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Chronic Lymphocytic LeukemiaPhase 2NCT07734038

Venetoclax Plus Zanubrutinib for the Treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Kerry Rogers at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase II trial tests the effect of venetoclax in combination with standard of care (SOC) zanubrutinib in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
155 participants
Where
1 siteUnited States
Study dates
1 Oct 2026to 31 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

  • Diagnosis of CLL/SLL meeting criteria established in International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
  • Age ≥ 18 years
  • Indications for treatment as defined by the iwCLL 2018 Guidelines
  • Received prior treatment or not depending on cohort
  • Frontline cohort:
  • CLL/SLL who are treatment-naïve and have met criteria 1 through 3 above
Show all 20Show fewer
  • Second line cohort:
  • Must have received time-limited venetoclax based therapy in the front line. This is defined as treatment with venetoclax and an-anti-CD20 antibody, venetoclax and a BTKi, or treatment with venetoclax and a BTKi, and an anti-CD20 monoclonal antibody that was given for a fixed-duration. Patients who discontinue ibrutinib, due to intolerance, in a BTKi and venetoclax +/- obinutuzumab combination are eligible provided they completed other drugs in the regimen and in the opinion of the treating investigator the intolerance will not limit treatment with zanubrutinib and venetoclax. Patients who discontinued BTKi other than ibrutinib or who discontinued venetoclax due to intolerance will be excluded
  • At least 2 years since completion of initial CLL treatment
  • Only 1 prior line of therapy. Treatment with rituximab or other anti-CD20 monoclonal antibody for idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA) is not considered a prior line of CLL/SLL therapy
  • Eastern Cooperative Oncology Group (ECOG) performance 0-2
  • Absolute neutrophil count (ANC) > 1000/mm^3 (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL/SLL)
  • Platelets > 30,000/mm^3 at screening (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL/SLL)
  • Hemoglobin > 7 g/dL (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL/SLL)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x the upper limit of normal (ULN) or ≤ 5 x ULN with documented liver involvement
  • Bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented liver involvement and/or Gilbert's disease
  • Creatinine clearance (CrCl) ≥ 50 according to modified Cockcroft-Gault equation
  • Willing and able to complete study activities and treatment
  • Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
  • Willingness of men and women of reproductive potential and their partners to observe conventional and highly effective or acceptable birth control methods for the duration of treatment and for 1 week following the last dose of zanubrutinib or 30 days following the last dose of venetoclax, whichever is longer

Who cannot join

  • Second line arm only: Patients who progressed per iwCLL 2018 criteria on therapy or within two years of completing time-limited, venetoclax based treatment
  • Frontline arm only: Patients with deletion 17p and/or TP53 mutation
  • Active Richter's transformation
  • Prior zanubrutinib exposure
  • Known hypersensitivity to any of the excipients of zanubrutinib or venetoclax
  • Need for treatment with warfarin or other vitamin K antagonist during study treatment
Show all 35Show fewer
  • History of stroke or intracranial hemorrhage within 6 months
  • Known bleeding diathesis
  • Inability to take pills or oral medications
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of either zanubrutinib or venetoclax
  • Active second malignancy unless in remission and with life expectancy > 2 years. Adjuvant endocrine therapy for breast or prostate cancer that is expected to be cured is allowed. Non-melanoma skin cancers are permitted if adequately treated
  • Psychiatric illness, or social situations that would limit compliance with study requirements
  • Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts
  • Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator may pose a risk for patient participation. Screening for chronic conditions is not required
  • Significant cardiovascular disease defined as:
  • Unstable angina or acute coronary syndrome within the past 2 months
  • History of myocardial infarction within 3 months
  • Documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% within 12 months
  • ≥ grade 3 New York Heart Association (NYHA) functional classification system of heart failure
  • Uncontrolled or symptomatic arrhythmias
  • Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
  • Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF)
  • Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation
  • Correction for underlying bundle branch block (BBB) allowed
  • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
  • Hepatitis B virus (HBV): Patients with positive hepatitis B surface antibody (HBsAb) are not excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before inclusion. Patients who are hepatitis B PCR positive at time of screening will be excluded. Those who have hepatitis B core antibody positive and a negative PCR will be included if they are agreeable to receive antiviral prophylaxis
  • Hepatitis C virus (HCV): If hepatitis C antibody is positive, patients will need to have a negative result for hepatitis C ribonucleic acid (RNA) before inclusion. Patients who are hepatitis C RNA positive at time of screening will be excluded. Patients previously treated for hepatitis C > 6 months previously with a negative RNA test are eligible
  • Patients who are receiving intravenous immunoglobulin (IVIG) who test positive for any hepatitis B or C serologies and have a negative PCR and who are deemed likely to have received antibodies passively through IVIG and not from prior infection will be included without viral prophylaxis
  • Treatment with a strong cytochrome P450 (CYP)3A inhibitor or inducer and/or strong P-glycoprotein (P-gp) inhibitors within 3 days of starting and during study treatment
  • Patients may not plan to consume grapefruit or grapefruit products, Seville oranges or products from Seville oranges, or star fruit
  • Pregnancy, lactation, or plan to breastfeed during treatment with or within 2 weeks of the last dose of zanubrutinib or 1 month of the last dose of venetoclax
  • Major surgery within 4 weeks prior to screening
  • Vaccination with live vaccine within 28 days of screening
  • Currently incarcerated
  • Current central nervous system involvement by CLL/SLL

