Recruiting

Phase 2

Pirtobrutinib & ObinutuzumabFixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia

Sponsor:

Inhye Ahn

Code:

NCT06333262

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pirtobrutinib

Obinutuzumab

Study Details

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).

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Study ID

NCT06333262

Start date

Apr 22, 2024

Status verified date

Jan, 2026

Completion date

Jul 1, 2032

Anticipated

Primary completion date

Jul 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key 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.

Key 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.

Study Design

Enrollment

60 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

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

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).

Primary outcome measure

Rate of complete response after initial therapy [ Time Frame: 1 year since treatment initiation ]

Central Contacts and Locations

Central contacts

Hang Phan, BS

857-215-1258 hang_phan@dfci.harvard.edu

Locations

New England Cancer Specialists

Recruiting

Scarborough, Maine, United States, 04074

Contacts

Cindy Taylor

207-303-3420 tayloc@newecs.org

Principal Investigator:

John P Winters, III, MD

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Jon Arnason, MD

Brigham & Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Inhye Ahn, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Megan Forsyth

857-215-1405 megan_forsyth@dfci.harvard.edu

Principal Investigator:

Inhye Ahn, MD

More Information

Sponsor

Inhye Ahn

Last update posted

Jan 21, 2026

Last verified

Jan, 2026

Keywords

Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Bruton's tyrosine kinase inhibitor
Pirtobrutinib
Obinutuzumab
Fixed-duration

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Inhye Ahn on 2026-01-21.