O’Brien R50 Research Specialist (Clinician Scientist) Project Summary/Abstract While many children with acute lymphoblastic leukemia (ALL) are cured with frontline therapy, for those who experience relapse, outcomes remain suboptimal. I am a pediatric oncologist specializing in the care of children, adolescents, and young adults with high-risk and relapsed leukemias with a research focus on clinical trials of novel therapies in both the relapsed and frontline settings. My clinical research efforts are conducted primarily through collaborative studies that are made possible by the National Clinical Trials Network (NCTN), specifically the Children’s Oncology Group (COG), where I am currently spearheading the pediatric development of inotuzumab ozogamicin as the Study Chair or Co-Chair of two large COG ALL trials, am a member of the COG Relapsed ALL Steering Committee, and am the Vice-Chair of the APAL2020SC screening trial for molecular characterization of relapsed leukemias with allocation to targeted clinical trials. Beginning in October 2023, I will serve as the COG ALL Committee Vice-Chair for Precision Medicine/Relapse. My research interests include improving our understanding of the toxicities of novel agents, identifying patients at highest risk for side effects and devising optimal management approaches for diverse patient populations based on clinical features, leukemia biology, and pharmacogenomic factors. In this era of multiple novel agents with activity in ALL including bidirectional antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapy, and targeted agents including kinase inhibitors and modulators of apoptosis, the development of well-designed and efficient clinical trials to determine how to incorporate these agents for different populations will be critical to moving the field of ALL therapy forward over the next decade. Locally, I serve as the Medical Director of the Leukemia/Lymphoma Program at Cincinnati Children’s Hospital Medical Center with a focus on pilot studies of novel agents that, if promising, can be further developed in COG. The long-term objective of this application is to support the time needed over the next five years to complete the active COG inotuzumab ozogamicin trials (NCT03959085, NCT02981626) and to lead development of the COG portfolio of trials for both newly diagnosed and relapsed ALL.