Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes
Intervention: alvocidib; mitoxantrone hydrochloride; cytarabine; pharmacological study; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: Cytarabine; Mitoxantrone; Alvocidib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying two different schedules of alvocidib to compare
      how well they work when given together with cytarabine and mitoxantrone in treating patients
      with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib,
      cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells,
      either by killing the cells or by stopping them from dividing. It is not yet known which
      schedule of alvocidib is more effective when given together with cytarabine and mitoxantrone
      in treating patients with acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed newly diagnosed acute myeloid leukemia (AML) meeting the
             following criteria:

               -  Subtypes M0, M1, M2, M4-7

               -  No acute promyelocytic leukemia (M3)

          -  At least 50 years of age OR >= 18 years of age with >= 1 of the following poor-risk
             disease features:

               -  Antecedent hematologic disorder, including myelodysplastic syndromes
                  (MDS)-related AML or prior myeloproliferative disorder (MPD)

               -  Treatment-related AML, AML with trilineage dysplasia

               -  Myeloid sarcoma, myeloid proliferations related to Down Syndrome, or blastic
                  plasmacytoid dendritic cell neoplasm

               -  AML with trilineage dysplasia

          -  AML with adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q,
             21q, or 17p; t[6;9]; t[9;22]; trisomy 8; trisomy 13, complex karyotypes [>= 3
             unrelated abnormalities]),

          -  No hyperleukocytosis with >= 50,000 blasts/uL (leukapheresis or hydroxyurea allowed
             for cytoreduction immediately prior to the first dose of alvocidib)

          -  No active CNS leukemia

          -  ECOG performance status 0-2

          -  Serum creatinine =< 2.0 mg/dL

          -  ALT/AST =< 5 times upper limit of normal

          -  Bilirubin =< 2.0 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  No active uncontrolled infection

          -  Infection that is under active treatment allowed provided it is controlled with
             antibiotics

          -  No other life-threatening illness

          -  No mental deficits and/or psychiatric history that would preclude giving informed
             consent or following study requirements

          -  At least 24 hours since prior leukapheresis or hydroxyurea for cytoreduction

          -  Prior non-cytotoxic therapies (e.g., thalidomide or lenalidomide, interferon,
             cytokines, low-dose 5-azacytidine, or low-dose cytoxan) for MDS or MPD allowed

          -  Prior chemotherapy or bone marrow/stem cell transplantation for non-AML malignancy
             allowed

          -  No prior alvocidib

          -  No other concurrent chemotherapy, radiotherapy, or immunotherapy

          -  No other concurrent investigational or commercially-available antitumor therapies for
             AML

          -  LVEF >= 45%