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A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse.
MedLine Citation:
PMID:  23321953     Owner:  NLM     Status:  Publisher    
The mTORC1 signaling pathway is constitutively activated in almost all AML patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10 mg to 70 mg were administrated orally on days 1 and 7 of a 3+7 daunorubicin + cytarabine conventional induction chemotherapy regimen. Twenty eight patients were enrolled in this trial. The treatment was well tolerated with less than 10% toxicity, mainly involving the gastrointestinal tract and lungs. In this phase Ib trial, the RAD001 maximum tolerated dose was not reached at 70 mg. Sixty eight percent of patients achieved CR, of which 14 received a double induction. Eight subsequently were intensified with allogeneic-stem cell transplant. Strong plasma inhibition of P-p70S6 K was observed after RAD001 administration, still detectable at day 7 at the 70 mg dosage. CR rates in patients with RAD001 areas under or above the curve median were 85% vs 53%. A 70 mg dose of RAD001 at days 1 and 7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment.Leukemia accepted article preview online, 16 January 2013; doi:10.1038/leu.2013.17.
S Park; N Chapuis; F S Marcoux; C Recher; T Prebet; P Chevallier; J-Y Cahn; T Leguay; P Bories; F Witz; T Lamy; P Mayeux; C Lacombe; C Demur; J Tamburini; A Merlat; R Delepine; N Vey; F Dreyfus; M C Béné; N Ifrah; D Bouscary
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K     Volume:  -     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1] Service d'hématologie, Hôpital Cochin, AP-HP, Paris, France [2] Institut Cochin, Département d'Immuno-Hématologie, CNRS, UMR8104, INSERM, Paris, France.
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