Clinical Trial - A Randomized, Open-Label, Multi-Center Trial Comparing Thalidomide plus Dexamethasone (Thal/Dex) versus DOXIL®plus Dexamethasone and Thalidomide (Dd-T) in Subjects with Newly Diagnosed Multiple Myeloma

Title:	A Randomized, Open-Label, Multi-Center Trial Comparing Thalidomide plus Dexamethasone (Thal/Dex) versus DOXIL® plus Dexamethasone and Thalidomide (Dd-T) in Subjects with Newly Diagnosed Multiple Myeloma

Phase:	III

Purpose:	To determine the effectiveness of the investigational use of thalidomide, Doxil®, and dexamethasone in treating patients with multiple myeloma

Eligibility:	Inclusion Criteria: Male or female at least 18 years of age Previously untreated, histologically confirmed, symptomatic multiple myeloma as defined by International Myeloma Working Group, (Br. J. Hematol., Kyle et al 2003) ECOG performance status 0-2 Previous radiation therapy for palliation of cord compression or pathologic fractures are permitted provided last dose is given 14 days prior to initiation of chemotherapy and does not involve the mediastinum Subjects with radiographic evidence of lytic bone disease receiving concomitant bisphosphonate therapy may be enrolled Adequate bone marrow function: ANC ≥ 1,000/m³ (if BM has > 50% plasma cells/mm3, then no specific minimum) Platelet count >75,000 cells/mm3 (without transfusion support for 7 days prior to study entry) (if BM has > 50% plasma cells/mm3, minimum platelet count > 20,000 cells mm3) Hemoglobin ≥ 8.0 g/dL (without transfusion support for 7 days prior to study entry)(If BM has > 50% plasma cells/mm3, then transfusion is allowed up to the time of enrollment to maintain Hgb ≥ 7.0g/dL) Corrected serum calcium < 12 mg/dL (3.0 mmol/L) or ionized calcium < 6.5 mg/dL (1.6mmol/L). This level may be achieved by appropriate supportive care but it must be reached before the subject can be randomized Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment Willing and eligible to sign up for the S.T.E.P.S program Negative pregnancy test, according to the S.T.E.P.S program, for subjects of childbearing potential Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Treated with more than two pulses of dexamethasone within 2 weeks of randomization Non-secretory disease (defined as no measurable paraprotein in serum or urine, urine paraprotein level ≤ 200 mg/24 hours) Peripheral neuropathy of Grade 2 or greater severity as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Active Infection requiring intravenous antibiotic treatment Known to be HIV positive (an HIV test is not required for participation in the trial) Inadequate renal function: Creatinine > 4 mg/dL (> 200 µmol/L) Inadequate liver function: Bilirubin > 2 institutional upper limits of normal ALT and AST > 2.5X upper limit of normal Life expectancy of less than 3 months Pregnant or lactating subjects No prior malignancy is allowed, except for adequately treated basal cell or squamous cell skin cancer, or cervical cancer in-situ, or other cancer from which the subject has been disease-free for at least 3 years Solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCl, or the components of DOXIL, dexamethasone or thalidomide Multiple gated acquisition (MUGA) showing the LVEF less than <45% History of cardiac disease, with New York Heart Association Class II or greater, or clinical evidence of congestive heart failure History of deep venous thrombosis (DVT) within one year before enrollment in the study or subjects currently receiving anticoagulation for DVT History of life-threatening thromboembolic event of any kind (i.e.: myocardial infarction, pulmonary, embolism, stroke or others) within one year before enrollment in the study Uncontrolled medical problems such as diabetes mellitus, cardiac (ie congestive heart failure, coronary artery disease, arrhythmias), pulmonary, hepatic, and renal diseases unless renal insufficiency is felt by the investigator to be secondary to multiple myeloma Major surgery within 4 weeks before randomization. Vertebroplasty and kyphoplasty for a myeloma indication are not considered to be major surgery. Psychiatric or central nervous systems disorders interfering with compliance of orally administered medication Experimental drug or experimental regimen within 4 weeks before randomization Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator

Treatment:	According to the treatment assignment at randomization, subjects will receive the investigational combination of either thalidomide-dexamethasone (Thal-Dex: ARM 1) or DOXIL, thalidomide plus dexamethasone (DOXIL-Thal-Dex: ARM 2). Subjects will be scheduled to receive a minimum of 4 and a maximum of 12 cycles of study treatment. The duration of each cycle is 28 days (+/- 3 days). Prior to the start of each cycle, beginning with Cycle 2, subjects will be evaluated for myeloma response or progression. Barring any dose delays, the maximum duration of protocol therapy would be 48 weeks.

