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

Inclusion Criteria:

1. Males and females age ≥ 18 years;
2. 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:

   1. Refractory to at least 1 cycle of induction chemotherapy, or
   2. Relapsed after at least 1 cycle of induction chemotherapy, or
   3. Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
3. 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;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
5. 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;
6. Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
7. Serum creatinine ≤ 2.0 mg/dL;
8. Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
9. Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
10. Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
11. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
12. Written informed consent must be provided.

Exclusion Criteria:

1. Histologic diagnosis of acute promyelocytic leukemia;
2. Clinically active central nervous system leukemia;
3. 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);
4. Bone marrow transplant within 2 months prior to study;
5. Active, uncontrolled infection;
6. Major surgery within 4 weeks prior to study;
7. Radiation therapy within 4 weeks prior to, or concurrent with, study;
8. Human immunodeficiency virus positivity;
9. Active hepatitis B or C or other active liver disease;
10. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
11. 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.