PMID- 29090473
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20231104
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Print)
IS  - 0361-8609 (Linking)
VI  - 93
IP  - 2
DP  - 2018 Feb
TI  - Results of a phase 1 study of quizartinib as maintenance therapy in subjects with 
      acute myeloid leukemia in remission following allogeneic hematopoietic stem cell 
      transplant.
PG  - 222-231
LID - 10.1002/ajh.24959 [doi]
AB  - FLT3-ITD-mutated acute myeloid leukemia (AML) has very high risk of relapse and 
      is associated with poor outcome following allogeneic hematopoietic-cell 
      transplant (allo-HCT). This two-part, phase 1, multicenter, open-label, 
      sequential-group, dose-escalation study aimed to determine dose-limiting 
      toxicities (DLTs), maximum tolerated dose (MTD), and safety/tolerability of 
      quizartinib, a selective and highly potent FLT3 inhibitor, when administered as 
      maintenance therapy after allo-HCT. Thirteen subjects with documented 
      FLT3-ITD-mutated AML in morphological remission following allo-HCT received one 
      of two quizartinib dihydrochloride dose levels (DL): 40 mg/d (DL1; n = 7) and 60 
      mg/d (DL2; n = 6), administered orally in 28-day cycles for up to 24 cycles. 
      Median age of participants was 43 years. All subjects received human leukocyte 
      antigen (HLA)-matched allo-HCT. One subject treated at DL1 and 1 treated at DL2 
      had DLTs that required drug interruption (grade 3 gastric hemorrhage and grade 3 
      anemia, respectively). Ten subjects (77%) received quizartinib for >1 year; 5 
      (38%) completed 24 cycles. Four subjects (31%) discontinued quizartinib due to 
      adverse events. One subject (8%) experienced relapse during cycle 1 and 
      discontinued treatment. Most common grade 3/4 adverse events were neutropenia 
      (23%), anemia (15%), leukopenia (15%), lymphopenia (15%), and thrombocytopenia 
      (15%). This study demonstrated acceptable tolerability and early evidence of 
      reduced relapse rate following allo-HCT with quizartinib maintenance compared to 
      historical cohorts. No MTD was identified, but 60 mg daily was selected as 
      highest dose for continuous daily administration based on randomized comparison 
      of daily 30 and 60 mg doses in relapsed/refractory AML.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Sandmaier, Brenda M
AU  - Sandmaier BM
AUID- ORCID: 0000-0002-9767-9739
AD  - Fred Hutchinson Cancer Research Center, Seattle, Washington.
AD  - University of Washington School of Medicine, Seattle, Washington.
FAU - Khaled, Samer
AU  - Khaled S
AD  - City of Hope, Duarte, California.
FAU - Oran, Betul
AU  - Oran B
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Gammon, Guy
AU  - Gammon G
AD  - Independent consultant, San Diego, California.
FAU - Trone, Denise
AU  - Trone D
AD  - Independent consultant, San Diego, California.
FAU - Frankfurt, Olga
AU  - Frankfurt O
AD  - Northwestern University, Chicago, Illinois.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20171117
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Benzothiazoles)
RN  - 0 (Phenylurea Compounds)
RN  - 7LA4O6Q0D3 (quizartinib)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Adult
MH  - Benzothiazoles/*administration & dosage/adverse effects
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Leukemia, Myeloid, Acute/complications/*drug therapy/therapy
MH  - Maintenance Chemotherapy/adverse effects/methods
MH  - Maximum Tolerated Dose
MH  - Phenylurea Compounds/*administration & dosage/adverse effects
MH  - Recurrence
MH  - Remission Induction
MH  - Transplantation, Homologous
MH  - fms-Like Tyrosine Kinase 3/genetics
PMC - PMC6585789
EDAT- 2017/11/02 06:00
MHDA- 2018/12/12 06:00
PMCR- 2019/06/20
CRDT- 2017/11/02 06:00
PHST- 2017/10/11 00:00 [received]
PHST- 2017/10/23 00:00 [revised]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/02 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/11/02 06:00 [entrez]
PHST- 2019/06/20 00:00 [pmc-release]
AID - AJH24959 [pii]
AID - 10.1002/ajh.24959 [doi]
PST - ppublish
SO  - Am J Hematol. 2018 Feb;93(2):222-231. doi: 10.1002/ajh.24959. Epub 2017 Nov 17.