Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome
Condition: Leukemia
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of this clinical research study is to learn if the combination of clofarabine,
      idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can
      help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of
      these study drug combinations will also be studied.
    

Detailed description: 
      The Study Drugs:

      Clofarabine is designed to interfere with the growth and development of cancer cells.

      Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of
      cells). This may cause the cancer cells to die.

      Cytarabine and Fludarabine are designed to insert themselves into the DNA of cancer cells and
      stop the 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. Up to 4 groups of 6 participants will be enrolled in
      the Phase I portion of the study. Up to 280 participants will be enrolled in Phase II.

      Phase I:

      If you are enrolled in the Phase I portion, the dose of clofarabine you receive will depend
      on when you joined this study. The first group of participants will receive the lowest dose
      level of clofarabine. Each new group will receive a higher dose of clofarabine than the group
      before it, if no intolerable side effects were seen. This will continue until the highest
      tolerable dose of clofarabine is found.

      All participants will receive the same dose level of idarubicin and cytarabine.

      Phase II:

      If you are enrolled in the Phase II portion, you will be randomly assigned (as in the flip of
      a coin) to 1 of 2 groups:

        -  If you are in Group 1, you will receive clofarabine, idarubicin, and cytarabine. You
           will receive clofarabine at the highest dose that was tolerated in the Phase I portion.

        -  If you are in Group 2, you will receive fludarabine, idarubicin, and cytarabine.

      Study Drug Administration:

      Study drug(s) will be given in what are called "cycles." Each cycle is 28 days.

      Phase I:

      On Days 1-5:

        -  You will receive clofarabine by vein over about 1 hour.

        -  You will receive cytarabine by vein over about 2 hours.

        -  On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

      Phase II (Induction):

      The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you
      will have up to 2 Induction cycles.

      If you are in Group 1:

      On Days 1-5 of each cycle:

        -  You will receive clofarabine by vein over about 1 hour.

        -  You will receive cytarabine by vein over about 2 hours.

        -  On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

      If you are in Group 2:

      On Days 1-5 of each cycle:

        -  You will receive fludarabine by vein over about 30 minutes.

        -  You will receive cytarabine by vein over about 2 hours.

        -  On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

      If the doctor thinks it is needed, you may receive less than 5 days of treatment in the
      induction cycle.

      If the doctor thinks it is needed, your dose level will be reduced after Induction.

      Phase II (Consolidation):

      If the disease responds to the study drugs, you may receive up to 6 more cycles of study
      drugs. This is called Consolidation.

      If you are in Group 1:

      On Days 1-3 of each cycle :

        -  You will receive clofarabine by vein over about 1 hour.

        -  You will receive cytarabine by vein over about 2 hours.

        -  After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin
           by vein over about 30 minutes.

      If you are in Group 2:

      On Days 1-3 of each cycle:

        -  You will receive fludarabine by vein over about 30 minutes

        -  You will receive cytarabine by vein over about 2 hours.

        -  After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin
           by vein over about 30 minutes

      If the cancer does not completely respond after Cycle 1, you may repeat induction (Cycle 1).
      If the cancer completely responds, you will begin the consolidation cycles.

      If the doctor thinks it is needed, you may receive less than 3 days of treatment in the
      consolidation cycles.

      Study Visits:

      You will have a physical exam, including measurement of your vital signs before the start of
      each cycle. Blood (about 2 teaspoons) will be drawn for routine tests every 3-7 days.

      On Day 28 of every 2-3 cycles (+/- 7 days), if the doctor thinks it is needed, you will have
      a bone marrow aspirate to check the status of the disease. To collect a bone marrow aspirate,
      an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn
      through a large needle.

      Length of Study:

      You may continue taking the study drugs for as long as the doctor thinks it is in your best
      interest or up to 8 total cycles. You will no longer be able to take the study drugs if the
      disease gets worse or intolerable side effects occur.

      Your participation on the study will be over once you have completed the long-term follow-up.

      Long-Term Follow-up:

      Every 3 months for 1 year after you are off study, you will be called and asked how you are
      feeling, about any side effects you may be having, and about any other drugs you may be
      taking. These calls should last about 5 minutes each.

      This is an investigational study. Cytarabine and Idarubicin are FDA approved and commercially
      available for the treatment of AML. Fludarabine is FDA approved and commercially available
      for the treatment of chronic lymphocytic leukemia (CLL). Clofarabine is FDA approved and
      commercially available for the treatment of acute lymphoblastic leukemia (ALL). The
      combination of these study drugs is investigational.

      Up to 292 patients will take part in Phase I and Phase II of this study. All will be enrolled
      at MD Anderson.
    

Intervention name(s): Clofarabine; Idarubicin; Cytarabine; Fludarabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle.
Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.; 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.; 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.; 30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Other intervention name(s): Clofarex; Clolar; Idamycin; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Fludara
Intervention MeSH terms: Cytarabine; Fludarabine; Idarubicin; Clofarabine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Myelogenous Leukemia; AML; High-Risk Myelodysplastic Syndrome; MDS; Relapsed; Refractory; Clofarabine; Clofarex; Clolar; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride