[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07734038":3,"trial-entities:NCT07734038":256,"trial-summary:NCT07734038":260},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":22,"primary_purpose":23,"phases":24,"enrollment_info":26,"interventions":29,"primary_outcomes":114,"secondary_outcomes":123,"sex":159,"minimum_age":160,"maximum_age":161,"healthy_volunteers":162,"eligibility_criteria":163,"std_ages":222,"locations":225,"central_contacts":243,"overall_officials":248,"references":251,"see_also_links":252},"NCT07734038","OSU-25150","Venetoclax Plus Zanubrutinib for the Treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma","A Phase Two Study of Venetoclax Plus Zanubrutinib in Newly Diagnosed CLL and After Front-Line Time-Limited Venetoclax-Based Therapy","NOT_YET_RECRUITING","2027-12-31","2026-07","2026-07-29","2026-10-07","Kerry Rogers","OTHER",true,"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.","PRIMARY OBJECTIVE:\n\nI. To determine undetectable minimal residual disease (uMRD) rates in CLL patients receiving fixed-duration combined treatment with venetoclax plus zanubrutinib.\n\nSECONDARY OBJECTIVES:\n\nI. 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)\n\nEXPLORATORY OBJECTIVES:\n\nI. 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.\n\nVI. BH3 profiling at baseline and after cycle (C)3 of treatment with zanubrutinib.\n\nVII. 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.\n\nOUTLINE: Patients who have not previously been treated are assigned to Cohort I and patients who completed initial treatment are assigned to Cohort II.\n\nCOHORT 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.\n\nCOHORT 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.\n\nAdditionally, patients undergo blood sample collection, bone marrow biopsy and aspiration, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.\n\nAfter 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.",[19,20],"Chronic Lymphocytic Leukemia","Small Lymphocytic Lymphoma",[],"INTERVENTIONAL","TREATMENT",[25],"PHASE2",{"count":27,"type":28},155,"ESTIMATED",[30,42,46,52,69,89,105],{"type":31,"name":32,"description":33,"armGroupLabels":34,"otherNames":37},"PROCEDURE","Biospecimen Collection","Undergo blood sample collection",[35,36],"Cohort I (SOC zanubrutinib, venetoclax)","Cohort II (SOC zanubrutinib, venetoclax)",[38,39,40,41],"Biological Sample Collection","Biospecimen Collected","Sample Collection","Specimen Collection",{"type":31,"name":43,"description":44,"armGroupLabels":45},"Bone Marrow Aspiration","Undergo bone marrow biopsy and aspiration",[35,36],{"type":31,"name":47,"description":44,"armGroupLabels":48,"otherNames":49},"Bone Marrow Biopsy",[35,36],[50,51],"Biopsy of Bone Marrow","Biopsy, Bone Marrow",{"type":31,"name":53,"description":54,"armGroupLabels":55,"otherNames":56},"Computed Tomography","Undergo CT",[35,36],[57,58,59,60,61,62,63,64,65,66,67,68],"CAT","CAT Scan","Computed Axial Tomography","Computerized Axial Tomography","Computerized axial tomography (procedure)","Computerized Tomography","Computerized Tomography (CT) scan","CT","CT Scan","Diagnostic CAT Scan","Diagnostic CAT Scan Service Type","tomography",{"type":31,"name":70,"description":71,"armGroupLabels":72,"otherNames":73},"Magnetic Resonance Imaging","Undergo MRI",[35,36],[74,75,76,77,78,79,80,81,82,83,84,85,86,87,88],"Magnetic Resonance","Magnetic Resonance Imaging (MRI)","Magnetic resonance imaging (procedure)","Magnetic Resonance Imaging Scan","Medical Imaging, Magnetic Resonance \u002F Nuclear Magnetic Resonance","MR","MR Imaging","MRI","MRI Scan","MRIs","NMR Imaging","NMRI","Nuclear Magnetic Resonance Imaging","sMRI","Structural MRI",{"type":90,"name":91,"description":92,"armGroupLabels":93,"otherNames":94},"DRUG","Venetoclax","Given PO",[35,36],[95,96,97,98,99,100,101,102,103,104],"ABT 199","ABT-0199","ABT-199","ABT199","GDC 0199","GDC-0199","GDC0199","RG7601","Venclexta","Venclyxto",{"type":90,"name":106,"description":92,"armGroupLabels":107,"otherNames":108},"Zanubrutinib",[35,36],[109,110,111,112,113],"BGB 3111","BGB-3111","BGB3111","Brukinsa","BTK-InhB",[115,119],{"measure":116,"description":117,"timeFrame":118},"Rate of undetectable minimal residual disease (uMRD) (Firstline Cohort)","Will be defined as \\\u003C 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.","At end of cycle 15 (cycle