Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06333262
• Other study ID #: 24-017
• Status: Recruiting
• Phase: Phase 2
• Start date: April 22, 2024
• Est. completion date: February 1, 2029

Study information

• Verified date: May 2024
• Source: Dana-Farber Cancer Institute
• Contact: Megan Forsyth
• Phone: 857-215-1405
• Email: megan_forsyth[@]dfci.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 1, 2029
• Est. primary completion date: February 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Inhye Ahn	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate	Defined by the 2018 IWCLL guidelines	1 year since treatment initiation
Secondary	Rate of partial response	Defined by the 2018 IWCLL guidelines	1 year since treatment initiation
Secondary	Time to next line of therapy	Time from the initiation of study therapy until the next line of therapy (excluding pirtobrutinib re-treatment)	5 years after the last enrollment
Secondary	Event-free survival	Time from the initiation of study therapy until pre-defined events (progression, death, or start of a new treatment)	5 years after the last enrollment
Secondary	Progression-free survival	Time from the initiation of study therapy until disease progression or death	5 years after the last enrollment
Secondary	Overall survival	Time from the initiation of study therapy until death	5 years after the last enrollment
Secondary	Rate of re-treatment with pirtobrutinib	Rate of re-treatment with pirtobrutinib on study	5 years after the last enrollment