Fixed-duration treatment for chronic lymphocytic leukemia with pirtobrutinib and obinutuzumab

A Phase 2 Study of Fixed Duration Therapy With Pirtobrutinib and Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia (POP)

This study is testing a year-long treatment combining two medications, pirtobrutinib and obinutuzumab, to see if it helps people with chronic lymphocytic leukemia feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dana-Farber Cancer Institute (other)
• Drugs / interventions: pirtobrutinib, prednisone, obinutuzumab
• Locations: 4 sites (Scarborough, Maine and 3 other locations)
• Trial ID: NCT06333262 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a fixed-duration therapy combining pirtobrutinib and obinutuzumab for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Participants will receive 6 cycles of pirtobrutinib alone, followed by 6 cycles of the combination therapy, totaling approximately one year of treatment. The study aims to assess the efficacy and safety of this regimen as a first-line treatment option. Participants will be monitored for up to 10 years to evaluate long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with newly diagnosed CLL or SLL who meet specific eligibility criteria and have not received prior systemic therapy.

Not a fit: Patients with a history of Richter's transformation, central nervous system involvement, or certain bleeding disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new first-line therapy option for patients with CLL or SLL, potentially improving outcomes and quality of life.

How similar studies have performed: While pirtobrutinib has been approved for relapsed or refractory CLL, this specific combination and fixed-duration approach is novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Scarborough, Maine and 3 other locations

• New England Cancer Specialists — Scarborough, Maine, United States (RECRUITING)
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (RECRUITING)
• Brigham & Women's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Inhye E Ahn, MD — Dana-Farber Cancer Institute
• Study coordinator: Hang Phan, BS

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