Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT04458610
Zanubrutinib and Rituximab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase 2 study testing Rituximab and Zanubrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well zanubrutinib and rituximab work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma for which the patient has not received treatment in the past (previously untreated). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- What is being tested?
- Rituximab and Zanubrutinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2020to 26 May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a diagnosis chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and be previously untreated
- Patients must have an indication for treatment by 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
- Patients must understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate
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- An alanine aminotransferase (ALT) =< 2.5 x ULN
- An estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft-Gault equation unless disease related
- Free of prior malignancies for 3 years with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. If patients have another malignancy that was treated within the last 3 years, such patients can be enrolled, after consultation with the principal investigator, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy
- A urine pregnancy test (within 7 days of day 1) is required for women with childbearing potential
Who cannot join
- Pregnant or breast-feeding females
- Prior therapy with zanubrutinib or other kinase inhibitors that target BCR signaling (such as ibrutinib, idelalisib)
- Prior CLL-directed treatment including chemotherapy, chemo-immunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial. Patients that receive zanubrutinib salvage therapy cannot have received any other CLL-directed therapy besides frontline zanubrutinib plus rituximab
- Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to grade 1 or less prior to first dose of study drug
- Systemic fungal, bacterial, viral, or other infection not controlled by antimicrobial therapy, in the assessment of the treating physician(s) and/or the principal investigator
- Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP), i.e. with laboratory signs of active hemolysis or thrombocytopenia, requiring support with blood products and/or with rapid decline in hemoglobin (> 1 gram/dL per day) or platelet counts (> 10,000/uL per day)
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- Patients with severe hematopoietic insufficiency, as defined by an absolute neutrophil count of less than 500/uL, unless disease-related, and/or a platelet count of less than 30,000/uL at time of screening for this protocol
- Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with zanubrutinib and rituximab
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Patients with a history of paroxysmal atrial fibrillation (PAF) or deep vein thrombosis or pulmonary embolism (DVT/PE) can be included if they had no signs of PAF or DVT/PE in the last 6 months before enrolment. Patients with ongoing atrial fibrillation (AFib) or ongoing PAF or DVT/PE should be excluded
- History of stroke or cerebral hemorrhage within 6 months
- Evidence of bleeding diathesis or coagulopathy within 3 months
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1, anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1. Bone marrow aspiration and/or biopsy are allowed
- Serious, non-healing wound, ulcer, or bone fracture
- Treatment with warfarin (Coumadin) or any other vitamin K antagonist. Patients who recently received warfarin must be off warfarin for at least 7 days prior to start of the study. Patients receiving novel oral anticoagulant (NOAC), also termed direct oral anticoagulant (DOAC) are permitted to enroll. Patients who are currently on a vitamin K antagonist must be switched to a non-vitamin K antagonist, such as a NOAC/DOAC
- Patients with active hepatitis B (hepatitis B virus [HBV]) or hepatitis C
- Patients with known human immunodeficiency virus (HIV) infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: BTK Inhibitor Zanubrutinib (BGB-3111) in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL)
This phase II trial studies how well zanubrutinib and rituximab work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma for which the patient has not received treatment in the past (previously untreated). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The study is being done to find out if zanubrutinib combined with rituximab can help control previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the proportion of patients who have treatment-free remission 6 months after discontinuation of zanubrutinib.
SECONDARY OBJECTIVES:
- To determine clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of zanubrutinib.
II. To determine the treatment-free remission length. III. To evaluate the efficacy of re-treatment with zanubrutinib plus rituximab in patients who relapse.
OUTLINE:
FRONTLINE THERAPY: Patients receive zanubrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients with complete response (CR) continue zanubrutinib PO BID on days 1-28 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients with partial response (PR) or stable disease (SD) continue zanubrutinib PO BID on days 1-28 and rituximab IV over 3-4 hours on day 1 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 13, patients with CR continue zanubrutinib PO BID on days 1-28 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 13, patients with PR or SD continue zanubrutinib PO BID on days 1-28 for up to 12 additional cycles in the absence of disease progression or unacceptable toxicity. Patients who do not have a PR after 24 cycles either continue zanubrutinib if there is a clinical benefit, or pursue alternative therapy per treating physician discretion.
RE-TREATMENT FOR RELAPSED DISEASE: Patients with disease relapse and active disease that requires salvage therapy may restart zanubrutinib PO BID on days 1-28 and rituximab IV over 3-4 hours on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients continue zanubrutinib PO BID on days 1-28 for up to 18 additional cycles in the absence of disease progression or unacceptable toxicity and then discontinue if in CR. Beginning cycle 25, patients with PR or SD may continue zanubrutinib PO BID on days 1-28 for up to 36 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 60 days, and then every 120 days for up to 5 years or until disease progression or start of a new treatment.
- Being tested
- Rituximab, Zanubrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
ZanubrutinibDrug
Also called BGB-3111, Brukinsa, BTK-InhB
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (zanubrutinib, rituximab) | Experimental | See Detailed Description. Receives: Biological: Rituximab; Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success rate
Will estimate the proportion of patients who have treatment-free remission 6 months after discontinuation of zanubrutinib. Success rate will be estimated with 95% credible interval and confidence interval.