length = 28 days)",{"measure":120,"description":121,"timeFrame":122},"Rate of uMRD (Second Line Cohort)","Will be defined at \\\u003C 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.","At end of cycle 27 (cycle length = 28 days)",[124,128,130,134,137,140,144,146,148,150,152,154,156],{"measure":125,"description":126,"timeFrame":127},"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.","Up to 5 years",{"measure":129,"description":126,"timeFrame":127},"Rate of complete remission (Frontline Cohort)",{"measure":131,"description":132,"timeFrame":133},"Duration of clinical response (Frontline Cohort)","The method of Kaplan-Meier will be used to estimate.","From date of achieving response to progression or death, assessed up to 5 years",{"measure":135,"description":132,"timeFrame":136},"Duration of uMRD if achieved (Frontline Cohort)","From date of achieving uMRD to progression or death, assessed up to 5 years",{"measure":138,"description":132,"timeFrame":139},"Time to next treatment (Frontline Cohort)","From date of treatment start to the start date of the next treatment, assessed up to 5 years",{"measure":141,"description":142,"timeFrame":143},"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.","Up to 28 days after last dose of study treatment",{"measure":145,"description":126,"timeFrame":127},"Overall response rate (Second Line Cohort)",{"measure":147,"description":126,"timeFrame":127},"Rate of complete remission (Second Line Cohort)",{"measure":120,"description":126,"timeFrame":149},"At cycle 15 of treatment (cycle length = 28 days)",{"measure":151,"description":132,"timeFrame":133},"Duration of clinical response (Second Line Cohort)",{"measure":153,"description":132,"timeFrame":136},"Duration of uMRD if achieved (Second Line Cohort)",{"measure":155,"description":132,"timeFrame":139},"Time to next treatment (Second Line Cohort)",{"measure":157,"description":158,"timeFrame":143},"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.","ALL","18 Years",null,false,{"inclusion":164,"exclusion":185,"raw_text":221},[165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184],"Diagnosis of CLL\u002FSLL 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\u002FSLL 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 +\u002F- 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\u002FSLL therapy","Eastern Cooperative Oncology Group (ECOG) performance 0-2","Absolute neutrophil count (ANC) \\> 1000\u002Fmm\\^3 (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)","Platelets \\> 30,000\u002Fmm\\^3 at screening (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)","Hemoglobin \\> 7 g\u002FdL (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)","Aspartate aminotransferase (AST)\u002Falanine 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\u002For 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",[186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220],"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\u002For 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\u002For 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\u002FSLL","Inclusion Criteria:\n\n* Diagnosis of CLL\u002FSLL meeting criteria established in International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria\n* Age ≥ 18 years\n* Indications for treatment as defined by the iwCLL 2018 Guidelines\n* Received prior treatment or not depending on cohort\n\n  * Frontline cohort:\n\n    * CLL\u002FSLL who are treatment-naïve and have met criteria 1 through 3 above\n  * Second line cohort:\n\n    * 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 +\u002F- 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\n    * At least 2 years since completion of initial CLL treatment\n    * 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\u002FSLL therapy\n* Eastern Cooperative Oncology Group (ECOG) performance 0-2\n* Absolute neutrophil count (ANC) \\> 1000\u002Fmm\\^3 (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)\n* Platelets \\> 30,000\u002Fmm\\^3 at screening (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)\n* Hemoglobin \\> 7 g\u002FdL (independent of growth factor support at screening, unless cytopenias are due to marrow involvement by CLL\u002FSLL)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 3 x the upper limit of normal (ULN) or ≤ 5 x ULN with documented liver