B-Cell Non-Hodgkin Lymphoma-Recurrent Clinical Trial
Official title:
Early, Risk Adapted CC-99282 + Rituximab Post CAR T-Cell Therapy for Non-Hodgkin's Lymphoma
This phase I trial tests the safety, side effects and best dose of CC-99282 with rituximab for the treatment of patients who have received chimeric antigen receptor (CAR) T cell therapy for non-Hodgkins lymphoma and in whom have had a sub-optimal response early on to CAR T-cell therapy. Immunotherapy with CC-99282 may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. 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 CC-99282 with rituximab may be a safe and effective treatment option for patients who have received CAR-T cell therapy for relapsed or refractory non-Hodgkin's lymphoma.
PRIMARY OBJECTIVE: I. To determine the safety profile and maximum tolerated dose (MTD) of early, risk adapted golcadomide (CC-99282)/rituximab for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) post-commercial CD19.CAR-T infusion. SECONDARY OBJECTIVES: I. To perform a preliminary efficacy analysis of CC-99282 and rituxan early post CD19.CAR-T defined as the progression free survival (PFS) rate at day+150 post initiation of CC-99282. II. To describe disease response rates in patients with active disease who are treated with CC-99282 + rituximab. III. To estimate PFS in subjects treated with CC-99282 + rituximab. IV. To estimate the overall survival (OS) in subjects treated with CC-99282 + rituximab. EXPLORATORY OBJECTIVES: I. To describe CD19.CAR-T cell expansion and persistence following treatment with CC-99282/rituximab. II. To evaluate CC-99282/rituximab's effect on CAR T-cells and other immune cell subsets composition and how this effects clinical outcomes. III. To evaluate CC-99282/rituximab's effect on CAR T-cell and other immune cell subset function and how this effects clinical outcomes. IV. To evaluate CC-99282/rituximab's effect on the tumor microenvironment (TME) and how this effects clinical outcomes. OUTLINE: This is a dose-escalation study of CC-99282 in combination with fixed-dose rituximab. Patients receive rituximab intravenously (IV) on day 1 of each cycle and CC-99282 orally (PO) once daily (QD) on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 24 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial. Patients may undergo biopsy at screening. After completion of study treatment, patients are followed up at days 240, 365, 455, 547, 637, and 730. ;