Time-limited Triplet Combination of Pirtobrutinib, Venetoclax, and Obinutuzumab for Patients With Treatment-naïve Chronic Lymphocytic Leukemia (CLL) or Richter Transformation (RT)
brief summary
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.
detailed description
Primary Objective:
1\. Estimate the therapeutic activity (undetectable measurable residual disease \[U-MRD\] rate) of combined pirtobrutinib, venetoclax, and obinutuzumab in patients with previously untreated CLL/SLL (cohort 1) by undetectable measurable residual disease (U-MRD) rate and Richter transformation (cohort 2) by overall response rate (ORR) (defined as CMR//PMR).
Secondary Objectives:
1. To estimate the therapeutic activity of combination therapy by determining:
1. Combined response rate (defined as CR/CRi/PR) as assessed by the investigator for cohort 1 (CLL/SLL) 2. Progression free survival (PFS) and overall survival (OS). 3. U-MRD response with next generation sequencing assay for cohort 2 2. To determine the safety and tolerability of this combination therapy
Exploratory Objective:
1. To study immunological and molecular changes in the peripheral blood and bone marrow in response to pirtobrutinib, venetoclax, and obinutuzumab. 2. To evaluate the kinetics of MRD response over time