RECRUITING

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

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 2 Study of Odronextamab in Relapsed/ Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Before and After Chimeric Antigen Receptor (CAR) T-Cell Therapy

Quick Facts

Study Start:2025-08-07

Study Completion:2029-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06854159

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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) * Irrespective of the presence of lymphoma infiltration of the liver, a participant with an AST \> 3 x ULN and/or ALT \> 3 x ULN concurrent with a total bilirubin \> 1.5 x ULN will be excluded * Creatinine clearance ≥ 30 mL/min/1.73 m\^2 by Cockcroft-Gault * Hemoglobin ≥ 8 g/dL or ≥ 7 g/dL for patients with bone marrow involvement * NOTE: Growth factor or transfusion support is allowed as per treating physician's discretion * Alkaline phosphatase 2.5 x ULN (≤ 5 x ULN for patients with documented liver involvement or bone metastases) * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN * NOTE: This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose * Cardiac ejection fraction \> 50% by echocardiogram or multigated acquisition (MUGA) scan * Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance by Cockcroft Gault formula ≥ 50 mL/min * For participants infected with HIV: * No history of AIDS-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm\^3 prior to beginning combination antiretroviral therapy (ART) * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to ≥ 250/mm\^3 * At the time of study entry, the HIV viral load must be undetectable by standard laboratory assay * During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV+ status * No history of non-adherence to ART and willing to adhere to ART while on study * Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed * People with hepatitis B or C on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible * People of child-bearing potential and reproductive partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months (180 days) after the last dose of study agent. Egg and sperm donation is prohibited during the study and for 6 months after the last dose of study agent * Willing and able to provide informed consent	* 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) * Standard radiotherapy within 14 days of first administration of study treatment * Prior organ transplantation * Administration of live vaccination within 28 days of study first dose * Use of any other experimental drug or therapy within 28 days (or 5 half-lives of the drug, whichever is shorter) of initiating study treatment * Concurrent use of other anti-cancer treatments except for certain therapeutics (e.g., maintenance hormonal-based therapy) per the treating physician's discretion * Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) * Pregnancy or lactation * Known allergic reactions or hypersensitivity to allopurinol, rasburicase, or compounds of similar chemical or biological components

Inclusion Criteria

Exclusion Criteria

* 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)
* Irrespective of the presence of lymphoma infiltration of the liver, a participant with an AST \> 3 x ULN and/or ALT \> 3 x ULN concurrent with a total bilirubin \> 1.5 x ULN will be excluded
* Creatinine clearance ≥ 30 mL/min/1.73 m\^2 by Cockcroft-Gault
* Hemoglobin ≥ 8 g/dL or ≥ 7 g/dL for patients with bone marrow involvement
* NOTE: Growth factor or transfusion support is allowed as per treating physician's discretion
* Alkaline phosphatase 2.5 x ULN (≤ 5 x ULN for patients with documented liver involvement or bone metastases)
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
* NOTE: This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose
* Cardiac ejection fraction \> 50% by echocardiogram or multigated acquisition (MUGA) scan
* Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance by Cockcroft Gault formula ≥ 50 mL/min
* For participants infected with HIV:
* No history of AIDS-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm\^3 prior to beginning combination antiretroviral therapy (ART)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to ≥ 250/mm\^3
* At the time of study entry, the HIV viral load must be undetectable by standard laboratory assay
* During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV+ status
* No history of non-adherence to ART and willing to adhere to ART while on study
* Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed
* People with hepatitis B or C on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible
* People of child-bearing potential and reproductive partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months (180 days) after the last dose of study agent. Egg and sperm donation is prohibited during the study and for 6 months after the last dose of study agent
* Willing and able to provide informed consent

* 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)
* Standard radiotherapy within 14 days of first administration of study treatment
* Prior organ transplantation
* Administration of live vaccination within 28 days of study first dose
* Use of any other experimental drug or therapy within 28 days (or 5 half-lives of the drug, whichever is shorter) of initiating study treatment
* Concurrent use of other anti-cancer treatments except for certain therapeutics (e.g., maintenance hormonal-based therapy) per the treating physician's discretion
* Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
* Pregnancy or lactation
* Known allergic reactions or hypersensitivity to allopurinol, rasburicase, or compounds of similar chemical or biological components

Contacts and Locations

Principal Investigator

Joseph M Tuscano

PRINCIPAL_INVESTIGATOR

University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

Collaborators and Investigators

Sponsor: University of California, Davis

Joseph M Tuscano, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-07

Study Completion Date2029-04

Study Record Updates

Study Start Date2025-08-07

Study Completion Date2029-04

Terms related to this study

Additional Relevant MeSH Terms

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