-dose therapy and stem cell transplantation due to an unacceptable risk of treatment-related morbidity. b. Failure to achieve a complete response or partial response following salvage therapy. c. Failure to collect stem cells or inability to undergo stem cell collection, as assessed by the investigator.
Exclusion criteria
1. Participants had non-Hodgkin lymphoma other than classical histology diffuse large B-cell lymphoma (not otherwise specified), including but not limited to: 1. Diffuse large B-cell lymphoma transformed from indolent lymphomas 2. Primary mediastinal (thymic) large B-cell lymphoma 3. Primary cutaneous diffuse large B-cell lymphoma 4. Primary effusion lymphoma 5. Central nervous system lymphoma 2. Participants had a history of allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy. 3. Participants had prior exposure to a Bruton's tyrosine kinase inhibitor. 4. Participants had received any of the following treatments within the specified timeframe prior to the first dose of study drug: 1. Corticosteroids administered with antineoplastic intent within two weeks prior to study treatment. A short course (seven days or fewer) of systemic corticosteroids at doses of 20 milligrams per day or less of prednisone equivalent for control of lymphoma-related symptoms was permitted prior to enrollment, provided the corticosteroids were tapered off within five days after initiation of study treatment. 2. Chemotherapy or radiotherapy within two weeks. 3. Monoclonal antibody therapy within two weeks. 4. Investigational therapy within two weeks. 5. Chinese patent medicine administered with antineoplastic intent within two weeks. 5. Participants had a history of other active malignancies within two years prior to study entry, with the exception of: 1. Adequately treated carcinoma in situ of the cervix; 2. Localized basal cell carcinoma or squamous cell carcinoma of the skin; or 3. A previous malignancy that was confined and treated locally (by surgery or other modality) with curative intent. Note: Other protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Response was assessed every 12 weeks for the first 24 months and every 24 weeks thereafter. Maximum time on study was 36.4 months | Defined as the percentage of participants who achieved complete response (CR) or partial response (PR) by investigator assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | Response was assessed every 12 weeks for the first 24 months and every 24 weeks thereafter. Maximum time on study was 36.4 months | CRR was defined as the percentage of participants who achieved a complete response as their best overall response, as determined by investigator assessment according to the Lugano classification for NHL. |
| Duration of Response (DOR) | From the date of first documented response until to the data cutoff date (31MAR2025). Maximum time on study was 36.4 months | DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed to the date of first documented disease progression or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. |
| Progression-free Survival (PFS) | From first dose until the data cutoff date (31MAR2025). Maximum time on study was 36.4 months | PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first as determined by investigator assessment according to the Lugano classification for NHL. Median PFS was estimated using the Kaplan-Meier method. |
| Time to Response (TTR) | From first dose until disease progression or death, assessed up to the data cutoff date (31MAR2025). Maximum time on study was 36.4 months | TRR was defined as the time from randomization to the first date that response criteria (CR or PR) were met, as determined by investigator assessment per the Lugano classification for NHL. Only participants who achieved an overall response were included in the analysis. |
| Overall Survival (OS) | From first dose until the data cutoff date (31MAR2025). Maximum time on study was 36.4 months | OS was defined as the time from randomization to the date of death from any cause. Median OS was estimated using the Kaplan-Meier method. |
| Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose until 30 days after the last dose of zanubrutinib, death, or initiation of new anticancer therapy, whichever occurred first, assessed up to the data cutoff date (31MAR2025). Maximum treatment duration was 36.4 months | An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it was linked to the study drug. |
Countries
China
Contacts
STUDY_DIRECTORStudy Director
BeiGene
Participant flow
Recruitment details
Participants were enrolled at 20 study centers in China.
Pre-assignment details
Participants were screened, treated until discontinuation, and completed end-of-treatment and safety follow-up visits. Those who stopped treatment without disease progression continued tumor assessments. Long-term follow-up monitored survival, secondary malignancies, and subsequent therapies.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 9.88 |
| Race/Ethnicity, Customized Asian | 65 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 34 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (fully Active) | 12 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Limited strenuous activity; light work possible) | 43 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Self-care intact; no work; up >50% of day) | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 32 / 65 |
| other Total, other adverse events | 57 / 65 |
| serious Total, serious adverse events | 16 / 65 |
Outcome results
None listed