Pirtobrutinib for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Bone Marrow Biopsy; Other: Electronic Health Record Review; Drug: Pirtobrutinib; Procedure: Bone Marrow Aspiration

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate rate of discontinuation and overall response rate (ORR) of pirtobrutinib after 12 cycles in patients who are ≥ 75 with CLL.

SECONDARY OBJECTIVE:

I. To assess the safety and efficacy of patients with CLL treated with pirtobrutinib.

EXPLORATORY OBJECTIVE:

I. Assess the treatments effect on quality of life and on geriatric assessments.

OUTLINE:

Patients receive pirtobrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), blood sample collection, and bone marrow biopsy and aspiration throughout the study.

After completion of study treatment, patients are followed up within 7-30 days and then every 6 months for up to 8 years.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 1-800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Jennifer A. Woyach, MD; Phone Number: 614-293-3196; Email: Jennifer.Woyach@osumc.edu
      • Principal Investigator: Jennifer A. Woyach, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (pirtobrutinib); Patients receive pirtobrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, blood sample collection, and bone marrow biopsy and aspiration throughout the study.

Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy and aspiration; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Other: Electronic Health Record Review; Ancillary studies; Drug: Pirtobrutinib; Given PO; Other Names: LOXO-305; LY3527727; 5-Amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-((2S)-1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide; BTK Inhibitor LOXO-305; LOXO 305; LOXO305; Jaypirca; Procedure: Bone Marrow Aspiration; Undergo bone marrow biopsy and aspiration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of treatment discontinuation	Will be calculated among all evaluable patients. The rates will be provided together with 95% exact confidence intervals.	Up to 12 cycles (Cycle length = 28 days)
Overall response rate	Will be determined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL). Will be calculated among all evaluable patients. The rates will be provided together with 95% exact confidence intervals.	Up to 12 cycles (Cycle length = 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Will be estimated using the method of Kaplan-Meier.	From treatment start to the date of the corresponding event, assessed up to 5 years
Overall survival	Will be estimated using the method of Kaplan-Meier.	From treatment start to the date of the corresponding event, assessed up to 8 years after completion of study treatment
Duration of response	Will be estimated using the method of Kaplan-Meier.	From the date where the first response is achieved to the date of progression or death, assessed up to 8 years after completion of study treatment
Time to next treatment	Will be estimated using the method of Kaplan-Meier.	From treatment start to the date of the corresponding event, assessed up to 8 years after completion of study treatment
Incidence of adverse events (AEs)	Will determine rate of treatment related AEs, and proportion of patients who discontinue therapy due to AEs. The toxicity profile will be described through the summary of AE data. AE will be summarized by type and severity according to Common Terminology Criteria for Adverse Events, Version 5.0 for non-hematologic toxicity, and the iwCLL 2018 criteria for hematologic toxicity, with a focus on grade 3 or higher adverse events.	Up to 30 days after completion of study treatment

Collaborators and Investigators

• Sponsor: Jennifer Woyach
• Investigators: Principal Investigator: Jennifer A Woyach, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy; Specimen Handling; pirtobrutinib
• Other Study ID Numbers: OSU-25034 (Other Identifier: Ohio State University Comprehensive Cancer Center); NCI-2026-04232 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No