Chapter

Design of Early-Phase Trials

DOI: 10.1007/978-1-4419-8459-3_4

ABSTRACT The development of new agents for children with relapsed ALL represents a unique challenge. Given that attainment of remission
is a prerequisite for cure, and given that regimens composed of standard agent combinations remain effective in achieving
morphologic remission for many patients following relapse, treating physicians and investigators faced with a child in relapse
of ALL are understandably reluctant to turn to a new agent or combination of new agents with no proven efficacy. The poor
accrual to single-agent phase I studies of new agents in childhood ALL reflects this reluctance. Thus, the successful evaluation
of new agents against childhood ALL requires novel trial designs that take into account the desire of treating physicians
to utilize standard agents while simultaneously allowing for the demonstration of activity and the evaluation of toxicity
of the new drug(s) under study. Clinical trial designs that simultaneously allow for the attainment of both objectives have
been developed and are now in use in the Children’s Oncology Group.

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