A Single Arm Study of Acalabrutinib Conbimed With Obinutuzumab in Chinese Patients With Previously Untreated CLL

Exclusion Criteria

• •1. Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
• •2. Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
• •3. Known CNS lymphoma or leukemia.
• •4. Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
• •5. Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (\> 20 mg daily of prednisone daily or equivalent).
• •6. Corticosteroid use \> 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses \> 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or WBC count lowering are excluded.
• •7. Major surgery within 30 days before first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• •8. History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
• •1. a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
• •2. b. Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment.
• •9. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
• •10. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
• •11. Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• •12. Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
• •13. Received a live virus vaccination within 28 days of first dose of study drug.
• •14. Known history of infection with HIV.
• •15. Any active significant infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus \[CMV\] DNA polymerase chain reaction \[PCR\]).
• •16. Serologic status reflecting active hepatitis B or C infection.
• •1. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded.
• •2. Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
• •17. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
• •18. History of bleeding diathesis (e.g., hemophilia, von Willebrand disease).
• •19. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• •20. Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited.
• •21. Breastfeeding or pregnant.
• •22. Concurrent participation in another therapeutic clinical trial.
• •23. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
• •24. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.