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Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT00801489

Description:

This phase II trial studies the side effects and how well fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride work in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as fludarabine phosphate, cytarabine, and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Immunotherapy with monoclonal antibodies, such as gemtuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Colony-stimulating factors, such as filgrastim-sndz, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride may kill more cancer cells.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Refractory Anemia with Excess Blasts
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Fludarabine, Cytarabine, Filgrastim, Gemtuzumab Ozogamicin, and Idarubicin in Core Binding Factor (CBF) Leukemias
  • Official Title: A Phase 2 Study of Fludarabine, Cytarabine, Filgrastim, Gemtuzumab Ozogamicin and Idarubicin in Newly Diagnosed Core Binding Factor Associated Acute Myelogenous Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2007-0147
  • SECONDARY ID: NCI-2012-01659
  • NCT ID: NCT00801489

Conditions

  • Acute Myelogenous Leukemia

Interventions

DrugSynonymsArms
FludarabineFludara®Remission Induction Group
CytarabineCytosar-U, Ara-CRemission Induction Group
G-CSF (Filgrastim, Neupogen)Neupogen, Granulocyte Colony-Stimulating Factor, G-CSFRemission Induction Group
IdarubicinIdamycinRemission Induction Group
Gemtuzumab ozogamicinGemtuzumab, MylotargRemission Induction Group

Purpose

The goal of this clinical research study is to learn if gemtuzumab ozogamicin and idarubicin can be added to the combination of fludarabine, cytarabine, and Neupogen (Filgrastim) without increasing the risk of side effects. This study will also look at whether the addition of gemtuzumab ozogamicin and idarubicin will increase the long-term chances of patients remaining disease free. This is an investigational study. Cytarabine is 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). Filgrastim is FDA approved and commercially available to treat fever associated with low white cell counts in patients with AML. Gemtuzumab ozogamicin and Idarubicin are FDA approved and commercially available for the treatment of acute leukemias, lymphomas, Hodgkin's disease and breast cancer. At this time, their use in combination is for research purposes only. Decitabine is FDA approved for treatment of myelodysplastic syndrome and is commercially available. The study doctor will explain how the study drugs are designed to work. Up to 200 patients will take part in this study. All will be enrolled at MD Anderson.

Detailed Description

      Parts of the Study:

      There will be 2 parts to this study. The first part of the study is called induction therapy.
      During induction, the study doctor will try to get rid of the leukemia cells from your bone
      marrow. If induction causes the leukemia cells to be removed from your bone marrow and your
      blood counts return to normal, you will be in remission. Induction usually lasts 4-6 weeks.

      If you are in remission, you will begin the second part of the study, called post-remission
      therapy. You will receive up to 4-6 cycles (1 cycle every 4-6 weeks) of post-remission
      therapy, depending on your blood counts. Each study cycle lasts 4-6 weeks.

      Study Drug Administration:

      If you are found to be eligible to take part in this study, during induction therapy, you
      will be given fludarabine and cytarabine through a needle in your vein every day, for 5 days
      in a row (Days 1-5). You will receive fludarabine over 30 minutes and cytarabine over 4
      hours.

      Filgrastim will be given one time daily as an injection just under the skin starting on the
      day before you receive fludarabine and cytarabine, and you will continue to receive
      filgrastim one time daily until your white blood cell count is near normal.

      Once you complete chemotherapy, your doctor may decide to give a dose of pegfilgrastim
      instead of daily filgrastim.

      You will receive idarubicin through a needle in your vein over 30 minutes on Days 3 and 4
      right after you receive fludarabine. You will receive gemtuzumab on Day 1 through by vein
      over 2 hours. If you are 66 years or older, and the doctor thinks it is in your best
      interest, you will receive fewer days of cytarabine, fludarabine and idarubicin. The doctor
      will discuss this with you.

      Gemtuzumab may cause allergic reactions, nausea, and vomiting. To help prevent such side
      effects, you will receive Tylenol (acetaminophen), Benadryl (diphenhydramine) and
      corticosteroids. You can receive these drugs by vein, or by mouth.

      During post-remission therapy, you will receive fludarabine and cytarabine for 3 days (Days
      1-3) instead of 5 days. During Cycle 4 of post-remission therapy, you will receive idarubicin
      at the same dose as given during induction therapy on Days 2 and 3.

      During either Cycles 2 or 3, and or in Cycles 5 or 6 of post-remission therapy, you will
      receive gemtuzumab at the same dose as given during induction.

      You will receive filgrastim one time on the day before each post-remission cycle and you will
      continue to receive filgrastim one time daily until your white blood cell count is near
      normal.

      Your doctor may decide to give a dose of pegfilgrastim instead of daily filgrastim

      During post-remission therapy, you may begin receiving decitabine instead of fludarabine,
      cytarabine, filgrastim, gemtuzumab, and idarubicin if you are 60 years or older, or if you
      have had intolerable side effects. If the doctor thinks it is in your best interest, you will
      begin receiving decitabine infusions over 1 hour, for 5 days in a row, every 4-6 weeks for up
      to 12 cycles. The doctor will discuss this with you.

      Study Visits:

      During induction therapy, blood (about 2 teaspoons) will be drawn at least once a week for
      routine testing.

      After 3 weeks (Between Days 18-24), you will have a bone marrow aspirate to check the status
      of the disease. If the leukemia cells are not completely gone from your bone marrow by the
      end of 3 weeks, your study doctor may decide to repeat the test.

