Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia

NCT06333262 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-017
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rate of complete response after initial therapy

  Defined by the 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines

  1 year since treatment initiation

Secondary Outcomes (7)

• Overall response rate

  1 year since treatment initiation

• Rate of partial response

  1 year since treatment initiation

• Time to next line of therapy

  5 years after the last enrollment

• Event-free survival

  5 years after the last enrollment

• Progression-free survival

  5 years after the last enrollment

Study Arms (1)

Pirtobrutinib-Obinutuzumab

EXPERIMENTAL

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.

Drug: Pirtobrutinib; Drug: Obinutuzumab

Interventions

Pirtobrutinib 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

Pirtobrutinib-Obinutuzumab

Obinutuzumab 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).

Pirtobrutinib-Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Inhye Ahn: lead
• Eli Lilly and Company: collaborator

Study Sites (4)

New England Cancer Specialists

Scarborough, Maine, 04074, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Brigham & Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Related Publications (1)

• Davids MS. BRUIN 313 and 314 Trials Open the Door for Noncovalent Bruton Tyrosine Kinase Inhibition as Initial Therapy for Chronic Lymphocytic Leukemia. J Clin Oncol. 2026 Feb 20;44(6):435-439. doi: 10.1200/JCO-25-02691. Epub 2025 Dec 9. No abstract available.

  PMID: 41363770 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

pirtobrutinib; obinutuzumab

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

Study Officials

• Inhye E Ahn, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hang Phan, BS

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 27, 2024
• Study Start: April 22, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2032
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)