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 known cytogenetic and genomic group for which treatment in Group A, B, or C is allowed by the sub-study where age 18 and older is allowed. In such case, waiting for Foundation Medicine test results would not be required to proceed with sub-study treatment. Patients < 60 years old who are screened but do not fall within the cytogenetic and genomic open sub-studies would still be followed on the M1 Master Protocol and not considered screen fails.
• Patients must be able to understand and provide written informed consent
• Cohort Inclusion Criteria - Group A: Patients must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Patients with myeloid malignancies [e.g. myelodysplastic syndrome (MDS) or other disease], will be allowed to enroll to this group. For previously untreated subjects with ≥ 20% blasts in bone marrow or blood only: Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted. For select group, patients who cannot wait or choose not to wait for results of genomic testing as specified in this protocol, will be allowed to enroll to select sub-studies that allow enrollment and treatment of all patients regardless of their genomic mutations or cytogenetics. For this group, patients will proceed to enroll to that select sub-study without waiting for results of genomic testing and genomic samples will be collected to be analyzed retrospectively after patients' enrollment.
• Cohort Inclusion Criteria - Group B: Patients must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve a complete response (CR) or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. For select genomic aberrations specified in the sub-studies, patients ≥ 18 years of age may be allowed to enroll in this portion of the study. Patients with relapsed or refractory myeloid malignancies (e.g., MDS or other diseases) will be allowed to enroll to this group.
• Cohort Inclusion Criteria - Group C: For select sites which are not part of the Beat AML core sites. These sites will only participate in select sub-studies. Patients in this group will enroll under the Beat AML M1 Master protocol with the intent to enroll into these select sub-studies and following screening on Beat M1 Master protocol, they will come off M1 Master protocol.

Exclusion Criteria

• Acute promyelocytic leukemia
• Clinically active central nervous system (CNS) involvement by AML. A patient may be considered eligible if CNS leukemia is showing response to treatment at study entry and should continue to receive intrathecal therapy as clinical indicated. Patients who require or are undergoing craniospinal irradiation of disease control would not be eligible for participation.
• 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 otherwise preclude them from giving informed consent, following the protocol (including failure to collect genomics samples for screening), or potentially hamper compliance with study treatment and follow-up
• Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial. BAML-16-001-S17 -