Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy

PRIMARY OBJECTIVE: I. Evaluate efficacy as measured by the disease control rate (complete metabolic response \[CMR\], partial metabolic response \[PMR\], and no metabolic response \[NMR\]) by Lugano 2014 positron emission tomography (PET)-computed tomography (CT) based assessment after 2 cycles of therapy. SECONDARY OBJECTIVES: I. To further evaluate clinical efficacy as measured by overall response rate (ORR), complete response (CMR) rate, disease control rate by Lugano PET-CT based criteria. II. To evaluate the safety and tolerability of golcadomide + rituximab combination therapy as measured by the incidence and severity of treatment related adverse events (TRAE). III. To evaluate efficacy as a bridging therapy as measured by the number of patients proceeding to CAR-T and response to CAR-T. IV. To evaluate duration of response, progression-free survival, and overall survival. EXPLORATORY OBJECTIVES: I. Improvement of symptoms (compressive, pain, B symptoms \[fever, night sweats, weight loss\]) associated with the disease as determined by the investigator. II. To evaluate the diversity of CAR-T products received in patients proceeding to CAR-T. OUTLINE: ELIGIBLE FOR CAR-T: Patients receive golcadomide orally (PO) once daily (QD) on days 1-14 of each cycle and rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Cycles repeat every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. After 1 cycle, patients undergo leukapheresis and receive an additional cycle of golcadomide and rituximab (bridging therapy) prior to undergoing standard of care CAR-T therapy. Patients may also receive optional bridging therapy with golcadomide and rituximab per physician choice (1-2 cycles) prior to undergoing standard of care CAR-T therapy. INELIGIBLE FOR CAR-T: Patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Patients eligible for CAR-T after 2 cycles receive additional bridging therapy and undergo leukapheresis. Patients ineligible for CAR-T after 2 cycles, receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles (cycles 3-5) in the absence of disease progression or unacceptable toxicity. Patients eligible for CAR-T after 5 cycles receive additional bridging therapy and undergo leukapheresis. Patients ineligible for CAR-T after 5 cycles, receive golcadomide PO QD on days 1-14 of each cycle. Cycles repeat every 28 days for 6 cycles (cycles 6-12) in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT or CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy as clinically indicated. CAR-T ineligible patients are followed up at 28 days and then every 3 months for 1 year from end of treatment until progression of disease, death, or initiation of new systemic anticancer therapies. CAR-T eligible patients are followed up at 30 and 90 days post CAR-T therapy, 180 days post CAR-T therapy, and then every 6 months until progression or subsequent treatment for up to 2 years