Time-limited Triplet Combination of Pirtobrutinib, Venetoclax, and Obinutuzumab for Patients With Treatment-naïve Chronic Lymphocytic Leukemia (CLL) or Richter Transformation (RT)
To learn if the combination of pirtobrutinib (also called LOXO-305), venetoclax, and obinutuzumab is safe and effective when given to patients with chronic lymphocytic leukemia (CLL) or Richter transformation (RT) who have not previously received treatment.
• Patients with a diagnosis of previously untreated CLL/SLL meeting iwCLL 2018 indication for treatment (cohort 1) or with a diagnosis of previously untreated or relapsed/refractory RT arising from CLL (cohort 2). Previously untreated patients with RT must have received prior therapy for CLL.
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2
• Adequate hepatic function
‣ Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease or documented disease involvement of liver (In pts with elevated total bilirubin due to increased indirect bilirubin, pts with direct bilirubin ≤1.5 x ULN are eligible)
⁃ ALT and AST ≤3.0 x ULN, or ≤5.0 x ULN if documented disease involvement of liver
• Adequate renal function
• a. Creatinine clearance ≥ 50 ml/min (calculated using CKD-EPI formula)
• Adequate hematologic function a. Platelet count ≥50 x109/L and hemoglobin ≥ 8 g/dL (≥ 80 g/L). Platelet and hemoglobin requirements are independent of transfusions within 7 days of screening assessment and first dose of study drugs.
• b. Absolute neutrophil count ≥ 0.75 x 109/L. Absolute neutrophil count is independent of growth factor support within 7 days of screening assessment and first dose of study drugs.
• Ability to swallow tablets and comply with outpatient treatment, laboratory monitoring, and required clinic visit for the duration of study participation
• Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 6 months following the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal greater than 2 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug