Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006)
Condition: AML; Acute Myeloid Leukemia; Myelodysplastic Disorders
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      A primary goal of this clinical research study is to find the highest safe dose of sorafenib
      that can be given in combination with idarubicin and Ara-C for the treatment of acute
      myelogenous leukemia (AML) and high-risk, myelodysplastic syndrome (MDS).

      Once the highest safe dose is found, researchers will then try to learn if this combination
      treatment can help control AML and high-risk MDS in newly diagnosed patients. The safety of
      this treatment combination will also be studied.
    

Detailed description: 
      The Study Drugs:

      Sorafenib is designed to block the function of important proteins in cancer cells. When
      active, these proteins help cause abnormal growth and behavior of leukemia cells.

      Idarubicin and Ara-C are both designed to insert themselves into DNA (the genetic material of
      cells) and to stop DNA from repairing itself.

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a study
      group based on when you join this study.

      If you are enrolled in the Phase I part of this study, the dose of sorafenib you receive with
      Ara-C and idarubicin will depend on when you enrolled in this study. Each new group of 3
      participants will receive a higher dose level of sorafenib than the previous group until the
      highest safe dose of sorafenib that can be given in combination with Ara-C and idarubicin is
      reached.

      If you are enrolled in the Phase II portion of this study, you will receive the highest safe
      dose of sorafenib in combination with Ara-C and idarubicin found in the Phase I part.

      Study Drug Administration:

      During the study, you will receive treatment over 28-day "cycles." The doses of idarubicin
      and Ara-C are the same for all study participants.

      On Days 1-4 (Days 1-3 if you are older than 60) of each induction cycle (#1 and possibly #2),
      you will receive Ara-C through a nonstop infusion (through a needle in your vein). You will
      also receive steroids by mouth or through a vein every day to reduce the risks of side
      effects, such as rash.

      On Days 1-3 of each induction cycle (#1 and possibly #2), you will receive idarubicin by vein
      over 1 hour once a day.

      In general, sorafenib will be taken by mouth twice daily on Days 1-7, unless otherwise
      instructed. However, the dose of sorafenib may differ among study participants. Sorafenib
      should be taken with water on an empty stomach. Your study doctor will give you complete
      instructions on when and how to take sorafenib.

      Depending on the side effects that you may have, the dose of sorafenib may be decreased,
      stopped until side effects go away, or even stopped completely, if your doctor thinks that
      this is in your best interest.

      Study Visits:

      During Cycles 1-2, you will have study visits about 2 times a week. You may need to have
      study visits more often when the study doctor thinks it is necessary. At these visits, you
      will have the following procedures performed.

        -  You will be asked about any side effects you may have experienced and any medications
           you may be taking.

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

      During Cycles 1 and 2, between Days 21-28, you will have a bone marrow aspirate and/or biopsy
      performed to check the status of the disease.

      For Cycle 3 and in further cycles, you will have a bone marrow aspirate as determined
      necessary by your doctor. If your doctor thinks you have responded to the treatment, you will
      then have bone marrow aspirates collected every 3-6 months, if your doctor feels this to be
      necessary.

      Consolidation Therapy:

      If it is found that the disease is responding to treatment, you may receive 5 additional
      cycles of therapy. These cycles are called "consolidation" therapy and will be given every
      4-6 weeks.

      On Days 1-3, Ara-C will be given as a nonstop infusion. You will also receive steroids either
      by mouth or by vein to help reduce the risk of side effects.

      On Days 1-2, idarubicin will be given by vein over 1 hour.

      Sorafenib will be taken twice daily by mouth for 7 or more days, at a schedule determined by
      your study doctor.

      After each cycle, about every 4-6 weeks, blood (about 2 teaspoons) will be drawn to check
      your blood count levels.

      Maintenance Therapy:

      After 5 cycles of consolidation therapy, and according to your response to consolidation
      therapy, you may continue on this study to receive "maintenance" treatment, as needed, and as
      determined by your study doctor for up to 7 more cycles.

      You will take sorafenib twice a day every day during the 28-day cycle.

      Every 1-4 weeks, blood (about 2 teaspoons) will be drawn for routine tests.

      Length of Study:

      You may receive up to 14 cycles in total of therapy. You may be taken off this study if the
      leukemia gets worse, develop another illness that interferes with taking the study drugs, or
      you have intolerable side effects.

      This is an investigational study. Sorafenib is FDA approved and commercially available for
      the treatment of metastatic renal cancer only. Idarubicin is FDA approved for use in
      combination with other approved antileukemic drugs for the treatment of acute myeloid
      leukemia (AML) in adults. Cytarabine is FDA approved for use in the treatment of leukemia.
      The use of sorafenib combined with idarubicin and Ara-C in the treatment of AML and high-risk
      MDS is investigational and authorized for use in research only. Up to 75 patients will take
      part in this study. All patients will be enrolled at M. D. Anderson Cancer Center.
    

Intervention name(s): Idarubicin; Sorafenib; Ara-C
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 12 mg/m^2 IV over 1 hour daily (days 1-3); Starting dose 400 mg by mouth for 7 days; 1.5 g/m^2 IV over 24 hours daily (days 1-4)
Other intervention name(s): Idamycin®; Nexavar®; Cytarabine; Cytosar-U®; Arabinosylcytosine
Intervention MeSH terms: Cytarabine; Sorafenib; Idarubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; AML; High-Risk MDS; Acute Myeloid Leukemia; High-Risk Myelodysplastic Disorder; Idarubicin; Ara-C; Cytarabine; Sorafenib; BAY43-9006