A phase 2 study of fixed duration therapy with pirtobrutinib and obinutuzumab in previously untreated chronic lymphocytic leukemia (POP)
Trial Description
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).
Eligibility Requirements
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.