Sonrotoclax, Rituximab, and Zanubrutinib for Lymphoma and Leukemia
This study is testing a combination of medicines for people with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL). These cancers can be newly diagnosed, have come back, or not responded to previous treatments. The study will look at the side effects of sonrotoclax when given after an initial treatment with either zanubrutinib or rituximab. Rituximab is a monoclonal antibody that targets a protein on cancer cells. Zanubrutinib is a kinase inhibitor that blocks a protein called Bruton's tyrosine kinase (BTK) to stop cancer growth. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL-2). The main goals are to see how many side effects occur and if participants can reach certain doses of sonrotoclax. About 30 people are planned to join this study.
- Study design
- This is a dose escalation study, meaning the dose of sonrotoclax will be slowly increased. It plans to enroll 30 participants.
- What's involved
- You would undergo blood sample collections, CT scans, and potentially bone marrow biopsies and endoscopies. Treatment cycles repeat every 28 days for up to 15 cycles or 13 cycles, depending on the arm.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoints for adverse events and sonrotoclax dosing are measured at specific times, such as Day 12 and from Baseline to Day 4 or Day 12.
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NCT06839053
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Recruiting
PHASE2Ages 18+InterventionalTreatmentFred Hutchinson Cancer CenterInvestigator-initiated
~30 participants
Updated 2026-04-22 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow BiopsyComputed TomographyGastrointestinal EndoscopyRituximabSonrotoclax
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events (AEs) during an escalated inpatient ramp-up of sonrotoclax
Measured over At day 12
+2 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesWashington1
Study leadership
- Mazyar Shadman, MD, MPH · PRINCIPAL_INVESTIGATOR · Fred Hutch/University of Washington Cancer Consortium
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses
Age 18 years or older
Confirmed diagnosis (per World Health Organization \[WHO\] guidelines, unless otherwise noted) of one of the following:
CLL/SLL COHORT: CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia criteria:
Meeting the following sets of prior treatment criteria:
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)
Requiring treatment per International Workshop on CLL (iwCLL) criteria
MCL COHORT: WHO-defined MCL
R/R MCL is defined as a disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
Measurable disease, defined as:
CLL/SLL: 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 \>= 5 x 109/L present on peripheral blood flow cytometry
MCL, or SLL: at least 1 lymph node \> 1.5 cm in the longest diameter OR 1 extranodal lesion \> 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions by CT/MRI
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L =\< 7 days before the first dose of the study drug with or without growth factor support. There is an exception for patients with bone marrow involvement, in which case ANC must be \>= 0.75 x 10\^9/L before the first dose of the study drug
Platelets \> 75,000 x 10\^9/L (\> 75,000 cells/mm\^3) =\< 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions. Patients with bone marrow involvement will be allowed to have a platelet count \> 50,000 x 10\^9/L (\> 50,000 cells/mm\^3) =\< 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions
Hemoglobin \> 75 g/L =\< 7 days before the first dose of the study drug (with or without transfusion)
Creatinine clearance or glomerular filtration rate (GFR) \>= 50 mL/min as estimated by one of the following:
Cockcroft-Gault equation
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
24-hour urine collection
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase =\< 2 x upper limit of normal (ULN)
Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase =\< 2 x ULN
Total bilirubin level =\< 1.5 x ULN (unless documented Gilbert's syndrome). For patients with documented Gilbert's syndrome, total bilirubin may exceed this value, but direct bilirubin must be =\< 1.0 x ULN
Serum amylase =\< 1.5 x ULN
Serum lipase =\< 1.5 x ULN
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test =\< 7 days before the first dose of the study drug. In addition, they must use a highly effective method of birth control initiated before the first dose of the study drug, for the duration of the study treatment period, and for \>= 180 days after the last dose of the study drug
NOTE: WOCBP is a woman who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)
NOTE: Highly effective contraceptive methods include the following:
Combined (estrogen and progestogen-containing) hormonal contraception associated with the inhibition of ovulation. Combined hormonal contraception may be oral, intravaginal, or transdermal
Progestogen-only hormonal contraception associated with the inhibition of ovulation. Progesterone-only hormonal contraception may be oral, injectable, or implantable
An intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal
Vasectomized partner
