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Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT07812246

Zanubrutinib and Sonrotoclax for the Treatment of Relapsed Chronic Lymphocytic Leukemia /Small Lymphocytic Leukemia, ZeuS-2 Trial

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 3 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial tests how well giving zanubrutinib and sonrotoclax works for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) that has come back after a period of improvement (relapsed). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
3 sitesUnited States
Study dates
4 Aug 2027to 13 Aug 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative.
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Age: ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Histological or flow cytometry confirmed diagnosis of B-CLL/SLL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO)
  • CLL has progressed at least 6 months after completion of first-line fixed-duration novel drug (non-chemotherapy) regimen, including but not limited to venetoclax (V) + CD20 monoclonal antibody (monoclonal antibody [mAb], e.g., obinutuzumab (O); BTK inhibitor (zanubrutinib or acalabrutinib or ibrutinib) + V ± CD20 mAb
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  • Active disease meeting criteria for requiring treatment per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines (one of the following):
  • A minimum of any one of the following constitutional symptoms:
  • Unintentional weight loss > 10% within the previous 6 months prior to screening.
  • Extreme fatigue (unable to work or perform usual activities).
  • Fevers of greater than 100.5°F for ≥ 2 weeks without evidence of infection.
  • Night sweats without evidence of infection.
  • Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia.
  • Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly.
  • Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy.
  • Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months.
  • Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids.
  • Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine)
  • Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
  • Without bone marrow involvement: absolute neutrophil count (ANC) ≥ 1,000/mm^3, with bone marrow involvement: ANC ≥ 500/mm^3
  • NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement.
  • Neupogen or biosimilar may be administered for patients with ANC < 1000 with risk for development of febrile neutropenia as determined by treating physician. Dosing will be at 5 mcg/kg rounded to the nearest vial size
  • Without bone marrow involvement: Platelets ≥ 50,000/mm^3, with bone marrow involvement: platelets ≥ 30,000/mm^3
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Hemoglobin ≥ 7 g/dL
  • NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert's disease or compensated hemolysis directly attributable to CLL)
  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Creatinine clearance of ≥ 30 mL/min/ per 24-hour urine test or the Cockcroft-Gault formula
  • Fridericia's corrected QT interval (QTcB) ≤ 480 ms
  • Note: To be performed within 28 days prior to Day 1 of protocol therapy
  • Seronegative for hepatitis C virus (HCV), active hepatitis B virus (HBV) (Surface antigen negative) OR
  • If seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • Meets other institutional and federal requirements for infectious disease titer requirements
  • Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 week after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Chronic use of corticosteroids in excess of 20 mg/day prednisone
  • Major surgery (under general anesthesia) ≤4 weeks of the first dose of study drug
  • Prior chemotherapy
  • Refractory to prior BTK or BCL2 inhibitor (defined as relapsed within/< 6 months after completion of initial fixed duration regimen)
  • Vaccination with a live vaccine within 35 days prior to the first dose of study drug or at any time during planned study treatment
  • Requires ongoing treatment with a strong CYP3A inducer
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  • Requires ongoing treatment with inhibitors of P-gp and BCRP
  • Requires ongoing treatment with warfarin or warfarin derivatives
  • Concurrent participation in another therapeutic clinical trial
  • Use of the following substances prior to the first dose of study drug:
  • ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug: strong and moderate inhibitors or inducers of CYP3A
  • ≤ 7 days before the first dose of study drug: corticosteroid (> 20 mg prednisone or equivalent) given with antineoplastic intent
  • Known current central nervous system involvement by lymphoma/leukemia
  • Known Richter's transformation
  • Any uncontrolled or clinically significant cardiovascular disease including the following:
  • Myocardial infarction (MI) within 6 months before screening
  • New York Heart Association (NYHA) (New York Heart Association) heart failure class III-IV
  • Unstable angina within 3 months before screening
  • History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).
  • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
  • Prior malignancy except:
  • Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study
  • Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
  • Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease
  • Asymptomatic prostate cancer managed with "watch and wait" strategy
  • Uncontrolled immune hemolysis or thrombocytopenia
  • Significant bleeding disorder (stable therapeutic anticoagulation acceptable)
  • History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
  • Severe or debilitating pulmonary disease
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Active fungal, bacterial and/or viral infection requiring systemic therapy
  • Underlying medical conditions that, in the investigator's opinion, will render the administration of study drugs hazardous or obscure the interpretation of toxicity or adverse events (AEs)
  • Known active infection with HIV
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents
  • Uncontrolled autoimmune anemia and/or autoimmune thrombocytopenia (e.g., idiopathic thrombocytopenia purpura)
  • Any condition which in the discretion of the investigator would compromise the ability to comply with study procedures
  • Females only: Pregnant or breastfeeding
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States3 sites

  • City of Hope Medical Center

    Duarte, California, 91010

    Tanya Siddiqi, 626-803-3458, tsiddiqi@coh.org

    Tanya Siddiqi

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Tanya Siddiqi, 626-803-3458, tsiddiqi@coh.org

