This phase I/II study evaluated @entity2213 as a @entity2467 inhibitor combined with @entity2664 , @entity2879 and @entity2592 therapy for @entity1 with primary refractory or relapsed @entity2467 + @entity3052 ( @entity3052 ). @entity2213 was escalated through three dose levels in successive six @entity1 cohorts. The combination was well tolerated up to 400   mg/day @entity2213 . Of 21 @entity1 treated at this dose, 13 (62%) achieved complete response (CR), 7 (33%) were non-responders and one died during induction. The CR rate was 80% in @entity1 with standard-risk karyotype versus 33% in @entity1 with adverse karyotype. The CR rate for primary non-responders was 6/14 (43%) versus 7/7 (100%) for relapsed @entity1 . @entity3052 blasts from peripheral blood were assayed for phosphorylated @entity584 (pAkt) and phosphorylated @entity3963 (pERK) by flow cytometry before to and after @entity2213 dosing. Of eight @entity1 achieving CR with reinduction, seven demonstrated marked (>= 60%) pAkt inhibition with @entity2213 therapy. In contrast, all the six non-responders to reinduction demonstrated <60% pAkt inhibition (P=0.005). There was no correlation between pERK inhibition and response to therapy. These results indicate that lack of pAkt inhibition in vivo is associated with resistance to reinduction therapy using this regimen. Further studies using agents that are able to inhibit @entity584 more effectively are warranted.

A phase I/II study of @entity2213 plus reinduction therapy for @entity2467 -positive relapsed/refractory @entity3052 : inhibition of XXXX activation correlates with complete response.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity2664 :: ('MESH:D008942', 'Chemical') :: ['mitoxantrone'] @entity3963 :: ('5594', 'Gene') :: ['ERK'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity2592 :: ('MESH:D003561', 'Chemical') :: ['cytarabine'] @entity2879 :: ('MESH:D005047', 'Chemical') :: ['etoposide'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia', 'AML'] @entity2467 :: ('3815', 'Gene') :: ['c-kit'] @entity2213 :: ('MESH:C097613', 'Chemical') :: ['imatinib', 'Imatinib']
@entity584 :: (207,Gene) :: ['Akt']
