Leukemia, Lymphocytic, Chronic, B-CellPhase 2NCT05650723
Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab
A Phase 2 study testing Zanubrutinib Pill, Venetoclax Pill and Obinutuzumab Injection in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- Zanubrutinib Pill, Venetoclax Pill and Obinutuzumab Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2023to Dec 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
- Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
- Subject must be ≥ 18 years of age.
- Subject must have confirmed diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
- Please note, participants with SLL must have identifiable B-cells in peripheral blood or bone marrow consistent with CLL/SLL immuno-phenotype, based on flow-cytometry, in order to be enrolled
- Subject must have indications for treatment per the 2018 iwCLL Guidelines.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
Show all 15Show fewer
- Subject must have adequate organ function defined as:
- Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or the Modification of Diet in Renal Disease equation, or as measured by nuclear medicine scan or 24-hour urine collection).
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal (ULN) unless due to CLL/SLL.
- Serum total bilirubin < 3.0 × ULN (unless documented Gilbert's syndrome)
- Subject must have adequate bone marrow function and meet the below thresholds unless approved by sponsor if cytopenias are felt to be due to significant marrow involvement of CLL:
- Absolute neutrophil count ≥ 1.0 x103/μL
- Hemoglobin ≥ 7 g/dL (can be transfused up to 1 week prior to study enrollment)
- Platelets ≥ 75,000 cells/μL OR platelets ≥ 30,000 cells/μL if clearly due to disease under study (per investigator discretion)
- Subjects of childbearing potential must be willing to comply with pregnancy prevention interventions (as defined in Section 4.4)
Who cannot join
- A subject will be ineligible for the study if he/she meets the following criteria:
- Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy.
- Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 35 years from treatment end will be allowed to enroll. Adjuvant hormonal therapy will be allowed at time of enrollment if the subject otherwise is not excluded by the 3-year waiting period.
- Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
- Subjects with active autoimmune hemolytic anemia or immune thrombocytopenia purpura.
- Subject with prolymphocytic leukemia or Richter's Transformation.
Show all 30Show fewer
- Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
- Subject requires warfarin or equivalent vitamin K antagonist.
- Uncontrolled or active significant infection requiring systemic treatment, subjects are eligible if they have completed antibiotic therapy 2 weeks prior to study enrollment.
- History of suspected or confirmed PML
- Clinically significant cardiovascular disease including the following:
- Myocardial infarction within 6 months before screening.
- Unstable angina within 3 months before screening.
- New York Heart Association class III or IV congestive heart failure
- History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).
- QT interval corrected with Fridericia's formula (QTcF) > 480 milliseconds based on Fridericia's formula.
- History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place.
- Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg at screening.
- Patients with stroke or CNS hemorrhage within 6 months.
- Pregnant or breastfeeding.
- 14. Major surgical procedure within 28 days of first dose of study drug. If a subject had surgery, they must have recovered adequately from any toxicity or complications before the first dose of study drug.
- 15. Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
- 16. Subject is known to be positive for human immunodeficiency virus (HIV). 17. Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR. 18. Active hepatitis B infection documented by a positive PCR for Hep B DNA. If hepatitis B serology is positive for hepatitis B core antibody, but Hep B DNA PCR is negative, patient is eligible to enroll.
- 19. Subject requires:
- Strong and moderate CYP3A inhibitors within 7 days prior to the initiation of study treatment.
- Strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- Steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration.
- Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration.
- 20. Known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use.
- 21. Vaccination with live vaccine ≤28 days prior to start of treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medicine/NewYork-Presberteryian Hospital
New York, New York, 10021
About this study
Official title: Zanubrutinib and Venetoclax as Initial Therapy for CLL With Obinutuzumab Consolidation in Patients With Minimal Residual Disease Positivity (BruVenG)
Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease [MRD]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test this hypothesis by treating subjects with 3 cycles of a zanubrutinib monotherapy lead-in, in order to debulk and mitigate tumor lysis risk, followed by 13 cycles of zanubrutinib and venetoclax combination therapy. Subjects who are both peripheral blood and bone marrow MRD negative at the completion of the 13 cycles of combination therapy will stop treatment and enter an observation phase every 3 months. Subjects that are MRD positive will continue combination therapy with zanubrutinib and venetoclax for an additional 6 cycles but also receive 6 cycles of obinutuzumab in order to augment response and increase MRD negative rates for the overall treated cohort.
