Atezolizumab (PD-L1 mAb) in Combination With Obinutuzumab and Venetoclax for Patients With Chronic Lymphocytic Leukemia and Richter Transformation
This phase II trial studies how well atezolizumab, obinutuzumab, and venetoclax work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma or Richter syndrome that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as atezolizumab and obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab, obinutuzumab, and venetoclax may work better in treating patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or Richter syndrome.
• Patients will have a diagnosis of CLL or SLL or RTand are: a) Cohort 1: Patients with treatment naïve CLL/SLL who meet IWCLL criteria for treatment or b) Cohort 2: RT (treatment-naïve or R/R)
• Age \>/= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status \</= 2
• Patients must have adequate renal and hepatic function: -- Serum bilirubin \</= 1.5 x upper limit of normal (ULN). For patients with Gilbert's disease, serum bilirubin up to \</= 3 x ULN is allowed provided normal direct bilirubin. -- Serum creatinine \</= 1.5 x ULN, -- Alanine aminotransferace (ALT) and aspartate aminotransferase (AST) \</= 2.5 x ULN
• Females of childbearing potential \[A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>/=12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)\] must have a negative serum or urine beta human chorionic gonadotrophin (b-hCG) pregnancy test result within 14 days prior to the first dose of treatment and must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for 6 months following the last dose of the study drugs. Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• #5 Continued - Males who have partners of childbearing potential must agree to use an effective contraceptive method such as a barrier method during the study and for 6 months following the last dose of study drugs. Males should also refrain from donating sperm.
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Patients or their legally authorized representative must provide written informed consent