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New treatment option for Recurrent Transformed Chronic Lymphocytic Leukemia
Official title Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation
ClinicalTrials.gov ID: NCT06735664
What this study is testing
What is Odronextamab?
Odronextamab is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for recurrent transformed chronic lymphocytic leukemia.
Also referred to as Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody REGN1979, REGN1979.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
- Time commitment: about 3 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
You likely can't join if
- 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...
- 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
See the full eligibility criteria
Who can join
- 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...
- 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...
- Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition...
- 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...
What rules you out
- 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...
- 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...
- 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...
- 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...
- 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...
- 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 how well it works assessment...
- 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)
The study team makes the final eligibility decision.
Where it's taking place
- Duarte, California, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 3 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Duarte, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.