Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: asparaginase; cytarabine; daunorubicin hydrochloride; etoposide; gemtuzumab ozogamicin; mitoxantrone hydrochloride
Intervention description: Given intramuscularly; Given IV; Given IV over 6 hours; Given IV over 1-4 hours; Given IV over 2 hours; Given IV over 1 hour
Intervention MeSH terms: Cytarabine; Etoposide; Daunorubicin; Mitoxantrone; Asparaginase; Gemtuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1070.0
Sex: All
Maximum age: 29 Years
Healthy volunteers: No
Keywords: 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); untreated adult acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); childhood acute basophilic leukemia; childhood acute eosinophilic leukemia; childhood acute minimally differentiated myeloid leukemia (M0); childhood acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia with maturation (M2); childhood acute myelomonocytic leukemia (M4); childhood acute monocytic leukemia (M5b); childhood acute monoblastic leukemia (M5a); childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7)

Summary:

      RATIONALE: Drugs used in chemotherapy 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, 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. Giving combination chemotherapy together with gemtuzumab
      may kill more cancer cells. It is not yet known whether combination chemotherapy is more
      effective with or without gemtuzumab in treating patients with newly diagnosed acute myeloid
      leukemia.

      PURPOSE: This randomized phase III trial is studying combination chemotherapy and gemtuzumab
      to see how well they work compared with combination chemotherapy alone in treating young
      patients with newly diagnosed acute myeloid leukemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Newly diagnosed acute myeloid leukemia (AML)

               -  Meets customary criteria for AML with ≥ 20% bone marrow blasts (by WHO
                  classification)

                    -  Patients with < 20% bone marrow blasts and cytopenia or myelodysplastic
                       syndromes (e.g., chronic myelomonocytic leukemia, refractory anemia (RA), RA
                       with excess blasts, RA with ringed sideroblasts) are eligible provided 1 of
                       the following criteria is met:

                         -  Karyotypic abnormality characteristic of de novo AML (t[8;21][q22;q22],
                            inv[16][p13q22], t[16;16][p13;q22], or 11q23 abnormalities)

                         -  Unequivocal presence of megakaryoblasts (by WHO classification)

               -  Isolated myeloid sarcoma (i.e., myeloblastoma or chloroma) allowed regardless of
                  bone marrow results

          -  Infants < 1 month of age with progressive disease* are eligible NOTE: *Infants < 1
             month of age with AML may be given supportive care until it is clear that the leukemia
             is not regressing (i.e., the disappearance of peripheral blasts and the normalization
             of peripheral blood counts)

          -  Patients with Down syndrome ≥ 4 years of age are eligible

          -  No juvenile myelomonocytic leukemia

          -  No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone
             marrow failure syndrome

          -  No promyelocytic leukemia (M3)

          -  No secondary or treatment-related AML

          -  Matched family donor criteria (for patients with intermediate-risk or high-risk
             disease):

               -  HLA-A, -B, -C, and beta chain (-DRB1), identical or 1 antigen or allele
                  mismatched by molecular high resolution technique

               -  All available first-degree family members (parents and siblings) must be HLA
                  typed

               -  No syngeneic donors

          -  Matched alternative donor criteria (for patients with high-risk disease):

               -  HLA-A, -B, -C, and -DRB1, identical or 1 antigen or allele mismatched donor

               -  HLA-A, -B, and -DRB1 4 of 6 antigen matched unrelated cord blood donor

               -  Mismatched family member donor with ≥ 1 haplotype match or 5 of 6 antigen
                  phenotypic match

        PATIENT CHARACTERISTICS:

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy, radiation therapy, or any antileukemic therapy

               -  Topical or inhalation steroids for other conditions allowed

               -  Intrathecal cytarabine given at diagnosis allowed

          -  No other prior treatment for AML

          -  No concurrent peripheral blood stem cell transplantation in patients with matched
             family donor