Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different
      ways to stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in
      different ways. Some block the ability of cancer cells to grow and spread. Others find cancer
      cells and help kill them or carry cancer-killing substances to them. It is not yet known
      whether cytarabine and daunorubicin followed by gemtuzumab ozogamicin is more effective than
      cytarabine and daunorubicin in treating acute myeloid leukemia or myelodysplastic syndromes.

      PURPOSE: This randomized phase III trial is studying cytarabine and two different doses of
      daunorubicin to see how well they work compared to cytarabine and daunorubicin followed by
      gemtuzumab ozogamicin in treating older patients with acute myeloid leukemia or
      myelodysplastic syndromes.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the event-free and disease-free survival of older patients with acute myeloid
           leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated
           with induction therapy comprising cytarabine in combination with two different doses of
           daunorubicin followed by cytarabine alone with or without post-induction therapy
           comprising gemtuzumab ozogamicin.

      Secondary

        -  Compare the complete remission rate in patients treated with these regimens.

        -  Compare the overall survival of patients treated with these regimens.

        -  Compare the toxicity of these regimens in these patients.

        -  Determine the probability of relapse and death during first complete remission in
           patients treated with post-induction gemtuzumab ozogamicin.

        -  Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or
           cytogenetics) with probability of complete remission and overall, event-free, and
           disease-free survival of patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes
      [MDS]) for induction therapy. Patients are stratified according to participating center,
      diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy
      (complete remission [CR] vs no CR) for post-induction therapy.

        -  Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment
           arms.

             -  Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV
                over 3 hours on days 1-3.

             -  Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at
                a higher dose.

      Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows
      evidence of resistant disease), patients in both arms proceed to course 2 of induction
      therapy.

        -  Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice
           daily on days 1-6.

      After completion of course 2, patients undergo assessment of remission status. Patients who
      do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction
      therapy and undergo a second randomization.

        -  Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.

             -  Arm I: Patients receive no further chemotherapy.

             -  Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and
                57 in the absence of disease relapse or unacceptable toxicity.

      After completion of study treatment, patients are followed monthly for 1 year, every 3 months
      for 2 years, every 4-6 months for 2 years, and then periodically thereafter.

      PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.
    

Intervention name(s): cytarabine; daunorubicin hydrochloride; gemtuzumab ozogamicin
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Cytarabine; Daunorubicin; Gemtuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; de novo myelodysplastic syndromes; adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); secondary myelodysplastic syndromes