Decitabine Followed by Clofarabine, Idarubicin, and Cytarabine in Acute Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of Phase I of this clinical research study is find the highest tolerable dose of
      clofarabine that can be given with decitabine, idarubicin, and cytarabine to patients with
      acute leukemia.

      The goal of Phase II of this study is to learn if decitabine followed by the combination of
      clofarabine, idarubicin, and cytarabine can help to control acute leukemia. The safety of
      this drug combination will also be studied.

      Decitabine and idarubicin are designed to damage the DNA (the genetic material of cells).
      This may cause cancer cells to die.

      Clofarabine is designed to interfere with the growth and development of cancer cells.

      Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.
    

Detailed description: 
      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 3 groups of 6 participants will be enrolled in
      the Phase I portion of the study. Up to 74 participants will be enrolled in Phase II.

      Phase I:

      If you are enrolled in the Phase I portion, the number of days of clofarabine you receive
      will depend on when you joined this study. The first group of participants will receive
      clofarabine for 4 days. Each new group will receive clofarabine for the same number of days,
      if no intolerable side effects were seen. The number of days may be reduced to 3. The
      clofarabine dose per day is the same from group to group.

      All participants will receive the same dose level of decitabine, idarubicin and cytarabine.

      Phase II:

      If you are enrolled in the Phase II portion, you will receive decitabine, idarubicin, and
      cytarabine. You will receive clofarabine for the highest number of days that was tolerated in
      the Phase I portion.

      All participants will receive the same dose level of decitabine, idarubicin, cytarabine, and
      clofarabine.

      Study Drug Administration:

      Each study drug cycle is 33 days. The first cycle of study drugs is called Induction. If the
      doctor thinks it is needed, you will have up to 2 Induction cycles.

      Phase I (Induction):

      On Days 1-5 of each cycle, you will receive decitabine 1 time a day by vein over about 1
      hour.

      On Days 6-10 of each cycle:

        -  You will receive cytarabine 1 time a day by vein over about 2 hours.

        -  On Days 6-8 only, you will receive idarubicin 1 time a day by vein over about 30
           minutes.

        -  You will receive clofarabine 1 time a day by vein over about 1 hour on Days 6-8 or 6-9,
           depending on when you join the study.

      If the doctor thinks it is needed, your dose level will be reduced after Induction.

      If the doctor thinks it is needed, you may receive fewer days of treatment in the Induction
      cycle(s).

      Phase II (Induction):

      On Days 1-5 of each cycle, you will receive decitabine 1 time a day by vein over about 1
      hour.

      On Days 6-10 of each cycle:

        -  You will receive cytarabine 1 time a day by vein over about 2 hours.

        -  On Days 6-8 only, you will receive idarubicin 1 time a day by vein over about 30
           minutes.

        -  You will receive clofarabine 1 time a day by vein over about 1 hour on Days 6-8 or 6-9,
           depending on the highest number of days clofarabine was tolerated in the Phase I portion
           of the study.

      If the doctor thinks it is needed, your dose level will be reduced after Induction.

      If the doctor thinks it is needed, you may receive fewer days of treatment in the Induction
      cycle(s).

      Phases I and II (Consolidation):

      If the disease responds to the study drugs, you may receive up to 6 more study drug cycles.
      This is called Consolidation.

      On Days 1-5 of each cycle:

      °You will receive decitabine 1 time a day by vein over 1 hour.

      On Days 6-8 of each cycle:

        -  You will receive cytarabine 1 time a day by vein over about 2 hours.

        -  You will receive clofarabine 1 time a day by vein over about 1 hour.

        -  On Days 6-7 only, you will receive idarubicin 1 time a day by vein over about 30
           minutes.

      If the doctor thinks it is needed, you may receive fewer days of treatment in the
      Consolidation cycles.

      Study Visits:

      Before the start of each cycle, you will have a physical exam, including measurement of your
      vital signs.

      Every 3-7 days, blood (about 2 teaspoons) will be drawn for routine tests.

      On Day 33 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 Treatment:

      You may continue taking the study drugs for up to 8 cycles. You will no longer be able to
      take the study drugs if the disease gets worse, if intolerable side effects occur, or if you
      are unable to follow study directions.

      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 your last study drug dose, the study staff will call you and
      ask 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. Decitabine is FDA approved and commercially available to
      treat myelodysplastic syndrome (MDS). Clofarabine is FDA approved and commercially available
      to treat ALL in children. Idarubicin and cytarabine are FDA approved and commercially
      available to treat AML. The study drug combination is investigational.

      Up to 92 participants will be enrolled in this study. All will take part at MD Anderson.
    

Intervention name(s): Decitabine; Idarubicin; Cytarabine; Clofarabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Phase I and II - 20 mg/m2 by vein daily for 5 days (days 1-5); Phase I and II - 10 mg/m2 by vein daily for 3 days (days 6-8); Phase I and II - 1 g/m2 by vein daily for 5 days (days 6-10); Phase I Starting Dose - 15 mg/m2 by vein daily for 4 days (days 6-9)
Phase II Starting Dose - Maximum tolerated dose from Phase I (number of days selected based on Phase I portion).
Other intervention name(s): Dacogen; Idamycin; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Clofarex; Clolar
Intervention MeSH terms: Cytarabine; Decitabine; Clofarabine; Idarubicin
Intervention model: Sequential Assignment
Intervention model description: Starting with Dose level 1, the participants were enrolled by cohort of 3. Once the DLT assessment is completed, another cohort of 3 patients will be enrolled. If at any time, we see more than 30% patients experiencing DLT, we will de-escalate to dose level (-1).
Period 1: Dose level 1 Clofarabine 15mg/m^2 daily x 4 days (days 6-9)
Period 2: Dose level-1 Clofarabine 15mg/m^2 daily x 3 days (days 6-8)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Acute Leukemia; Acute myelogenous leukemia; AML; Acute lymphoblastic leukemia; ALL; Maximum Tolerated Dose; MTD; Response Rate; Decitabine; Dacogen; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride