E1900 A Phase III Trial in Adult Myeloid Leukemia: Daunorubicin Dose-Intensification and Gemtuzumab-Ozogamicin Consolidation Therapy Prior to Autologous Stem Cell Transplantation.

Principal Investigator: Robert M. Rifkin, MD, FACP

Protocol Number: RMBMT-131

Major Objectives

Patient Selection

Inclusion Criteria:

1. The diagnosis of AML will include patients with >20% blasts in the peripheral blood or marrow. Patients must have morphologic proof of acute myeloid leukemia of one of the following types:
   1. AML with recurrent cytogenetic translocations
      • AML with t(8;21)(q22;q22)
      • AML wit abnormal bone marrow eosinophils inv(16)(p13;q22) or t(16;16)(p13;q22)
      • AML with 11q23 abnormalities.
   2. AML with multilineage dysplasia
      • No presence of myelodysplastic syndrome
   3. Other types
      • AML not otherwise categorized
      • AML minimally differentiated
      • AML without maturation
      • AML with maturation
      • Acute myelomonocytic leukemia
      • Acute monocytic leukemia
      • Acute erythroid leukemia
      • Acute megakaryocytic leukemia
      • Acute basophilic leukemia
2. Patients must have an ECOG performance status of 0 or 1
3. Patients must not have been previously treated with radiation or cytotoxic chemotherapy. Previous therapy with corticosteroids or hydroxyurea will not exclude the patient.
4. Patients must be ≥ 16 ears of age and < 61 years of age.
5. Within 14 days randomization, patients must have a serum creatinine of ≤ 2.0mg/dl and creatinine clearance ≥ 50ml/min.
6. Within 14 days of randomization, patients must have a serum direct bilirubin ≤ 2.0mg/dl unless related to Gilbert’s syndrome or hemolysis and alkaline phosphatatse and SGOT , 4 x upper limit of normal.
7. Patients must have left ventricular ejection fraction 2.0mg/dl unless related to Gilbert’s syndrome or hemolysis and alkaline phosphatatse and SGOT , 4 x upper limit of normal.
8. Patients must have left ventricular ejection fraction ≥ 45%
9. Women must not be pregnant or breastfeeding due to the potential harmful effects to the fetus/baby.
10. Women of childebearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
11. Patients may have CNS disease/
12. Patients must not have had a prior malignancy for which chemotherapy or radiation therapy were given.
13. Patients must not have had blastic transformation of chronic myelogenous leukemia or secondary AML. AML which has evolved within 6 months form MDS will be allowed.
14. Patients must not have had significant cardiac disease shich requires active therapy.

Exclusion Criteria:

1. AML with recurrent cytogenetic translocations
   • Acute PML with t(15;17)(q22;q21)
   • Variant acute PML with t(v;17)
2. AML with multilineage dysplasia
   • With prior myelodysplastic syndrome
3. Other types
   • Acute panmyelosis with myelofibrosis.