LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to learn about the safety of LY2510924 in
      combination with cytarabine and idarubicin in patients with relapsed or refractory AML. We
      will also study if LY2510924 in combination with cytarabine and idarubicin can help to
      control relapsed or refractory AML.

      LY2510924 is designed to help cancer cells move from the bone marrow into the bloodstream,
      where they are exposed to chemotherapy (in this case, cytarabine and idarubicin).

      This is an investigational study. LY2510924 is not FDA approved or commercially available.
      Its use in this study is investigational. Cytarabine and idarubicin are approved to treat
      certain types of leukemia. Their use in this study in combination with LY2510924 is
      investigational.

      Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
    

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 up to 6 participants each will be
      enrolled in the Dose Escalation part of the study, and up to 18 participants will be enrolled
      in Dose Expansion part of the study.

      If you are enrolled in the Dose Escalation part of the study, the dose of LY2510924 you
      receive will depend on when you join this study. The first group of participants will receive
      the lowest dose level of LY2510924. Each new group will receive a higher dose of LY2510924
      than the group before it, if no intolerable side effects were seen. This will continue until
      the highest tolerable dose of LY2510924 is found.

      If you are enrolled in the Dose Expansion part of the study, you will receive LY2510924 at
      the highest dose that was tolerated in the Dose Expansion part of the study.

      All participants will also receive idarubicin and cytarabine. Your dose level will be
      assigned based on your age.

      Study Drug Administration:

      Treatment on this study is given in 2 phases: Induction and Consolidation. Each phase is made
      up of 28-day study cycles.

      Induction Phase:

      You will receive 1-2 cycles during the Induction phase. During Cycle 1, you will be admitted
      to the inpatient Leukemia service when you receive the study drugs.

      You will receive LY2510924 alone each day for 7 days and then together with chemotherapy on
      Days 8, 9 and 10 and also on Day 11 if you are under the age of 60, of every 28-day cycle.

        -  On days that you do not receive idarubicin/cytarabine, LY2510924 will be given as an
           injection under the skin at about 8:00 am (+/- 1½ hours).

        -  On days when you do receive idarubicin/cytarabine, it will be given about 4 hours (+/- ½
           hour) before you receive idarubicin.

      On Days 8 and 9, in addition to LY2510924:

        -  You will receive idarubicin by vein over about 1 hour.

        -  You will receive cytarabine by vein over about 24 hours.

      On Day 10, in addition to LY2510924:

        -  You will receive cytarabine by vein over about 24 hours.

        -  If you are under age 60, you will receive idarubicin by vein over about 1 hour.

      If you are under age 60, on Day 11, in addition to LY2510924, you will receive cytarabine by
      vein over about 24 hours.

      On days that you are receiving the cytarabine infusions, you will receive drugs to help
      reduce the risk of side effects. You will receive dexamethasone before the cytarabine
      infusion by vein over about 30 minutes. You will also receive corticosteroid-containing eye
      drops during this time and for 2 days following the last dose of cytarabine.

      If the disease does not respond during Cycle 1, you may be allowed to receive an additional
      Induction cycle, which will also be called Cycle 1.If you do respond to Induction, you can
      move to the Consolidation phase.

      Consolidation Phase:

      If you are benefitting from the treatment, you may continue with Consolidation therapy for an
      additional 4-6 cycles.

      During these cycles, you will receive LY2510924 in the same way as during earlier cycles, for
      3 days with chemotherapy. During Consolidation, all participants will receive idarubicin by
      vein over 1 hour on Days 1 and 2, and cytarabine by vein over 24 hours on Days 1-3.

      Study Visits:

      During Days 1-12 of Cycle 1 (if over the age of 60, Days 1-10), blood (about 4 teaspoons)
      will be drawn for routine tests. During Days 1-7, blood (about 2 teaspoons) will be drawn 4
      hours after your injection with LY2510924 for routine tests.

      On Days 8 and 28 of Cycle 1, you will have a bone marrow biopsy/aspirate to check the status
      of the disease.

      After Day 11 of Cycle 1, blood (about 4 teaspoons) will be drawn every 2-4 days for routine
      tests.

      Every 1-2 weeks during Cycles 2-6, blood (about 4 teaspoons) will be drawn for routine tests.

      Every 2-4 weeks during Cycles 2-6, you will have a physical exam.

      After Cycles 4 and 6, you will have a bone marrow biopsy and aspiration to check the status
      of the disease. You will also have an EKG and either an ECHO or MUGA scan.

      Any time the doctor thinks it is needed, you will have additional blood tests.

      Length of Study:

      You may receive up to 8 cycles of the study drugs. You will be taken off study if the disease
      gets worse, you experience intolerable side effects, or if the study doctor thinks it is in
      your best interest.

      Your participation on this study will be over after you complete the End-of-Treatment Visit.

      End-of-Treatment Visit:

      About 30 days (+/- 5 days) after your last dose of the study drugs, blood (about 2 teaspoons)
      will be drawn for routine tests.

      Long Term Follow-up:

      Every 2-3 months for up to 2 years after you stop receiving the study drugs, blood (about 4
      teaspoons) will be drawn for routine tests. This can be performed at your local doctor's
      office. You should also have a bone marrow aspiration/biopsy every 3 months for the first
      year, and then more after that if the doctor thinks it is in your best interest. If any of
      these tests show abnormal results, you will return to the study clinic for follow-up testing.
    

Intervention name(s): LY2510924; Idarubicin; Cytarabine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients.
Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase.; Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days.
Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days.; Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only.
Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.
Other intervention name(s): Idamycin; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride
Intervention MeSH terms: Cytarabine; Idarubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Acute Myeloid Leukemia; AML; Relapsed or Refractory; Acute myelogenous leukemia; LY2510924; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride