A Study of PS-341 Given to Patients With Multiple Myeloma Who Experienced Progressive Disease After Receiving Dexamethasone in M34101-039

An International, Non-Comparative, Open-Label Study of PS-341 Administered to Patients With Multiple Myeloma Who Experienced Relapsed or Progressive Disease After Receiving at Least Four Previous Treatment Regimens or Experienced Progressive Disease After Receiving Dexamethasone in Millennium Protocol M34101-039

The purpose of this study is to allow patients to receive VELCADE™ (bortezomib) for Injection who experienced progressive disease(PD) while receiving high-dose dexamethasone from the M34101-039 study.

The rationale for Amendment 2 is 2-fold. First, it is intended that this study serve as a rollover protocol for patients who experience progressive disease (PD) after receiving the comparator treatment, high-dose dexamethasone, in MPI Study M34101-039, thereby ultimately providing all patients who participate in Study M34101-039 and require treatment for their disease access to VELCADE™ (bortezomib) for Injection, formerly known as MLN341, LDP-341 and PS-341.

Inclusion Criteria

• Patient experienced PD, as defined by SWOG+ criteria during or after treatment with high-dose dexamethasone in MPI Study M34101-039, but has not received alternate anti-neoplastic therapy. Intolerance to high-dose dexamethasone therapy as administered in MPI study M34101-039 does not qualify as PD.
• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Female patient is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from Screening through the End of Treatment visit.
• Male patient agrees to use an acceptable barrier method for contraception from Screening through the End of Treatment visit.
• Patient meets the following pretreatment laboratory criteria at and within 14 days before Baseline (Day 1 of Cycle 1, before study drug administration). (Note that the End of Treatment assessments of MPI study M34101-039 may qualify as the Screening assessments for MPI study M34101-040 if performed within 14 days of the Baseline visit.):
• Platelet count ≥20 X 10E+9/L, with or without transfusion support.
• Hemoglobin ≥7.0 g/dL, with or without transfusion support.
• Absolute neutrophil count (ANC)≥0.5 x 10E+9/L, without growth factor support.
• Serum calcium <14 mg/dL (3.5 mmol/L).
• Aspartate transaminase (AST):≤2.5 x the upper limit of normal (ULN).
• Alanine transaminase (ALT):≤2.5 x the ULN.
• Total bilirubin:≤1.5 x the ULN.
• If calculated or measured creatinine clearance: ≥20 mL/minute, assessments are as specified in the protocol. If calculated or measured creatinine clearance is <20 mL/minute.

Exclusion Criteria

• Patient participated in M34101-039 and did not have confirmed PD. Dexamethasone intolerance does not qualify as PD.
• Patient had PD on the dexamethasone arm of the MPI Study M34101-039, and then received alternate anti-neoplastic therapy.
• Patient has not recovered from dexamethasone-related toxicity experienced during MPI Study M34101-039.
• Patient is known to be human immunodeficiency virus (HIV)-positive.(Patients assessed by the investigator to be at risk for HIV infection should be tested in accordance with local regulations.)
• Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection.(Patients assessed by the investigator to be at risk for hepatitis B or C infection should be tested in accordance with local regulations.)
• Female patient is pregnant or breast-feeding.
• Patient developed a new or experienced worsening of an existing illness during or after completion of Study M34101-039 that, in the investigator's opinion, may put the patient at risk of participation in this study.