Immune Profiling of CLL/SLL Treated With First-Line Pirtobrutinib
Background: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. Pirtobrutinib is a drug approved to treat CLL and SLL after 2 previous treatments. Researchers want to know how this drug affects the immune system in those who have not yet started other treatments for CLL or SLL.
Objective: To test pirtobrutinib as a first-line treatment for CLL or SLL.
Eligibility: People aged 18 years and older with untreated CLL or SLL.
Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and tests of their heart function. They will have a lymph node biopsy: A large needle will be inserted into a lymph node to collect a small piece of tissue. Pirtobrutinib is a tablet taken by mouth. Participants will take 2 to 4 tablets daily in 4-week cycles. Participants will have clinic visits once every 4 weeks for the first 3 months. Then they will be seen once every 3 months. Imaging scans, lymph node biopsy, and other tests will be repeated at various study visits. A bone marrow biopsy (collection of soft tissue from inside a bone) may be done if there is no evidence of disease after 1 year of treatment with the study drug. Participants may opt to have cancer and immune cells collected from their blood. The cells will be used for research. Participants will have a clinic visit 1 month after their last dose of the study drug. Then they will have follow-up visits or phone calls every 6 to 12 months....
⁃ In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures
• Age \>=18 years
• Confirmed diagnosis of CLL or SLL according to International Workshop on CLL (iwCLL) guidelines
∙ Coexpression of CD5, CD19, CD20, and CD23 expression and light-chain restriction; CD23 dim or negative expression is acceptable as long as other parameters are consistent with a diagnosis of CLL.
‣ CLL: clonal B-lymphocytosis \>=5,000 cells/mL
• OR
• SLL: lymphadenopathy with the tissue morphology of CLL but that are not leukemic, \<5,000 cells/mL
• Active disease requiring treatment according to iwCLL guidelines
• Measurable disease characterized by \>=1 of the following:
∙ Lymphadenopathy: \>=1 lymph node measuring \>=1.5 cm in the greatest diameter
‣ Splenomegaly: spleen measuring \>13 cm in craniocaudal length
‣ Lymphocytosis: \>=5,000 B cells/microL
‣ Bone marrow infiltration: CLL comprising \>= 30% of all cells
• Previously untreated CLL with \>=1 LN amenable to core-needle biopsy
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• The patient has adequate organ function for all of the following criteria, as defined below:
‣ System: Hepatic
• Laboratory Value: ALT or AST: \<= 3 x the ULN or \<= 5 x ULN with documented liver involvement
∙ Laboratory Value: Total bilirubin: \<= 1.5 x ULN or \<= 3 x ULN with documented liver involvement and/or Gilbert s Disease
⁃ System: Renal
∙ -Laboratory Value: Serum creatinine: Calculated creatinine clearance \>= 30 ml/min according to Cockcroft/Gault Formula: \[(140-age) x body weight (kg) x 0.85 (if female)\]/ \[serum creatinine (mg/dL) x 72\]
⁃ System: Hematologic
• Laboratory Value: Hemoglobin: \>= 8 g/dL (\>= 80 g/L)
∙ Laboratory Value: ANC: \>= 0.75 x 10\^9/L
∙ Laboratory Value: Platelets: \>= 50 x 10\^9/L
• Notes:
• Hgb and platelets: independent of transfusions within 7 days of Screening assessment.
• ANC: independent of growth factor support within 7 days of Screening assessment.
• Criteria must be met on C1D1 without transfusion/G-CSF within 7 days of assessment.
• Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST =aspartate aminotransferase; ULN = upper limit of normal.
• Adequate coagulations, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or international normalized ratio (INR) not greater than 1.5 X ULN.
⁃ Willingness of WOCBP and their partners to observe highly effective birth control methods for the duration of treatment and for 1 month following the last dose of study treatment.
⁃ Ability to take oral medication and be willing to adhere to the study drug regimen
⁃ Agreement to adhere to Lifestyle Considerations throughout study duration
⁃ Able to understand and willing to sign a written informed consent document.