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Kerry A. Rogers, MD, 614-366-9338, Kerry.Rogers@osumc.edu

    Kerry A. Rogers, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase Two Study of Venetoclax Plus Zanubrutinib in Newly Diagnosed CLL and After Front-Line Time-Limited Venetoclax-Based Therapy

This phase II trial tests the effect of venetoclax in combination with standard of care (SOC) zanubrutinib in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. It is a type of tyrosine kinase inhibitor. Giving venetoclax in combination with SOC zanubrutinib may be safe and tolerable and may reduce the number of cancer cells that remain in the body in patients with CLL or SLL that have not previously received treatment or at least two years have passed since completing initial treatment.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine undetectable minimal residual disease (uMRD) rates in CLL patients receiving fixed-duration combined treatment with venetoclax plus zanubrutinib.

SECONDARY OBJECTIVES:

  1. Overall response rate. (Frontline Cohort) II. Rate of complete remission. (Frontline Cohort) III. Duration of response. (Frontline Cohort) IV. Duration of uMRD if achieved. (Frontline Cohort) V. Time to next treatment. (Frontline Cohort) VI. Rate of adverse events with zanubrutinib and venetoclax treatment. (Frontline Cohort) VII. Overall response rate. (Second Line Cohort) VIII. Rate of complete remission. (Second Line Cohort) IX. Rate of uMRD at cycle 15 of treatment. (Second Line Cohort) X. Duration of response. (Second Line Cohort) XI. Duration of uMRD if achieved. (Second Line Cohort) XII. Time to next treatment. (Second Line Cohort) XIII. Rate of adverse events with zanubrutinib and venetoclax treatment. (Second Line Cohort)

EXPLORATORY OBJECTIVES:

  1. Estimated 36-months progression-free survival. II. Progression-free survival for both cohorts. III. Overall survival for both cohorts. IV. Patient and disease characteristics associated with achieving uMRD status. V. Development of resistance mutations associated with BTK inhibitor (BTKi) and venetoclax.

VI. BH3 profiling at baseline and after cycle (C)3 of treatment with zanubrutinib.

VII. Impact of treatment on measures of immune function. VIII. Incidence of laboratory and clinical tumor lysis syndrome (TLS) during venetoclax ramp-up, change in TLS risk category after zanubrutinib lead-in (C1-3), and interventions for electrolyte changes.

OUTLINE: Patients who have not previously been treated are assigned to Cohort I and patients who completed initial treatment are assigned to Cohort II.

COHORT I (FRONTLINE COHORT): Patients receive SOC zanubrutinib orally (PO) once daily (QD) or twice daily (BID) per physician discretion on days 1-28 of each cycle. Starting with cycle 4, patients also receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity.

