A Phase I Study of Covalent BTK Inhibitor Zanubrutinib in Combination With a CD3-CD20 Bispecific Antibody Odronextamab in Patients With Richter's Transformation
City of Hope Medical Center
Summary
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.
Description
PRIMARY OBJECTIVE: I. To evaluate safety and tolerability of zanubrutinib administered in combination with odronextamab in patients with Richter's transformation (RT). SECONDARY OBJECTIVE: I. To evaluate efficacy of zanubrutinib administered in combination with odronextamab, based on overall response rate (ORR), complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). EXPLORATORY OBJECTIVE: I. To characterize the T-cell population balance in patients treated with zanubrutinib and odronextamab. OUTLINE: Patients receive odronext…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 \[IHC\]…
Interventions
- ProcedureBiopsy
Undergo ultrasound guided biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Biopsy
Undergo optional bone marrow biopsy
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography
Undergo ECHO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- BiologicalOdronextamab
Location
- City of Hope Medical CenterDuarte, California