Testing Sonrotoclax with Zanubrutinib for Untreated CLL/SLL
This study is looking at whether adding the anti-cancer drug sonrotoclax to the standard treatment zanubrutinib works better than zanubrutinib alone for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who haven't been treated before. Sonrotoclax works by blocking a protein called Bcl-2, which helps cancer cells survive. Zanubrutinib blocks another protein called BTK, which can help stop cancer cells from growing and spreading. The study aims to see if this combination can prevent the cancer from getting worse for a longer time. You might be able to join if you are 65 or older, and have untreated CLL/SLL. The study is currently unclear on its recruitment status.
- Study design
- This is a phase III interventional study planning to enroll 466 participants. It compares two treatment approaches: zanubrutinib alone versus zanubrutinib with sonrotoclax.
- What's involved
- Participants will receive either zanubrutinib or a combination of zanubrutinib and sonrotoclax by mouth. They will also undergo CT scans, bone marrow aspirations, and blood sample collections.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed from their initial randomization date until the cancer progresses or they pass away, for up to 10 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07321652
Testing the Addition of Anti-Cancer Drug Sonrotoclax, to the Standard Treatment Zanubrutinib, for Previously Untreated CLL/SLL
Recruiting
PHASE3Ages 65+InterventionalTreatmentAlliance for Clinical Trials in OncologyInvestigator-initiated
~466 participants
Updated 2026-08-05 on ClinicalTrials.gov
What's tested:ZanubrutinibSonrotoclaxComputed TomographyBone Marrow AspirationBiospecimen CollectionSurvey Administration
At a glance
Recruiting sites
181 of 182 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression free survival (PFS)
Measured over From initial randomization date until the earlier of disease progression or death from any cause, up to 10 years
Conditions
Where it's being run
182 sites across 26 statesIllinois30
Kansas23
Iowa17
Missouri14
Ohio14
Minnesota12
Wisconsin10
Idaho7
Study leadership
- Jennifer R Brown, MD · STUDY_CHAIR · Alliance for Clinical Trials in Oncology
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
STEP 0: This bone marrow or peripheral blood submission to Adaptive is mandatory prior to registration/randomization for real-time identification of the clone needed for MRD testing. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible to confirm registration eligibility
STEP 0: Patients must be diagnosed with CLL/SLL according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria that includes all of the following:
≥ 5 x10\^9 /L B lymphocytes (5000/μL) in the peripheral blood (CLL) or a lymph node biopsy demonstrating SLL with the below immunophenotype (SLL)
On morphologic review, the leukemic cells must be small mature lymphocytes
Immunophenotype of CLL cells (performed locally) must reveal a clonal B-cell population, which coexpress the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in \> 10% of cells must lack t(11;14) translocation by interphase cytogenetics
STEP 0: Patients must meet criteria for treatment as defined by IWCLL 2018 guidelines which includes at least one of the following criteria:
Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia), typically hemoglobin (Hb) \< 10 g/dL, platelet count \< 100,000/mm\^3
Massive (\> 6 cm below the costal margin), progressive or symptomatic splenomegaly
Massive nodes (ie, \> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
Constitutional symptoms, which include any of the following:
Unintentional weight loss of ≥ 10% within the previous 6 months
Significant fatigue (ie. Eastern Cooperative Oncology Group \[ECOG\] performance status \[PS\] ≥ 2)
Fevers \>100.5 °F or 38.0°C for 2 weeks or more without evidence of infection
Night sweats \> 1 month without evidence of infection
STEP 0: Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
STEP 0: Treatment with rituximab and/or high-dose corticosteroids for autoimmune complications of CLL must be completed prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
STEP 0: Age ≥ 65 years
STEP 0: ECOG performance status ≤ 2
STEP 0: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
STEP 0: Patients with a history of hepatitis C virus (HCV), infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
STEP 0: Patients must not be receiving active systemic anticoagulation with warfarin. Patients must be off warfarin therapy for at least 5 half-lives washout and with normal INR prior to enrollment
STEP 0: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better.
STEP 0: No patients with a history of a severe bleeding disorder or a history of hemorrhagic stroke or intracranial hemorrhage
STEP 0: No patients with known active progressive central nervous system (CNS) disease
STEP 0: No known medical condition causing an inability to swallow oral formulations of agents
STEP 1: The adaptive report confirming a measurable and trackable B cell clone
STEP 1: Patients may not have had major surgery within 7 days of enrollment, or minor surgery within 5 days of enrollment. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician
STEP 1: No patients with ongoing active fungal, bacterial or viral infection requiring systemic therapy except those described in the protocol document
STEP 1: Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily
STEP 1: Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
STEP 1: Patients must not have continued requirement for therapy with a strong CYP3A4/5 inhibitor or inducer. Any such inhibitor or inducer must have been discontinued at least 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug
STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mm3 unless due to marrow involvement
STEP 1: Platelet count ≥ 30,000/mm3
STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to liver involvement, hemolysis or Gilbert's disease)
STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x upper limit of normal (ULN) unless due to disease infiltration of the liver
STEP 1: Calculated (calc.) creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) ≥ 30 mL/min
STEP 1: Urine protein to creatinine ratio \< 1 or urine protein ≤ 1+
STEP 2: Detectable MRD ≥ 10 residual clonal cells per million nucleated cells in peripheral blood at the C15 restaging evaluation from ClonoSEQ
STEP 2: Response of PR, PR-L, CR, CCR or CRi to zanubrutinib sonrotoclax therapy
What this trial measures
- Progression free survival (PFS)From initial randomization date until the earlier of disease progression or death from any cause, up to 10 years
From initial randomization date until the earlier of disease progression or death from any cause. PFS estimates for zanubrutinib plus sonrotoclax therapy to continuous Zanubrutinib.