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

Purpose: 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.

Experimental Design: 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).

Results: 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).

Conclusions: 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.