Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Alvocidib; Cytarabine; Daunorubicin
Intervention description: IV bolus followed by IV infusion; continuous infusion; IV bolus
Intervention MeSH terms: Cytarabine; Daunorubicin; Alvocidib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this Phase I study is to determine the safety and tolerability including the
      maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a
      range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults
      with newly diagnosed and previously untreated AML
    

Eligibility criteria:

        Inclusion Criteria:

          -  To be eligible for participation in the study, patients must meet all of the following
             inclusion criteria:

               1. Be between the ages of ≥18 and ≤65 years

               2. Have an established, pathologically confirmed diagnoses of AML by World Health
                  Organization (WHO) criteria with ≥20% bone marrow blasts based on histology or
                  flow cytometry

               3. Be newly diagnosed and previously untreated

               4. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

               5. Have a serum creatinine level ≤1.8 mg/dL

               6. Have an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level
                  ≤5 times upper limit of normal (ULN)

               7. Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome,
                  hemolysis, or leukemia)

               8. Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or
                  multigated acquisition (MUGA) scan

               9. 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 prior to study entry, for the duration of
                  study participation, and for at least 6 months after the last dose of study drug.

              10. Be able to comply with the requirements of the entire study.

              11. 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:

          -  Patients meeting any one of these exclusion criteria will be prohibited from
             participating in this study.

               1. Received any previous treatment for AML

               2. Diagnosed with APL-M3 or CBF-AML

               3. Require concomitant chemotherapy, radiation therapy, or immunotherapy.
                  Hydroxyurea is allowed up to the evening before starting (but not within 12
                  hours) of starting Induction therapy.

               4. Received >200 mg/m2 equivalents of daunorubicin

               5. Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #3 above)

               6. Have active central nervous system (CNS) leukemia

               7. Have evidence of uncontrolled disseminated intravascular coagulation

               8. Have an active, uncontrolled infection

               9. Have other life-threatening illness

              10. Have other active malignancies or diagnosed with other malignancies within the
                  last 6 months, except nonmelanoma skin cancer or cervical intraepithelial
                  neoplasia

              11. Have mental deficits and/or psychiatric history that may compromise the ability
                  to give written informed consent or to comply with the study protocol.

              12. Are pregnant and/or nursing