Study of Biomarker-Based Treatment of Acute Myeloid Leukemia

Inclusion Criteria:

• Adults, age 60 years or older at the time of diagnosis unless in a specific knowncytogenetic and genomic group for which treatment in Group A or B is allowed by thesub-study where age 18 and older is allowed. Patients < 60 years old who arescreened but do not fall within the cytogenetic and genomic open sub-studies wouldstill be followed on the Master Protocol and not considered screen fails.

• Subjects must be able to understand and provide written informed consent

• Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acutemyeloid leukemia (AML) according to the WHO classification with no prior treatmentother than hydroxyurea. Subjects with blasts % in bone marrow of 10% to 19% orblasts in blood of 10% to 19% will be allowed to enroll to this group. Forpreviously untreated subjects with ≥ 20% blasts in bone marrow or blood only: Priortherapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), oraplastic anemia is permitted but not with hypomethylating agents.

• Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AMLaccording to the WHO classification. For study purposes, refractory AML is definedas failure to ever achieve CR or recurrence of AML within 6 months of achieving CR;relapsed AML is defined as all others with disease after prior remission. For selectgenomic aberrations specified in the studies, patients ≥ 18 years of age may beallowed to enroll in this portion of the study.

Exclusion Criteria:

• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvementwith AML or involved with 10% to 19% blasts to enter the study)

• Acute promyelocytic leukemia

• Symptomatic central nervous system (CNS) involvement by AML

• Signs of leukostasis requiring urgent therapy

• Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis

• Patients with psychological, familial, social, or geographic factors that otherwisepreclude them from giving informed consent, following the protocol, or potentiallyhamper compliance with study treatment and follow-up

• Any other significant medical condition, including psychiatric illness or laboratoryabnormality, that would preclude the patient participating in the trial or wouldconfound the interpretation of the results of the trial