Trial Title:
Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia
NCT ID:
NCT06333262
Condition:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Obinutuzumab
Pirtobrutinib
Conditions: Keywords:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Bruton's tyrosine kinase inhibitor
Pirtobrutinib
Obinutuzumab
Fixed-duration
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pirtobrutinib
Description:
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
Arm group label:
Pirtobrutinib-Obinutuzumab
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
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).
Arm group label:
Pirtobrutinib-Obinutuzumab
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
New England Cancer Specialists
Address:
City:
Scarborough
Zip:
04074
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cindy Taylor
Phone:
207-303-3420
Email:
tayloc@newecs.org
Investigator:
Last name:
John P Winters, III, MD
Email:
Principal Investigator
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jon Arnason, MD
Investigator:
Last name:
Jon Arnason, MD
Email:
Principal Investigator
Facility:
Name:
Brigham & Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Inhye Ahn
Investigator:
Last name:
Inhye Ahn, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Megan Forsyth
Phone:
857-215-1405
Email:
megan_forsyth@dfci.harvard.edu
Investigator:
Last name:
Inhye Ahn, MD
Email:
Principal Investigator
Start date:
April 22, 2024
Completion date:
February 1, 2029
Lead sponsor:
Agency:
Inhye Ahn
Agency class:
Other
Collaborator:
Agency:
Loxo Oncology, Inc.
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06333262