Zanubrutinib and Sonrotoclax for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma in Underrepresented Minorities
This study is testing a combination of two medicines, zanubrutinib and sonrotoclax, for people from underrepresented ethnic and racial minority groups who have B-cell non-Hodgkin lymphoma that has returned or not responded to previous treatments. Zanubrutinib works by blocking a protein called Bruton tyrosine kinase (BTK) to stop cancer growth, while sonrotoclax blocks another protein called B-cell lymphoma-2 (Bcl-2) that helps cancer cells survive. The main goal is to see how practical it is for participants to complete the initial treatment with these two drugs and to keep people in the study for a steady dose of the combination therapy. This study aims to enroll 37 participants who are at least 18 years old and meet specific health criteria.
- Study design
- This is an interventional study with a planned enrollment of 37 participants. The phase of the study is not specified.
- What's involved
- You would undergo procedures such as biopsies, bone marrow aspirations and biopsies, and CT scans. You would also provide urine and blood samples.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study measures feasibility of completing treatment through the end of cycle 3 (each cycle is 28 days) and patient retention through the end of cycle 5.
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NCT06859008
Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Recruiting
PHASE1Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~37 participants
Updated 2026-04-20 on ClinicalTrials.gov
What's tested:BiopsyBiospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyMagnetic Resonance Imaging
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Feasibility of completing zanubrutinib lead-in (cycle 1 and cycle 2) and sonrotoclax ramp up (cycle 3)
Measured over From start of cycle 1 through end of cycle 3 (cycle length = 28 days)
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Geoffrey Shouse · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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)
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)
Exclusion
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
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)
What this trial measures
- Feasibility of completing zanubrutinib lead-in (cycle 1 and cycle 2) and sonrotoclax ramp up (cycle 3)From start of cycle 1 through end of cycle 3 (cycle length = 28 days)
Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.
- Feasibility of patient retention through 2 cycles of the combination therapy at a steady doseFrom start of cycle 4 though end of cycle 5 (cycle length = 28 days)
Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.