An open-label, multicenter study of polyethylene glycol-L-asparaginase for the treatment of acute lymphoblastic leukemia

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Abstract
Background. L-asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L-asparaginase is a foreign protein, the potential exists for severe, dose-limiting hypersensitivity reactions. To reduce this toxicity, L-asparaginase has been linked with polyethylene glycol (PEG). Methods. Patients with ALL in relapse were entered in a Phase II, open-label clinical trial (ASP-201A) to evaluate the toxicity and efficacy of PEG-L-asparaginase. PEG-L-asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half-life relative to native enzyme. PEG-L-asparaginase (2000 IU/m2 every 2 weeks) was used as single-agent induction therapy during an initial 14-day investigational window. Thereafter, the regimen consisted of PEG-L-asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L-asparaginase; one of these patients was hypersensitive to L-asparaginase at enrollment. Results. During the 14-day investigational window with PEG-L-asparaginase monotherapy, 22% of patients examined achieved a complete or partial remission. By completion, of the 35-day induction period, 78% (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L-asparaginase. Conclusions. As administered in this study, PEG-L-asparaginase can be given safely with a spectrum of toxicity similar to that of native L-asparaginase. Single-agent activity was documented in patients with ALL in bone marrow relapse. Cancer 1995;75:1176–81.