Clinical trial NCT06333262: Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia
Official title: A Phase 2 Study of Fixed Duration Therapy With Pirtobrutinib and Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia (POP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Bruton's tyrosine kinase inhibitor
Pirtobrutinib
Obinutuzumab
Fixed-duration
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Loxo Oncology, Inc.
First posted: 2024-03-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of complete response after initial therapy
timeFrame: 1 year since treatment initiation
Secondary outcomes:
measure: Overall response rate
timeFrame: 1 year since treatment initiation
measure: Rate of partial response
timeFrame: 1 year since treatment initiation
measure: Time to next line of therapy
timeFrame: 5 years after the last enrollment
measure: Event-free survival
timeFrame: 5 years after the last enrollment
measure: Progression-free survival
timeFrame: 5 years after the last enrollment
measure: Overall survival
timeFrame: 5 years after the last enrollment
measure: Rate of re-treatment with pirtobrutinib
timeFrame: 5 years after the last enrollment
Other outcomes:
Locations:
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Inhye E Ahn, MD
role: PRINCIPAL_INVESTIGATOR
References: