Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Intervention: sargramostim; busulfan; cyclophosphamide; cytarabine; gemtuzumab ozogamicin (GO); Daunorubicin; Autologous HCT; Allogeneic HCT
Intervention description: Given IV or as an injection; Given IV; Given IV; Given as a continuous infusion; Given IV; Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.; Autologous hematopoietic cell transplantation; Allogeneic hematopoietic cell transplantation
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Busulfan; Daunorubicin; Gemtuzumab; Sargramostim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 657.0
Sex: All
Minimum age: 16 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: acute myeloid leukemia; autologous transplantation; gemtuzumab ozogamicin

Summary:

      RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the
      growth of cancer cells. It also helps stop the patient's immune system from rejecting the
      transplanted stem cells. When the healthy stem cells are infused into the patient they may
      help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
      platelets. If the patient's stem cells are to be transplanted, the patient is also treated
      with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells
      or deliver cancer-killing substances to them without harming normal cells. It is not yet
      known whether combination chemotherapy is more effective with or without gemtuzumab
      ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

      PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab
      ozogamicin, and stem cell transplant to see how well they work compared to combination
      chemotherapy and peripheral stem cell transplant alone in treating patients with acute
      myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the
             peripheral blood or marrow) meeting any of the following criteria:

               -  Recurrent cytogenetic translocations

                    -  t(8;21)(q22;q22)

                    -  Bone marrow eosinophil abnormalities

                         -  inv(16)(p13;q22)

                         -  t(16;16)(p13;q22)

                    -  11q23 abnormalities

               -  Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)

               -  Minimally differentiated AML

               -  AML without maturation

               -  AML with maturation

               -  AML not otherwise categorized

               -  Acute myelomonocytic leukemia

               -  Acute monocytic leukemia

               -  Acute erythroid leukemia

               -  Acute megakaryocytic leukemia

               -  Acute basophilic leukemia

          -  Patients undergoing allogeneic transplantation must have a sibling donor match defined
             as human leukocyte antigen (HLA) match or haplotype match with one locus mismatch on
             other haplotype

          -  Age 16 to 60

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-4

          -  Aspartate aminotransferase (AST) less than 4 times upper limit of normal (ULN)

          -  Alkaline phosphatase less than 4 times ULN

          -  Creatinine no greater than 2.0 mg/dL

          -  Creatinine clearance at least 50 mL/min

          -  Left ventricular ejection fraction (LVEF) at least 45% by post-induction multigated
             acquisition (MUGA) scan

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  HIV negative

          -  Prior hydroxyurea allowed

          -  Prior corticosteroids allowed

        Exclusion Criteria:

          -  Recurrent cytogenetic translocations

               -  Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)

               -  Variant acute PML with t(v;17)

          -  Multilineage dysplasia with prior MDS

          -  Acute panmyelosis with myelofibrosis

               -  Blastic transformation of chronic myelogenous leukemia

               -  Secondary AML (chemotherapy-induced or evolved from MDS)

               -  Pregnant or nursing

               -  Bilirubin greater than 2.0 mg/dL (unless related to Gilbert's syndrome or
                  hemolysis)

               -  Significant cardiac disease requiring active therapy (e.g., digoxin, diuretics,
                  antiarrhythmics, or antianginal medications)

               -  Prior biologic therapy

               -  Prior cytotoxic chemotherapy for any malignancy

               -  Prior radiotherapy for any malignancy