Measured: At 6 months after discontinuation of zanubrutinib
Secondary outcomes (3)
Clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of zanubrutinib
To assess the contribution of various factors to relapse risk, will use Cox's proportional hazards analysis of predictors that have a p value < 0.2 in the univariate analysis.
Measured: Up to 5 years after discontinuation of zanubrutinib
Treatment-free remission length
The median treatment-free remission duration will be calculated by Kaplan-Meier analysis, and stratified groups will be compared with the log-rank test.
Measured: Up to 5 years after discontinuation of zanubrutinib
Overall response
Defined as complete response or partial response after patients received 6 cycles of treatments.
Measured: After 6 cycles of treatment (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start26 May 2020
- Primary completion26 May 2027 (estimated)
- Study completion26 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jan A Burger, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04458610
- Sponsor's protocol ID
- 2019-0012
- Other IDs
- NCI-2020-05053, 2019-0012
- Status last verified
- May 2026
- First submitted
- 2 Jul 2020
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BTK Inhibitor Zanubrutinib (BGB-3111) in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT04458610
- Acronym / sponsor ID
- 2019-0012
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 May 2020 (actual)
- Primary completion
- 26 May 2027 (estimated)
- Study completion
- 26 May 2027 (estimated)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well zanubrutinib and rituximab work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma for which the patient has not received treatment in the past (previously untreated). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The study is being done to find out if zanubrutinib combined with rituximab can help control previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.
Detailed description
PRIMARY OBJECTIVE:
- To determine the proportion of patients who have treatment-free remission 6 months after discontinuation of zanubrutinib.
SECONDARY OBJECTIVES:
- To determine clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of zanubrutinib.
II. To determine the treatment-free remission length. III. To evaluate the efficacy of re-treatment with zanubrutinib plus rituximab in patients who relapse.
OUTLINE:
FRONTLINE THERAPY: Patients receive zanubrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients with complete response (CR) continue zanubrutinib PO BID on days 1-28 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients with partial response (PR) or stable disease (SD) continue zanubrutinib PO BID on days 1-28 and rituximab IV over 3-4 hours on day 1 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 13, patients with CR continue zanubrutinib PO BID on days 1-28 for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 13, patients with PR or SD continue zanubrutinib PO BID on days 1-28 for up to 12 additional cycles in the absence of disease progression or unacceptable toxicity. Patients who do not have a PR after 24 cycles either continue zanubrutinib if there is a clinical benefit, or pursue alternative therapy per treating physician discretion.
RE-TREATMENT FOR RELAPSED DISEASE: Patients with disease relapse and active disease that requires salvage therapy may restart zanubrutinib PO BID on days 1-28 and rituximab IV over 3-4 hours on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients continue zanubrutinib PO BID on days 1-28 for up to 18 additional cycles in the absence of disease progression or unacceptable toxicity and then discontinue if in CR. Beginning cycle 25, patients with PR or SD may continue zanubrutinib PO BID on days 1-28 for up to 36 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 60 days, and then every 120 days for up to 5 years or until disease progression or start of a new treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (zanubrutinib, rituximab) | Experimental | Biological: Rituximab, Drug: ZanubrutinibSee Detailed Description. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have a diagnosis chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and be previously untreated
- Patients must have an indication for treatment by 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
- Patients must understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients of childbearing potential must be willing to practice highly effective birth control (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
Key exclusion criteria (17 listed)
- Pregnant or breast-feeding females
- Prior therapy with zanubrutinib or other kinase inhibitors that target BCR signaling (such as ibrutinib, idelalisib)
- Prior CLL-directed treatment including chemotherapy, chemo-immunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial. Patients that receive zanubrutinib salvage therapy cannot have received any other CLL-directed therapy besides frontline zanubrutinib plus rituximab
- Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to grade 1 or less prior to first dose of study drug
- Systemic fungal, bacterial, viral, or other infection not controlled by antimicrobial therapy, in the assessment of the treating physician(s) and/or the principal investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Treatment (zanubrutinib, rituximab) |
| ZanubrutinibAlso: BGB-3111, Brukinsa, BTK-InhBGiven PO | Drug | Treatment (zanubrutinib, rituximab) |
Primary outcome
Success rate
Time frame: At 6 months after discontinuation of zanubrutinib
Will estimate the proportion of patients who have treatment-free remission 6 months after discontinuation of zanubrutinib. Success rate will be estimated with 95% credible interval and confidence interval.
3 secondary outcomes
Clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of zanubrutinib
Time frame: Up to 5 years after discontinuation of zanubrutinib
Treatment-free remission length
Time frame: Up to 5 years after discontinuation of zanubrutinib
Overall response
Time frame: After 6 cycles of treatment (each cycle is 28 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan A Burger principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab and Zanubrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success rate (time frame: At 6 months after discontinuation of zanubrutinib). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.