title: A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia.
abstract: The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation. We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. IM was dose escalated using a 3 by 3 design. Phosphorylated STAT5 was absent to minimally present in residual blasts on day 14 bone marrows. The maximum tolerated dose of IM was 300 mg. The dose-limiting toxicity was Grade 3-4 hepatic toxicity. The CR/CRp rate was 57%. Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA. advania@ccf.org
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Advani
authors.forename: Ramon
authors.initials: R
authors.lastname: Tiu
authors.forename: Yogen
authors.initials: Y
authors.lastname: Saunthararajah
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Maciejewski
authors.forename: Edward A
authors.initials: EA
authors.lastname: Copelan
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bates
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Rush
authors.forename: Barbara
authors.initials: B
authors.lastname: Tripp
authors.forename: August
authors.initials: A
authors.lastname: Salvado
authors.forename: Elysa
authors.initials: E
authors.lastname: Noon
authors.forename: Matthew
authors.initials: M
authors.lastname: Howard
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.forename: Eric
authors.initials: E
authors.lastname: Hsi
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lim
authors.forename: Claudiu V
authors.initials: CV
authors.lastname: Cotta
authors.forename: Courtney
authors.initials: C
authors.lastname: Price
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D019009:Proto-Oncogene Proteins c-kit; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; D003561:Cytarabine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D003630:Daunorubicin