Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
Trial ID or NCT#
This Primary objective is evaluating the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) for the treatment of previously untreated chronic lymphocytic leukemia (CLL). Secondary objectives: 1) To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) based on IRC assessment of PFS per IWCLL 2008 criteria. 2)To compare obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib plus obinutuzumab (Arm B) and obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) in terms of: IRC-assessed objective response rate (ORR); Tine to next treatment (TTNT); Overall Survival (OS).
A Randomized, Multicenter, Open-Label, 3 Arm Phase 3 Study of Obinutuzumab in Combination With Chlorambucil, Acalabrutinib (ACP-196) in Combination With Obinutuzumab, and Acalabrutinib Monotherapy in Subjects With Previously Untreated CLL
- 1. Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed). 2. Known CNS lymphoma or leukemia. 3. Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome. 4. Missing or incomplete documentation of FISH results reflecting the presence or absence of 17p del and the percentage of cells with the deletion in subject records before randomization. 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 4 weeks before first dose of study drug. 8. History of prior malignancy except for the following: 1. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician. 2. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer. 3. Adequately treated cervical carcinoma in situ without current evidence of disease. 9. Significant cardiovascular disease such as uncontrolled or 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, or QTc > 480 msec at screening. 10. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. 11. Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment. 12. Known history of infection with HIV. 13. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. 14. Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded. 15. History of stroke or intracranial hemorrhage within 6 months before randomization. 16. Known history of a bleeding diathesis (e.g., hemophilia, von Willebrand disease). 17. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug. 18. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). 19. Breast feeding or pregnant. 20. 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. 21. Concurrent participation in another therapeutic clinical trial. 22. Requires treatment with a strong CYP3A inhibitor/inducer. 23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
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