The primary objectives are a) to establish the maximum tolerated dose (MTD) of gemtuzumab ozogamicin in combination with cytarabine and daunorubicin, and b) to assess the safety of gemtuzumab ozogamicin when given concurrently with cytarabine and daunorubicin.

Condition	Treatment or Intervention	Phase
Acute Myeloid Leukemia	Drug: Gemtuzumab Ozogamicin	Phase II

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

All adult patients with relapsed or refractory AML, as well as younger de novo AML patients are eligible for the study. Relapsed, refractory, and de novo AML patients are allowed in Phase I of this study. Phase II will only allow enrollment of younger de novo AML. All patients must also fulfill the following criteria:

• Age 18 years or older for relapsed or refractory patients if enrolled in Phase I. De novo patients must be greater than or equal to 18 years and less than 60 years.
• Morphologic diagnosis of AML from bone marrow aspirate and biopsy. At the discretion of the attending physician, peripheral blood may substitute for a bone marrow aspirate and biopsy if the peripheral blood blast count is adequate to obtain diagnostic material.
• Flow cytometry, performed at the study site, must demonstrate that the patient has AML that is CD33-positive, based on local laboratory criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 inclusive.
• Serum creatinine less than or equal to 2.0 mg/dL (177 μmol/L).
• Serum total bilirubin less than or equal to 1.5 mg/dL (26 μmol/L).
• Serum AST (SGOT) and ALT (SGPT) less than or equal to 5 x ULN (less than or equal to NCI grade 2, version 2 of the NCI Grade Toxicity Scale).
• Capable of giving signed and dated informed consent.
• Negative serum pregnancy test within 1 week prior to first treatment if the patient is a woman of childbearing potential. Male and female patients of childbearing potential must use a medically acceptable and effective method of contraception throughout the study.
• Cardiac ejection fraction as determined by radionuclide scanning (measured in %) or echocardiography (measured as abnormal or normal) is within normal limits within 14 days of study Day 1.

Exclusion Criteria:

• AML following an antecedent hematologic disorder (myelodysplasia or myeloproliferation) of greater than 2 months duration.
• De novo patients with M3 AML.
• AML secondary to exposure to chemotherapy or radiation.
• Known central nervous system (CNS) involvement with AML. A lumbar puncture is not required unless CNS involvement with AML is clinically suspected.
• Prior treatment with any type of HSCT for relapsed and refractory patients (including autologous, allogenic, and mini-allogeneic HSCT) if enrolled in Phase I. (Only de novo patients will be enrolled in Phase II.)
• Pregnant women and nursing mothers.
• Prior therapy with anti-CD33 antibodies.
• Other active malignancy (with the exception of basal and squamous cell skin cancer) at the time of study entry.
• Uncontrolled infections.
• Severe pulmonary or cardiac disease.
• Known to be HIV positive
• Investigational agent within 4 weeks of study start.

Florida
      University of Miami - Division of Hematology/Oncology, Miami,  Florida,  33136,  United States; No longer recruiting
Illinois
      Northwestern  School  Of  Medicine, Chicago,  Illinois,  60611,  United States; No longer recruiting
Massachusetts
      Dana Farber Cancer Institute - Dept. of Oncology, Boston,  Massachusetts,  02115,  United States; No longer recruiting
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States; No longer recruiting
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; No longer recruiting
New York
      New York Medical College, Valhalla,  New York,  10595,  United States; No longer recruiting
Australia
      Westmead Hospital, Westmead,  2145,  Australia; Recruiting
Italy
      Policlinico Universitario - Divisione di Ematologia, Udine,  33100,  Italy; No longer recruiting
Netherlands
      Erasmus MC, Rotterdam,  3015 GD,  Netherlands; Recruiting
Spain
      Hospital Clinic i Provincial, Barcelona,  8036,  Spain; Recruiting
United Kingdom
      University Hospital of Wales, Cardiff,  CF4 4XW,  United Kingdom; Recruiting
      Department of Clinical Haematology - University College Hospital, London,  WC1E 6AU,  United Kingdom; Recruiting

Study ID Numbers:  0903B1-206-US
Record last reviewed:  September 2004
Record first received:  May 17, 2002
ClinicalTrials.gov Identifier:  NCT00037583
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29