Study was closed to enrollment when it became clear that enrollment was too slow to complete full enrollment target within time frame allowed.

The current study is being conducted to evaluate the possibility that a different schedule of bortezomib, doxorubicin HCl liposome, and dexamethasone might decrease the incidence of peripheral neuropathy yet maintain similar efficacy and allow maintenance of bortezomib dosing for a longer period.

Inclusion Criteria:

• Patient is at least 18 years of age.
• Patient has confirmed diagnosis of relapsed/refractory multiple myeloma with measurable disease by serum or urine. Measurable disease defined as monoclonal protein of ≥ 1g/dl on serum protein electrophoresis (SPEP) or > 200 mg urine M protein/ 24 hours
• Patient has received at least 1 prior treatment regimen. (Prior treatment with bortezomib is allowed.)
• Patient has ECOG ≤ 2
• Patient provides voluntary written informed consent before performance of any study-relates procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Patients who have received prior high dose chemotherapy with stem cell support are eligible for this study.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., 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.

Exclusion Criteria:

• Patient has a platelet count of < 50, 000 cells/mm³, within 14 days before enrollment.
• Patient has an absolute neutrophil count (ANC) ≤ 750/mm³ within 14 days before enrollment.
• Patient has a calculated or measured creatinine clearance of < 20 mL/min within 14 days before enrollment and/or serum creatinine ≥ 2.5 mg/dl.
• Patient has hemoglobin < 7.5 g/dl.
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
• Patient has received a total cumulative dosage of anthracyclines exceeding 550 mg/m2.
• Patient has hypersensitivity to boron or mannitol.
• Patient has history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of DOXIL.
• Patient has clinically significant coexisting illness unrelated to myeloma.
• Patient has uncontrolled diabetes.
• Patient has plasma cell leukemia.
• Patient has serum bilirubin > 1.5 x upper normal limit, alanine aminotransaminase (ALT), aspartate aminotransferase (AST) > 2.5 x upper normal limit (ULN), or alkaline phosphatase > 2.5 x ULN.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG)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.
• Patient has serious medical or psychiatric illness likely to interfere with participation in this clinical study.

A copy of the disclosure must be given to Millennium for review at least 30 days before it is submitted for publication or disclosure. If a Development is contained in the disclosure, Research Organization and/or Principal Investigator defer publication or disclosure for 90 days from the time Millennium notifies that it wants to file a patent application on the Development provided such notice was provided by Millennium within 30 days of the copy first provided to Millennium.