Actively Recruiting
A Phase I Study of Zanubrutinib Combined With Odronextamab for Patients With Richter's Transformation
Led by City of Hope Medical Center · Updated on 2025-09-16
23
Participants Needed
1
Research Sites
N/A
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
Researchers are evaluating the safety and side effects of zanubrutinib combined with odronextamab in treating patients with Richter's transformation, a type of transformed chronic lymphocytic leukemia. This phase I trial also looks at how well this combination works by measuring response rates, survival, and T-cell balance. Both drugs target specific proteins involved in cancer cell growth and spread, aiming to control the disease. Participants receive intravenous odronextamab on multiple days during the first four cycles and less frequently afterward, with cycles initially lasting 21 days then extending to 28 days up to cycle 12. Zanubrutinib is taken orally once or twice daily starting from cycle 2, and patients may continue it beyond 12 cycles if advised. The study includes procedures like echocardiography or MUGA scans, biopsies of lymph nodes and optionally bone marrow, blood sample collections, and imaging scans such as PET or CT. Throughout the study, participants are monitored for safety and treatment effects with regular assessments including biopsies and imaging. After completing treatment, follow-up visits occur at 4 and 12 weeks, then every six months for up to three years. The main outcomes include dose limiting toxicities and adverse events, with secondary outcomes tracking response rates, duration of response, progression-free survival, and overall survival.
CONDITIONS
Brief 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...
- Participants aged 18 years or older
- Histologically confirmed Richter's transformation with diffuse large B-cell lymphoma histology
- Evidence of CD20 positivity
- Treatment-naïve or relapsed/refractory disease
- Measurable lymphadenopathy (≥1.5 cm), splenomegaly, or bone marrow involvement by DLBCL/RT
- ECOG performance status of 0 to 2
- Adequate blood counts and organ function as defined
- Negative pregnancy test for women of childbearing potential
- Agreement to use effective contraception or abstain from heterosexual activity during and 6 months after treatment
- Seronegative or controlled infection status for HBV, HCV, and HIV
- Ability to swallow and retain oral medication
- Provided informed consent or assent when appropriate
You will not qualify if you...
- Allogeneic bone marrow or organ transplant within 6 months or active graft versus host disease
- Prior CD20-targeted bispecific antibody therapy
- Chronic corticosteroid use exceeding 10 mg/day prednisone equivalent within 72 hours before treatment
- Recent therapeutic anticancer antibodies, radioimmunoconjugates, or investigational therapies within defined timeframes
- Live vaccine within 28 days before treatment
- Prior organ transplantation
- Recent chemotherapy or targeted therapy within specified intervals
- Treatment requiring strong CYP3A4 inducers/inhibitors
- Uncontrolled immune hemolysis or thrombocytopenia
- Allergic reactions to similar compounds or known hypersensitivity to allopurinol and rasburicase
- Unstable cardiac disease or recent cardiac events
- Recent thrombotic or embolic events within 3 months
- Active uncontrolled cardiac arrhythmia or angina
- Interstitial lung disease or severely impaired lung function
- Central nervous system involvement within 6 months
- Major surgery within 30 days prior to treatment
- Clinically significant uncontrolled illness or active infection requiring treatment
- Active COVID-19 infection
- Uncontrolled infection with HIV, HBV, or HCV
- Detectable CMV infection without successful antiviral treatment
- Other active malignancy unless adequately treated and stable
- Pregnant or breastfeeding females
- Inability to swallow or retain oral medication
- Any condition judged unsafe for participation by the investigator
- Inability to comply with study procedures due to feasibility or logistics
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 screening and enrollment visit
Duration - Up to 12 cycles (each cycle 21 or 28 days) plus possible continuation afterward
Participants receive odronextamab intravenously on specific days during each cycle and start oral zanubrutinib from cycle 2. Treatment cycles repeat every 21 days for cycles 1-4 and then every 28 days up to cycle 12. After 12 cycles, participants may continue zanubrutinib as decided by their investigator.
Multiple treatment visits across cycles with odronextamab infusions on days 1, 2, 8, 9, 15, and 16 of cycle 1; days 1, 8, and 15 of cycles 2-4; and days 1 and 15 of remaining cycles
Duration - Up to 3 years
Participants are followed up after completing study treatment to monitor safety and outcomes.
Visits at 4 and 12 weeks after treatment, then every 6 months
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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