Laromustine, Daunorubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as laromustine, daunorubicin, and cytarabine,
      work in different ways to stop the growth of cancer cells, either by killing the cells or by
      stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill
      more cancer cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of laromustine when
      given together with daunorubicin and cytarabine in treating patients with acute myeloid
      leukemia.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the dose of laromustine that can be combined with daunorubicin
           hydrochloride and cytarabine in patients with previously untreated acute myeloid
           leukemia with unfavorable cytogenetics. (Phase I)

        -  To determine the complete remission rate of this regimen as induction therapy. (Phase
           II)

      Secondary

        -  To determine the complete response rate.

        -  To determine the safety profile of this regimen.

        -  To determine the overall and relapse-free survival.

        -  To evaluate the prognostic value of the molecular markers FLT3, duplications of MLL, and
           Evi-1.

      OUTLINE: This is a multicenter, phase I dose-escalation study of laromustine followed by a
      phase II study.

        -  Induction treatment: Patients receive laromustine IV on day 4, daunorubicin
           hydrochloride IV on days 1-3, and cytarabine IV continuously on days 1-7. Patients not
           attaining complete remission (CR) after first induction receive a second induction
           treatment comprising daunorubicin hydrochloride IV on days 1-3 and cytarabine IV twice
           daily on days 1-4. Patients in CR after 1 or 2 induction treatments proceed to
           consolidation treatment.

        -  Consolidation treatment: Patients receive mini-consolidation treatment comprising
           amsacrine on day 1 and cytarabine IV twice daily on days 1-5 followed by 2 courses of
           continuing consolidation treatment comprising mitoxantrone hydrochloride on days 1 and 2
           and cytarabine IV over 12 hours on days 1-5.

        -  Allogeneic or autologous stem cell transplantation: Patients receive busulfan four times
           daily for 4 days and melphalan followed by allogeneic or autologous stem cell
           transplantation.

      After completion of study treatment, patients are followed periodically for 5 years.
    

Intervention name(s): amsacrine; busulfan; cytarabine; daunorubicin hydrochloride; laromustine; melphalan; mitoxantrone hydrochloride; allogeneic hematopoietic stem cell transplantation; autologous hematopoietic stem cell transplantation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Cytarabine; Melphalan; Busulfan; Daunorubicin; Mitoxantrone; Amsacrine
Allocation: Non-Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; untreated adult acute myeloid leukemia