A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients With Newly Diagnosed Multiple Myeloma (MM)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma based on the following criteria:

- Major criteria

- Plasmacytomas on tissue biopsy (1)

- Bone marrow plasmacytosis (> 30% plasma cells) (2)

- Monoclonal immunoglobulin spike on serum electrophoresis IgG > 3.5 g/dL or
IgA > 2.0 g/dL and kappa or lambda light chain excretion > 1 g/day on
24-hour urine protein electrophoresis (3)

- Minor criteria

- Bone marrow plasmacytosis (10% to 30% plasma cells) (a)

- Monoclonal immunoglobulin present but of lesser magnitude than given under
major criteria (b)

- Lytic bone lesions (c)

- Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL (d)

- Meets 1 of the following sets of diagnostic criteria:

- Any two of the major criteria

- Major criteria 1 and minor criteria b, c, and d

- Major criteria 3 and minor criteria a or c

- Minor criteria a, b, c, OR a, b, d

- Measurable disease, defined as a monoclonal immunoglobulin spike on serum
electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/24
hours, or evidence of lytic bone disease

- No nonmeasurable disease (i.e., non-secretory or oligosecretory multiple
myeloma)

- Symptomatic, newly diagnosed, and previously untreated multiple myeloma

- No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein [M-protein], and skin changes)

- No plasma cell leukemia

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy > 3 months

- ANC ≥ 1,500/mm^³ (≥ 1,000/mm^³ if bone marrow is extensively infiltrated)

- Platelet count ≥ 75,000/mm^³ (≥ 50,000/mm^³ if bone marrow is extensively
infiltrated)

- Hemoglobin ≥ 8.0 g/dL

- AST and ALT ≤ 3.0 times upper limit of normal (ULN)

- Serum bilirubin ≤ 2.0 times ULN

- Creatinine clearance ≥ 30 mL/min OR creatinine > 10 mL/min and < 30 mL/min for
patients with significant myelomatous involvement of the kidneys

- Serum potassium ≥ lower limit of normal (LLN)

- Serum sodium ≥ LLN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior malignancy within the past 5 years except basal cell or squamous cell skin
cancer or carcinoma in situ of the cervix

- No peripheral neuropathy ≥ grade 2 within past 14 days

- No impaired cardiac function or clinically significant cardiac disease, including any
one of the following:

- Myocardial infarction within the past 6 months

- New York Heart Association class II-IV heart failure

- Uncontrolled angina

- Clinically significant pericardial disease

- Severe uncontrolled ventricular arrhythmias

- LVEF below normal by ECHO or MUGA scan

- ECG evidence of acute ischemia or active conduction system abnormalities

- Screening ECG abnormality must be documented by the investigator as not
medically relevant

- No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L])

- No poorly controlled hypertension, diabetes mellitus, or other serious medical or
psychiatric illness that could preclude study treatment

- No known HIV positivity or hepatitis B or C positivity

- Baseline testing for HIV and hepatitis B or C is not required

- No history of allergic reaction attributable to compounds of similar chemical or
biological composition to doxorubicin, bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior or concurrent anti-myeloma therapy except steroids

- Prior prednisone for ≤ 4 days at a total of 400 mg (or an equivalent potency of
another steroid) allowed

- No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent) other than
dexamethasone

- More than 4 weeks since prior major surgery and recovered

- Prior kyphoplasty with oncotherapeutic drugs allowed at the investigator's
discretion

- More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy

- More than 14 days since other prior and no other concurrent investigational drugs