Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different
      ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies,
      such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver
      cancer-killing substances to them without harming normal cells. Giving monoclonal antibody
      therapy together with chemotherapy may kill more cancer cells. Giving healthy stem cells from
      a donor whose blood closely resembles the patient's blood will help the patient's bone marrow
      make new stem cells that become red blood cells, white blood cells, and platelets.

      PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together
      with gemtuzumab ozogamicin works in treating patients with previously untreated high-risk
      myelodysplastic syndrome or acute myeloid leukemia secondary to myelodysplastic syndrome.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the feasibility of combining gemtuzumab ozogamicin with idarubicin and
           cytarabine with or without cyclophosphamide with total body irradiation vs busulfan
           followed by allogeneic stem cell transplantation in patients with previously untreated
           high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS.

        -  Determine the toxicity profile of this regimen in these patients.

        -  Determine the antileukemic/anti-MDS activity of this regimen in these patients.

      Secondary

        -  Determine the hepatotoxicity of this regimen, in terms of veno-occlusive disease, in
           these patients.

        -  Determine the severity of pancytopenia and duration of recovery in patients treated with
           this regimen.

      OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.

        -  Group 1 (for patients with no HLA-matched sibling donor): Patients receive
           remission-induction chemotherapy comprising idarubicin IV over 5 minutes on days 1, 3,
           and 5; cytarabine IV continuously over 24 hours on days 1-10; and gemtuzumab ozogamicin
           IV over 2 hours on day 7. Treatment continues for a second course in the absence of
           unacceptable toxicity.

        -  Group 2 (for patients with an HLA-matched sibling donor): Patients are randomized to 1
           of 2 treatment arms.

             -  Arm I: Patients receive myeloablative consolidation chemotherapy comprising
                cyclophosphamide on days -6 and -5 and total body irradiation twice daily on days
                -4 to -2.

             -  Arm II: Patients receive myeloablative consolidation chemotherapy comprising
                busulfan on days -8 to -5 and cyclophosphamide on days -4 and -3.

      Patients in both arms may alternatively undergo T-cell depletion and/or a reduced-intensity
      conditioning regimen.

      Approximately 4-8 weeks after completion of consolidation chemotherapy, all patients in group
      2 undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell
      transplantation. Patients in group 2 then proceed to remission-induction chemotherapy as in
      group 1.

      Patients achieving complete remission are recommended for consolidation therapy off study.

      Patients are followed monthly for 6 months, every 2 months for 6 months, and then every 3
      months thereafter.

      PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study within 10 months.
    

Intervention name(s): busulfan; cyclophosphamide; cytarabine; gemtuzumab ozogamicin; idarubicin; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Busulfan; Idarubicin; Gemtuzumab
Allocation: Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated adult acute myeloid leukemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes