A Phase 3 interventional study of Zanubrutinib and Bendamustine in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, sponsored by BeiGene. Active, not recruiting at 158 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-09.
Sponsored by BeiGene · Phase 3, Interventional, and Treatment
To compare efficacy between zanubrutinib versus bendamustine and rituximab in patients with previously untreated CLL/SLL, as measured by progression free survival assess by Independent Central Review.
This is a global phase 3, open label, randomized study of zanubrutinib versus bendamustine plus rituximab (B+R) in participants with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), including participants without del(17p) [Cohort 1] and participants with del(17p) [Cohort 2 and Cohort 3]. Participants in Cohort 1 are randomized 1:1 to zanubrutinib (Arm A) or bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage, immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region. Participants in Cohort 2 will receive treatment with zanubrutinib. Participants in Cohort 3 will receive treatment with zanubrutinib and venetoclax.
2,036 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 237 are open to participants now.
This study's enrollment of 590 is above the median of 39 across 1,603 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →BeiGene is the lead sponsor of 125 studies on the registry; 2 are open to participants now.
Of its 55 completed or terminated interventional studies of FDA-regulated products, 32 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B)
Drug: Bendamustine · Drug: Rituximab
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A)
Drug: Zanubrutinib
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B, China only)
Drug: Bendamustine · Drug: Rituximab
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A, China only)
Drug: Zanubrutinib
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm C)
Drug: Zanubrutinib
Approximately 110 participants, 50 without del17p and 60 with del\[17p\] or TP53 mutation will receive zanubrutinib plus venetoclax; Participants will also receive zanubrutinib starting on Cycle 1 Day 1 then daily for a minimum of 27 cycles, or until unacceptable toxicity or disease progression, whichever occurs first. Participants will receive venetoclax starting Cycle 4 Day 1 according to a 5-week dose-up schedule then daily until unacceptable toxicity, disease progression, or for a maximum of 24 cycles. Each cycle is 28 days. (Arm D)
Drug: Zanubrutinib · Drug: Venetoclax
Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day)
Also known as: BGB-3111, BRUKINSA
Administered intravenously (IV) at a dose of 90 mg/m\^2/day on the first 2 days of each cycle for 6 cycles.
Also known as: Treanda, Ribomustin, and Levact
Administered intravenously (IV) at a dose of 375 mg/m\^2 on day 0 of cycle 1, and at a dose of 500 mg/m\^2 on day 1 of cycles 2 to 6
Also known as: Rituxan, MabThera
400 mg tablets administered orally once daily.
Also known as: Venclexta, Venclyxto
Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)
PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the ICR per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with small lymphocytic lymphoma (SLL).
Time frame: Up to approximately 3 years and 7 months (as of cut-off date of 07MAY2021)
Cohort 1: Overall Response Rate (ORR) Between Treatment Groups as Determined by ICR
ORR in Cohort 1 is defined as the percentage of participants who achieve a complete response, complete response with incomplete bone marrow recovery, partial response, or partial response with lymphocytosis, determined by the ICR.
Time frame: Up to 5 years
Pooled Cohort 1/1a: Overall Response Rate (ORR) Between Treatment Groups
Time frame: Up to 5 years
Cohort 1: Overall Survival (OS) Between Treatment Groups as Determined by the ICR
OS in Cohort 1 is defined as the time from randomization to the date of death due to any reason.
Time frame: Up to 5 years
Cohort 1: Duration of Response (DOR) Between Treatment Groups as Determined by the ICR
Duration of response in Cohort 1 determined using the iwCLL criteria with modification for treatment related lymphocytosis (in participants with CLL) and the Lugano Classification for non-Hodgkin lymphoma (NHL; in participants with SLL), is defined as the time from the date that criteria for response (ie, partial response with lymphocytosis \[PR-L\] or better) are first met to the date that disease progression is objectively documented or death, whichever occurs first.
Time frame: Up to 5 years
Pooled Cohort 1/1a: Duration of Response (DOR) Between Treatment Groups
Time frame: Up to 5 years
Cohort 1: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the investigator per iwCLL guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.
Time frame: Up to 5 years
Pooled Cohort 1/1a: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
Time frame: Up to 5 years
Cohort 1: Patient-reported Outcomes as Assessed by the (European Quality Of Life 5D 5L) EQ-5D-5L Questionnaire
Time frame: Up to 5 years
Cohort 1: Patient-reported Outcomes as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Questionnaire.
Time frame: Up to 5 years
Cohort 2: Overall Response Rate (ORR)
Time frame: Up to 5 years
Cohort 2: Progression-free Survival (PFS)
Time frame: Up to 5 years
Cohort 2: Duration of Response (DOR)
Time frame: Up to 5 years
Cohort 3: Overall Response Rate (ORR)
Time frame: Up to 5 years
Cohort 3: Progression-free Survival (PFS)
Time frame: Up to 5 years
Cohort 3: Duration of Response (DOR)
Time frame: Up to 5 years
Cohort 3: Rate of Undetectable Minimal Residual Disease (MRD4)
Time frame: Up to 5 years
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 5 years
Apparent Rate of Clearance of Zanubrutinib From Plasma (CL/F)CL/F
Time frame: Predose up to 12 hours postdose
Cohort 1 Zanubrutinib Only Arms: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12)
Time frame: Predose up to 12 hours postdose
Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib
Time frame: Predose up to 12 hours postdose
Available data are presented as of the primary analysis data cut-off date of 07MAY2021; as of the data cut-off date, all cohorts were ongoing.
