A phase I-II study to determine the maximum tolerated infusion rate of rituximab with special emphasis on monitoring the effect of rituximab on cardiac function.

Abstract

This phase I infusion rate escalation trial was undertaken to evaluate the maximum applicable infusion rate for rituximab without steroid premedication in patients having received one previous rituximab infusion. Cohorts of at least three patients were assigned to rituximab with or without concomitant chemotherapy. The initial infusion rate was 200 mg/h in the first cohort, and was increased by 100 mg/h in each subsequent cohort to a maximum of 700 mg/h. In each patient the infusion rate was increased by 100 mg/h every 30 minutes to the total dose (375 mg/m2). In the first six cohorts (21 patients), two well-tolerated rituximab administrations were required; in the 7th cohort (11 patients) one previously well-tolerated rituximab infusion was required. Patients did not receive steroid premedication and were monitored with electrocardiograms (ECG), echocardiograms, Holter ECGs, troponin, and brain natriuretic peptide (BNP). Thirty-two patients were included and 128 cycles were done, 85 at a rate of 700 mg/h. Patients tolerated infusion rates without major side effects. There were no new clinically relevant ECG alterations. Troponin (< 0.1 ng/L) and mean cardiac ejection fraction (65%) remained in the reference range; BNP baseline level increased significantly 24 hours after rituximab administration (from 30.4 to 64.1 ng/L; P < 0.0001). Rituximab can be administered safely at 700 mg/h without steroid premedication in patients having received at least one rituximab dose in the previous 3 months.