Clinical Trials

Inclusion Criteria:

• Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:
  1. Greater than or equal to 75 years of age
  2. Antecedent hematologic disease
  3. Known adverse cytogenetic risk
  4. Eastern Cooperative Oncology Group (ECOG) PS = 2
• Patient must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity
• ECOG PS 0 to 2
• Expected survival longer than 3 months from enrollment in the study
• Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
• Male patients who agree to practice effective barrier contraception or agree to practice true abstinence
• Voluntary written consent must be given before performance of any study-related procedure
• Suitable venous access for the study-required blood sampling
• Adequate clinical laboratory values during the screening period as specified in the protocol
• Able to undergo bone marrow aspiration and biopsy at screening

Exclusion Criteria:

• Previous treatment with azacitidine or decitabine
• Known favorable cytogenetic risk
• Any serious medical or psychiatric illness
• Treatment with any investigational products
• Known hypersensitivity to azacitidine or mannitol
• Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis
• Active uncontrolled infection or severe infectious disease
• Major surgery within 14 days before the first dose of study drug
• Life-threatening illness unrelated to cancer
• Clinically uncontrolled central nervous system (CNS) involvement
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiac/cardiopulmonary disease
• Left ventricular ejection fraction
• Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis
• Body mass index > 40 kg/m²
• Treatment with CYP3A inducers within 14 days before the first dose of MLN4924
• Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
• Patients who are unwilling or unable to refrain from using hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) starting 5 days before the initial study drug administration and throughout the study will not be permitted to enroll