Phase I/II Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

The combination of mitoxantrone and etoposide is an active regimen in refractory/relapsed
AML patients. In order to improve the efficacy of mitoxantrone and etoposide as second line
therapy in patients with AML we proposed to conduct a phase I/II clinical trial combining
gemtuzumab ozogamicin with mitoxantrone and etoposide. The phase I portion of the trial will
determine the maximum tolerated dose of gemtuzumab ozogamicin combined with mitoxantrone and
etoposide and the phase II portion of the trial will determine the efficacy and safety of
the combined regimen in patients with AML.

Inclusion Criteria:

- Able to understand and have the ability to provide written consent

- Between 18 and 70 years of age

- Patients with CD33 positive (determined as CD33 expression in ≥ 20% of leukemic
blasts) de novo AML that did not respond to first line induction therapy

- ECOG Performance Status of 0-2

- Patients must have the following laboratory values within 48 hours prior to beginning
protocol treatment: Serum creatinine ≤ 1.5 mg/ml and calculated creatinine clearance
≥ 50mL/min (using the Cockcroft-Gault equation); AST ≤ 59 IU/L; ALT ≤ 72 IU/L; Total
bilirubin ≤ 1.3 mg/ml; Note: Hematologic abnormalities will not be used as a criteria
for entry or exclusion.

- Patients must have left ventricular ejection fraction (LVEF) ≥50%

- Females of child-bearing potential must have a negative pregnancy test during
screening and all subjects must agree to use an effective method of contraception.

Exclusion Criteria:

- Patients with acute promyelocytic leukemia

- Prior use of mitoxantrone or etoposide or gemtuzumab ozogamicin

- Antecedent hematologic disorder preceding initial presentation of AML or therapy
related AML

- History of thromboembolic event within the past 12 months

- Hepatitis B or C or HIV positive serology

- Symptomatic central nervous system (CNS) involvement

- History of congestive heart failure

- Myocardial infarction in the past 6 months

- Uncontrolled, life-threatening infection that is not responding to antimicrobial
therapy

- History of psychiatric disorder which may compromise compliance with the protocol or
which does not allow for appropriate informed consent

- Patient may not be receiving any other anti neoplastic investigational agents

- INR> 1.5 or patient is receiving systemic anticoagulation (e.g warfarin)

- Patient undergone autologous or allogeneic stem cell transplantation

- Other active malignancies except for non-melanoma skin cancer or cervical
intraepithelial neoplasia

- Women who are pregnant or breastfeeding.