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Improvements in survival for children with cancer residing in high-income countries have been driven by the results of successive clinical trials conducted by large multi-center cooperative groups. These survival improvements have not translated to low- and middle-income countries (LMICs), where the majority of children with cancer live. The emergence of LMIC cooperative trial groups will help define the optimal treatment for their populations and improve survival. In this manuscript, we outline recent trends in the results of studies conducted by the Children’s Oncology Group (COG) Acute Lymphoblastic Leukemia (ALL) Committee as an example of what can be accomplished through collaborative multi-institutional trials. We also discuss what implications the COG ALL experience holds for trial groups in LMIC settings.