CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML.

Abstract

TPS199 Background: The prognosis for patients (pts) with AML is variable and dependent on the presence of mutations in the FLT3 tyrosine kinase. Internal tandem duplications (ITD) in the juxtamembrane region and mutations in the tyrosine kinase domain (TKD) cause constitutive activation of FLT3 and lead to blast proliferation. Preclinical data suggested that chemotherapy combined with FLT3 inhibitors, including midostaurin, could synergistically kill leukemic cells. In a phase Ib study of midostaurin 50 mg BID with chemotherapy, 92% of FLT3mut pts and 74% of FLT3WT pts achieved a CR. OS of FLT3mut pts was similar to FLT3WT pts (Stone, ASH 2009), supporting the rationale for the ongoing study (NCT00651261). Methods: This is a CALGB-led intergroup, international, randomized, double-blind, PBO controlled trial of adult (age 18-59), untreated FLT3mut AML pts treated with induction chemotherapy and 4 post-remission cycles of high dose ara-C with PBO or midostaurin 50 mg BID on d8-21 of each cycle, followed by ...