COHORT II (SECOND LINE COHORT): Patients receive SOC zanubrutinib PO QD or BID per physician discretion on days 1-28 of each cycle. Starting with cycle 4, patients also receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo blood sample collection, bone marrow biopsy and aspiration, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed up at 28 days, every 12 weeks (3 months) up to progression then every 6 months for up to year 5.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Magnetic Resonance Imaging
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.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

  • ZanubrutinibDrug

    Also called BGB 3111, BGB-3111, BGB3111, Brukinsa

    Given PO

Study groups in NCT07734038
Study groupRoleWhat they receive
Cohort I (SOC zanubrutinib, venetoclax)ExperimentalPatients receive SOC zanubrutinib PO QD or BID per physician discretion on days 1-28 of each cycle. Starting with cycle 4, patients also receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, bone marrow biopsy and aspiration, and CT or MRI throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Venetoclax; Drug: Zanubrutinib
Cohort II (SOC zanubrutinib, venetoclax)ExperimentalPatients receive SOC zanubrutinib PO QD or BID per physician discretion on days 1-28 of each cycle. Starting with cycle 4, patients also receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, bone marrow biopsy and aspiration, and CT or MRI throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Venetoclax; Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of undetectable minimal residual disease (uMRD) (Firstline Cohort)

    Will be defined as < 1 x 10^-4 by ClonoSEQ in the peripheral blood, after 12 cycles of combined venetoclax plus zanubrutinib assessed by ClonoSEQ. Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: At end of cycle 15 (cycle length = 28 days)

  2. Rate of uMRD (Second Line Cohort)

    Will be defined at < 1 x 10^-4 by ClonoSEQ in the peripheral blood, after 24 cycles of combined venetoclax plus zanubrutinib. Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: At end of cycle 27 (cycle length = 28 days)

Secondary outcomes (13)

  1. Overall response rate (Frontline Cohort)

    Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: Up to 5 years

  2. Rate of complete remission (Frontline Cohort)

    Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: Up to 5 years

  3. Duration of clinical response (Frontline Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of achieving response to progression or death, assessed up to 5 years

  4. Duration of uMRD if achieved (Frontline Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of achieving uMRD to progression or death, assessed up to 5 years

  5. Time to next treatment (Frontline Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of treatment start to the start date of the next treatment, assessed up to 5 years

  6. Rate of adverse events (AEs) (Frontline Cohort)

    Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Hematologic AEs will be graded according to chronic lymphocytic leukemia (CLL)-specific criteria described in the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 guidelines. The maximum grade for each type of toxicity will be tabulated for each patient, and frequency tables will be reviewed to determine toxicity patterns. Will assess AEs of all grades with focus on grade 3 or higher toxicity. AEs regardless of attribution will be summarized first, and those attributable to study drug will also be listed separately. The incidence of serious AEs or those of special interest will be described. To assess tolerability, will also capture the proportion of patients who go off treatment due to AEs.

    Measured: Up to 28 days after last dose of study treatment

  7. Overall response rate (Second Line Cohort)

    Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: Up to 5 years

  8. Rate of complete remission (Second Line Cohort)

    Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: Up to 5 years

  9. Rate of uMRD (Second Line Cohort)

    Will be calculated separately in each cohort among all eligible patients who start any amount of study drug, and the 95% exact confidence interval will be provided with the estimated rate.

    Measured: At cycle 15 of treatment (cycle length = 28 days)

  10. Duration of clinical response (Second Line Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of achieving response to progression or death, assessed up to 5 years

  11. Duration of uMRD if achieved (Second Line Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of achieving uMRD to progression or death, assessed up to 5 years

  12. Time to next treatment (Second Line Cohort)

    The method of Kaplan-Meier will be used to estimate.

    Measured: From date of treatment start to the start date of the next treatment, assessed up to 5 years

  13. Rate of AEs (Second Line Cohort)

    Will be graded according to NCI CTCAE v 5.0. Hematologic AES will be graded according to CLL-specific criteria described in the IWCLL 2018 guidelines. The maximum grade for each type of toxicity will be tabulated for each patient, and frequency tables will be reviewed to determine toxicity patterns. Will assess AEs of all grades with focus on grade 3 or higher toxicity. AEs regardless of attribution will be summarized first, and those attributable to study drug will also be listed separately. The incidence of serious AEs or those of special interest will be described. To assess tolerability, will also capture the proportion of patients who go off treatment due to AEs.

    Measured: Up to 28 days after last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2026
  2. Study start1 Oct 2026 (estimated)
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
155 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07734038
Sponsor's protocol ID
OSU-25150
Other IDs
NCI-2026-05223, STUDY20251617
Status last verified
Aug 2026
First submitted
24 Jul 2026
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Kerry Rogers 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 20 inclusion and 35 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: looking for participants now, as of the sponsor's last update on 31 Aug 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?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of undetectable minimal residual disease (uMRD) (Firstline Cohort) (time frame: At end of cycle 15 (cycle length = 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07734038.

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 31 Aug 2026.

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