| Inclusion Criteria: | 1) Males and females age >/= 18 years
2) Understand and voluntarily sign the informed consent form for this study
3) Available for periodic follow-up at the investigative site
4) Able to swallow the liquid study drug
5) Morphologically documented primary AML or AML secondary to MDS, as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution, & confirmed later by the Sponsor-designated central lab. Patients must also meet the following criteria: 1) >/= 60 yrs of age who are relapsed after 1 first-line chemo regimen (with or without consolidation) and after first complete remission (CR1) <12 months or are primary refractory to first-line chemotherapy, or 2) >/= 18 yrs of age who are relapsed or refractory after 1 second line (salvage) regimen or are relapsed or refractory after HSCT
6) **continued from above: 3) Must provide a sample for determination of FLT3-ITD mutation status.
7) ECOG performance status of 0 to 2
8) In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents including immunosuppressive therapy post HSCT. The use of chemotherapeutic or antileukemic agents other than hydroxyurea is not permitted during the study with the possible exception of intrathecal (IT) therapy for patients with CNS leukemia in remission at the discretion of the Investigator and with the agreement of the Sponsor.
9) Persistent chronic clinically significant non-hematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be </= Grade 1
10) Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220.
11) Serum creatinine </= 1.5 × ULN (upper limit of normal) and glomerular filtration rate (GFR) > 30 mL/min (calculated by Cockcroft and Gault formula)
12) Serum potassium, magnesium, and calcium levels (corrected serum calcium values for hypoalbuminemia should be used) should be at least within institutional normal limits, and every effort should be made to keep potassium concentrations above 4.0 mEq/dL, magnesium concentrations above 1.8 mg/dL, and serum calcium at normal concentration (corrected serum calcium values for hypoalbuminemia are acceptable) with administration of oral/IV potassium and/or magnesium and/or calcium replacement during the study.
13) **continued from above: If this is not possible, potassium, magnesium and calcium concentrations should at least be kept within institutional normal limits.
14) Total serum bilirubin </= 1.5 × ULN
15) Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) </= 2.5 × ULN
16) Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if their sexual partners are women of child bearing potential (WOCBP).
17) WOCBP must be using an adequate and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 3 months after the study in such a manner that the risk of pregnancy is minimized. WOCBP includes any female that has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not post menopausal (defined as amenorrhea > 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL).
18) **continued from above: Additionally, women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or are practicing abstinence or where the partner is sterile (eg, vasectomy), should be considered to be of childbearing potential.
19) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 72 hours prior to the start of study drug. |