The DFCI-based ALL Consortia consist of a 9-institution pediatric group and 8-institution adult group. Thepediatric consortium has conducted multi-institutional trials since 1981, whereas the adult program began in2003 with the initiation of a pilot/feasibility protocol for patients > 18-50 years old. Upon completion of theadult pilot in 2005, we propose to initiate a common adult/pediatric clinical trial for patients age 1-50 yearswith de novo ALL, as well as to enroll patients with relapsed or refractory ALL in studies testing agentsdiscovered and screened in Projects 1-5 in the context of 'investigational windows'. Our pediatric consortiumhas a well-established record of successfully conducting randomized clinical trials and performing detailedstudies of chemotherapeutic pharmacokinetics, acute morbidities, and late effects, all in the context ofextremely favorable event-free survival outcomes. Our clinical trials of newly diagnosed ALL have acommon treatment philosophy based on intensive early therapy, with research focused on minimizingtoxicities without compromising efficacy. In childhood ALL, we have demonstrated differences incytotoxicity, pharmacokinetics, toxicity and efficacy of various asparaginase preparations. We have alsomade fundamental contributions to the characterization and prevention of doxorubicin cardiotoxicity and lateoccurring neuropsychological toxicity, and have extensively evaluated quantitative measures of quality of lifeoutcomes. In addition to clinical trials in newly diagnosed patients (ages 1-50 years), we are committed todeveloping novel therapies, and continuing our investigations into the pathogenesis ofALL , as well as chemical genomic markers of disease variability and potential targets for futuretherapy. The combined pediatric and adult consortia will provide approximately 180 patients peryear, thus enabling the unique age-unrestricted clinical and laboratory studies described in Projects 1-6.
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