Experimental combo targets Hard-to-Treat blood cancer
NCT ID NCT06735664
First seen Jun 26, 2026 · Last updated Sep 17, 2026 · Updated 2 times
Summary
This early-phase trial is testing whether combining two drugs—zanubrutinib and odronextamab—is safe for people with Richter's transformation, a rare and aggressive form of blood cancer that arises from chronic lymphocytic leukemia. The study will enroll 23 adults and monitor for side effects and signs that the cancer shrinks or disappears. The goal is to find a tolerable dose and see if this approach is worth studying further.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- zanubrutinib and odronextamab
- What this could lead to
- If this combination proves safe and effective, it could offer a new treatment option for people with Richter's transformation, a rare and aggressive blood cancer.
- What could go wrong
- This is a very early Phase 1 trial with only 23 participants, so the main goal is safety, not effectiveness. The combination may cause serious side effects like cytokine release syndrome, and it may not work for everyone.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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About 23 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Aug 2025
- Expected to finish
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Dec 2027
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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 Criteria: * 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)
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
1 site. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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City of Hope Medical Center
RECRUITINGDuarte, California, 91010, United States
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