About this trial
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.
Eligibility criteria
Qualifiers
Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses
Age 18 years or older
For the R/R cohort, disease that relapsed after, or was refractory to, at least 1 prior therapy
For the treatment-naïve cohort, patients should have no prior treatment for CLL/SLL (other than 1 aborted regimen < 2 weeks in duration and > 4 weeks before enrollment)
Disqualifiers
Exposure to a Bcl-2 inhibitor within the last 12 months or a history of disease progression while taking a Bcl-2 inhibitor
Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, melanoma, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score =< 6 prostate cancer
Underlying medical conditions that may render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results
Known current central nervous system involvement by lymphoma/leukemia
Trial design
Treatments tested in this trial
- Biospecimen Collection
- Bone Marrow Biopsy
- Computed Tomography
- Gastrointestinal Endoscopy
- Rituximab
- Sonrotoclax
- Zanubrutinib
Treatment groups
Sponsors and collaborators
Fred Hutchinson Cancer Center
Lead sponsor
BeOne Medicines
Collaborator