Phase I Study of Oral Clofarabine Consolidation in Adults Aged 60 and Older With Acute Myeloid Leukemia
The prognosis of acute myeloid leukemia (AML) in patients 60 and older is dismal with
traditional therapy. Several factors contribute to the poor prognosis of older individuals,
including the increased incidence of the multidrug resistance efflux pump, comorbidities and
unfavorable cytogenetics. The recently reported AML-13 and ALFA trials suggest that less
intense consolidation in this population is at least equivalent to more intense, induction
Clofarabine is a next generation nucleoside analogue that was designed to optimize the
favorable attributes of fludarabine and cladribine, while minimizing toxicity. The
intravenous formulation has shown considerable activity in older patients with AML who have
been considered either unfit for or unlikely to benefit from conventional therapy.
Additionally, clofarabine has an oral formulation that patients may find more acceptable for
consolidation therapy rather than multiple courses of intravenous medications, administered
over several days.
This study is designed as a traditional 3x3 phase I trial with the intention of defining the
maximum tolerated dose of oral clofarabine consolidation for older patients with AML in
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and dose limiting toxicity
Camille N. Abboud, M.D.
United States: Food and Drug Administration
08-0853 / 201108049
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