Document Detail

Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3.
MedLine Citation:
PMID:  20733134     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Mutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3 mutations.
PATIENTS AND METHODS: Ninety-five patients with AML or MDS with either wild-type (n = 60) or mutated (n = 35) FLT3 were randomly assigned to receive oral midostaurin at 50 or 100 mg twice daily. The drug was discontinued in the absence of response at 2 months, disease progression, or unacceptable toxicity. Response was defined as complete response, partial response (PR), hematologic improvement, or reduction in peripheral blood or bone marrow blasts by ≥ 50% (BR).
RESULTS: The rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin.
CONCLUSION: These results suggest that midostaurin has hematologic activity in both patients with FLT3-mutant and wild-type. The degree of clinical activity observed supports additional studies that combine midostaurin and other agents such as chemotherapy especially in FLT3-mutant AML.
Thomas Fischer; Richard M Stone; Daniel J Deangelo; Ilene Galinsky; Elihu Estey; Carlo Lanza; Edward Fox; Gerhard Ehninger; Eric J Feldman; Gary J Schiller; Virginia M Klimek; Stephen D Nimer; D Gary Gilliland; Catherine Dutreix; Alice Huntsman-Labed; Jodi Virkus; Francis J Giles
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-08-23
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  28     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-30     Completed Date:  2010-11-02     Revised Date:  2014-08-24    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4339-45     Citation Subset:  IM    
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MeSH Terms
Administration, Oral
Antineoplastic Agents / administration & dosage,  adverse effects,  therapeutic use*
Leukemia, Myeloid, Acute / drug therapy*,  enzymology,  genetics*
Myelodysplastic Syndromes / drug therapy*,  enzymology,  genetics*
Receptor Protein-Tyrosine Kinases / genetics
Staurosporine / administration & dosage,  adverse effects,  analogs & derivatives*,  therapeutic use
Treatment Outcome
fms-Like Tyrosine Kinase 3 / genetics*
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 120685-11-2/4'-N-benzoylstaurosporine; EC Protein-Tyrosine Kinases; EC Tyrosine Kinase 3; H88EPA0A3N/Staurosporine

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