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

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Leukemia

Eligibility Criteria

Sex

ALL

Age

65 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Zanubrutinib — DRUG
  Given PO
• Sonrotoclax — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo CT scan
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Survey Administration — OTHER
  Ancillary studies

Study Details

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 Dates

First listed

Jan 7, 2026

Start date

Apr 30, 2026

Status verified

Sep 2026

Primary completion

Sep 30, 2028

Completion

Sep 30, 2038

Study Design

Enrollment

466 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm 1 (zanubrutinib)
  Patients receive zanubrutinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo restaging starting at cycle 15 day 1. Patients with at least partial remission continue therapy as described above. Patients with progressive disease proceed to follow up. Patients undergo CT scan, bone marrow aspiration and blood sample collection throughout the study.
• Experimental: Arm 2 (zanubrutinib and sonrotoclax)
  Patients receive zanubrutinib PO BID on days 1-28 of each cycle. Starting cycle 4 day 1 patients also receive sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo restaging starting at cycle 15 day 1. Patients with undetectable MRD and a response of PR, PR-L, CR, CCR or CRi stop therapy at cycle 15 day 28 and proceed to follow up. Patients with detectable MRD and an objective response to therapy are re-randomized to arm 2B or arm 2C. ARM 2B: Patients continue zanubrutinib PO BID sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for an additonal 12 cycles in the absence of disease progression or unacceptable toxicity. ARM 2C: Patients discontinue therapy starting at cycle 15 day 28 and proceed to follow up. Patients undergo CT scan, bone marrow aspiration and blood sample collection

Primary Outcome Measure

Progression free survival (PFS) [ Time Frame: From initial randomization date until the earlier of disease progression or death from any cause, up to 10 years ]

Central Contacts

• Jayke Giese
  773-702-9171
  [email protected]

Locations (210)

Find similar trials in Birmingham, AL

Related Studies

• A Long-term Extension Study of PCI-32765 (Ibrutinib)
  PHASE3 · Recruiting · Janssen Research & Development, LLC · Orange, California
• Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
  PHASE1 · Recruiting · Baylor College of Medicine · Houston, Texas
• The Prospective Collection, Storage and Reporting of Data on Patients Undergoing Hematopoietic Stem Cell Transplantation Utilizing a Standard Preparative Regimen
  Recruiting · Wake Forest University Health Sciences · Winston-Salem, North Carolina
• Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
  PHASE2 · Recruiting · Masonic Cancer Center, University of Minnesota · Minneapolis, Minnesota