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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 1NCT06859008

Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

A Phase 1 study testing Biopsy, Biospecimen Collection and Bone Marrow Aspiration in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase I trial tests zanubrutinib in combination with sonrotoclax for treating underrepresented ethnic and racial minorities with B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Bone Marrow Aspiration
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteUnited States
Study dates
25 Aug 2025to 31 Jan 2029
Phase
Phase 1
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 on the day of signing the informed consent form
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Patients are of the following self-identified racial/ethnic groups:
  • Cohort 1: Patients in any of the following categories:
Show all 60Show fewer
  • Black or African American
  • Hispanic or Latino
  • American Indian/Native Alaskan
  • Pacific Islander/Native Hawaiian
  • Any other patient that does not fit the definition of Cohort 2
  • Cohort 2: Patients in either of following categories:
  • Non-Hispanic White
  • Non-Hispanic Asian
  • Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following disease subtypes. Note that for disease subtypes that are known to respond to BTK inhibitor (BTKi) and/or BCL2 inhibitor (BCL2i) (e.g., marginal zone lymphoma [MZL], mantle cell lymphoma [MCL], CLL/SLL), newly diagnosed or r/r patients are allowed
  • Diffuse large B cell lymphoma (DLBCL)
  • R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least 2 prior lines of therapy. Patients should be considered by the investigator to be refractory to or not a candidate for approved therapies with proven efficacy including but not limited to chimeric antigen receptor (CAR) T cell therapy or bispecific antibody therapy
  • Active disease requiring treatment
  • Follicular lymphoma (FL)
  • R/R FL (grade 1, 2 or 3a based on WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy. Patients should be considered by the investigator for all approved therapies with proven efficacy including but not limited to CAR T cell therapy or bispecific antibody therapy
  • Active disease requiring treatment
  • Marginal zone lymphoma (MZL)
  • R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least 1 prior therapy
  • Active disease requiring treatment
  • Mantle cell lymphoma (MCL)
  • R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
  • Requiring treatment in the opinion of the investigator
  • Chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL)
  • CLL/SLL diagnosis that meets the International Workshop on CLL (International Workshop on Chronic Lymphocytic Leukemia [IWCLL]) criteria
  • Patients with previously untreated and/or r/r CLL defined as disease that relapsed after, or was refractory to, at least 1 prior therapy will be included
  • Patients must have an indication to start treatment
  • Measurable disease, defined as:
  • CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions by computed tomography (CT)/magnetic resonance imaging (MRI) or clonal lymphocytes measured by flow cytometry
  • DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions by CT/MRI. For MZL, isolated splenomegaly is considered measurable for this study. For MCL, clonal lymphocytes measured by flow cytometry is considered measurable
  • Life expectancy of ≥ 6 months
  • Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm^3
  • NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
  • 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
  • Without bone marrow involvement: Platelets ≥ 75,000/mm^3
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
  • 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 ≥ 7g/dL
  • NOTE: Red blood cell transfusions are not permitted within 7 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)
  • 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 formula-corrected QT interval (QTcF) ≤ 480 ms
  • Note: Performed within 28 days prior to day 1 of protocol therapy
  • Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR
  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • 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 90 days 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

  • Major surgery ≤ 4 weeks of the first dose of study drug
  • Prior autologous stem cell transplant unless ≥ 30 days after transplant; or prior chimeric antigen receptor T cell (CAR-T) therapy unless ≥ 30 days after cell infusion
  • Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
  • Prior therapy ≥ 2 months with or progression on a Bcl2 inhibitor (eg, venetoclax)
  • Vaccination or requirement for 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 warfarin or warfarin derivatives
  • Concurrent participation in another therapeutic clinical trial
  • Use of the following substances prior to the first dose of study drug:
  • ≤ 28 days before first dose of study drug: Any biologic and/or immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, eg, rituximab, and/or cancer vaccine therapy)
  • ≤ 14 days before the first dose of study drug: systemic chemotherapy or radiation therapy
  • ≤ 7 days before the first dose of study drug: corticosteroid given with antineoplastic intent other than control of BTK inhibitor withdrawal flare
  • ≤ 5 half-lives before the first dose of study drug: BTK inhibitor, tyrosine kinase inhibitor, or other targeted small molecule given with antineoplastic intent
  • Known current central nervous system involvement by lymphoma/leukemia
  • Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
  • Any uncontrolled or clinically significant cardiovascular disease including the following:
  • Myocardial infarction (MI) within 6 months before screening
  • NYHA (New York Heart Association) heart failure class III-IV
  • Unstable angina within 3 months before screening
  • History of clinically significant arrhythmias (e.g., 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 within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer
  • History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
  • 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, or serologic status reflecting active hepatitis B or C infection as follows:
  • Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable (< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation
  • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV ribonucleic acid (RNA) is undetectable
  • Any condition which in the discretion of the investigator would compromise the ability to comply with study procedures
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents
  • Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (e.g., idiopathic thrombocytopenia purpura)
  • 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

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

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Geoffrey Shouse, 626-239-5289, gshouse@coh.org

    Geoffrey Shouse

    Recruiting

Other trials in United States

About this study

Official title: Feasibility of Treating Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma With Zanubrutinib in Combination With the BCL2 Inhibitor, Sonrotoclax, Focusing on Access for Underrepresented Ethnic/Racial Minorities

This phase I trial tests zanubrutinib in combination with sonrotoclax for treating underrepresented ethnic and racial minorities with B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Many racial and ethnic minorities face additional treatment challenges which may lead to poorer outcomes, however, there are fewer racial and ethnic minorities participating in clinical trials. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood cancer cells to survive and grow. When sonrotoclax blocks Bcl-2, it slows down or stops the growth of cancer cells and causes them to die. Zanubrutinib and sonrotoclax have been shown to be an effective treatment for B-cell cancers. Giving zanubrutinib in combination with sonrotoclax may be effective in treating ethnic and racial minorities with relapsed or refractory B-cell non-Hodgkin lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the feasibility of completing zanubrutinib lead-in and sonrotoclax ramp up in underrepresented minorities with relapsed/refractory (r/r) B cell non-Hodgkin lymphoma (B-NHL).