Read the detailed description
This is an open label, phase II, investigator-initiated clinical trial of 50 subjects. Subjects with CLL/SLL who have treatment indications per the 2018 International Workshop for CLL (iwCLL) will be eligible to enroll. The investigators hypothesize that anti-CD20 therapy may not be required for all patients and a response-adapted strategy will prevent over treatment of a significant number of patients and reduce toxicity of treatment while still achieving a high rate of MRD negativity. The investigators also hypothesize that late addition of anti-CD20 therapy can eliminate low burden residual disease in subjects and maximize undetectable MRD negativity in subjects who remain MRD positive.
All subjects will initiate induction therapy with 3 cycles of zanubrutinib monotherapy in order to debulk subjects and mitigate tumor lysis risk. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination. Standard ramp-up protocols for venetoclax based on TLS risk assessed prior to C4D1 will be utilized. All subjects will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Subjects will continue on combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all subjects will be on treatment for at least 16 full cycles. Subjects that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Subjects that meet definition of MRD positivity will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all subjects will stop study treatment regardless of MRD status.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- Zanubrutinib Pill, Venetoclax Pill, Obinutuzumab Injection
- Keywords
- Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
- 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.
Zanubrutinib PillDrug
Also called Brukinsa
320 mg once per day by mouth
Venetoclax PillDrug
Also called Venclexta
400 mg once per day by mouth following the standard ramp-up schedule (20mg daily PO week 1, 50mg daily PO week 2, 100mg daily PO week 3, 200mg daily PO week 4, followed by 400mg PO daily week 5)
Obinutuzumab InjectionDrug
Also called Gazyva
1000 mg IV given every 28 days
| Study group | Role | What they receive |
|---|---|---|
| Double Therapy (Zanubrutinib plus Venetoclax) | Experimental | All participants will receive an initial 3 cycles of zanubrutinib monotherapy. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination therapy. All participants will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Participants will continue on double combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all participants will be on treatment for at least 16 full cycles. Participants that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Participants that remain MRD positive at C16D1 will enter the triple therapy (zanubrutinib, venetoclax, and obinutuzumab) arm. Receives: Drug: Zanubrutinib Pill; Drug: Venetoclax Pill |
| Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) | Experimental | Participants that meet definition of MRD positivity at C16D1 will enter the triple therapy arm (zanubrutinib, venetoclax, and obinutuzumab). These participants will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all participants will stop study treatment regardless of MRD status. Receives: Drug: Zanubrutinib Pill; Drug: Venetoclax Pill; Drug: Obinutuzumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via peripheral blood
The primary endpoint of C16 peripheral blood MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
Measured: Cycle 16 (Month 16)
Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via bone marrow aspirate
The primary endpoint of C16 bone marrow MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
Measured: Cycle 16 (Month 23)
Percentage of eligible patients that have achieved undetectable minimal residual disease (MRD) at cycle 23, as assessed via peripheral blood
The co-primary endpoint of C23 peripheral blood MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
Measured: Cycle 23 (Month 23)
Percentage of eligible patients that have achieved undetectable minimal residual disease (MRD) at cycle 23, as assessed via bone marrow aspirate
The co-primary endpoint of C23 bone marrow MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
Measured: Cycle 23 (Month 23)
Secondary outcomes (10)
Percentage of total participants who experience adverse events (AEs) through cycle 16
The secondary endpoints measuring toxicity will be tabulated using CTCAE 5.0. Numbers of participants experiencing adverse events (AEs) will be represented as a percentage through cycle 16.
Measured: Cycle 16 (Month 16)
Percentage of participants receiving triplet therapy who experience AEs through cycle 23
The secondary endpoints measuring toxicity will be tabulated using CTCAE 5.0. Participants who were MRD positive at cycle 16 and who receive obinutuzumab will have AEs tabulated as a percentage of total patients in the obinutuzumab consolidation phase of the study.
Measured: Cycle 23 (Month 23)
36-month Progression Free Survival (PFS)
Thirty-six-month PFS will be determined via Kaplan-Meier methods. PFS will be defined as the time from first treatment day until progression or death from any cause, as assessed at 36 months. Patients who do not experience an event or lost to follow-up will be censored.
Measured: 36 months
36-month Overall Survival (OS)
36-month OS will be determined via Kaplan-Meier methods. OS will be defined as the time from first treatment day until death from any cause as assessed at 36-months. Patients who do not experience an event or lost to follow-up will be censored.
