A Phase 2 Trial of Single-Agent Pirtobrutinib for Elderly Patients With CLL
This phase II trial studies how well pirtobrutinib works in treating elderly patients with chronic lymphocytic leukemia (CLL). Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib work by blocking the action of the BTK protein that signals cancer cells to multiply. These are very effective, tolerable, and commonly used to treat people with CLL, but they may lead to drug resistance over time. Pirtobrutinib, also a BTK inhibitor, may work better in treating elderly patients with CLL.
• Men and women ≥ 75 years of age
• Diagnosis of CLL/small lymphocytic lymphoma (SLL) meeting criteria established in the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines
• Must be treatment-naive: Received no prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL, with the exceptions of palliative loco-regional radiotherapy, rituximab for autoimmune conditions, or corticosteroids for symptoms control. For radiation, broad field radiation (≥ 30% of bone marrow or whole brain radiotherapy) must be completed 14 days before study enrollment; palliative limited field radiation must be completed 7 days prior to study enrollment. For rituximab, washout of 2 weeks is required prior to study enrollment
• Must require treatment according to 2018 iwCLL guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
• Total bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented liver involvement and/or Gilbert's syndrome
• Creatinine clearance ≥ 30 mL/minute using Cockcroft-Gault formula
• Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin time (PT) or (international normalized ratio \[INR\]) not greater than 2.0 × ULN
• Absolute neutrophil count (ANC) ≥ 0.75 x 10\^9 (on or within 7 days of cycle 1 day 1 \[C1D1\] before treatment); the patient may enroll below threshold if there is documented bone marrow involvement of CLL considered to impair hematopoiesis. Granulocyte colony-stimulating factor (GCSF) support is allowed
• Platelet count ≥ 30 x 10\^9 not requiring transfusion support (on or within 7 days of C1D1 before treatment); the patient may enroll below this threshold if there is documented bone marrow involvement of CLL considered to impair hematopoiesis
• Hemoglobin ≥ 6 mg/dL not requiring transfusion support or growth factors (on or within 7 days of C1D1 before treatment); the patient may enroll below this threshold if there is documented bone marrow involvement of CLL considered to impair hematopoiesis
• If patients require transfusion support due to bone marrow involvement of CLL, they must be responsive to transfusion support
• Male patients are sexually active with a woman of childbearing potential must use highly effective methods of contraception during treatment
• The patient is able to take oral medications
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information