SONIC: Escalated Inpatient Ramp-Up of Sonrotoclax in Patients With Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Mantle Cell Lymphoma (MCL) (SONIC Study)
Fred Hutchinson Cancer Center
Summary
This phase II trial studies the side effects of an escalated ramp-up of sonrotoclax following initial debulking with zanubrutinib or rituximab in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL) that is newly diagnosed, has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill tumor cells. Zanubrutinib may stop the growth of tumor cells by blocking a protein called Bruton's tyrosine kinase (BTK), which is needed for tumor cell growth. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. Giving an increased dose of sonrotoclax over a shorter period of time in combination with zanubrutinib or rituximab may be safe and tolerable in treating patients with newly diagnosed, relapsed or refractory CLL, SLL, and MCL.
Description
OUTLINE: This is a dose escalation study of sonrotoclax in combination with zanubrutinib or rituximab. Patients are assigned to 1 of 2 arms. ARM I: Patients not refractory to a Bruton's tyrosine kinase inhibitor (BTKi) undergo debulking and receive zanubrutinib orally (PO) once daily (QD) on day 1 of cycles 1-15. Beginning on day 1 of cycle 4, patients receive a ramp up of sonrotoclax PO QD until target dose is reached. Then patients will continue sonrotoclax PO QD and zanubrutinib PO QD through Cycle 15. Cycles repeat every 28 days for up to 15 cycles in the absence of disease progression or…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses * Age 18 years or older * Confirmed diagnosis (per World Health Organization \[WHO\] guidelines, unless otherwise noted) of one of the following: * CLL/SLL COHORT: CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia criteria: * Meeting the following sets of prior treatment criteria: * For the R/R cohort, disease that relapsed after, or was refractory to, at least 1 prior therapy * For the treatment-n…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- ProcedureComputed Tomography
Undergo CT
- ProcedureGastrointestinal Endoscopy
Undergo endoscopy
- BiologicalRituximab
Given IV
- DrugSonrotoclax
Given PO
- DrugZanubrutinib
Given orally (PO)
Location
- Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington