Phase 2 Study of Golcadomide With Rituximab as a Bridging Therapy Prior to CAR-T for Patients With Relapsed or Primary Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (NHL)
This phase II trial tests the effectiveness of golcadomide and rituximab as bridging treatment before chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Patients that are able to receive CAR T-cell therapy have a potential for cure, however, many will not be qualified to receive therapy due to relapse. Bridging therapy is therapy intended to transition a patient from one therapy or medication to another or maintain their health or status until they are a candidate for a therapy or have decided on a therapy. Golcadomide may help block the formation, growth or spread of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving golcadomide and rituximab as bridging therapy before CAR T-cell therapy may kill more tumor cells and may improve the chance of proceeding to CAR T-cell therapy in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.
• Age ≥ 18 years
• Confirmed pathology diagnosis according to 2016 World Health Organization (WHO) classification including patients with diseases listed below with relapsed, progressive and/or refractory disease (Cheson et al. 2014) following treatment with one or two prior lines of standard therapy, no more than two lines of therapy are permitted:
‣ Diffuse large B-cell lymphoma not otherwise specified (NOS) including:
• Transformed lymphoma
∙ Germinal center B-cell type
∙ Activated B-cell type
⁃ High-grade B-cell lymphoma (HGBCL), NOS
⁃ High grade B-cell lymphoma with MYC and BCL2 translocation
⁃ Primary mediastinal (thymic) large B-cell lymphoma
⁃ Grade 3B follicular lymphoma
⁃ T-cell/histiocyte-rich large B-cell lymphoma
⁃ Large B-cell lymphoma with IRF4 rearrangement
⁃ Primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type
⁃ Epstein-Barr virus (EBV) positive DLBCL, NOS
⁃ DLBCL associated with chronic inflammation
⁃ Intravascular large B-cell lymphoma
⁃ ALK positive large B-cell lymphoma
⁃ NOTE: Richters transformation patients are excluded
• Measurable disease by PET-CT with at least one lymph node or other type of lesion that has a size \> 1.5 cm in the transverse diameter, as defined by Lugano classification
‣ NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible
• Patient is potentially eligible for CAR-T therapy as determined by treating physician
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Hemoglobin \> 7.0 g/dL (obtained ≤ 14 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1000/mcL (obtained ≤ 14 days prior to registration); growth factor support allowed at physician discretion
• Platelet count ≥ 75,000/mcL (obtained ≤ 14 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration); if total bilirubin is \> 1.5 ULN, direct bilirubin must be normal
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if there is evidence of parenchymal liver involvement with lymphoma) (obtained ≤ 14 days prior to registration)
• Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)
• Have 2 negative pregnancy tests as verified by the investigator prior to starting CC-99282:
‣ A negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening (between 10 to 14 days prior to cycle 1 day 1)
⁃ A negative serum or urine pregnancy test (investigator's discretion) within 24 hours prior to cycle 1 day 1 of study treatment
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Subjects must agree not to donate blood while receiving golcadomide, during dose interruptions and for ≥ 28 days following the last dose of golcadomide