involvement\n* Bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented liver involvement and\u002For Gilbert's disease\n* Creatinine clearance (CrCl) ≥ 50 according to modified Cockcroft-Gault equation\n* Willing and able to complete study activities and treatment\n* 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\n* 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\n\nExclusion Criteria:\n\n* Second line arm only: Patients who progressed per iwCLL 2018 criteria on therapy or within two years of completing time-limited, venetoclax based treatment\n* Frontline arm only: Patients with deletion 17p and\u002For TP53 mutation\n* Active Richter's transformation\n* Prior zanubrutinib exposure\n* Known hypersensitivity to any of the excipients of zanubrutinib or venetoclax\n* Need for treatment with warfarin or other vitamin K antagonist during study treatment\n* History of stroke or intracranial hemorrhage within 6 months\n* Known bleeding diathesis\n* Inability to take pills or oral medications\n* Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of either zanubrutinib or venetoclax\n* 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\n* Psychiatric illness, or social situations that would limit compliance with study requirements\n* 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\n* 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\n* Significant cardiovascular disease defined as:\n\n  * Unstable angina or acute coronary syndrome within the past 2 months\n  * History of myocardial infarction within 3 months\n  * Documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% within 12 months\n  * ≥ grade 3 New York Heart Association (NYHA) functional classification system of heart failure\n  * Uncontrolled or symptomatic arrhythmias\n\n    * Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker\n* Prolongation of the QT interval corrected for heart rate (QTcF) \\> 470 msec. QTcF is calculated using Fridericia's Formula (QTcF)\n\n  * 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\n  * Correction for underlying bundle branch block (BBB) allowed\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:\n\n  * 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\n  * 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\n  * 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\n* Treatment with a strong cytochrome P450 (CYP)3A inhibitor or inducer and\u002For strong P-glycoprotein (P-gp) inhibitors within 3 days of starting and during study treatment\n* Patients may not plan to consume grapefruit or grapefruit products, Seville oranges or products from Seville oranges, or star fruit\n* 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\n* Major surgery within 4 weeks prior to screening\n* Vaccination with live vaccine within 28 days of screening\n* Currently incarcerated\n* Current central nervous system involvement by CLL\u002FSLL",[223,224],"ADULT","OLDER_ADULT",[226],{"facility":227,"city":228,"state":229,"zip":230,"country":231,"contacts":232,"geoPoint":240},"Ohio State University Comprehensive Cancer Center","Columbus","Ohio","43210","United States",[233,238],{"name":234,"role":235,"phone":236,"email":237},"Kerry A. Rogers, MD","CONTACT","614-366-9338","Kerry.Rogers@osumc.edu",{"name":234,"role":239},"PRINCIPAL_INVESTIGATOR",{"lat":241,"lon":242},39.96118,-82.99879,[244],{"name":245,"role":235,"phone":246,"email":247},"The Ohio State University Comprehensive Cancer Center","800-293-5066","OSUCCCClinicaltrials@osumc.edu",[249],{"name":250,"affiliation":227,"role":239},"Kerry A Rogers, MD",[],[253],{"label":254,"url":255},"The Jamesline","https:\u002F\u002Fcancer.osu.edu\u002F",{"nct_id":4,"conditions":257,"biomarkers":258},[19,20],[259],"BCL2 Gene",{"nct_id":4,"found":15,"summary":261,"prompt_version":271},{"design":262,"status":263,"heading":264,"summary":265,"follow_up":266,"word_count":267,"commitments":268,"compensation":269,"drugs_mentioned":270},"This is an interventional study planning to enroll 155 participants. It is not specified if it is randomized or blinded.","completed","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\u002FSLL, 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.","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.",119,"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).","Not stated in the trial record.",[],"v2"]