Actively Recruiting
Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation
Led by City of Hope Medical Center · Updated on 2025-09-16
23
Participants Needed
1
Research Sites
121 weeks
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and/or effective in treating patients with Richter's transformation.
CONDITIONS
Official Title
Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent from participant or legal representative
- Age 18 years or older
- ECOG performance status 0, 1, or 2
- Histologically confirmed Richter transformation with diffuse large B-cell lymphoma subtype
- Evidence of CD20 positivity at screening by immunohistochemistry or flow cytometry
- Treatment naive or relapsed/refractory disease including prior CLL therapy
- Measurable lymphadenopathy (≥ 1.5 cm), splenomegaly, or bone marrow involvement by DLBCL/RT
- Fully recovered from acute toxic effects of prior anticancer therapy except alopecia (≤ grade 1)
- Adequate neutrophil count (ANC ≥ 1,000/mm3 without bone marrow involvement or ≥ 500/mm3 with involvement)
- Adequate platelet count (≥ 50,000/mm3 without bone marrow involvement or ≥ 25,000/mm3 with involvement)
- Hemoglobin ≥ 7 g/dL if bone marrow involvement present
- Total bilirubin ≤ 2 x ULN or ≤ 3 x ULN for Gilbert's disease or compensated hemolysis
- AST ≤ 3 x ULN
- ALT ≤ 3 x ULN
- ALP ≤ 2.5 x ULN or ≤ 5 x ULN if due to liver lymphoma involvement
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min
- INR and PT within normal limits or therapeutic range if on anticoagulants
- aPTT within normal limits or therapeutic range if on anticoagulants
- Left ventricular ejection fraction ≥ 45% within 28 days prior to treatment
- Seronegative for HCV, HBV, and no HIV history, or controlled infections as specified
- Negative pregnancy test for women of childbearing potential
- Agreement to use effective birth control or abstain during and 6 months after treatment
You will not qualify if you...
- Allogeneic bone marrow or organ transplant within past 6 months or active graft versus host disease
- Prior CD20-targeted bispecific antibody therapy
- Chronic systemic corticosteroid use > 10 mg/day prednisone equivalent within 72 hours before treatment
- Recent therapeutic anticancer antibodies, radio- or toxin-immunoconjugates, live vaccines, investigational therapies, or radiotherapy within specified timeframes
- Prior organ transplantation
- Chemotherapy or targeted therapy within specified washout periods
- Need for strong CYP3A4 inducers or inhibitors during treatment
- Uncontrolled immune hemolysis or thrombocytopenia
- Allergic reactions to study drug components or hypersensitivity to allopurinol and rasburicase
- Unstable cardiac disease or recent serious cardiac events
- Recent thrombotic or embolic events within 3 months
- Active uncontrolled cardiac arrhythmia or unstable angina
- History or current interstitial lung disease or severely impaired lung function
- Central nervous system involvement within 6 months prior to treatment
- Major surgery within 30 days before treatment
- Clinically significant uncontrolled illness
- Active infections requiring treatment or with risk of severe disease
- Active COVID-19 infection
- Uncontrolled HIV, HBV, or HCV infections
- Detectable cytomegalovirus infection until controlled
- Active malignancy except certain treated or stable cancers
- Pregnant or breastfeeding females
- Inability to swallow or retain oral medication
- Any other condition deemed unsafe or interfering with study participation by investigator
AI-Screening
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Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
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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