Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML)

Current enrollment is open only to FLT3-ITD positive, Cohort 1.

Inclusion Criteria:

Males and females age ≥18 years in second relapse or refractory.
Males and females age ≥60 years in first relapse or refractory.
Must have baseline bone marrow sample taken.
Morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS with ≥20% bone marrow or peripheral blasts), as defined by the World Health Organization (WHO) criteria, confirmed by pathology review at treating institution.
Able to swallow the liquid study drug.
Eastern Cooperative Oncology Group performance status of 0 to 2
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. The use of chemotherapeutic or antileukemic agents other than hydroxyurea is not permitted during the study with the possible exception of intrathecal (IT) therapy at the discretion of the Investigator and with the agreement of the Sponsor.
Persistent chronic clinically significant non-hematological toxicities from prior treatment must be ≤Grade 1.
Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220.
Serum creatinine ≤1.5 × upper limit of normal (ULN) and glomerular filtration rate (GFR) > 30 mL/min
Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits.
Total serum bilirubin ≤1.5 × ULN
Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 × ULN
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:

Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor.
Diagnosis of acute promyelocytic leukemia
Diagnosis of chronic myelogenous leukemia (CML) in blast crisis
AML in relapse or refractory after 3 or more previous lines of chemotherapy (and/or HSCT) treatment
AML or antecedent MDS secondary to prior chemotherapy
Persistent clinically significant non-hematological toxicity that is Grade >1 by NCI CTCAE v4 from prior chemotherapy
Patients who have had HSCT and are within 100 days of transplant and/or are still taking immunosuppressive drugs and/or have clinically significant graft-versus-host disease requiring treatment and/or have >Grade 1 persistent non hematological toxicity related to the transplant
Clinically active central nervous system (CNS) leukemia. Patients with CNS leukemia, which is controlled, but who are still receiving IT therapy at study entry may be considered eligible and continue receive IT therapy at the discretion of the Investigator and with agreement of the Sponsor.
Patients who have previously received AC220
Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment)
Major surgery within 4 weeks prior to enrollment in the study
Radiation therapy within 4 weeks prior to, or concurrent with study
Use of concomitant drugs that prolong the time between the start of the Q wave and the end of the T wave (QT)/corrected interval between the Q wave and T wave (QTc) interval and/or are CYP3A4 inhibitors are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient.
Uncontrolled or significant cardiovascular disease
Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential
Men who are unwilling to use contraception if their partners are of childbearing potential
Active, uncontrolled infection
Human immunodeficiency virus positivity
Active hepatitis B or C or other active liver disease
History of cancer, except Stage 1 cervix or nonmelanotic skin cancer, with the possible exception of patients in complete remission