IV-PEG asparaginase compared to IM-EC in children with acute lymphoblastic leukemiaPEG-asparaginase shows lower toxicity in childhood leukemia trial

Status: COMPLETED | Phase: PHASE3 Condition(s): Drug/Agent Toxicity by Tissue/Organ, Leukemia Intervention(s): asparaginase (DRUG), cyclophosphamide (DRUG), cytarabine (DRUG), dexamethasone (DRUG), dexrazoxane hydrochloride (DRUG) RATIONALE: L-asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia, but is also associated with notable side-effects, including hypersensitivity, pancreatitis, and thrombosis. We have previously reported that patients with acute lymphoblastic leukemia in whom asparaginase treatment was discontinued because of intolerable side-effects had survival outcomes that were inferior to those who received all or nearly all of their intended doses. Two bacterial sources of asparaginase exist: Escherichia coli (E coli) and Erwinia chrysanthemia (Erwinia). Generally, the E coli-derived enzyme has been used as front-line therapy and the Erwinia-derived preparation has been reserved for patients who develop hypersensitivity reactions. Pegylated E coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than native E coli L-asparaginase, and has been used as the initial asparaginase preparation in some pediatric acute lymphoblastic leukemia treatment regimens. PURPOSE: Although the pharmacokinetics of each of these asparaginase preparations: intravenous PEG-asparaginase (IV-PEG) and intramuscular native E coli L-asparaginase (IM-EC) have been well characterized, their relative efficacy and toxicity have not been studied extensively. Detailed: RISK CLASSIFICATION: Patients received were classified into initial risk groups defined as: High Risk (HR) High risk patients had any of the following features: age 10 years and older, a white blood cell count of 50 000 cells per μL or higher, initial spinal fluid sample with the presence of lymphoblasts and five or more white blood cells per high power field \[Central Nervous System (CNS)-3\], or a T-cell phenotype. Standard Risk (SR) All other patients were classified as standard risk. Patients who achieved complete remission (CR) after 32 days of induction therapy defined as a marrow specimen with less than 5% marrow blasts and evidence of normal haemopoiesis, absence of extramedullary disease, and recovery of peripheral blood counts were randomly assigned in a 1:1 ratio to receive Primary Outcome(s): Asparaginase-Related Toxicity Rate Enrollment: 800 (ACTUAL) Lead Sponsor: Dana-Farber Cancer Institute Start: 2005-04 | Primary Completion: 2014-08 Results posted: 2017-06-14