Venetoclax-Obinutuzumab +/- Acalabrutinib in R/R CLL

Exclusion Criteria

• •Prior therapy with a BTK inhibitor (e.g. acalabrutinib) or BCL2 inhibitor (e.g. venetoclax), with the following exception:
• •Known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients
• •Participants who are receiving any other investigational agents unless authorized by the overall study principal investigator
• •Known active histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)
• •Active malignancy or systemic therapy for another malignancy within 3 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted; active prostate cancer that is considered low-risk and appropriate for continued active surveillance strategy is permitted.
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to Cycle 1, Day 1
• •Known bleeding diathesis
• •Pregnant women are excluded from this study because the study agents have 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 with the study agents, breastfeeding should be discontinued if the mother is treated with study therapy.
• •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 (PML)
• •History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
• •* Patients 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. These patients must be willing to take appropriate anti-viral prophylaxis as indicated and undergo monthly DNA testing.
• •* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• •Congestive heart failure, New York Heart Association classification III/IV
• •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• •Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
• •Known condition or other clinical situation that would affect oral absorption
• •Psychiatric illness/social situations that would interfere with study compliance
• •Receipt of therapy with strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9 and CYP2C19, within 7 days prior to the first dose of study drug administration
• •Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug administration.
• •Requires dual antiplatelet therapy or anticoagulation with warfarin