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.
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
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
Single group
Biopsy
Procedure/SurgeryUndergo ultrasound guided biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Biopsy
Procedure/SurgeryUndergo optional bone marrow biopsy
Computed Tomography
Procedure/SurgeryUndergo CT
Echocardiography
Procedure/SurgeryUndergo ECHO
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Odronextamab
Biological/VaccineGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Ultrasound Imaging
Procedure/SurgeryUndergo ultrasound guided biopsy
Zanubrutinib
DrugGiven PO
Dose limiting toxicity (DLT)
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)
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.
Overall response rate (ORR)
ORR will be defined as the proportion of response evaluable patients who achieve a best response of complete response (CR) or partial response (PR) according to Lugano 2014 guidelines on study before any documented disease progression or any subsequent non-Hodgkin lymphoma (NHL) treatment. ORR will be estimated by the binary proportion, along with the 95% exact binomial confidence intervals (CIs).
CR rate
Will be defined as the proportion of response evaluable patients who achieve a best response of complete response according to Lugano 2014 guidelines on study before any documented disease progression or any subsequent NHL treatment. CR rate will be estimated by the binary proportion, along with the 95% exact binomial CIs.
Duration of response (DOR)
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% CI will be constructed based on log-log transformation. Median DOR will be estimated when available.
Progression-free survival (PFS)
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% CI will be constructed based on log-log transformation. Median PFS will be estimated when available.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
