Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma

Part of paid clinical trials in Seattle, Washington.

Sponsor
Fred Hutchinson Cancer Center
Study ID
NCT06839053
Phase
PHASE2
Status
Recruiting
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Conditions

  • Chronic Lymphocytic Leukemia
  • Mantle Cell Lymphoma
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Mantle Cell Lymphoma
  • Refractory Small Lymphocytic Lymphoma
  • Small Lymphocytic Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Biospecimen Collection — PROCEDURE
    Undergo blood sample collection
  • Bone Marrow Biopsy — PROCEDURE
    Undergo bone marrow biopsy
  • Computed Tomography — PROCEDURE
    Undergo CT
  • Gastrointestinal Endoscopy — PROCEDURE
    Undergo endoscopy
  • Rituximab — BIOLOGICAL
    Given IV
  • Sonrotoclax — DRUG
    Given PO
  • Zanubrutinib — DRUG
    Given orally (PO)

Study Details

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.

Key Dates

Start date
Jun 2, 2025
Status verified
Apr 2026
Primary completion
Aug 1, 2028
Completion
Jul 1, 2032

Study Design

Enrollment
30 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment (zanubrutinib + sonrotoclax)
    Patients 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.
  • Experimental: Treatment (rituximab + sonrotoclax)
    Patients 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.

Primary Outcome Measure

Incidence of adverse events (AEs) during an escalated inpatient ramp-up of sonrotoclax [ Time Frame: At day 12 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Fred Hutch/University of Washington Cancer ConsortiumSeattleWashington98109
Mazyar Shadman, MD, MPH
[email protected]
206-667-5467
Mazyar Shadman, MD, MPH (PRINCIPAL_INVESTIGATOR)

Find similar trials in Seattle, WA

By condition
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By research site
Fred Hutch/University of Washington Cancer Consortium· Seattle, WA

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