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

Recruiting now · Phase 1

Conditions studied: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3a Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Nodal Marginal Zone Lymphoma, Recurrent Splenic Marginal Zone Lymphoma, Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Refractory Grade 1 Follicular Lymphoma, Refractory Grade 2 Follicular Lymphoma, Refractory Grade 3a Follicular Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Nodal Marginal Zone Lymphoma, Refractory Splenic Marginal Zone Lymphoma

In brief

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.

Key facts

Study ID: NCT06859008
Run by: City of Hope Medical Center
People needed: 37
Starts: 2025-08-25
Expected to finish: 2029-01-31
Last updated by the study team: 2026-04-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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:
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)

You may not qualify if…

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
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

Where it is running

City of Hope Medical Center — Duarte, California, United States (enrolling)

Full record on ClinicalTrials.gov

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