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

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 relapsed refractory and older de novo AML patients are allowed in Phase I of this study. (De novo patients will not participate in Phase I, Step 1a, when the Day 1 and Day 8 gemtuzumab ozogamicin alone schedule is utilized). Phase II will only allow enrollment of older de novo AML patients. All patients must also fulfill the following criteria:

• Morphologic diagnosis of AML from bone marrow aspirate and biopsy. At the discretion of the attending physician and the peripheral blood blast count is adequate to obtain diagnostic material, peripheral blood may substitute for a bone marrow aspirate and biopsy.
• Flow cytometry, performed at the study site, must demonstrate that the patient has AML that is CD33+, based on local laboratory criteria.
• Age 18 years or older for relapsed or refractory patients for Phase I of this study. De novo patients must be age 60 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Serum creatinine less than or equal to 2.0 mg/dL.
• Serum total bilirubin less than or equal to 1.5 mg/dL.
• Transaminase levels (AST/SGOT, ALT/SGPT) less than or equal to 5X ULN (upper limit of normal).
• 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

Exclusion Criteria:

• Patients with de novo AML of the M3 subtype.
• AML following an antecedent hematologic disorder (myelodysplasia or myeloproliferation) of > 2 months duration.
• AML secondary to exposure to chemotherapy or radiation.
• Prior HSCT including allogeneic, mini-allogeneic and autologous if enrolled in Phase 1. (only de novo patients will be enrolled in Phase II.)
• Peripheral white blood count (WBC) greater than or equal to 30,000/uL at the time of initial gemtuzumab ozogamicin administration. In order to reduce the peripheral blood count, patients may be treated with hydroxyurea or leukapheresis.
• Known central nervous system (CNS) involvement with AML. A lumbar puncture is not required unless CNS involvement with AML is clinically suspected.
• Prior therapy with anti-CD33 antibodies.
• Other active malignancy at time of study entry, except basal cell and squamous cell skin cancer.
• Uncontrolled infections
• Severe pulmonary or cardiac disease.
• Known to be HIV positive.
• Investigational agent within 4 weeks of study start.
• Pregnant women or nursing mothers.

California
      Stanford Medical Center - Hematology Department, Stanford,  California,  94305,  United States
Indiana
      IOHC/Methodist Hospital in Clarian, Indianapolis,  Indiana,  46202,  United States
Massachusetts
      New England Medical Center - Div. of Hematology/Oncology, Boston,  Massachusetts,  02111,  United States
New York
      New York Hospital - Cornell Medical Center, New York,  New York,  10021,  United States
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
Switzerland
      Universitatsspital - Abteilung fur Onkologie, Zurich,  8091,  Switzerland

Study ID Numbers:  0903B1-205-US
Record last reviewed:  June 2004
Record first received:  May 17, 2002
ClinicalTrials.gov Identifier:  NCT00037596
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-14