| Milestone | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) |
|---|---|---|---|
| Started | 238 | 241 | 111 |
| Treated | 227 | 240 | 111 |
| Completed | 0 | 0 | 0 |
| Not completed | 238 | 241 | 111 |
| Withdrew: Remained on study at time of data cut-off | 202 | 219 | 102 |
| Withdrew: Death | 14 | 16 | 8 |
| Withdrew: Withdrawal by subject | 16 | 5 | 1 |
| Withdrew: Physician decision | 5 | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 |
PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the ICR per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with small lymphocytic lymphoma (SLL).
| Months | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) |
|---|---|---|
| Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR) | 33.7 (28.1 to NA) | NA (NA to NA) |
ORR in Cohort 1 is defined as the percentage of participants who achieve a complete response, complete response with incomplete bone marrow recovery, partial response, or partial response with lymphocytosis, determined by the ICR.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
OS in Cohort 1 is defined as the time from randomization to the date of death due to any reason.
Results for this outcome have not been posted.
Duration of response in Cohort 1 determined using the iwCLL criteria with modification for treatment related lymphocytosis (in participants with CLL) and the Lugano Classification for non-Hodgkin lymphoma (NHL; in participants with SLL), is defined as the time from the date that criteria for response (ie, partial response with lymphocytosis \[PR-L\] or better) are first met to the date that disease progression is objectively documented or death, whichever occurs first.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the investigator per iwCLL guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Collected over All-cause mortality and adverse events (AEs): Up to approximately 3 years and 7 months (as of data cut-off date of 07MAY2021). Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: Bendamustine + Rituximab Without Del(17p) | 14/238 (5.9%) | 113/227 (49.8%) | 214/227 (94.3%) |
| Cohort 1: Zanubrutinib Without Del(17p) | 16/241 (6.6%) | 88/240 (36.7%) | 208/240 (86.7%) |
| Cohort 2: Zanubrutinib With Del(17p) | 8/111 (7.2%) | 45/111 (40.5%) | 104/111 (93.7%) |
| Event | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) |
|---|---|---|---|
| PyrexiaGeneral disorders | 17/227 | 2/240 | 2/111 |
| PneumoniaInfections and infestations | 7/227 | 4/240 | 6/111 |
| Febrile neutropeniaBlood and lymphatic system disorders | 11/227 | 1/240 | 1/111 |
| COVID-19Infections and infestations | 1/227 | 8/240 | 1/111 |
| Infusion related reactionInjury, poisoning and procedural complications | 7/227 | 0/240 | 0/111 |
| COVID-19 pneumoniaInfections and infestations | 0/227 | 7/240 | 1/111 |
| Atrial fibrillationCardiac disorders | 1/227 | 4/240 | 3/111 |
| FallInjury, poisoning and procedural complications | 2/227 | 0/240 | 3/111 |
| SepsisInfections and infestations | 6/227 | 2/240 | 0/111 |
| AnaemiaBlood and lymphatic system disorders | 5/227 | 2/240 | 1/111 |
| Event | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) |
|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 101/227 | 30/240 | 13/111 |
| NauseaGastrointestinal disorders | 74/227 | 24/240 | 18/111 |
| Upper respiratory tract infectionInfections and infestations | 27/227 | 41/240 | 23/111 |
| PyrexiaGeneral disorders | 46/227 | 15/240 | 6/111 |
| ContusionInjury, poisoning and procedural complications | 8/227 | 46/240 | 22/111 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 19/227 | 32/240 | 22/111 |
| ConstipationGastrointestinal disorders | 43/227 | 24/240 | 17/111 |
| RashSkin and subcutaneous tissue disorders | 42/227 | 26/240 | 16/111 |
| AnaemiaBlood and lymphatic system disorders | 41/227 | 11/240 | 5/111 |
| DiarrhoeaGastrointestinal disorders | 26/227 | 33/240 | 20/111 |
Intent-to-treat analysis set included all enrolled participants who were assigned to a treatment group (as of cut-off date of 07MAY2021)
| Age, Categorical(Participants) | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 46 | 45 | 16 | 107 |
| >=65 years | 192 | 196 | 95 | 483 |
| Sex: Female, Male(Participants) | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) | Total |
|---|---|---|---|---|
| Female | 94 | 87 | 32 | 213 |
| Male | 144 | 154 | 79 | 377 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 4 | 5 | 1 | 10 |
| Not Hispanic or Latino | 211 | 218 | 99 | 528 |
| Unknown or Not Reported | 23 | 18 | 11 | 52 |
| Race (NIH/OMB)(Participants) | Cohort 1: Bendamustine + Rituximab Without Del(17p) | Cohort 1: Zanubrutinib Without Del(17p) | Cohort 2: Zanubrutinib With Del(17p) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 9 | 4 | 1 | 14 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 1 |
| Black or African American | 1 | 4 | 0 | 5 |
| White | 206 | 221 | 105 | 532 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 22 | 11 | 5 | 38 |
Showing the first 100 of 158 sites across 15 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
Time frame: See plan description
Access criteria: See plan description
Data sharing details ↗ · beigene.com
Ran from Oct 2017 to primary completion in May 2021, 42 months.
Results were first posted in Nov 2023, 2 years 6 months after primary completion.
Of 57 industry-sponsored phase 3 interventional studies under Leukemia, Lymphocytic, Chronic, B-Cell, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 73. This study's 42 months is below that.
Counting every sponsor, half of 83 studies reached it within 59 months; a quarter within 43 and three quarters within 76.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
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Studies of the drugs tested here: Zanubrutinib · Bendamustine · Rituximab
Leukemia, Lymphocytic, Chronic, B-Cell →