Actively Recruiting
SONIC: Escalated Inpatient Ramp-Up of Sonrotoclax with Zanubrutinib or Rituximab in Patients with Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Led by Fred Hutchinson Cancer Center · Updated on 2026-04-22
30
Participants Needed
1
Research Sites
204 weeks
Total Duration
On this page
Sponsors
F
Fred Hutchinson Cancer Center
Lead Sponsor
B
BeOne Medicines
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating an escalated ramp-up dosing schedule of sonrotoclax combined with either zanubrutinib or rituximab in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL). These patients may have newly diagnosed disease, relapsed after previous treatment, or refractory disease that does not respond to prior therapy. The study aims to assess the side effects and tolerability of this combination treatment approach in these blood cancers. Participants are assigned to one of two treatment groups based on whether they are refractory to Bruton's tyrosine kinase inhibitors (BTKi). In the first group, patients not refractory to BTKi receive oral zanubrutinib daily for 15 cycles, each lasting 28 days. Starting cycle 4, sonrotoclax is introduced and gradually increased to the target dose, continuing with zanubrutinib through cycle 15. In the second group, patients refractory to BTKi receive rituximab intravenously over one cycle and then begin sonrotoclax ramp-up from cycle 2, continuing sonrotoclax through cycle 13 alongside rituximab infusions during cycles 3 to 6. Both groups undergo computed tomography scans during screening and treatment, blood sample collections, and may have bone marrow biopsies and endoscopies. After finishing the treatment cycles, participants are followed closely at 14 days, 1 month, and then monitored up to five years. Researchers collect safety data including adverse events and track the ability to reach specific sonrotoclax dose levels early in the ramp-up. They also assess long-term outcomes such as overall response rates, progression-free survival, and overall survival. The study includes detailed imaging, laboratory tests, and clinical evaluations throughout and after treatment to understand the treatment's effects and safety profile.
CONDITIONS
Brief Title
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent before any study procedures
- Age 18 years or older
- Confirmed diagnosis of CLL, SLL, or MCL according to WHO criteria
- For CLL/SLL: treatment-naive or relapsed/refractory after at least one prior therapy
- Measurable disease with lymph nodes or lesions meeting size criteria
- ECOG performance status 0 to 2
- Adequate blood counts and organ function as defined
- Negative pregnancy test and use of effective contraception for women of childbearing potential
- Men must use effective contraception and not donate sperm during and after treatment
- Life expectancy over 6 months
- Ability to comply with study requirements
You will not qualify if you...
- Prior Bcl-2 inhibitor use within last 12 months or progression during such treatment
- Other malignancies within past 2 years except certain treated cancers
- Medical conditions that pose risk or interfere with study results
- Central nervous system lymphoma/leukemia involvement
- Prior stem cell transplant or CAR-T therapy within specified timeframes
- Severe bleeding disorders or significant cardiovascular disease
- Active infections requiring systemic therapy
- Recent biologic, chemotherapy, radiation, or corticosteroid treatments
- Pregnancy or lactation
- Inability to swallow capsules or significant gastrointestinal disorders
- Use of certain drugs that affect sonrotoclax metabolism
- History of interstitial lung disease or uncontrolled lung disease
- Autoimmune anemia or thrombocytopenia poorly controlled
- Ongoing liver diseases or drug-induced liver injury
- Vaccination with live vaccines within 35 days before treatment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 15 cycles of 28 days each
Participants receive study treatments including zanubrutinib or rituximab combined with a ramp-up of sonrotoclax taken orally. Treatment cycles repeat every 28 days for up to 15 cycles depending on group assignment and tolerance. During treatment, participants undergo blood sample collection and may have bone marrow biopsies and endoscopies as part of the study assessments.
Multiple visits for treatment cycles and assessments
Duration - Up to 5 years
After completing treatment, participants are followed for safety and disease status at 14 days, 1 month, and up to 5 years.
Visits at 14 days, 1 month, and periodic visits up to 5 years
Trial Site Locations
Total: 1 location
1
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Actively Recruiting
Research Team
M
Mazyar Shadman, MD, MPH
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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