Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma

Inclusion Criteria:

- Patients must have a histologically confirmed diagnosis of symptomatic multiple
myeloma with evaluable disease parameters

- Patients may not have undergone any prior therapy, with the following exceptions:

- Prior plasmapheresis with plasma exchange (PLEX) for a hyperviscosity syndrome
is allowed, providing the patient has no current evidence of hyperviscosity and
has not required PLEX for at least one week prior to initiation of therapy

- Prior radiation therapy to areas of spinal cord compression by plasmacytomas,
painful lesions due to bony involvement, or other myeloma related indications,
is allowed provided that radiation will have been completed 3 weeks before
initiation of therapy

- Prior surgical intervention, such as for bony fractures or other myeloma related
complications, is allowed provided that this will have been completed 3 weeks
before the initiation of therapy, and patients have recovered from surgery

- Prior therapy with corticosteroids for indications other than multiple myeloma
is allowed, provided such therapy has been discontinued at least two weeks prior
to study entry, and at least two weeks before their baseline disease evaluation

- Prior supportive therapy with bisphosphonates or erythropoietin is allowed

- Non-pregnant and Non-nursing

- Inclusion of females of childbearing potential requires a negative pregnancy
test

- ECOG Performance Status =< 2

- Patients may not have a prior history of a hypersensitivity reaction to pegylated
liposomal doxorubicin or doxorubicin, bortezomib or other boronic acid-based
compounds; patients with a history of reactions to liposomal drug formulations other
than Pegylated liposomal doxorubicin will be evaluated individually, and if their
reactions were felt to have been due to the liposomal component itself, as opposed to
the encapsulated agent, they will be excluded at the discretion of the investigators

- Patients who are known to be HIV-seropositive and are taking anti-retrovirals may not
participate in this study because of potential interactions between these medications
and the investigational agent; patients who are HIV seropositive and not on
anti-retroviral therapy, and who otherwise meet the organ function criteria, will be
eligible for the study

- Patients who are known to have active hepatitis A, B, or C viral infection may not
participate in this study; active disease is defined as patients with a known viral
hepatitis whose liver function tests are elevated beyond the criteria indicated

- No EKG evidence of acute ischemia

- No EKG evidence of medically significant conduction system abnormalities

- No history of myocardial infarction within the last 6 months

- Left ventricular ejection fraction (LVEF) must be >= 45% by either echocardiography
or radionuclide-based multiple gated acquisition (RNV or MUGA)

- No Class 3 or Class 4 New York Heart Association Congestive Heart Failure

- Creatinine < 2.5 mg/dL

- ALT (SGPT) and AST (SGOT) =< 2.5 times the upper limit of the institutional normal
value

- Total bilirubin =< 1.2 times the upper limit of the institutional normal value

- ANC >= 1,000/ul

- Platelets >= 100,000/ul

- Hemoglobin >= 8 g/dl (transfusion- and/or growth factor-dependent patients are not
excluded if the above parameters can be achieved with such support)

- For those patients receiving warfarin (Coumadin), unfractionated Heparin, or
low-molecular weight Heparin therapy, the applicable coagulation parameter that is
being monitored must be within the accepted therapeutic ranges for those indications