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

ConditionsChronic Lymphocytic LeukemiaMantle Cell LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Mantle Cell LymphomaRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Mantle Cell LymphomaRefractory Small Lymphocytic LymphomaSmall Lymphocytic Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFred Hutchinson Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses

Age 18 years or older

For the R/R cohort, disease that relapsed after, or was refractory to, at least 1 prior therapy

For the treatment-naïve cohort, patients should have no prior treatment for CLL/SLL (other than 1 aborted regimen < 2 weeks in duration and > 4 weeks before enrollment)

Disqualifiers

Exposure to a Bcl-2 inhibitor within the last 12 months or a history of disease progression while taking a Bcl-2 inhibitor

Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, melanoma, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score =< 6 prostate cancer

Underlying medical conditions that may render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results

Known current central nervous system involvement by lymphoma/leukemia

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Gastrointestinal Endoscopy

    Procedure/Surgery

    Undergo endoscopy

  • Rituximab

    Biological/Vaccine

    Given IV

  • Sonrotoclax

    Drug

    Given PO

  • Zanubrutinib

    Drug

    Given orally (PO)

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Treatment (zanubrutinib + sonrotoclax)Experimental treatment 6 interventions
Group B: Treatment (rituximab + sonrotoclax)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Incidence of adverse events (AEs) during an escalated inpatient ramp-up of sonrotoclax

Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 measuring the frequency of AEs, including episodes of laboratory and clinical tumor lysis syndrome. Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
At day 12
2

Percentage of patients who reach an 80mg dose of sonrotoclax

Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
Baseline to day 4
3

Percentage of patients who reach a 320mg dose of sonrotoclax

Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
Baseline to day 12

Secondary outcomes

1

Overall response rate

Defined by International Workshop on CLL (iwCLL) criteria. Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
2

Complete response (CR)

Defined by iwCLL criteria. The time to CR will also be reported for the group that achieves this response. Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
3

Partial response rate

Defined by iwCLL criteria. Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.

Time frame
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
4

Progression-free survival

Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals. Analysis will be summarized using the method of Kaplan and Meier. Continuous measures will be summarized using means/medians, standard deviations, and ranges.

Time frame
From the time of receiving first treatment to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fred Hutchinson Cancer Center

Lead sponsor

BeOne Medicines

Collaborator

Source ClinicalTrials.gov
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