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
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.
• 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