Phase 2, Multicenter Studies of Pegaspargase in Pediatric Patients With Previously Untreated Acute Lymphoblastic Leukemia in Russia: Comparative Study of Liquid and Lyophilized Pegaspargase and Roll-Over Study of Lyophilized Formulation.

Pegaspargase, a well-established pediatric acute lymphoblastic leukemia (ALL) therapy, is available as a liquid formulation, and a lyophilized formulation with an improved shelf life. The pharmacokinetics and safety of lyophilized and liquid pegaspargase were assessed in pediatric patients with ALL in Russia. In Study 1, patients were randomly assigned (1:1) to receive 1 intravenous injection of lyophilized or liquid pegaspargase; patients who benefited from pegaspargase continued into Study 2 and received lyophilized pegaspargase every 2 weeks for 9 infusions. Of the 89 patients in Study 1, 74 continued into Study 2. In Study 1, maximum observed plasma asparaginase activity and area under the PAA-time curve were similar between groups. Geometric mean ratios were 93.5% (90% confidence interval [CI]: 82.9, 105.5) and 102.8% (90% CI: 91.4, 115.6), respectively; therefore, the 90% CIs were completely contained within the predefined acceptance interval of 80% to 125%. Pegaspargase-related adverse events occurred in 88.4% and 91.1% in the lyophilized and liquid groups, respectively, in Study 1. The safety profile of lyophilized pegaspargase after repeated infusion in Study 2 was consistent with the known safety profile of pegaspargase. Pharmacokinetic exposure does not depend on pegaspargase formulation. These studies support the use of lyophilized pegaspargase.