Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia

NCT ID: NCT06333262

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-22
• Study Completion Date: 2032-07-01

Brief Summary

This study will evaluate fixed-duration therapy with pirtobrutinib and obinutuzumab given over 12 cycles (approximately 1 year) as first-line treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL or SLL).

Detailed Description

This is an open-label, multicenter, single-arm phase 2 study of pirtobrutinib with obinutuzumab for participants with CLL or SLL. Eligible participants will receive 6 cycles of pirtobrutinib alone followed by an additional 6 cycles of pirtobrutinib-obinutuzumab combination therapy. All participants will stop treatment after 12 cycles in total (approximately 1 year).

If CLL progresses and requires treatment after 1-year of therapy, participants will receive retreatment with pirtobrutinib only. Participants will be followed for up to a total of 10 years. Up to 60 participants will take part in this study.

The U.S. Food and Drug Administration (FDA) has approved pirtobrutinib for continuous treatment of CLL that has relapsed or become refractory to other treatments. Pirtobrutinib is not approved for the first-line treatment of CLL/SLL nor for fixed-duration therapy. The FDA has approved obinutuzumab for the treatment of CLL.

The research study procedures include screening for eligibility, study treatment visits, electrocardiograms, imaging (e.g. computerized tomography or CT scans), blood tests, saliva tests, bone marrow biopsies, and/or lymph node biopsies (if feasible).

Loxo Oncology at Eli Lilly and Company is supporting this study by providing pirtobrutinib and research funding.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pirtobrutinib-Obinutuzumab

Eligible participants will receive initial treatment with pirtobrutinib and obinutuzumab for 12 cycles. Participants with progressive chronic lymphocytuc leukemia or small lymphocytic lymphoma during the off-treatment follow-up will receive continuous pirtobrutinib monotherapy.

Group Type: EXPERIMENTAL

Pirtobrutinib

Intervention Type: DRUG

Initial treatment:

• Pirtobrutinib 200 mg by mouth (PO) daily from Cycle 1 Day 1 until the end of Cycle 12. Each cycle is 28 days.

Re-treatment:

-Pirtobrutinib 200 mg PO daily continuously

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab is given intravenously from Cycle 7 to Cycle 12, for total 6 cycles during initial treatment only.

Initial treatment:

• Obinutuzumab intravenous (IV) following the standard schedule from Cycle 6 through Cycle 12 (total 6 cycles: 100 mg on Cycle 6 Day 1, 900 mg on Cycle 6 Day 2, 1000 mg on Cycle 6 Day 8 and Cycle 6 Day 15, 1000 mg on Day 1 of Cycle 7 through Cycle 12).

Interventions

Pirtobrutinib

Initial treatment:

• Pirtobrutinib 200 mg by mouth (PO) daily from Cycle 1 Day 1 until the end of Cycle 12. Each cycle is 28 days.

Re-treatment:

-Pirtobrutinib 200 mg PO daily continuously

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab is given intravenously from Cycle 7 to Cycle 12, for total 6 cycles during initial treatment only.

Initial treatment:

• Obinutuzumab intravenous (IV) following the standard schedule from Cycle 6 through Cycle 12 (total 6 cycles: 100 mg on Cycle 6 Day 1, 900 mg on Cycle 6 Day 2, 1000 mg on Cycle 6 Day 8 and Cycle 6 Day 15, 1000 mg on Day 1 of Cycle 7 through Cycle 12).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Meet 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for the diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Presence of measurable disease (absolute lymphocyte count > 5,000/µL, palpable or measurable lymph nodes ≥1.5cm on imaging, or bone marrow involvement of CLL ≥ 30%).
• No prior systemic therapy for CLL or SLL.
• Currently have an indication for treatment as defined by the following 2018 IWCLL guidelines
• Age ≥ 18 years
• Eastern Cooperative Oncology Group performance status ≤ 2
• Adequate organ and bone marrow function as defined by the study protocol
• Ability to take oral medications.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Known or suspected Richter's transformation or known central nervous system involvement.
• History of bleeding disorders
• History of stroke or intracranial hemorrhage within 6 months of starting study therapy.
• Significant cardiovascular disease such as uncontrolled arrhythmia, Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction < 40% by any methods in the 12 months prior to study therapy.
• History of other malignancies with life expectancy of < 2 years.
• Receiving any other investigational agents.
• Concurrent systemic immunosuppression < 28 days of study therapy or administration of > 20 mg of prednisone or equivalent daily < 7 days of study therapy.
• Vaccinated with live vaccine within 4 weeks of starting study therapy.
• Major surgery within 4 weeks of starting study therapy.
• Ongoing or recent infection requiring intravenous antimicrobials at time of screening. Prophylactic antibiotics are allowed if there is no evidence of active infection and the antibiotics is not included on the list of the prohibited medications.
• Patients who have tested positive for HIV are excluded due to potential drug-drug interactions between anti-retroviral medications and pirtobrutinib and risk of opportunistic infections with both HIV and irreversible BTK inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for enrollment.
• Active human T cell leukemia virus infection or active hepatitis B or C virus infection
• Known active cytomegalovirus infection
• Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment.
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug
• Active uncontrolled auto-immune cytopenia.
• Significant co-morbid condition or disease.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Inhye Ahn

OTHER

Sponsor Role: lead

Responsible Party

Inhye Ahn

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Inhye E Ahn, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

New England Cancer Specialists

Scarborough, Maine, United States

Site Status: RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Hang Phan, BS

Role: CONTACT

hang_phan@dfci.harvard.edu

857-215-1258

Facility Contacts

Cindy Taylor

Role: primary

tayloc@newecs.org

207-303-3420

Jon Arnason, MD

Role: primary

Inhye Ahn

Role: primary

Megan Forsyth

Role: primary

megan_forsyth@dfci.harvard.edu

857-215-1405

Other Identifiers

24-017

Identifier Type: -

Identifier Source: org_study_id