Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
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)
3 other identifiers
interventional
30
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2025
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 31, 2025
CompletedFirst Posted
Study publicly available on registry
February 21, 2025
CompletedStudy Start
First participant enrolled
June 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2032
April 22, 2026
April 1, 2026
3.2 years
January 31, 2025
April 17, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events (AEs) during an escalated inpatient ramp-up of sonrotoclax
Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 measuring the frequency of AEs, including episodes of laboratory and clinical tumor lysis syndrome. Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.
At day 12
Percentage of patients who reach an 80mg dose of sonrotoclax
Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.
Baseline to day 4
Percentage of patients who reach a 320mg dose of sonrotoclax
Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.
Baseline to day 12
Secondary Outcomes (5)
Overall response rate
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Complete response (CR)
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Partial response rate
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Progression-free survival
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Overall survival
From the time of receiving first treatment to the first observation of disease progression or death from any cause, assessed up to 5 years
Study Arms (2)
Treatment (zanubrutinib + sonrotoclax)
EXPERIMENTALPatients not refractory to a BTKi undergo debulking and receive zanubrutinib PO 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. Patients who tolerate receiving sonrotoclax continue to receive sonrotoclax together with zanubrutinib PO QD for all subsequent cycles. Cycles repeat every 28 days for up to 15 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT during screening and on study and blood sample collection throughout the study. Additionally, patients may undergo bone marrow biopsy and endoscopy on study.
Treatment (rituximab + sonrotoclax)
EXPERIMENTALPatients who are refractory to a BTKi undergo debulking and receive rituximab PO QD on days 1, 8, 15, and 22 of 1 cycle. Beginning on day 1 of cycle 2, patients receive a ramp up of sonrotoclax PO QD until target dose is reached. Patients will continue sonrotoclax PO QD through cycle 13. Patients also continue to receive rituximab PO QD on day 1 of cycles 3-6. Cycles repeat every 28 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT during screening and on study and blood sample collection throughout the study. Additionally, patients may undergo bone marrow biopsy and endoscopy on study.
Interventions
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo CT
Undergo endoscopy
Given IV
Given PO
Given orally (PO)
Eligibility Criteria
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
- +26 more criteria
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
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- BeOne Medicinescollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mazyar Shadman, MD, MPH
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 31, 2025
First Posted
February 21, 2025
Study Start
June 2, 2025
Primary Completion (Estimated)
August 1, 2028
Study Completion (Estimated)
July 1, 2032
Last Updated
April 22, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share