Inclusion Criteria:

• Be between the ages of ≥ 18 and ≤ 65 years old.
• Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of > 5% blasts based on histology or flow cytometry.
• Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR or CRi after treatment with an intensive regimen (e.g., anthracycline/cytarabine ± etoposide, gemtuzumab ozogamicin, or cladribine) or have newly diagnosed high-risk AML as defined in this protocol. 
  • *Induction therapy may involve 1 or 2 cycles of the same regimen.  Efficacy assessment of induction therapy must be > 21 days from the start of the previous induction cycle.
• Demonstrate MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow.

During Screening:

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Have a serum creatinine level ≤ 1.8 mg/dL.
• Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤ 5 times upper limit of normal (ULN).
• Have a total bilirubin level ≤ 2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia).
• Have a left ventricular ejection fraction (LVEF) > 45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
• Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate during and for at least 6 months after completion of study therapy.
• Be able to comply with the requirements of the entire study.
• Provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.).

Exclusion Criteria:

• Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see * below).
• Received any previous treatment with alvocidib or any other CDK inhibitor.
• Received a hematopoietic stem cell transplant within the previous 2 months.
• Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days.
• Require concomitant chemotherapy, radiation therapy, or immunotherapy.
  • *Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.
• Received > 360 mg/m^2 equivalents of daunorubicin.
• Have a peripheral blast count of > 30,000/mm^3 (may use hydroxyurea as above).
• Received antileukemic therapy within the last 3 weeks (with the exception of hydroxyurea or if the patient has definite refractory disease). Refractory patients who received therapy within the last 3 weeks may be eligible with prior approval of the Medical Monitor.
• Diagnosed with acute promyelocytic leukemia (APL, M3).
• Have active central nervous system (CNS) leukemia.
• Have evidence of uncontrolled disseminated intravascular coagulation.
• Have an active, uncontrolled infection.
• Have other life-threatening illness.
• Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia.
• Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
• Are pregnant and/or nursing.
• Have received any live vaccine within 14 days prior to first study drug administration.