Measured: 36 months
Percentage of patients treated with doublet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 24-months, as assessed via peripheral blood
The percentage of patients who were treated with doublet therapy of zanubrutinib and venetoclax who achieve undetectable MRD at 24 months, as assessed with via peripheral blood, will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
Measured: 24 months
Percentage of patients treated with doublet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 36-months, as assessed via peripheral blood
The percentage of patients who were treated with doublet therapy of zanubrutinib and venetoclax who achieve undetectable MRD at 36 months, as assessed with via peripheral blood, will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
Measured: 36 months
Percentage of patients treated with triplet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 36-months, as assessed via peripheral blood
The percentage of patients who were treated with triplet therapy who achieve undetectable MRD at 36 months, as assessed with via peripheral blood, will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
Measured: 36 months
36-month Time to Next Treatment (TTNT)
36-month TTNT will be determined via Kaplan-Meier methods. TTNT will be measured from the start of treatment to the date of next line of treatment after stopping therapy. Obinutuzumab consolidation will not be considered a second line of treatment. Any treatment directed at CLL after stopping therapy will be considered a next therapy. Subjects will be followed prospectively and for 36 months from start of initial therapy to calculate a 3 year TTNT. Subjects that die will be censored at time of death.
Measured: 36 months
Percentage Change in Tumor Lysis Syndrome (TLS) Risk Score From Baseline to Cycle 4
Tumor lysis risk of high, medium, or low will be collected at baseline/screening. After 3 cycles of zanubrutinib debulking, TLS risk will be reassessed prior to Cycle 4 day 1. Subjects will have their new assessment, high, medium, or low recorded. Change in TLS risk category will be reported in aggregate and as a percentage change after debulking.
Measured: Baseline; Cycle 4, Day 1 (Month 4)
Overall Response rate
Overall response rate including all categories of response will be tabulated and calculated as total percentage of patients achieving a specific response on an intention to treat basis.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2022
- Study start8 May 2023
- Primary completionMar 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- John Allan, M.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05650723
- Sponsor's protocol ID
- 22-05024874
- Status last verified
- Feb 2026
- First submitted
- 6 Dec 2022
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zanubrutinib and Venetoclax as Initial Therapy for CLL With Obinutuzumab Consolidation in Patients With Minimal Residual Disease Positivity (BruVenG)
- ClinicalTrials.gov ID
- NCT05650723
- Acronym / sponsor ID
- 22-05024874
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Keywords
- Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- BeiGene, Genentech, Inc.
- Study start
- 8 May 2023 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 14 Dec 2022 (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.
Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease [MRD]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test this hypothesis by treating subjects with 3 cycles of a zanubrutinib monotherapy lead-in, in order to debulk and mitigate tumor lysis risk, followed by 13 cycles of zanubrutinib and venetoclax combination therapy. Subjects who are both peripheral blood and bone marrow MRD negative at the completion of the 13 cycles of combination therapy will stop treatment and enter an observation phase every 3 months. Subjects that are MRD positive will continue combination therapy with zanubrutinib and venetoclax for an additional 6 cycles but also receive 6 cycles of obinutuzumab in order to augment response and increase MRD negative rates for the overall treated cohort.
Detailed description
This is an open label, phase II, investigator-initiated clinical trial of 50 subjects. Subjects with CLL/SLL who have treatment indications per the 2018 International Workshop for CLL (iwCLL) will be eligible to enroll. The investigators hypothesize that anti-CD20 therapy may not be required for all patients and a response-adapted strategy will prevent over treatment of a significant number of patients and reduce toxicity of treatment while still achieving a high rate of MRD negativity. The investigators also hypothesize that late addition of anti-CD20 therapy can eliminate low burden residual disease in subjects and maximize undetectable MRD negativity in subjects who remain MRD positive.
All subjects will initiate induction therapy with 3 cycles of zanubrutinib monotherapy in order to debulk subjects and mitigate tumor lysis risk. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination. Standard ramp-up protocols for venetoclax based on TLS risk assessed prior to C4D1 will be utilized. All subjects will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Subjects will continue on combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all subjects will be on treatment for at least 16 full cycles. Subjects that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Subjects that meet definition of MRD positivity will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all subjects will stop study treatment regardless of MRD status.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double Therapy (Zanubrutinib plus Venetoclax) | Experimental | Drug: Zanubrutinib Pill, Drug: Venetoclax PillAll participants will receive an initial 3 cycles of zanubrutinib monotherapy. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination therapy. All participants will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Participants will continue on double combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all participants will be on treatment for at least 16 full cycles. Participants that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Participants that remain MRD positive at C16D1 will enter the triple therapy (zanubrutinib, venetoclax, and obinutuzumab) arm. |
| Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) | Experimental | Drug: Zanubrutinib Pill, Drug: Venetoclax Pill, Drug: Obinutuzumab InjectionParticipants that meet definition of MRD positivity at C16D1 will enter the triple therapy arm (zanubrutinib, venetoclax, and obinutuzumab). These participants will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all participants will stop study treatment regardless of MRD status. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
- Subject must be ≥ 18 years of age.
