Ensayos clínicos

Inclusion Criteria:

• Diagnosis of previously-untreated, de novo, acute myeloid leukemia (AML) according to World Health Organization (WHO) classification (2008)
• Documented within 28 days prior to enrollment 
• Defined as > 20% myeloblasts on the marrow aspirate or peripheral blood differential
• With or without extramedullary involvement
• Has confirmatory immunophenotyping or immunocytochemistry (e.g. myeloperoxidase)
• Clonal, recurring cytogenetic abnormalities such as  t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) should be considered to have AML regardless of the blast percentage
• Either positive or negative FMS-like tyrosine kinase - internal tandem duplication (FLT3-ITD) mutation status
• An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Must have adequate renal, hepatic, and coagulation parameters as indicated by the following laboratory values
• A woman of childbearing potential  or a male subject with female partner of childbearing potential must agree to use a medically-approved method of contraception to avoid pregnancy throughout the study and for at least 3 months after the last dose of study drug
• A negative serum or urine pregnancy test (sensitivity ≤ 25 IU human chorionic gonadotropin [hCG]/L) within 72 hours prior to the start of study drug administration
• Able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 or World Health Organization (WHO) classification of APL with t(15;17)(q22;q12), or BCR-ABL positive leukemia (chronic myelogenous leukemia in blast crisis).
• Diagnosis of AML following an antecedent hematologic disorder (diagnosis of myelodysplasia or myeloproliferative neoplasm by bone marrow aspirate and/or biopsy documented at least 12 weeks prior to first dose of study drug)
• Diagnosis of acute bilineal/biphenotypic leukemia.
• Therapy-related AML
• Received previous treatment with AC220.
• Received previous therapy for AML
• Has uncontrolled disseminated intravascular coagulation.
• Has Central Nervous System (CNS) leukemia
  • Symptoms suggestive of CNS leukemia must undergo a lumbar puncture
  • A positive cerebrospinal fluid (CSF) for AML blasts is not eligible
• A known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
• Had major surgery within 4 weeks prior to the start of study drug.
• Uncontrolled or significant cardiovascular disease 
• Pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias).
• An active acute or chronic systemic fungal, bacterial, viral, or other infection.
• A concurrent disease (e.g. a history of serious organ dysfunction or disease) that may place the subject at undue risk to undergo induction therapy per protocol, or that might obscure assessments of drug safety.
• Requires treatment with concomitant drugs that prolong QT/QTc interval or strong cytochrome P-3A4 (CYP3A4) inhibitors or inducers with the exception of antibiotics, antifungals, and antivirals 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 subject.
• Requires treatment with anticoagulant therapy
• A female who is lactating
• Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.