Study of VELCADE® With Mitoxantrone and Etoposide for 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 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 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.