- Subject must have confirmed diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.
- Subject must have indications for treatment per the 2018 iwCLL Guidelines.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
Key exclusion criteria (30 listed)
- Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy.
- Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 35 years from treatment end will be allowed to enroll. Adjuvant hormonal therapy will be allowed at time of enrollment if the subject otherwise is not excluded by the 3-year waiting period.
- Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
- Subjects with active autoimmune hemolytic anemia or immune thrombocytopenia purpura.
- Subject with prolymphocytic leukemia or Richter's Transformation.
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 |
|---|---|---|
| Zanubrutinib PillAlso: Brukinsa320 mg once per day by mouth | Drug | Double Therapy (Zanubrutinib plus Venetoclax), Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) |
| Venetoclax PillAlso: Venclexta400 mg once per day by mouth following the standard ramp-up schedule (20mg daily PO week 1, 50mg daily PO week 2, 100mg daily PO week 3, 200mg daily PO week 4, followed by 400mg PO daily week 5) | Drug | Double Therapy (Zanubrutinib plus Venetoclax), Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) |
| Obinutuzumab InjectionAlso: Gazyva1000 mg IV given every 28 days | Drug | Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab) |
Primary outcome
Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via peripheral blood
Time frame: Cycle 16 (Month 16)
The primary endpoint of C16 peripheral blood MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution. A cycle is defined as 28 days.
Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via bone marrow aspirate
Time frame: Cycle 16 (Month 23)
The primary endpoint of C16 bone marrow MRD negativity at cycle 16 will be represented as a percentage of total patients. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
Percentage of eligible patients that have achieved undetectable minimal residual disease (MRD) at cycle 23, as assessed via peripheral blood
Time frame: Cycle 23 (Month 23)
The co-primary endpoint of C23 peripheral blood MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
Percentage of eligible patients that have achieved undetectable minimal residual disease (MRD) at cycle 23, as assessed via bone marrow aspirate
Time frame: Cycle 23 (Month 23)
The co-primary endpoint of C23 bone marrow MRD negativity rate will be presented as a percentage of patients that achieve undetectable MRD at C23, who were found to be MRD positive at C16 and went on to receive at least one dose of obinutuzumab. This will be calculated on both efficacy evaluable and intention to treat basis. These will be estimated with a 90% confidence interval using Clopper-Pearson method based on exact binomial distribution.
10 secondary outcomes
Percentage of total participants who experience adverse events (AEs) through cycle 16
Time frame: Cycle 16 (Month 16)
Percentage of participants receiving triplet therapy who experience AEs through cycle 23
Time frame: Cycle 23 (Month 23)
36-month Progression Free Survival (PFS)
Time frame: 36 months
36-month Overall Survival (OS)
Time frame: 36 months
Percentage of patients treated with doublet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 24-months, as assessed via peripheral blood
Time frame: 24 months
Percentage of patients treated with doublet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 36-months, as assessed via peripheral blood
Time frame: 36 months
Percentage of patients treated with triplet therapy (zanubrutinib and venetoclax) that have achieved undetectable minimal residual disease (MRD) at 36-months, as assessed via peripheral blood
Time frame: 36 months
36-month Time to Next Treatment (TTNT)
Time frame: 36 months
Percentage Change in Tumor Lysis Syndrome (TLS) Risk Score From Baseline to Cycle 4
Time frame: Baseline; Cycle 4, Day 1 (Month 4)
Overall Response rate
Time frame: 36 months
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 25 Feb 2026.
- Individual participant dataSharing planned: No
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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.
John Allan, M.D. principal investigator
Weill Medical College of Cornell University
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 Zanubrutinib Pill, Venetoclax Pill and Obinutuzumab Injection in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Weill Medical College of Cornell University 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 15 inclusion and 30 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 25 Feb 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?
Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via peripheral blood (time frame: Cycle 16 (Month 16)). The study lists 4 primary outcomes in all. 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 25 Feb 2026.