    Tanya Siddiqi

  • City of Hope Atlanta Cancer Center

    Newnan, Georgia, 30265

    Sabarish R. Ayyappan, 770-400-6568, sayyappan@coh.org

    Sabarish R. Ayyappan

Other trials in United States

About this study

Official title: Phase 2 Study of Fixed-Duration Zanubrutinib and Sonrotoclax (Z+S) All-Oral Combination Therapy in CLL/SLL Patients in 1st Relapse After Initial Fixed-Duration Novel Therapy (ZeuS-2 Trial)

This phase II trial tests how well giving zanubrutinib and sonrotoclax works for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) that has come back after a period of improvement (relapsed). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) and BCL-XL inhibitors. It may stop the growth of tumor cells and may kill them by blocking Bcl-2 and Bcl-XL, proteins needed for cell survival. Giving zanubrutinib and sonrotoclax may work well for the treatment of relapsed CLL/SLL.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Estimate overall response rate (ORR).

SECONDARY OBJECTIVES:

  1. Estimate complete response (CR) rate. II. Estimate minimal residual disease (MRD) negativity by flow cytometry every 6 months.

III. Estimate progression-free survival (PFS) at 2, 3, and 5 years. IV. Estimate duration of response (DOR) at 2, 3, and 5 years. V. Estimate overall survival (OS) at 2, 3, and 5 years.

EXPLORATORY OBJECTIVES:

  1. Identify mechanisms of resistance. II. Evaluate effect of treatment on immune cell repertoire. III. Evaluate clinical outcome stratified by first line therapy (anti-CD20 containing therapy: Yes versus [vs.] No) and time since stopping first line therapy (greater than 2 years: Yes vs. No).

OUTLINE:

CYCLE 1-4: Patients receive zanubrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CYCLE 5+: Patients receive zanubrutinib PO QD and sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow biopsy and aspiration, computed tomography (CT) scan/magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may undergo lymph node biopsy during screening and optionally at time of progression.

After completion of study treatment, patients are followed up at 30 days. Patients who discontinue study drug due to reasons other than disease progression will be followed every 3 months until patient exhibits first progression for up to 5 years. Patients who discontinue study drug and have progressed are followed up every 6 months for up to 5 years.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Lymph Node Biopsy
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Lymph Node BiopsyProcedure or surgery

    Also called Biopsy of Lymph Node

    Undergo lymph node biopsy

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • SonrotoclaxDrug

    Also called B-cell Lymphoma-2 Inhibitor BGB-11417, Bcl-2 Inhibitor BGB-11417, Beqalzi, BGB 11417

    Given PO

  • ZanubrutinibDrug

    Also called BGB 3111, BGB-3111, BGB3111, Brukinsa

    Given PO

Study groups in NCT07812246
Study groupRoleWhat they receive
Treatment (zanubrutinib and sonrotoclax)ExperimentalCYCLE 1-4: Patients receive zanubrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. CYCLE 5+: Patients receive zanubrutinib PO QD and sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and aspiration, CT scan/MRI and blood sample collection throughout the study. Patients may undergo lymph node biopsy during screening and optionally at time of progression.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Lymph Node Biopsy; Procedure: Magnetic Resonance Imaging; Drug: Sonrotoclax; Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    Overall response defined as achieving best response of complete response (CR) or partial response (PR) after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. Overall response rate will be calculated as the proportion of response-evaluable participants achieving an overall response. Will be estimated as a binary proportion; the 95% Clopper-Pearson confidence interval will be calculated when needed.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Complete response rate

    Complete response defined as achieving best response of CR after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. Complete response rate will be calculated as the proportion of response-evaluable participants achieving CR. Will be estimated as a binary proportion; the 95% Clopper-Pearson confidence interval will be calculated when needed.

    Measured: Up to 5 years

  2. Minimal residual disease (MRD) negativity

    MRD negativity is defined as less than 10^-4. MRD will be assessed in the blood by flow cytometry.

    Measured: Up to 5 years

  3. Progression free survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

    Measured: From start of protocol treatment to time of disease relapse/progression or death due to any cause, up to 5 years

  4. Duration of response

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

    Measured: From first achievement of CR or PR to time of disease relapse/progression or death due to any cause, up to 5 years

  5. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

    Measured: From start of protocol treatment to time of death, up to 5 years

  6. Incidence of adverse events

    Assessed by Common Terminology Criteira for Adverse Events version 5.0.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2026
  2. Study start4 Aug 2027 (estimated)
  3. Primary completion13 Aug 2028 (estimated)
  4. Study completion13 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07812246
Sponsor's protocol ID
251076
Other IDs
NCI-2026-06340, 251076, P30CA033572
Status last verified
Sep 2026
First submitted
4 Sep 2026
Last updated
10 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07812246.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.

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