      If the repeat bone marrow aspirate shows that you are not in remission, your study doctor may
      decide to give you another cycle of induction therapy.

      Once you begin post-remission therapy, you will have the following tests and procedures:

        -  You will have a physical exam, including measurement of your vital signs, including your
           weight.

        -  You will be asked how well you are able to perform the normal activities of daily living
           (performance status).

        -  Blood (about 2 teaspoons) will be drawn for routine blood tests.

      At Months 4 and 7, you will have a bone marrow aspirate to check the status of the disease.

      Part of the bone marrow sample collected at these bone marrow aspirations will be sent to the
      M.D. Anderson molecular lab for testing.

      If your study doctor thinks it is necessary, you may have a bone marrow aspirate after the
      first 7 months to check the status of the disease.

      Length of Study:

      You will be on study for one cycle of induction therapy and up to 6 cycles of post-remission
      therapy. You will be taken off study if the disease gets worse or intolerable side effects
      occur.

      Long-term follow up:

      You will have blood (about 2 teaspoons) drawn for routine testing every 6 months for 2 years
      after the study.
    

Trial Arms

NameTypeDescriptionInterventions
Remission Induction GroupExperimentalFludarabine by vein on Days 1, 2, 3, 4, and 5. Cytarabine by vein on Days 1, 2, 3, 4, and 5 infusion starting 3.5 hours after the completion of Fludarabine. Gemtuzumab ozogamicin by vein over on Day 1.Idarubicin by vein given immediately after Fludarabine administration on Days 3 and 4. Filgrastim starting Day -1 till recovery of absolute neutrophil count (ANC) to 1.0 X 10^9/L or above. (Filgrastim started after WBC count is < 5 X 10^9/L for patients with presenting WBC count > 10 X 10^9/L).
  • Fludarabine
  • Cytarabine
  • G-CSF (Filgrastim, Neupogen)
  • Idarubicin
  • Gemtuzumab ozogamicin
Post-Remission Therapy GroupExperimentalFludarabine, Cytarabine, and Filgrastim as during induction except that Fludarabine and Cytarabine given for 3, rather than 5 days. Idarubicin administered as in induction cycle, in one post-remission cycle (from cycle 3-6). Idarubicin given immediately after Fludarabine administration on Days 2 and 3. Filgrastim given on Day -1 of each post-remission cycle irrespective of WBC count. Gemtuzumab ozogamicin as in induction cycle, in post-remission cycle 1 or 2 and cycle 5 or 6.
  • Fludarabine
  • Cytarabine
  • G-CSF (Filgrastim, Neupogen)
  • Idarubicin
  • Gemtuzumab ozogamicin

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have untreated AML, or high-risk MDS [refractory anemia with excess
             blasts, (RAEB), or RAEB "in transformation" (RAEB-t)] characterized by t(8;21),
             inv(16), or t(16;16).The presence of additional abnormalities is irrelevant.

          2. Age equal to or greater than 18 years (the safety of GO in patients <18 years is not
             determined and advantage of fludarabine, cytarabine, idarubicin-based regimen in CBF
             leukemias in children is not demonstrated).

          3. Patients must provide written consent.

          4. Because of the high possibility of CR in CBF leukemias, participants will not be
             excluded based on performance status.For patients with Eastern Co-operative Oncology
             Group (ECOG) performance status >/= to 3 the dosing schedule will be discussed with
             study chairman.

          5. Patients with organ dysfunction will not be excluded from the study. For patients with
             evidence of organ dysfunction (creatinine >/= 1.5, cardiac ejection fraction </= 50%,
             total bilirubin >/=2 and AST/ALT >/= 3 times ULN, dose adjustments/omissions will be
             made.

          6. Up to one cycle of prior induction therapy will be permitted to include patients in
             whom presence of "good-risk" cytogenetics was initially missed. If the patient is in
             remission from induction therapy, he/she will receive post-remission therapy. If the
             patient is not in remission then he/she will receive induction therapy.

          7. Patients of child bearing potential should practice effective methods of
             contraception.

        Exclusion Criteria:

        1) Pregnant and lactating females will be excluded since the safety of GO or FLAG + Ida in
        pregnancy and lactation is unknown.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response (CR) Rate and Toxicity Rate
Time Frame:Weekly blood tests, bone marrow aspirate Days 18-24 and at 4 + 7 months, blood tests every 2-3 months for 2 years
Safety Issue:
Description:Response criteria recommended by the NCI and MDS International Working Group. Complete Response (CR): Peripheral blood counts, No circulating blasts, Neutrophil count ≥ 1.0 X 109/L, Platelet count ≥ 100 X 109/L, Bone marrow aspirate and biopsy, ≤5% blasts, No detectable auer rods, No extramedullary leukemia CRp: Response as in CR but platelets <100 X 109/L Partial response (PR): Peripheral blood counts, No circulating blasts, Neutrophil count ≥ 1.0 X 109/L, Platelet count ≥ 100 X 109/L, ≥ 50% reduction in bone marrow blasts over baseline

Secondary Outcome Measures

Measure:Event Free Survival
Time Frame:2 years
Safety Issue:
Description:Event free survival at 2 years defined as death and relapses.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Leukemia
  • Acute Myelogenous Leukemia
  • AML

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