A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL08P1.
AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children's Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events, and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥8 total doses of I-PEG and 50% (15/30) took ≤49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2 to 5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study.
*Mayo Clinic Children's Center, Division of Pediatric Hematology Oncology, Rochester, MN †Children's Oncology Group Data Center Biostatistics, University of Florida, Gainesville, FL ‡Walter Reed National Military Medical Center, Congressionally Directed Medical Research Program, US Army Medical Research and Materiel Command, Fort Detrick, MD ††Department of Pathology, Johns Hopkins University Sidney Kimmel Cancer Center, John Hopkins University, Baltimore, MD §Division Pediatric Hematology-Oncology, Primary Children's Hospital, University of Utah, Salt Lake City, UT ∥Division of Pediatric Hematology Oncology, UCSF Medical Center-Mssion Bay, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA ¶Department of Genetics, Children's Hospital of Alabama, University of Alabama at Birmingham, Birmingham, AL #Nationwide Children's Hospital, Cytogenetics, The Ohio State University, Columbus, OH **Seattle Children's Hospital, Laboratory Medicine, Seattle, WA ‡‡Midwest Children's Cancer Center, MACC Fund Research Center, Milwaukee, WI §§Division of Pediatric Hematology Oncology, University of Rochester Medical Center, Rochester ¶¶Laura and Isaac Perlmutter Cancer Center at NYU Langone, Hassendfeld Children's Center, New York, NY ∥∥Division Pediatric Hematology-Oncology, UT Southwestern/Simmons Cancer Center, Dallas, TX †††Baylor College of Medicine, Comprehensive Cancer Center, Pediatric Oncology, Houston, TX ##Division of Oncology, Children's Hospital of Philadelphia ***Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
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Brent L
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Michael J
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Michael J
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D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D008297:Male; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase