Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias

Inclusion Criteria:

- Female subject is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.

- Male subject agrees to use an acceptable method for contraception for the duration of
the study.

- Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute
Lymphoblastic Leukemia (ALL) will be eligible for the study.

- Patients must have failed initial therapy that may manifest in either of the
following ways:

- Demonstration of Primary Refractory Disease (Primary Induction Failure) as
evidenced by a mid-cycle bone marrow analysis showing lack of complete
tumor clearance (CTC).

- Relapse of initial disease after a period of attaining complete remission.

- Patients must be > 18 years of age, with no upper age limit.

- ECOG performance status of 0 or 1.

- Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and
renal function as measured by the following criteria:

- Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA
preferred)

- Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the
institution's clinical laboratory.

- Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine
outside normal range then creatinine clearance > 60 mL/min/m2

- Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute
Lymphoblastic Leukemia (ALL) will be eligible for the study.

- Patients must have failed initial therapy that may manifest in either of the
following ways:

- Demonstration of Primary Refractory Disease (Primary Induction Failure) as
evidenced by a mid-cycle bone marrow analysis showing lack of complete tumor
clearance (CTC).

- Relapse of initial disease after a period of attaining complete remission.

- Patients must be > 18 years of age, with no upper age limit.

- ECOG performance status of 0 or 1.

- Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and
renal function as measured by the following criteria:

- Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA
preferred)

- Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the
institution's clinical laboratory.

- Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine
outside normal range then creatinine clearance > 60 mL/min/m2

Exclusion Criteria:

- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.

- Myocardial infarction within 6 months prior to enrollment or has New York Hospital
Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities. Prior to study entry,
any ECG abnormality at screening has to be documented by the investigator as not
medically relevant.

- Patient has hypersensitivity to bortezomib, boron or mannitol.

- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum or urinary pregnancy test result
obtained during screening. Pregnancy testing is not required for post-menopausal or
surgically sterilized women.

- Patient has received other investigational drugs within 14 days before enrollment

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.