ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES: I. To evaluate safety and tolerability, and to determine the recommended phase II dose (RP2D) and schedule of CD47 antagonist ALX148 (ALX148) in combination with rituximab and lenalidomide in patients with relapsed or refractory B-non-Hodgkin lymphomas (NHLs) (both indolent and aggressive histology) in phase I. II. To evaluate the efficacy of the combination of ALX148, rituximab and lenalidomide at the RP2D (determined in phase I) in patients with previously untreated and high tumor burden indolent B-NHL in phase II. SECONDARY OBJECTIVE: I. To evaluate other toxicity and efficacy measures of the combination of ALX148, rituximab and lenalidomide. EXPLORATORY OBJECTIVE: I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance. OUTLINE: This is a phase I, dose-escalation study of ALX148 followed by a phase II study. Patients receive ALX148 intravenously (IV) over 1 hour once on days 1, 8, 15 and 22, or days 1 and 15, or day 1 depending on dose level. Patients also receive rituximab IV over 4-6 hours on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2-6, and lenalidomide orally (PO) daily once (QD) on days 1-21 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 7 and 30 days, then up to 3 years.