Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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, Erythroblastic, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      This randomized phase II trial is studying how alvocidib, cytarabine, and mitoxantrone
      hydrochloride work compared to cytarabine and daunorubicin hydrochloride in treating patients
      with newly diagnosed acute myeloid leukemia. Alvocidib may stop the growth of cancer cells by
      blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as
      cytarabine, mitoxantrone hydrochloride, and daunorubicin hydrochloride 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 whether giving alvocidib, cytarabine, and mitoxantrone
      hydrochloride is more effective than giving cytarabine and daunorubicin hydrochloride in
      treating patients with acute myeloid leukemia.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To compare the rate of complete remission (CR) after 1 course of induction therapy with
      the timed-sequential combination of alvocidib (flavopiridol), cytarabine (cytosine
      arabinoside [ara-C]), and mitoxantrone hydrochloride (FLAM) vs traditional "7+3" cytarabine
      and daunorubicin hydrochloride (ara-C + Daunorubicin) for adults (age 18 to 70) with newly
      diagnosed, previously untreated, intermediate-risk or poor-risk acute myelogenous leukemia
      (AML).

      SECONDARY OBJECTIVES:

      I. To evaluate and compare the toxicities of FLAM vs 7+3. II. To compare the 2-year
      disease-free survival (DFS) and overall survival (OS) in response to FLAM vs 7+3.

      III. To detect and compare the presence of minimal-residual disease (MRD) remaining after
      FLAM vs 7+3.

      IV. To determine the expression of ABC transport proteins multidrug resistance 1 (MDR1,
      ABCB1) and breast cancer resistance protein (BCRP, ABCG2) on AML blasts pretreatment and
      correlate the expressions of one or both proteins with CR and DFS in response to FLAM vs 7+3.

      OUTLINE: This is a multicenter study. Patients are stratified according to risk features: age
      (< 50 vs >= 50), secondary AML (pre-existing myelodysplatic syndrome [MDS],
      myeloproliferative diseases [MPD], treatment-related [t]-AML, or severe multi-lineage
      dysplasia) and/or known adverse cytogenetics, and hyperleukocytosis (white blood cells [WBC]
      >= 50,000/mm^3). Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive alvocidib intravenously (IV) over 1 hour on days 1-3, cytarabine IV
      over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9.
      Patients who achieve complete or partial response to the first course (completion of all
      doses) may receive a second course of treatment or high-dose cytarabine after 21-63 days
      following blood count recovery, and/or undergo allogeneic bone marrow transplant.

      ARM II: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin
      hydrochloride IV on days 1-3. Patients who have residual disease on day 14 may receive
      additional cytarabine for 5 days and daunorubicin hydrochloride for 2 days. Patients may
      undergo blood and bone marrow collection for correlative studies.

      After completion of study therapy, patients are followed up every 3 months for 2 years, every
      6 months for 5 years, and then annually thereafter.
    

Intervention name(s): alvocidib; daunorubicin hydrochloride; mitoxantrone hydrochloride; cytarabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given IV; Given IV
Other intervention name(s): FLAVO; flavopiridol; HMR 1275; L-868275; Cerubidin; Cerubidine; daunomycin hydrochloride; daunorubicin; RP-13057; CL 232315; DHAD; DHAQ; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside
Intervention MeSH terms: Cytarabine; Daunorubicin; Mitoxantrone; Alvocidib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment