Pirtobrutinib for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age75 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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

You cannot join if

• Active Richter's transformation (i.e. within 6 months of active therapy, or requiring treatment for Richter's transformation)
• Malabsorption syndrome or inability to absorb pirtobrutinib
• Patients with Class III or Class IV heart failure by New York Heart Association, those with unstable angina, those with uncontrolled arrhythmia, and those patients who experienced an myocardial infarction (MI) within 3 months of screening or acute coronary syndrome within 2 months of screening are not eligible
• Documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% in the 12 months prior to randomization
• Prolongation of QT interval corrected for heart rate (QTcF) > 470 msec
• Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
• History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
• Patients who have tested positive for human immunodeficiency virus (HIV) are excluded due to risk of opportunistic infections with both HIV and Bruton Tyrosine Kinase (BTK)-inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrollment
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• Hepatitis B virus (HBV):
• Patients with positive hepatitis B surface antigen (HBsAg) are excluded
• Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require a negative hepatitis B polymerase chain reaction (PCR) evaluation before starting study therapy
• Patients who are HBV deoxyribonucleic acid (DNA) PCR positive will be excluded
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded
• Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible
• Evidence of other clinically significant uncontrolled condition(s) including but not limited to: uncontrolled systemic infection, or other clinically significant active disease process which in the opinion of the investigator may pose a risk for patient participation. Screening for chronic conditions is not required
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
• Active second malignancy unless in remission and with life expectancy > 2 years
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
• Vaccination with live vaccines 28 days prior to registration for study screening
• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pirtobrutinib. An orally available, selective, non-covalent Bruton's tyrosine kinase (BTK) inhibitor with potential antineoplastic activity. Upon oral administration, pirtobrutinib selectively and reversibly binds to BTK. This prevents both the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways, thereby inhibiting the growth of malignant B-cells that overexpress BTK. Reversible binding of LOXO-305 may preserve antitumor activity in the presence of certain acquired resistance mutations, including C481 mutated BTK, and limit toxicity associated with inhibition of other non-BTK kinases. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B lymphocytes. NCI Drug Dictionary

Treatments listed in the registry

• Biospecimen Collection (Procedure): Undergo collection of blood samples
• Bone Marrow Aspiration (Procedure): Undergo bone marrow biopsy and aspiration
• Bone Marrow Biopsy (Procedure): Undergo bone marrow biopsy and aspiration
• Computed Tomography (Procedure): Undergo CT
• Electronic Health Record Review (Other): Ancillary studies
• Pirtobrutinib (Drug): Given PO
• Questionnaire Administration (Other): Ancillary studies

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• bone marrow: Part of the study plan
• blood samples: Part of the study plan
• CT scans: Part of the study plan
• questionnaires: Part of the study plan

Main goals

• Rate of treatment discontinuation (Up to 12 cycles (Cycle length = 28 days))
• Overall response rate (Up to 12 cycles (Cycle length = 28 days))

Other goals

• Progression-free survival
• Overall survival
• Duration of response
• Time to next treatment
• Incidence of adverse events (AEs)

Planned enrollment: 50 (estimated).

• Ohio State University Comprehensive Cancer Center, Columbus, Ohio

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07685717
• NCI Drug Dictionary: C158617

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 27, 2026. Public record; not medical advice.