Actively Recruiting
A Phase II Study Evaluating the Safety and Efficacy of the Combination of Zanubrutinib Plus Lisocabtagene Maraleucel for Richter's Syndrome
Led by Aseel Alsouqi · Updated on 2026-03-03
24
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
Sponsors
A
Aseel Alsouqi
Lead Sponsor
B
BeOne Medicines
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating how well zanubrutinib combined with lisocabtagene maraleucel (liso-cel) works for treating patients with Richter's syndrome that has returned or does not respond to previous treatments. Richter's syndrome is a condition where chronic lymphocytic leukemia or small lymphocytic leukemia changes into an aggressive lymphoma. Zanubrutinib is a kinase inhibitor that blocks proteins helping cancer cells grow, while liso-cel is a CAR T-cell therapy that modifies a patient's immune cells to attack cancer. In this phase II study, patients take zanubrutinib by mouth twice daily for up to 90 days and undergo leukapheresis at least 14 days after starting it to collect immune cells. Before receiving liso-cel by intravenous infusion, patients get chemotherapy drugs fludarabine and cyclophosphamide intravenously for three days. The trial includes biopsies of bone marrow and lymph nodes, and imaging scans such as CT, PET/CT, or MRI throughout the study to monitor disease and treatment effects. Participants will be followed for two years after completing the treatment, with visits every six months thereafter until disease progression or death. Researchers will measure the overall response rate 90 days after the liso-cel infusion along with safety, survival, progression-free survival, and duration of response over two years. Blood samples will be collected to study immune changes and inflammation related to the treatment.
CONDITIONS
Brief Title
Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of Richter's syndrome with diffuse large B-cell lymphoma and prior or concurrent chronic lymphocytic leukemia or small lymphocytic lymphoma
- Relapsed or refractory disease with at least one prior systemic therapy for CLL or Richter's syndrome
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- Total bilirubin less than or equal to 2.0 times the institutional upper limit of normal unless Gilbert's syndrome
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times the institutional upper limit of normal
- Creatinine clearance of 30 mL/min or greater
- Absolute lymphocyte count greater than 100/uL at screening
- Left ventricular ejection fraction 40% or greater
- Adequate bone marrow function or cytopenias due to disease involvement with specific blood count minimums
- Radiographically measurable lymphadenopathy or extra-nodal disease
- Meet institutional standards for CAR T-cell therapy
- Ability and willingness to sign informed consent
- Women of childbearing potential must use highly effective contraception or abstain during treatment and specified follow-up periods
- Men must use contraception or abstain and refrain from sperm donation during treatment and specified follow-up periods
You will not qualify if you...
- Prior CD19 directed therapy or alemtuzumab within 6 months before enrollment
- Prior allogeneic stem cell transplant or donor lymphocyte infusion within 2 months or active graft-versus-host disease
- Incomplete recovery from adverse events related to prior therapy to grade 1 or less (excluding certain conditions)
- Inability to swallow oral medication or significant gastrointestinal disease
- Active bleeding disorders or recent gastrointestinal ulcers
- Significant cardiovascular disease including recent heart attacks or heart failure class 3 or 4
- Use of warfarin or similar anticoagulants
- Prolonged clotting times exceeding twice the normal limit
- Use of moderate or strong CYP3A inhibitors or inducers within 7 days before starting zanubrutinib
- Active other diseases or cancers limiting survival to less than 5 years
- HIV positive at screening
- Uncontrolled infections, unstable angina, pulmonary problems, or psychiatric/social issues limiting compliance
- Pregnant or breastfeeding women
- Evidence of myelodysplasia on bone marrow biopsy
- Active hepatitis B or C infection
- Autoimmune diseases requiring immunosuppressive medication within 6 months
- Chronic corticosteroid use at or above 20mg prednisone equivalent daily
- Live vaccines given within 28 days before chemotherapy preparation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) including bone marrow and lymph node biopsies
Duration - Up to 90 days
Participants receive zanubrutinib orally twice daily for up to 90 days, undergo leukapheresis at least 14 days after starting zanubrutinib, receive fludarabine and cyclophosphamide intravenously on days -5 to -3, and receive lisocabtagene maraleucel infusion on day 0. Blood samples, CT, PET/CT, and/or MRI are collected throughout treatment.
Multiple visits including leukapheresis and drug administration visits
Duration - At least 24 months plus additional visits every 6 months until disease progression or death
Participants are followed for 24 months after study completion, with visits every 6 months thereafter until disease progression or death. Follow-up includes bone marrow and lymph node biopsies and collection of blood samples and imaging.
Regular follow-up visits every 6 months after initial 24 months
Trial Site Locations
Total: 3 locations
1
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Actively Recruiting
2
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
3
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Actively Recruiting
Research Team
T
The Ohio State University Comprehensive Cancer Center
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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