FLT3-internal tandem duplication (ITD) mutations occur in ∼25% of NDx AML pts and are associated with shorter response duration to standard chemotherapy (SC), higher relapse rate, and lower overall survival (OS) vs non–FLT3-ITD AML. Unlike the multi-kinase inhibitor, midostaurin, Quizartinib (Q), an oral, highly potent FLT3 inhibitor, has greater selectivity for FLT3. Early clinical studies of Q combined with SC demonstrated high clinical activity in NDx FLT3-ITD AML pts. This is an ongoing phase 3 trial of Q vs placebo (P) added to induction (IND) and consolidation (CON) chemotherapy and as maintenance therapy in NDx FLT3-ITD AML pts.
Pts age 18-75 years with NDx FLT3-ITD AML and ECOG PS 0-2 are eligible. Key exclusion criteria: any prior treatment (including Q or any FLT3 inhibitors), investigational drug or device ≤30 days (d), immunotherapy ≤2 weeks, history of central nervous system leukemia, significant cardiovascular disease, QTcF >450 msec, active liver disease. Pts are randomized 1:1 to Q 40 mg (equivalent to 35.4 mg free base) or P administered with IND and CON chemotherapy (≤4 cycles high-dose cytarabine ± hematopoietic stem cell transplant) then as maintenance (Q 30 mg titrated to 60 mg, ≤12 28-d cycles; or P). In IND cycle 1, pts receive cytarabine 100 (or 200 mg/m2/d per updated protocol) for 7 d + anthracycline (daunorubicin 60 mg/m2/d or idarubicin 12 mg/m2/d) on days 1-3 (7 + 3). Starting day 8 of each IND and day 6 of each CON cycle, pts receive 14 d of daily Q 40 mg or P. On the second IND cycle, pts receive the 7 + 3 protocol, or investigators may substitute 5 + 2 d of cytarabine and anthracycline, per institutional standards, with Q or P starting on day 8 or day 6, respectively. The primary endpoint is event-free survival based on centrally adjudicated response assessment using local morphology results. Secondary endpoints are OS, CR, CRc (CR + CRi per latest IWG definitions). Enrollment is underway at 167 sites with a target enrollment of 536 pts at 275 sites worldwide.
Clinical trial identification
NCT02668653 First Received/Release date: January 22, 2016
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc.
R. Schlenk: Reports grants and personal fees from Novartis, grants from Amgen, grants and personal fees from Pfizer, grants from AstraZenca, grants from PharmaMar. H. Dombret: Grants and personal fees- Pfizer, Incyte, Jazz Pharma, Kite Pharma, Amgen; personal fees- Novartis, Celgene, Agios, Sunesis, Daiichi Sankyo, Karyopharm, Menarini, Astellas, Janssen, Servier, Seattle Genetics, Cellectis. S. Amadori: Reports personal fees from Novartis, personal fees from Amgen, personal fees from Celgene. P. Montesinos: Reports research funding: Pfizer, Celgene and advisory board: Daiichi Sankyo, Novartis, Pfizer, Celgene. M. Levis: Reports personal fees from Daiichi-Sankyo. M.A. Sekeres: Celgene and Millennium, advisory Boards, and steering committee for Daichii-Sankyo. J. Cortes: Grants and personal fees from Ambit/Daiichi, during the conduct of the study; grants and personal fees from Astellas, grants and personal fees from Ariad, grants from Arog, grants and personal fees from Novartis. A. Perl: personal fees and non-financial support- Daiichi Sankyo, Novartis, Arog Pharmaceuticals, personal fees from Pfizer, Astellas, Asana biosciences. O. Zernovak, S. Macintyre, S. Gökmen, K. Kobayashi, D. Mires, H. Zhang, J. Hanyok, N. Ge: Employee of Daiichi Sankyo, Inc. H. Erba: Personal fees- Celgene, Incyte, Novartis, Amgen, Jazz, Daiichi, ImmunoGen, Millennium/Takeda, Ono, Pfizer, Seattle Gen, Sunesis, Glycomimetics; grants- Agios, Amgen, Astellas, grants-Celator, Daiichi, ImmunoGen, Janssen, Juno, Millennium/Takeda, Seattle Gen