A Phase 2 Trial Of The Combination Of Zanubrutinib, Sonrotoclax, And Obinutuzumab For Patients With Treatment-Naïve Chronic Lymphocytic Leukemia

Who cannot join

• 1. Major surgery within 4 weeks prior to the first dose of study drugs 2. Uncontrolled active systemic infection 3. Known positive serology for human immunodeficiency virus (HIV) 4. Active hepatitis B infection (defined as the presence of detectable HBV DNA, HBe antigen or HBs antigen). Patients with serologic evidence of prior vaccination (HBsAg negative, anti-HBs antibody positive, anti-HBc antibody negative) are eligible. Patients who are HBsAg negative/HBsAb positive but HBcAb positive are eligible, provided HBV DNA is negative and they are willing to take appropriate antiviral prophylaxis 5. Active hepatitis C infection (defined as detectable hepatitis C RNA in plasma by PCR) 6. Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible 7. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with >20 mg daily of prednisone or equivalent 8. Clinically significant, uncontrolled cardiovascular disease (≥3 NYHA heart failure, uncontrolled or symptomatic arrhythmias), or myocardial infarction within 6 months, or stroke within 6 months, or intracranial bleeding within 6 months prior to start of study drugs 9. Uncontrolled hypertension defined as 2 consecutive systolic blood pressure ≥160 mmHg and /or diastolic blood pressure ≥100 mmHg within 3 months 10. History of Mobitz II second degree or third-degree heart block without a permanent pacemaker in place 11. Prolongation of the QT interval corrected for heart rate (QTcF) >480 msec. Note: Patients with QTcF >480 msec should have EKG repeated. If QTcF again is >480 msec, then the patient should be referred to cardiology for evaluation. Patients can be enrolled later if cleared by cardiology and repeat QTcF less than 480 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33)
• 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. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker 12. Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment 13. Concurrent use of warfarin or another vitamin K antagonist 14. Receiving treatment with a strong CYP3A inhibitor or strong CYP3A inducer ≤14 days or 5 half-lives, whichever is longer, before the first dose of study treatment(s) OR requiring long-term use of strong CYP3A inhibitors or inducers.
• 15. Patients consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment 16. Known central nervous system involvement by CLL/SLL 17. Active second malignancy unless in remission and with life expectancy >2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin or carcinoma "in situ" of the cervix or breast who are eligible even if diagnosed within 2 years. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the Principal Investigator. 18. Known hypersensitivity to any component or excipient of study drugs 19. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drugs 20. Receipt of live-virus vaccines within 4 weeks prior to starting study drugs 21. History of bleeding diathesis and/or history of known bleeding disorder including hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 22. Known prolymphocytic leukemia or history of, or currently suspected, Richter transformation (biopsy based on clinical suspicion may be needed to rule our transformation)