Contact:	California Lalita Pandit, MD Lalita Pandit, MD, Inc 11160 Warner Avenue, Ste 417 Fountain Valley, CA 92708 Veronica Aguilar 714-432-9200 Ann Mohrbacher, MD USC/Norris Cancer Center Division of Hematology NOR 3434-MS-34 1441 Eastlake Avenue Los Angeles, CA 90089 Lori Vergara 323-865-3938 Colorado Robert Rifkin, MD Rocky Mountain Cancer Center 1800 William Street- Ste.200 Denver, CO 80218 Mary Ann Rauch 832-601-6447 Connecticut Richard Hellman, MD Oncology and Hematology Associates 3 Shaws Cove, Ste 201 New London, CT 06320 Steffany Willert 860-439-1770 Florida Deborah Zipin, MD Center for Hematology Oncology 1001 NW 13th Street, Ste 201 Boca Raton, FL 33486 Delores Preiser 561-416-8869 Ext 262 Illinois Ahmad Jajeh, MD Cook County Hospital 1900 West Polk St. Room 757 Chicago, IL 61612 Dcebal Griza 312-864-7250 Indiana David M. Loesch, MD Centra Indiana Cancer Centers 1346 E. Country Line Road Indianapolis, IN 46227 Mary Ann Rauch 832-601-6447 Minnesota Patrick Flynn, MD Minnesota Oncology Hematology, PA 913 East 26st. Suite 405/Piper Bldg. Minneapolis, MN 55404 Mary Ann Rauch 832-601-6447 Missouri Marcus Neubauer, MD Kansas City Cancer Centers LLC 1000 E. 101 St. Terrace Kansas City, MO 64131 Mary Ann Rauch 832-601-6447 David M. Schlossman, MD Missouri Cancer Centers 105 N. Keene St. Ste. 200 Columbia, MO 65201 Mary Ann Rauch 832-601-6447 New Jersey David Siegel, MD Cancer Center at Hackensack University Medical Center 20 Prospect Ave. Ste. 400 Hackensack, NJ 07601 Laura McBride (T) 201-336-8020 (F) 201-336-8979 New York Bernard Bernhardt, MD Advanced Oncology Associates 84 Business Park Drive, Ste 203 Armonk, NY 10504 Connie Brickson 914-273-2977 Brad Cohen, MD Union State Bank Cancer Center 160N. Midland Avenue Nyack, NY 10960 Sandra Narin 845-348-8507 Janice Dutcher, MD Our Lady of Mercy Medical Center 600 E. 233 St. Bronx, NY 10598 Linda Sacris 718.920.9057 North Carolina Hugh Wallace, MD Piedmont Hematology Oncology Assoc., PLLC 1010 Behesda Court Winstom-Salem, NC 27103 Isaac Deaton ideaton@phoa.org 336-277-8887 Oklahoma Remeo Mandanas, MD Cancer Care Associates 4205 McAuley Blvd. Ste. 375 Oklahoma city, OK 73120 Mary Ann Rauch 832-601-6447 Mark Olsen, MD Cancer Care Associates 6151 South Yale- Ste. 100 Tulsa, Ok 74136 Mary Ann Rauch 832-601-6447 Oregon Glenn S. Buchanan, MD Oncology Assoc. of Oregon, PC 520 Country Club Rd. Eugene, OR 97401-8122 Mary Ann Rauch 832-601-6447 Pennsylvania David Roodman, MD UPMC Cancer Center Hillman Cancer Center 5115 Centre Avenue Suite A41.11 Pittsburg, PA 15232 Patricia Schaefer 412.623.4881 Clifford Pemberton, MD Lankenau Cancer Center 100 Lancaster Avenue Wynewood, PA 19096 Rosemarie Tucci 610-645-2680 South Carolina John Hunter, MD Hematology and Oncology Associate of SC, LLC 109 Fleetwood Drive-Suite A Easley, SC 29640 Mary Ann Rauch 832-601-6447 Tennessee Howard Burris, MD The Sarah Cannon Cancer Center 250 25th Avenue North Ste. 110 Nashville, TN 37203 Mary Ann Rauch 832-601-6447 Texas Thomas Anderson, MD Texas Oncology, PA 1615 Hospital Parkway, Suite 300 Bedford, TX 76022 Mary Ann Rauch 832-601-6447 Jose Lopez, MD Cancer Care Network of South Texas- HOAST 204 W. Schubert Fredericksburg, TX 78624 Mary Ann Rauch 832-601-6447 Romeo McIntyre, MD Texas Oncology, PA 8220 Walnut Hill Ln.- Ste 700 Professional Bldg. II Dallas, TX 75231-4400 Mary Ann Rauch 832-601-6447 Donald Richards, MD Texas Oncology, PA 910 E. Houston Street - Ste. 100 Tyler, TX 75702 Mary Ann Rauch 832-601-6447 Michael Savin, MD Texas Oncology, PA 7777 Forest Ln. Bldg. D-400 Dallas, TX 75320 Mary Ann Rauch 832-601-6447 Virginia Joseph Evers, MD Virgina Cancer Institute 6605 West Broad Street, Ste B Richmond, VA 23230 Vicki Tolbert 804-330-7990 Paul Conkling, MD Virginia Oncology Assoc. Lake Wright Cancer Ctr. 5900 Lake Wright Dr. Norfolk, VA 23502 Mary Ann Rauch 832-601-6447 Washington Stephen Anthony, MD Cancer Care Northwest 605 E. Holland- Suite 100 Spokane, WA 99218 Mary Ann Rauch 832-601-6447 Thomas Boyd, MD Yakima Valley Memorial Hospital/North Star Ledge 808 North 30th Avenue Yakima, WA 98902 Mary Ann Rauch 832-601-6447 David A. Smith, MD Northwest Cancer Specialists, PC 210 SE 136th Ave. Vancouver, WA 98684 Mary Ann Rauch 832-601-6447

Please note: the trials indicated do not include the full inclusion or exclusion criteria. For full protocols, please contact the Principal Investigator (PI) listed.