Pirtobrutinib for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia

NCT07685717 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-25034NCI-2026-04232
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Progression-free survival

  From treatment start to the date of the corresponding event, assessed up to 5 years

• Overall survival

  From treatment start to the date of the corresponding event, assessed up to 8 years after completion of study treatment

• Duration of response

  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

  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)

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (pirtobrutinib)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Other: Electronic Health Record Review; Drug: Pirtobrutinib; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (pirtobrutinib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (pirtobrutinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (pirtobrutinib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (pirtobrutinib)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (pirtobrutinib)

Pirtobrutinib DRUG

Given PO

Also known as: 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, Jaypirca, LOXO 305, LOXO-305, LOXO305, LY3527727

Treatment (pirtobrutinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (pirtobrutinib)

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify 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

You may not qualify 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

Sponsors & Collaborators

• Jennifer Woyach: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Specimen Handling; Biopsy; pirtobrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Jennifer A Woyach, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

1-800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 6, 2026

Record last verified: 2026-06

Locations

US (1)