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day before the first dose of study treatment, for the duration of the study, and for \>= 180 days after the last dose of study drug. Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational medicinal product, and withdrawal are not acceptable methods of contraception
Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception, and, if used, this method must be used in combination with another acceptable method listed above
For patients using hormonal contraceptives such as birth control pills or devices, a second barrier method of contraception (e.g., condoms) must be used
Nonsterile men must use a highly effective method of birth control along with barrier contraception for the duration of the study treatment period and for ≥ 180 days after the last dose of the study drug. During this same period, they must not donate sperm. Sterile men must use barrier contraception
Life expectancy of \> 6 months
Able to comply with the requirements of the study
Exclusion
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
Known plasma cell neoplasm other than a monoclonal gammopathy of undetermined significance (MGUS), prolymphocytic leukemia, or history of or currently suspected Richter's syndrome
Prior autologous stem cell transplant unless \>= 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless \>= 3 months after cell infusion
Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for the treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
Use of the following substances prior to the first dose of the study drug:
=\< 28 days before the first dose of the 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, e.g., rituximab, and/or cancer vaccine therapy). If biological and/or immunologic-based therapy(ies) are used for non-oncological indications, enrollment will be at the discretion of the principal investigator (PI)
=\< 14 days before the first dose of the study drug:
Systemic chemotherapy or radiation therapy
=\< 7 days before the first dose of the study drug:
Corticosteroid given with antineoplastic intent
=\< 3 days (or 5 half-lives; whichever is shorter) before the first dose of the study drug:
Bruton's tyrosine kinase inhibitor (BTKi) or other small molecule inhibitor is given with antineoplastic intent
Active fungal, bacterial, and/or viral infection requiring systemic therapy
Note: oral antibiotics for minor bacterial infections are allowed
Major surgery =\< 4 weeks before the first dose of study treatment
Toxicity from prior anticancer therapy that has not recovered to grade =\< 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count)
Clinically significant cardiovascular disease including the following:
Myocardial infarction =\< 6 months before screening
Unstable angina =\< 3 months before screening
New York Heart Association class III or IV congestive heart failure
History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
Heart rate-corrected QT interval \> 480 milliseconds based on Fridericia's formula
History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements, at screening, showing systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg
Known infection with human immunodeficiency virus (HIV) or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:
Presence of viral hepatitis B surface antigen (HBsAg) or viral hepatitis B core antibody (HBcAb)
Note: Patients with the presence of HBcAb, but absence of HBsAg, are eligible if HBV deoxyribonucleic acid (DNA) is undetectable and if they are willing to take HBV reactivation prophylaxis and undergo monitoring for HBV reactivation
Presence of HCV antibody
Note: Patients with the presence of HCV antibody are eligible if HCV ribonucleic acid (RNA) is undetectable and if they are willing to undergo monitoring for HCV reactivation
Pregnant or lactating women
Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedure, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
Inability to comply with study procedures
Receiving any treatment with a strong or moderate CYP3A4 inhibitor =\< 14 days (or 5 half-lives, whichever is longer) before the first dose of sonrotoclax
Unwillingness to stop consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days before the first dose of sonrotoclax or during the study
Receiving any treatment with a strong CYP3A4 inducer =\< 14 days (or 5 half-lives, whichever is longer) before first dose of sonrotoclax
History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis and acute lung diseases
Autoimmune anemia and/or thrombocytopenia that is poorly controlled by corticosteroids or other standard therapy
Ongoing, drug-induced liver injury, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension
Receiving drugs known to prolong the QT/corrected QT (QTc) interval
Vaccination with a live vaccine =\< 35 days before the first dose of the study drug
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed
What this trial measures
- Incidence of adverse events (AEs) during an escalated inpatient ramp-up of sonrotoclaxAt day 12
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.
- Percentage of patients who reach an 80mg dose of sonrotoclaxBaseline to day 4
Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.
- Percentage of patients who reach a 320mg dose of sonrotoclaxBaseline to day 12
Analysis will be descriptive and incorporate the appropriate analysis set. Binary outcomes will be estimated as simple proportions with corresponding exact confidence intervals.