Actively Recruiting
Odronextamab for Relapsed/Refractory Large B-Cell Lymphomas Before Definitive Lymphoma-Directed Therapies
Led by University of Washington ยท Updated on 2026-05-06
27
Participants Needed
1
Research Sites
261 weeks
Total Duration
On this page
Sponsors
U
University of Washington
Lead Sponsor
R
Regeneron Pharmaceuticals
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the use of odronextamab as bridging therapy before chimeric antigen receptor T (CAR-T) cell therapy in adults with relapsed or refractory large B-cell lymphomas. Odronextamab is a bispecific antibody that targets CD3 on T-cells and CD20 on B-cells, potentially interfering with cancer cell growth. Bridging therapy given before leukapheresis aims to delay disease progression and improve the chances of successful CAR-T cell therapy in these patients. Patients receive odronextamab intravenously with a step-up dosing schedule in cycle 1, followed by weekly doses in cycles 2 to 4, and then every other week for up to 12 months total. After 2 cycles, leukapheresis is performed followed by lymphodepletion and CAR-T infusion according to standard care. If leukapheresis is delayed, up to 12 additional weeks of odronextamab may be given. Patients achieving complete response after 2 cycles may opt out of leukapheresis and CAR-T infusion and continue odronextamab if no disease progression or unacceptable toxicity occurs. During the study, participants undergo PET/CT scans, blood and oral or rectal swab sample collection, tissue biopsy, and possibly lumbar puncture and bone marrow aspiration or biopsy. After treatment completion, participants are followed for toxicity monitoring until 90 days or the start of new lymphoma therapy, with total follow-up up to 5 years. The primary outcome is failure to undergo leukapheresis, with additional assessments including response rates, progression-free survival, and adverse event incidence.
CONDITIONS
Brief Title
Odronextamab for Relapsed and Refractory Large B-cell Lymphomas Before CAR-T
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and follicular lymphoma grade 3B
- At least one measurable lesion 15 mm or larger on PET, CT, or MRI within one month of screening
- Prior frontline therapy for large B-cell lymphoma has failed
- Eligible for commercial axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel per FDA label
- 18 years of age or older
- Able to understand and provide written informed consent
- Prior treatment with an anti-CD20 antibody therapy
- Eastern Cooperative Oncology Group performance status of 0-1 (status 2 allowed if due to lymphoma)
- Creatinine clearance 45 mL/min or higher
- Total bilirubin 1.5 times the upper limit of normal or less (except Gilbert's syndrome)
- Aspartate aminotransferase and alanine aminotransferase 2.5 times the upper limit of normal or less
- Adequate pulmonary function with oxygen saturation 92% or higher on room air
- Adequate cardiac function with left ventricular ejection fraction 50% or higher and no pericardial effusion
- Platelet count 75 x 10^9/L or higher (25 x 10^9/L or higher if bone marrow involvement or splenic sequestration)
- Hemoglobin 9 g/dL or higher (7 g/dL or higher if bone marrow involvement or splenic sequestration)
- Absolute neutrophil count 1 x 10^9/L or higher (0.5 x 10^9/L or higher if bone marrow involvement or splenic sequestration)
- Negative serum pregnancy test within 2 days of starting odronextamab for women of childbearing potential
- Willingness to use highly effective contraception from recruitment to 6 months after CAR-T infusion
- No egg or sperm donation until at least 6 months after last odronextamab dose
You will not qualify if you...
- Presence of malignant cells in cerebrospinal fluid or brain metastases, or history of these within 3 months
- History of seizure disorder, cerebrovascular disease, dementia, cerebellar disease, or autoimmune disease with central nervous system involvement
- Recent standard chemotherapy within 5 times the half-life or 2 weeks prior to study drug
- Standard radiotherapy within 2 weeks prior to study drug
- Prior anti-CD20 x anti-CD3 bispecific therapy unless disease responded and no progression within 12 months
- Allogeneic stem cell transplant or prior CAR-T cell therapy
- Receiving other investigational agents
- Recent treatment with rituximab, alemtuzumab, or other biologic agents within 2 weeks
- Immunosuppressive therapy within 2 weeks
- Investigational non-biologic agent treatment within 2 weeks
- Allergic reactions to similar compounds or tetracycline antibiotics
- Active malignancy requiring systemic treatment unless approved by investigator
- Active uncontrolled infections
- Significant cardiovascular or pulmonary disease affecting study participation
- Ongoing systemic corticosteroid treatment over 10 mg/day prednisone equivalent except for non-tumor uses
- HIV infection without viral suppression or low CD4 count
- Chronic hepatitis B or C infection unless controlled
- Known hypersensitivity to allopurinol and rasburicase
- Pregnant or breastfeeding women
- Live vaccination within 28 days prior to study drug start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months
Participants receive odronextamab intravenously on a step-up dosing schedule during the first cycle, weekly dosing during cycles 2 to 4, and then every other week for up to 12 months. After 2 cycles, participants may undergo leukapheresis followed by lymphodepletion and CAR-T infusion per standard of care. Participants who achieve complete response after 2 cycles may opt out of leukapheresis and CAR-T infusion and continue odronextamab treatment if disease does not progress or unacceptable toxicity occurs.
Multiple visits each cycle: days 1, 2, 8, 9, 15, and 16 of cycle 1; days 1, 8, and 15 of cycles 2-4; then every other week for remaining cycles
Duration - Up to 5 years
After completing study treatment, participants are followed for toxicity checks until 90 days or the start of the next lymphoma-directed therapy. Total follow-up duration can be up to 5 years to monitor long-term outcomes and safety.
Periodic visits for up to 5 years after treatment
Trial Site Locations
Total: 1 location
1
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Actively Recruiting
Research Team
M
Mengyang Di, MD, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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