A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status

Inclusion Criteria:

Males and females age ≥ 18 years;

Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:

Refractory to at least 1 cycle of induction chemotherapy, or
Relapsed after at least 1 cycle of induction chemotherapy, or
Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;
Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
Serum creatinine ≤ 2.0 mg/dL;
Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
Written informed consent must be provided.

Exclusion Criteria:

Histologic diagnosis of acute promyelocytic leukemia;
Clinically active central nervous system leukemia;
Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);
Bone marrow transplant within 2 months prior to study;
Active, uncontrolled infection;
Major surgery within 4 weeks prior to study;
Radiation therapy within 4 weeks prior to, or concurrent with, study;
Human immunodeficiency virus positivity;
Active hepatitis B or C or other active liver disease;
Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.