Testing the Addition of Anti-Cancer Drug Sonrotoclax, to the Standard Treatment Zanubrutinib, for Previously Untreated CLL/SLL

Recruiting now · Phase 3

Conditions studied: Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia

In brief

This phase III trial compares the effect of adding sonrotoclax to zanubrutinib versus zanubrutinib alone for the treatment of patients with untreated chronic lymphoblastic leukemia (CLL)/small lymphocytic lymphoma (SLL). Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Giving sonrotoclax and zanubrutinib may be more effective than zanubrutinib alone for the treatment of untreated CLL/SLL.

Key facts

Study ID

NCT07321652

Run by

Alliance for Clinical Trials in Oncology

People needed

466

Starts

2026-04-30

Expected to finish

2038-09-30

Last updated by the study team

2026-08-05

Who can join

Age: 65 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Patients with acute cardiac events within 6 months prior to registration should be carefully evaluated for their suitability for enrollment

Where it is running

• Kaiser Permanente - Panorama City — Panorama City, California, United States (enrolling)
• Jupiter Medical Center — Jupiter, Florida, United States (enrolling)
• Mount Sinai Medical Center — Miami Beach, Florida, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States (enrolling)
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States (enrolling)
• Idaho Urologic Institute-Meridian — Meridian, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Sandpoint — Sandpoint, Idaho, United States (enrolling)
• Illinois CancerCare-Bloomington — Bloomington, Illinois, United States (enrolling)
• Illinois CancerCare-Canton — Canton, Illinois, United States (enrolling)
• Illinois CancerCare-Carthage — Carthage, Illinois, United States (enrolling)
• Northwestern University — Chicago, Illinois, United States (enrolling)
• University of Illinois — Chicago, Illinois, United States (enrolling)
• Carle at The Riverfront — Danville, Illinois, United States (enrolling)
• Cancer Care Specialists of Illinois - Decatur — Decatur, Illinois, United States (enrolling)
• Decatur Memorial Hospital — Decatur, Illinois, United States (enrolling)
• Illinois CancerCare-Dixon — Dixon, Illinois, United States (enrolling)
• Carle Physician Group-Effingham — Effingham, Illinois, United States (enrolling)
• Illinois CancerCare-Eureka — Eureka, Illinois, United States (enrolling)
• Illinois CancerCare-Galesburg — Galesburg, Illinois, United States (enrolling)
• Illinois CancerCare-Kewanee Clinic — Kewanee, Illinois, United States (enrolling)
• Illinois CancerCare-Macomb — Macomb, Illinois, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)

Full record on ClinicalTrials.gov

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