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.