Zanubrutinib and Odronextamab for Richter's Transformation
This study is testing the safety and side effects of two drugs, zanubrutinib and odronextamab, when given together to people with Richter's transformation (a type of aggressive lymphoma that can develop from chronic lymphocytic leukemia). Zanubrutinib works by blocking a protein that helps cancer cells grow. Odronextamab is a special antibody that can target cancer cells and help your immune system fight them. Researchers want to see if this combination is safe and effective. To join, you must be at least 18 years old and have a confirmed diagnosis of Richter's transformation. The study is currently unclear on its recruitment status and plans to enroll 23 participants.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It aims to enroll 23 participants.
- What's involved
- You would receive odronextamab intravenously (through a vein) and take zanubrutinib by mouth. You would also undergo procedures like blood draws, CT scans, and echocardiograms (heart ultrasound). Treatment cycles repeat every 21 or 28 days for up to 12 cycles, with potential to continue zanubrutinib.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your safety will be monitored for up to 28 days after your last dose of study treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06735664
Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation
Recruiting
PHASE1Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~23 participants
Updated 2026-09-16 on ClinicalTrials.gov
What's tested:BiopsyBiospecimen CollectionBone Marrow BiopsyComputed TomographyEchocardiographyMultigated Acquisition Scan
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Dose limiting toxicity (DLT)
Measured over During the first 2 cycles of protocol therapy (cycle length = 21 days)
+1 more outcome measured
Conditions
NCT06735664
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
City of Hope Medical Center
Duarte, Californiastudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Alexey V Danilov · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Want this trial checked against your situation?
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
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Age: ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Histologically confirmed diagnosis of Richter transformation (RT; transformed CLL). Only patients who have diffuse large B-cell lymphoma histology in transformation are eligible (for example, patients with transformation into Hodgkin lymphoma subtype are not eligible)
Evidence of CD20 positivity at screening (by immunohistochemistry \[IHC\] or flow cytometry)
Treatment naïve or relapsed/ refractory disease. Patients with either previously untreated RT and previously treated RT are eligible, regardless of whether or not they had received CLL-directed therapy
Radiographically measurable lymphadenopathy (≥ 1.5 cm) or splenomegaly, or bone marrow involvement by diffuse large B cell lymphoma (DLBCL)/RT
Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement
With bone marrow involvement: ANC ≥ 500/mm\^3
NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement
Without bone marrow involvement: Platelets ≥ 50,000/mm\^3
NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements
With bone marrow involvement: Platelets ≥ 25,000/mm\^3
NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements
With bone marrow involvement: Hemoglobin (Hgb) ≥ 7 g/dL
Total bilirubin ≤ 2 x upper limit of normal (ULN) or ≤ 3 x ULN for Gilbert's disease or compensated hemolysis directly attributable to CLL
Aspartate aminotransferase (AST) ≤ 3 x ULN
Alanine aminotransferase (ALT) ≤ 3 x ULN
Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ≤ 5 x ULN if attributed to lymphoma involvement of the liver
Serum creatinine ≤ 1.5 x ULN OR creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
Left ventricular ejection fraction (LVEF) ≥ 45%
Note: To be performed within 28 days prior to day 1 of protocol therapy
Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) and no history of HIV OR
If seropositive for HBV or HCV, 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
Women of childbearing potential (WOCBP): Negative serum pregnancy test
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 6 months after the last dose of study therapy. Sperm donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include:
Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated ≥ 2 menstrual cycles prior to screening
Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
Bilateral tubal ligation/occlusion
Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study patient and that the partner has obtained medical assessment of surgical success for the procedure)
Sexual abstinence, only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the clinical trial facilitation group guidance. Pregnancy testing and contraception are not required
Exclusion
Allogeneic bone marrow or organ transplant within 6 months or evidence of active graft versus host diseae (GVHD)
Prior CD20-targeted bispecific antibody therapy
Chronic systemic corticosteroid use \> 10 mg/day of prednisone or equivalent within 72 hours (h) of start of study treatment. Patients who received corticosteroid treatment with ≤ 10 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 10 days) course of systemic steroids (≤ 80 mg prednisone equivalent per day) up to 24 hours prior to initiation of study therapy for control of lymphoma-related symptoms
Therapeutic anticancer antibodies within 2 weeks prior to day 1 of protocol therapy
Radio- or toxin-immunoconjugates within 10 weeks prior to day 1 of protocol therapy
Live vaccine within 28 days prior to day 1 of protocol therapy
Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment
Standard radiotherapy within 14 days of first administration of study treatment
Prior organ transplantation
Chemotherapy, within 2 weeks prior to day 1 of protocol therapy; targeted therapy within 6 half-lives or two weeks, whichever is shorter
Requires treatment with a strong CYP3A4 inducers/ inhibitor while on protocol therapy
Uncontrolled immune hemolysis or thrombocytopenia
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug
Known hypersensitivity to both allopurinol and rasburicase
Unstable cardiac disease as defined by one of the following:
Cardiac events such as myocardial infarction (MI) within the past 6 months
NYHA (New York Heart Association) heart failure class III-IV
Uncontrolled atrial fibrillation or hypertension
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment
Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
Active uncontrolled cardiac arrythmia
History or concurrent condition of interstitial lung disease and/or severely impaired lung function
Evidence of central nervous system (CNS) involvement within 6 months prior to initiation of study therapy
Major surgery (under general anesthesia) within 30 days prior to day 1 of protocol therapy
Clinically significant uncontrolled illness
Evidence of any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other) at study enrollment or within 2 weeks of study enrollment, if requiring ongoing treatment and/or has the potential to cause disseminated disease or severe infection upon immunosuppression. There should be evidence that the infection has cleared or is well controlled by start of study therapy
Active COVID-19 infection
Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
NOTE: Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/uL either spontaneously or on a stable antiviral regimen) are permitted
NOTE: Participants who are hepatitis B surface antigen positive or who are hepatitis B core antibody positive should undergo evaluation by a specialist and be considered to have controlled infection (serum hepatitis B virus deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\] that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) before they are permitted onto study
NOTE: Participants who are HCV antibody positive who have controlled infection (undetectable HCV ribonucleic acid \[RNA\] by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted
Cytomegalovirus (CMV) infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay. Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility
Other active malignancy. Patients with a prior (in the past 5 years) or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. History of the following is allowed:
Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study
Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease
Asymptomatic prostate cancer managed with "watch and wait" strategy
Females only: Pregnant or breastfeeding
Inability to swallow and retain oral medication
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
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
- Dose limiting toxicity (DLT)During the first 2 cycles of protocol therapy (cycle length = 21 days)
All non-hematologic toxicities will be coded and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Hematologic toxicities will be assessed per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018. Cytokine release syndrome (CRS)/immune effector cell associated neurotoxicity syndrome (ICANS) will be coded by American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS/ICANS. DLTs will be summarized by type, severity, and attribution. DLTs will be individually described.
- Incidence of adverse events (AEs)Up to 28 days after last dose of study treatment
All non-hematologic toxicities will be coded and graded according to the NCI CTCAE v 5.0. Hematologic toxicities will be assessed per IWCLL 2018. CRS/ICANS will be coded by ASTCT grading for CRS/ICANS. AEs will be summarized by type, severity, and attribution.