This research study is evaluating an investigational combination of four drugs called Revlimid® (lenalidomide), Velcade® (bortezomib), Dexamethasone and Doxil® (RVDD) as a possible treatment for newly diagnosed multiple myeloma.

During the Phase I portion of this clinical trial, the doses of Revlimid® and Doxil® will be increased until the best and safest amount (or dose) is identified in combination with Velcade® and Dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Velcade®, Doxil®, Dexamethasone and Revlimid® investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

Each of these drugs, Velcade®, Doxil®, Dexamethasone and Revlimid® are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use for your type of cancer or any other type of cancer. Velcade® is currently approved by the United States Food and Drug Administration (US FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. Doxil® has recently been approved by the US FDA for multiple myeloma in combination with Velcade® in patients who have not previously received Velcade® and have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

After the Phase I clinical trial defines the safest doses of Velcade®, Doxil®, Dexamethasone and Revlimid® that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the four drugs.

Inclusion Criteria

• At least 18 years of age at the time of consent
• Measurable disease
• All necessary baseline studies completed
• LVEF (left ventricular ejection fraction) greater than or equal to 50 percent by MUGA (multigated acquisition scan) or ECHO (echocardiogram)
• Must be able to adhere to study visit schedule

Exclusion

• Greater than or equal to grade 2 peripheral neuropathy on clinical examination within 14 days of enrollment
• Renal insufficiency
• Evidence of mucosal or internal bleeding and/ or platelet refractory.
• Absolute neutrophil count less than 1000 cells/mm^2 within 14 days of enrollment.
• Acceptable labs
• Concomitant medications that include corticosteroids
• Myocardial infarction within 6 months prior to enrollment, uncontrolled angina, severe uncontrolled ventricular arrhythmias
• Clinically relevant active infection or serious medical condition that places the subject at unacceptable risk
• Any condition, including laboratory values that places the subject at an unacceptable risk
• Another malignancy within 3 years of enrollment, with the exception of the complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy
• Hypersensitivity to bortezomib, boron, or mannitol or any of the components of DOXIL
• Female subject that is pregnant or breastfeeding.
• Can not have received any other investigational drugs within 14 days of enrollment
• Serious medical or psychiatric illness
• Uncontrolled diabetes mellitus
• Hypersensitivity to acyclovir or similar antiviral drug
• POEMS (plasma cell dyscrasia with polyneuropathy)
• Known HIV
• Known hepatitis B or C
• Known intolerance to steroid therapy
• Known hypersensitivity to required prophylactic mediations