II. Assess the feasibility of patient retention through 2 cycles of combination therapy at a steady dose in underrepresented minorities with r/r B-NHL.

SECONDARY OBJECTIVES:

  1. Assess safety and tolerability. II. Estimate overall response rate (ORR). III. Estimate complete response (CR) rate. IV. Estimate time to response. V. Estimate progression free survival (PFS). VI. Estimate overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. Assess demographics potentially related to health care disparities including the highest level of education within the home, primary language spoken by patient, distance from patient's home to treating institution, time from diagnosis of r/r B-NHL until seen at trial center and socioeconomic status by zip code of participant.

II. Estimate minimum residual disease (MRD) rate for patients with chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL) only.

III. For the first 7 patients only: assess feasibility of using mobile phlebotomy for blood sample collection.

IV. Evaluate the relationship between three-factor risk estimate scale (Tres) comorbidity score and survival outcomes.

  1. Assess patient-reported quality-of-life outcomes. VI. Assess patient-reported perceptions of clinical trial participation and barriers.

OUTLINE:

Patients receive zanubrutinib orally (PO) once daily (QD) on days 1-28 of each cycle. Starting with cycle 3, patients also receive sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 28 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo biopsy at progression and bone marrow aspiration and biopsy throughout the study.

After completion of study treatment, patients are followed up at 30 days then every 3 months for up to 3 years.

Being tested
Biopsy, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo urine and blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow aspiration and biopsy

  • Computed TomographyProcedure or surgery

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

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

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

    Undergo MRI

  • Questionnaire AdministrationOther

    Ancillary studies

  • SonrotoclaxDrug

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

    Given PO

  • ZanubrutinibDrug

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

    Given PO

Study groups in NCT06859008
Study groupRoleWhat they receive
Treatment (zanubrutinib, sonrotoclax)ExperimentalPatients receive zanubrutinib PO QD on days 1-28 of each cycle. Starting with cycle 3, patients also receive sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 28 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection, and CT or MRI throughout the study. Additionally, patients may undergo biopsy at progression and bone marrow aspiration and biopsy throughout the study.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Sonrotoclax; Drug: Zanubrutinib

What is being measured

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

  1. Feasibility of completing zanubrutinib lead-in (cycle 1 and cycle 2) and sonrotoclax ramp up (cycle 3)

    Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

    Measured: From start of cycle 1 through end of cycle 3 (cycle length = 28 days)

  2. Feasibility of patient retention through 2 cycles of the combination therapy at a steady dose

    Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

    Measured: From start of cycle 4 though end of cycle 5 (cycle length = 28 days)

Secondary outcomes (6)

  1. Incidence of adverse events (AEs)

    Will be coded and graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. For chronic lymphocytic leukemia/small lymphocytic leukemia, hematologic AEs will be coded and graded by International Workshop on Chronic Lymphocytic Leukemia.

    Measured: Up to 30 days after last dose of study treatment

  2. Overall response rate

    Will be defined as achieving a best response of complete response (CR) or partial response (PR). Will be calculated as the proportion of response-evaluable participants achieving an overall response. Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

    Measured: After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 3 years

  3. CR rate

    Will be defined as achieving a best response of CR. CR rate will be calculated as the proportion of response-evaluable participants achieving CR. Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

    Measured: After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 3 years

  4. Time to response

    Will be summarized by descriptive statistics.

    Measured: From start of protocol treatment to the time CR or PR is first achieved, assessed up to 3 years

  5. Progression-free survival (PFS)

    PFS will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. The 95% confidence interval will be constructed based on log-log transformation. Media PFS will be estimated when available. Analysis will be performed in aggregate as well as separately for the two cohorts.

    Measured: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 3 years

  6. Overall survival (OS)

    OS will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. The 95% confidence interval will be constructed based on log-log transformation. Media OS will be estimated when available. Analysis will be performed in aggregate as well as separately for the two cohorts.

    Measured: From start of protocol treatment to time of death due to any cause, assessed up to 3 years

Timeline

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

  1. First posted5 Mar 2025
  2. Study start25 Aug 2025
  3. Primary completion31 Jan 2029 (estimated)
  4. Study completion31 Jan 2029 (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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06859008
Sponsor's protocol ID
24273
Other IDs
NCI-2025-01388, 24273, P30CA033572
Status last verified
Apr 2026
First submitted
28 Feb 2025
Last updated
20 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Biospecimen Collection and Bone Marrow Aspiration in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 1 site 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 60 inclusion and 36 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: looking for participants now, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Feasibility of completing zanubrutinib lead-in (cycle 1 and cycle 2) and sonrotoclax ramp up (cycle 3) (time frame: From start of cycle 1 through end of cycle 3 (cycle length = 28 days)). The study lists 2 primary outcomes in all. 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 NCT06859008.

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 20 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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