A Phase II Trial of Sirolimus with Standard Induction Chemotherapy in Patients with De Novo Acute Myeloid Leukemia

Background: The initial treatment of FLT3 wild type acute myeloid leukemia (AML) has not significantly changed since induction therapy with Ara-C and anthracyclines was first developed. Preclinical data suggests constitutive activation of the AKT3/mammalian target of rapamycin (mTOR) pathway may play a role in pathogenesis of this disease in a subset of AML patients. Previous data from our group has shown that the presence of phosphorylated ribosomal S6 (pS6) in AML blasts as detected by flow cytometry may predict response to the combination of sirolimus and induction chemotherapy. Here we report the clinical and pharmacodynamics results of a phase II study of the combination of these drugs.