Odronextamab for the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma Before and After Chimeric Antigen Receptor T-cell Therapy

NCT06854159 | Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: UCDCC310NCI-2025-00900P30CA093373UCHMC2329R1979-HM-2494
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well odronextamab works before and after standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapy in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR-T cell therapy is the SOC treatment most patients receive when other treatments have failed. CAR-T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Odronextamab is a monoclonal antibody that is called bispecific, as it individually targets 2 cell proteins, CD20 and CD3. Proteins are part of each cell in the body, which work together like little machines for the cell to function. CD20 is a protein that is found on the surface of both normal B-cells and B-cells that make up certain cancers, like DLBCL. CD3 is a protein that is found on the surface of T cells. T-cells and normal B-cells are types of white blood cells in the body and are a part of the immune system that fights infections. Odronextamab is designed to help T-cells find and kill the B-cells including the cancer cells in DLBCL. Giving odronextamab before and after CAR T-cell therapy may improve response in patients with relapsed or refractory DLBCL.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  Will be assessed by Lugano 2014. Will calculate the uniformly minimum variance unbiased estimator, p-value, and confidence intervals for CRR. The calculation will be performed using R clinfun package.

  From first dose through completion of 5 cycles (cycle length = 21 days for cycles 1-4 and 14 days for cycle 5) of odronextamab and chimeric antigen receptor (CAR) T cell infusion

Secondary Outcomes (4)

• Number of participants experiencing treatment-related adverse events (AEs)

  From first dose through 30 days post last odronextamab dose

• Number of participants with progression-free survival

  From the date of first odronextamab dose until the first occurrence of disease progression, or death from any cause, whichever occurs earlier, assessed up to 2 years

• Objective response rate

  From first dose to up to 2 years post last odronextamab dose

• Number of minimal residual disease (MRD) negative targets detected

  After cycle 4 (pre-CAR T-cell therapy) and 2 cycles post CAR T cell infusion (cycle length = 21 days for cycles 1-4 and 14 days for subsequent cycles)

Study Arms (1)

Treatment (odronextamab, CAR T-cell therapy)

EXPERIMENTAL

Patients receive odronextamab IV over 1-4 hours on days 1, 2, 8, 9, 15, and 16 of cycle 1, on days 1, 8, and 15 of cycles 2-4 then on days 1 and 15 of subsequent cycles until achievement of durable CR. Cycles repeat every 21 days in the absence of durable CR, disease progression, or unacceptable toxicity. Patients with durable CR for ≥ 9 months may then receive odronextamab IV over 1-4 hours on day 1 of each subsequent cycle. These cycles repeat every 28 days for up to a total of 2 years in the absence of disease progression or unacceptable toxicity. Patients receive SOC CAR T-cell therapy if disease assessment shows less than a CR after cycle 4, or after cycle 5 if disease assessment shows PD any time after cycle 5.

Biological: Chimeric Antigen Receptor T-Cell Therapy; Biological: Odronextamab

Interventions

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Receive CAR T-cell therapy

Also known as: CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell Infusion

Treatment (odronextamab, CAR T-cell therapy)

Odronextamab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody REGN1979, REGN1979, WHO 11035

Treatment (odronextamab, CAR T-cell therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 at the time of consent
• Patients must have histologically or cytologically confirmed relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL); transformed follicular lymphoma patients are eligible
• Patients must have failed at least 2 prior therapies
• Life expectancy ≥ 3 months
• Candidate for any Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cell therapy as per institutional guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)
• Leukocytes ≥ 2,500/µL
• Absolute neutrophil count ≥ 1,000/µL or \> 500/µL for patients with bone marrow involvement
• A participant may not have received granulocyte colony stimulating factor within 2 days prior to first dose of odronextamab in order to meet the absolute neutrophil count (ANC) eligibility criterion
• Platelets ≥ 50,000/µL or ≥ 25,000/µL for patients with bone marrow involvement
• A patient may not have received platelet transfusion therapy within 2 days prior to first dose of odronextamab in order to meet the platelet eligibility criterion
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• NOTE: patients with known Gilbert disease who have serum bilirubin level ≤ 3 x institutional ULN may be enrolled. Patients with known Gilbert syndrome will be excluded if the total bilirubin value is \> 4 x ULN
• Irrespective of the presence of lymphoma infiltration of the liver, a participant with an aspartate aminotransferase (AST) \> 3 x ULN and/or alanine aminotransferase (ALT) \> 3 x ULN concurrent with a total bilirubin \> 1.5 x ULN will be excluded
• AST(serum glutamic oxaloacetic transaminase \[SGOT\])/ALT(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (AST and/or ALT ≤ 5 x ULN for patients with liver involvement)

You may not qualify if:

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she/they were to participate in the study or confounds the ability to interpret data from the study as determined by the study principal investigator (PI) or enrolling physician
• Known involvement by primary central nervous system (CNS) lymphoma or known uncontrolled involvement by non-primary CNS non-Hodgkin lymphoma (NHL) at the time of study entry
• Known history (within last 12 months) of or current relevant CNS pathology, such as:
• Epilepsy, seizure, paresis, aphasia, apoplexy, severe brain injury, cerebellar disease, organic brain syndrome, psychosis, cerebrovascular stroke or
• Evidence for presence of inflammatory lesions and/or vasculitis on cerebral magnetic resonance imaging (MRI)
• Another active malignancy (aside from B-cell NHL) in the past 5 years, with the following exceptions: non-melanoma skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent as per treating investigator
• 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)
• Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/µL either spontaneously or on a stable antiviral regimen) are permitted.
• 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
• 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
• Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone/prednisolone or anti-inflammatory equivalent within 72 hours of start of assigned treatment
• Recent major surgery (within 4 weeks prior to the start of study treatment)

Sponsors & Collaborators

• Joseph Tuscano: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Joseph M Tuscano

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 3, 2025
• Study Start: August 7, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

US (1)