Venetoclax Plus Zanubrutinib for CLL and SLL
This study is testing a combination of two medicines, venetoclax and zanubrutinib, for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Venetoclax works by blocking a protein called Bcl-2, which cancer cells need to survive. Zanubrutinib blocks another protein called BTK, which can also help stop cancer cells from growing. The goal is to see if this combination is safe and helps reduce the number of cancer cells in your body. You may be able to join if you are 18 or older, have CLL/SLL, and meet specific treatment criteria, whether you've had prior treatment or not. The study will measure how many participants achieve undetectable minimal residual disease (uMRD), meaning very few cancer cells remain.
- Study design
- This is an interventional study planning to enroll 155 participants. It is not specified if it is randomized or blinded.
- What's involved
- You would undergo blood sample collection, bone marrow biopsies and aspirations, and imaging tests like CT scans and MRIs. The primary endpoints are measured at the end of cycle 15 or 27 (each cycle is 28 days).
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoints are measured at the end of cycle 15 (for the first-line group) or cycle 27 (for the second-line group), with each cycle lasting 28 days.
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NCT07734038
Venetoclax Plus Zanubrutinib for the Treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Not Yet Recruiting
PHASE2Ages 18+InterventionalTreatmentKerry RogersInvestigator-initiated
~155 participants
Updated 2026-07-29 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyMagnetic Resonance ImagingVenetoclax
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Rate of undetectable minimal residual disease (uMRD) (Firstline Cohort)
Measured over At end of cycle 15 (cycle length = 28 days)
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesOhio1
Study leadership
- Kerry A Rogers, MD · PRINCIPAL_INVESTIGATOR · Ohio State University Comprehensive Cancer Center
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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
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
Exclusion
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
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
What this trial measures
- Rate of undetectable minimal residual disease (uMRD) (Firstline Cohort)At end of cycle 15 (cycle length = 28 days)
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.
- Rate of uMRD (Second Line Cohort)At end of cycle 27 (cycle length = 28 days)
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.