AVENUE-2: Acalabrutinib in Combination With Venetoclax (AV) for Previously Treated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
This phase II trial is to evaluate the effects of acalabrutinib in combination with venetoclax in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that does not respond to treatment (refractory) or that has come back (recurrent). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Given acalabrutinib and venetoclax may kill more cancer cells.
• Men and women \>= 18 years of age.
• Diagnosis of CLL or small lymphocytic lymphoma (SLL) that meets the published diagnostic criteria.
• Active disease per IWCLL 2018 criteria that require treatment. At least one of the following:
‣ Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
⁃ Massive (\> 6 cm below left costal margin), progressive, or symptomatic splenomegaly
⁃ Massive nodes (\> 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy
⁃ Progressive lymphocytosis with an increase of \> 50% over a 2-month period or lymphocyte-doubling time of \< 6 months. Lymphocyte-doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of \< 30 x 109/L lymphocyte-doubling time should not be used as a single parameter to define treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (e.g., infection) should be excluded.
⁃ Constitutional symptoms, defined as any 1 or more of the following disease-related symptoms or signs
• Unintentional weight loss of \> 10% within the previous 6 months
∙ Significant fatigue
∙ Fevers \> 100.5 degrees Fahrenheit (F) or 38 degrees Celsius (C) for 2 weeks without other evidence of infection
∙ Night sweats for \> 1 month without evidence of infection
• Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL. A line of therapy is defined as completing at least 2 cycles of treatment of standard regimen according to current National Comprehensive Cancer Network (NCCN) guidelines, or of an investigational regimen on a clinical trial.
• Absolute neutrophil count (ANC) \>= 750 cells/microliter (0.75 x 10\^9/L); ANC \>= 500 cells/microliter (0.50 x 10\^9/L) in subjects with documented bone marrow involvement of CLL (independent of growth factor or transfusion support within 1 week of screening).
• Hemoglobin \>= 10 g/dL (independent of growth factor or transfusion support within 1 week of screening).
• Platelet count \>= 50,000 cells/microliter (50 x 10\^9/L); platelet count \>= 25,000 cells/microliter (25 x 10\^9/L) in subjects with documented bone marrow involvement of CLL (independent of growth factor or transfusion support within 1 week of screening).
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
• Total bilirubin =\< 2 x ULN, unless directly attributable to Gilbert's syndrome
• Estimated creatinine clearance of \>= 50 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Women of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 30 days after the last dose of acalabrutinib or venetoclax, whichever occurs later
• Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules or tablets without difficulty
• Ability to understand the purpose and the risks of the study and provide signed and dated informed consent and authorization to use protected health information