Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma

Recruiting now · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Mantle Cell Lymphoma, Refractory Small Lymphocytic Lymphoma, Small Lymphocytic Lymphoma

In brief

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.

Key facts

Study ID: NCT06839053
Run by: Fred Hutchinson Cancer Center
People needed: 30
Starts: 2025-06-02
Expected to finish: 2032-07-01
Last updated by the study team: 2026-04-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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-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)
Requiring treatment per International Workshop on CLL (iwCLL) criteria
MCL COHORT: WHO-defined MCL
R/R MCL is defined as a disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
Measurable disease, defined as:
CLL/SLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions by computed tomography (CT)/magnetic resonance imaging (MRI) or clonal lymphocytes >= 5 x 109/L present on peripheral blood flow cytometry
MCL, or SLL: at least 1 lymph node > 1.5 cm in the longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions by CT/MRI
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Absolute neutrophil count (ANC) >= 1.0 x 10\^9/L =< 7 days before the first dose of the study drug with or without growth factor support. There is an exception for patients with bone marrow involvement, in which case ANC must be >= 0.75 x 10\^9/L before the first dose of the study drug
Platelets > 75,000 x 10\^9/L (> 75,000 cells/mm\^3) =< 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions. Patients with bone marrow involvement will be allowed to have a platelet count > 50,000 x 10\^9/L (> 50,000 cells/mm\^3) =< 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions
Hemoglobin > 75 g/L =< 7 days before the first dose of the study drug (with or without transfusion)
Creatinine clearance or glomerular filtration rate (GFR) >= 50 mL/min as estimated by one of the following:
Cockcroft-Gault equation
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
24-hour urine collection
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase =< 2 x upper limit of normal (ULN)
Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase =< 2 x ULN
Total bilirubin level =< 1.5 x ULN (unless documented Gilbert's syndrome). For patients with documented Gilbert's syndrome, total bilirubin may exceed this value, but direct bilirubin must be =< 1.0 x ULN
Serum amylase =< 1.5 x ULN

You may not qualify if…

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
Known plasma cell neoplasm other than a monoclonal gammopathy of undetermined significance (MGUS), prolymphocytic leukemia, or history of or currently suspected Richter's syndrome
Prior autologous stem cell transplant unless >= 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless >= 3 months after cell infusion
Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for the treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
Use of the following substances prior to the first dose of the study drug:
=< 28 days before the first dose of the study drug:
Any biologic and/or immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, e.g., rituximab, and/or cancer vaccine therapy). If biological and/or immunologic-based therapy(ies) are used for non-oncological indications, enrollment will be at the discretion of the principal investigator (PI)
=< 14 days before the first dose of the study drug:
Systemic chemotherapy or radiation therapy
=< 7 days before the first dose of the study drug:
Corticosteroid given with antineoplastic intent
=< 3 days (or 5 half-lives; whichever is shorter) before the first dose of the study drug:
Bruton's tyrosine kinase inhibitor (BTKi) or other small molecule inhibitor is given with antineoplastic intent
Active fungal, bacterial, and/or viral infection requiring systemic therapy
Note: oral antibiotics for minor bacterial infections are allowed
Major surgery =< 4 weeks before the first dose of study treatment
Toxicity from prior anticancer therapy that has not recovered to grade =< 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count)
Clinically significant cardiovascular disease including the following:
Myocardial infarction =< 6 months before screening
Unstable angina =< 3 months before screening
New York Heart Association class III or IV congestive heart failure

Where it is running

Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

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