Prospective Randomized Phase II Study of Acalabrutinib + Obinutuzumab or Venetoclax in Previously Untreated CLL
This phase II trial tests whether acalabrutinib in combination with venetoclax or obinutuzumab works to shrink tumors in patients with treatment-naive chronic lymphocytic leukemia . Acalabrutinib is also an inhibitor that works in the body to block the activation of certain cells that lead to the growth of cancerous B cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib in combination with venetoclax or obinutuzumab may help ease symptoms, decrease the amount of cancer suggestive of improvement, prolonged disease-free remission and/or survival, and increased knowledge about cancer treatment in patients with chronic lymphocytic leukemia. Patients will be treated with acalabrutinib for 12 cycles, and then randomized to receive 6 cycles of acalabrutinib plus obinutuzumab or acalabrutinib plus venetoclax.
• Men and women \>= 18 years of age
• Diagnosis of CLL/small lymphocytic lymphoma (SLL) meeting criteria established in the 2018 International Workshop (iw)CLL guidelines
• Must be treatment-naive: Received no prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL, with the exceptions of palliative loco-regional radiotherapy, rituximab for autoimmune conditions, or corticosteroids for symptoms control
• Patients must meet criteria for treatment as defined by 2018 iwCLL guidelines which includes at least one of the following criteria:
‣ Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
⁃ Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
⁃ Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
⁃ Progressive lymphocytosis with a lymphocyte doubling time \< 6 months or an increase of \>= 50% over a 2 month period
⁃ Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
⁃ Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
⁃ Constitutional symptoms, which include any of the following:
• Unintentional weight loss of 10% or more within 6 months
∙ Significant fatigue
∙ Fevers \> 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
∙ Night sweats \>= 1 month without evidence of infection
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Adequate bone marrow independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/SLL and/or disease-related immune thrombocytopenia, or anemia. If cytopenias are due to disease in the bone marrow any degree of cytopenias are allowed. Patients with active uncontrolled autoimmune cytopenias are excluded
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelets \>= 30,000/mm\^3
• Hemoglobin \>= 7 g/dL
• Total bilirubin =\< 2.0 x upper limit of normal (ULN) (excepting Gilbert's syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Creatinine clearance \>= 30 mL/min/1.73m\^2
‣ Using 24-hour creatinine clearance or modified Cockcroft-Gault equation
• Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for at least 2 days after last acalabrutinib dose, 30 days after last venetoclax dose, and 6 months after last obinutuzumab dose
• Willing and able to participate in all required evaluations and procedures in this study protocol
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information