Clinical Research Directory

Inclusion Criteria: * Participant must have CLL or SLL (WHO criteria). * Participant must require treatment according to iwCLL guidelines. * Participants must have no prior systemic therapy for CLL or SLL, except: * Prior local radiation for symptomatic disease is permitted. * Short course systemic corticosteroids is permissible for disease control, improvement of performance status, or non-cancer indication. However, duration of steroid course must be ≤14 days with maximum daily dose of ≤100 mg prednisone, ≤20 mg dexamethasone, or equivalent, and must be discontinued prior to study treatment (last dose may be administered up until the morning of / prior to study treatment). Inhaled steroids, topical steroids, and replacement / stress corticosteroids are permitted independent of above rules. In cases of autoimmune complications of CLL (e.g., ITP or AIHA), steroid usage is permitted. * Age ≥18 years. * ECOG performance status of 0, 1 or 2. * Participants must meet the following organ and marrow function as defined below: * absolute neutrophil count ≥1,000/µL without growth factor support (filgrastim within 5 days or PEGfilgrastim within 10 days of test), unless clearly due to disease under study (per investigator) * platelets ≥75,000/µL, or ≥20,000/µL if clearly due to disease under study (per investigator) * total bilirubin ≤2 x institutional upper limit of normal (ULN), or ≤3 x institutional ULN if due to Gilbert's syndrome, or with PI approval if clearly due to disease under study * AST(SGOT)/ALT(SGPT) ≤2.5 x × institutional ULN * CrCl or GFR ≥30 mL/min as estimated by the Cockcroft-Gault equation, the CKD-EPI equation, or as measured by 24-hour urine collection * For females of childbearing potential, a serum pregnancy test must be negative within screening period. * For female patients of childbearing potential: agreement to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) or remain abstinent (refrain from heterosexual intercourse) during the treatment period and to continue its use for ≥ 30 days after the last dose of zanubrutinib or ≥ 90 days after the last dose of sonrotoclax, and for ≥18 months fter the last dose of obinutuzumab (whicher is later). * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. * Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. * For men with a female partner of childbearing potential or a pregnant female partner: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in addition to 1 of the highly effective methods of contraception listed below, from the time of taking the first dose of study drug , during the treatment period and to continue its use for ≥ 30 days after the last dose of zanubrutinib or ≥ 90 days after the last dose of sonrotoclax, and for ≥18 months fter the last dose of obinutuzumab (whicher is later). --The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. * Willingness to not donate or bank sperm or oocytes during the entire study treatment period and after treatment discontinuation for for ≥ 30 days after the last dose of zanubrutinib or ≥ 90 days after the last dose of sonrotoclax, and for ≥18 months fter the last dose of obinutuzumab (whicher is later). * Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged) Exclusion Criteria: * Known histologic transformation from CLL or SLL to an aggressive lymphoma (i.e., Richter's transformation). * Known central nervous system involvement with CLL or SLL. * Other diagnosis of active malignancy or systemic therapy within 2 years of study treatment. Note: An active malignancy or systemic therapy within 2 years for another malignancy, whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Also, local/regional therapy with curative intent such as surgical resection or localized radiation at any timepoint is permitted. * Any uncontrolled illness that in the opinion of the investigator would preclude administration of study therapy (e.g., significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction). * Congestive heart failure, New York Heart Association III/IV. Unstable angina within 3 months before screening, myocardial infarction within 6 months before screening. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes). Heart rate-corrected QT interval \> 480 milliseconds based on Fridericia's formula corrected for bundle branch block as appropriate. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place. * Receipt of a live-virus vaccine within 28 days prior to initiation of study treatment or need for live-virus vaccine at any time during study treatment. * Active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds). * Known bleeding diathesis. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention. * Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study. * Known CNS hemorrhage or stroke within 6 months of the study. * History of progressive multifocal leukoencephalopathy. * History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection. * Patients with a history of HIV infection that is well controlled on antiretroviral therapy are eligible if all of the following criteria are met: (1) undetectable HIV viral load by standard clinical assay AND (2) CD4+ T cell count of \>/=200 cells/microliter). NOTE: Many HIV regimens are excluded based on drug interactions, and concomitant antiretroviral therapy must be acceptable per protocol. * Participants with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable, and if the participant is willing to take appropriate anti-viral prophylaxis as indicated and HBV DNA monitoring on study. * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Known condition or other clinical situation resulting in inability to swallow oral medications, or that would impair absorption of oral medications. * Participant in a separate investigational therapeutic trial unless authorized by the PI. * Concurrent therapy with, or administration within 5 half-lives 14 days prior to the first dose of study drug (whichever is shorter), with moderate or strong inhibitors or inducers of CYP3A. * Concomitant use of warfarin or warfarin derivatives. * Concomitant use of dual antiplatelet therapy. * Prior systemic therapy for CLL or SLL, except for localized radiation or corticosteroids as per 3.1.3. * Prior anti-CD20 monoclonal antibody therapy for any indication (malignant or non-malignant). * Participants with a contraindication to obinutuzumab based on known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients. Hypersensitivity to zanubrutinib or sonrotoclax. * Consumption of one or more of the following within 3 days prior to the first dose of study drug: grapefruit or grapefruit products, Seville oranges including marmalade containing Seville oranges, or Star fruit (carambola). * Known psychiatric illness or social situation that would interfere with study adherence. * Pregnant women are excluded from this study given potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued prior to the first dose of study drug if the mother is treated. * Uncontrolled autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura), e.g., with need for ongoing corticosteroid treatment (see 3.2.24). * Requires ongoing need for corticosteroid treatment. NOTE: Systemic corticosteroids must be fully tapered off/stopped before first study drug. * Uncontrolled hypertension at Screening, defined as systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg by ≥ 2 consecutive measurements. In patients NOT meeting these parameters for uncontrolled hypertension, repeat blood pressure measurement is NOT required for eligibility.