A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

- Each patient must meet all of the following inclusion criteria to be enrolled in the
study:

1. Has a diagnosis of multiple myeloma based on standard criteria (Durie 1986)

2. Currently has multiple myeloma with measurable disease (serum m protein >
1.0g/dl and/or 24 hr urine m protein > 200mg/24 hr)

3. Currently has progressive multiple myeloma that has relapsed or is refractory

4. Voluntarily signed an informed consent

5. Age 18 years

6. Able to adhere to the study visit schedule and other protocol requirements

7. ECOG performance < 2

8. Life-expectancy > 3 months

9. Laboratory test results within these ranges:

- ANC 1.5 x 109/L; if the bone marrow is extensively infiltrated (> 70%
plasma cells) then 1.0 x 109/L

- Platelet count 75 x 109/L; if the bone marrow is extensively infiltrated (>
70% plasma cells) then 50 x 109/L

- Hg > 8 g/dL

- Calculated or measured creatinine clearance > 30 mL/minute.

- Total bilirubin 2.0 x upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) 3 x ULN or 5 x ULN if hepatic metastases are
present

- Serum potassium within the normal range

10. Disease free of prior malignancies for 5 years with exception of currently
treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ"
of the cervix or breast

11. Registered into the mandatory RevAssist® program, willing and able to comply
with the requirements of RevAssist®.

12. Females of childbearing potential must have a negative serum or urine pregnancy
test and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control.

13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation
(patients intolerant to ASA may use warfarin or low molecular weight heparin)

Exclusion Criteria:

- Patients meeting any of the following exclusion criteria are not to be enrolled in
the study:

1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,
monoclonal protein and skin changes syndrome

2. Plasma cell leukemia

3. Non-measurable multiple myeloma

4. Grade 2 peripheral neuropathy within 14 days before enrollment

5. Impaired cardiac function or clinically significant cardiac diseases, including
any one of the following:

- Myocardial infarction within 6 months prior to enrollment

- New York Heart Association (NYHA) Class II or greater heart failure

- Uncontrolled angina

- Clinically significant pericardial disease

- Severe uncontrolled ventricular arrhythmias

- Echocardiogram or MUGA evidence of LVEF below institutional normal within
28 days prior to enrollment

- Electrocardiographic evidence of acute ischemia or active conduction system
abnormalities. Prior to study entry, any ECG abnormality at Screening has
to be documented by the investigator as not medically relevant.

6. Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for
albumin

7. Any serious medical condition, laboratory abnormality, or psychiatric illness
that would prevent the subject from signing the informed consent form

8. Any condition, including the presence of laboratory abnormalities, which places
the subject at unacceptable risk if he/she were to participate in the study or
confounds the ability to interpret data from the study

9. Undergone major surgery within 28 days prior enrollment or has not recovered
from side effects of such therapy (Kyphoplasty is not considered to be a major
surgery; however, the investigator is to discuss enrollment of a patient with a
recent history of kyphoplasty with the medical monitor).

10. Pregnant or breast feeding females. (Lactating females must agree not to breast
feed while taking lenalidomide)

11. Received the following prior therapy:

- Chemotherapy within 3 weeks of enrollment (6 wks for nitrosoureas)

- Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of
enrollment

- Immunotherapy or antibody therapy as well as thalidomide, lenalidomide,
arsenic trioxide or bortezomib within 21 days before enrollment

- Radiation therapy within 28 days before enrollment, receipt of localized
radiation therapy does not preclude enrollment

- Use of any other experimental drug or therapy within 28 days of enrollment

12. Known hypersensitivity to compounds of similar chemical or biological
composition to thalidomide, doxorubicin, bortezomib, boron or mannitol.

13. The development of erythema nodosum if characterized by a desquamating rash
while taking thalidomide or similar drugs

14. Concurrent use of other anti-cancer agents or treatments

15. Known positivity for human immunodeficiency virus (HIV) or hepatitis B or C;
baseline testing for HIV and hepatitis B or C is not required