A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia.
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.
Advani
Anjali S
AS
Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA. advania@ccf.org
Tiu
Ramon
R
Saunthararajah
Yogen
Y
Maciejewski
Jaroslaw
J
Copelan
Edward A
EA
Sobecks
Ronald
R
Sekeres
Mikkael A
MA
Bates
Jennifer
J
Rush
Mary Lynn
ML
Tripp
Barbara
B
Salvado
August
A
Noon
Elysa
E
Howard
Matthew
M
Jin
Tao
T
Hsi
Eric
E
Egorin
Merrill J
MJ
Lim
Kathleen
K
Cotta
Claudiu V
CV
Price
Courtney
C
Kalaycio
Matt
M
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
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; D003561:Cytarabine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D003630:Daunorubicin