RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide and thalidomide may also stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide, thalidomide, and dexamethasone together may kill more cancer cells.

PURPOSE: This randomized phase III trial is studying lenalidomide and low-dose dexamethasone to see how well it works compared to lenalidomide and standard-dose dexamethasone, given with or without thalidomide, in treating patients with multiple myeloma.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma	Drug: dexamethasone  Drug: lenalidomide  Drug: thalidomide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: endocrine therapy  Procedure: growth factor antagonist therapy  Procedure: hormone therapy  Procedure: non-specific immune-modulator therapy  Procedure: steroid therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the response rate in patients with newly diagnosed multiple myeloma treated with lenalidomide and standard-dose vs low-dose dexamethasone.
• Compare the toxicity of these regimens in these patients.

Secondary

• Determine the response rate in patients who do not achieve an objective response at any point during the first 4 courses of lenalidomide and dexamethasone and are subsequently treated with salvage therapy comprising thalidomide and dexamethasone.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral lenalidomide once daily on days 1-21 and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
• Arm II: Patients receive oral lenalidomide as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. In both arms, courses repeat every 28 days for up to 1 year in the absence of unacceptable toxicity or disease progression. Patients not responding at any point during the first 4 courses of lenalidomide and dexamethasone are assigned to 1 of 2 salvage therapy arms. Patients who progress during treatment on arms I or II have the option to register on salvage therapy arms III or IV respectively.
• Arm III (patients with no response after treatment on arm I): Patients receive oral thalidomide once daily on days 1-28 and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
• Arm IV (patients with no response after treatment on arm II): Patients receive oral thalidomide as in arm III and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. In both salvage therapy arms, courses repeat every 28 days for up to 1 year in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 412 patients (206 per treatment arm) will be accrued for this study within 24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma within the past 90 days, confirmed by the following criteria:
• Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells OR biopsy-proven plasmacytoma within the past 4 weeks
• Measurable monoclonal protein ≥ 1.0 g/dL by serum protein electrophoresis OR monoclonal light chain ≥ 200 mg by 24-hour urine protein electrophoresis within the past 4 weeks
• Symptomatic disease
• Prior plasmacytoma treated with curative-intent radiotherapy allowed provided disease progressed to active multiple myeloma
• No smoldering myeloma
• No monoclonal gammopathy of undetermined significance

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin > 7 g/dL
• Platelet count > 75,000/mm^3
• Absolute neutrophil count > 1,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• ALT and AST ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine < 2.5 mg/dL

Cardiovascular

• No uncontrolled hypertension
• No uncontrolled cardiac arrhythmia
• No symptomatic congestive heart failure
• No unstable angina
• No prior or concurrent deep vein thrombosis

Pulmonary

• No prior or concurrent pulmonary embolism

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception (1 highly effective and one additional method) for 4 weeks prior, during, and for 4 weeks after completion of study treatment
• No other active malignancy
• Prior malignancy with a low expectation of recurrence within the next 6 months allowed
• No prior Stevens Johnson syndrome
• No active uncontrolled seizure disorder
• No seizures within the past 6 months
• No active uncontrolled infection
• No uncontrolled psychiatric illness or social situation that would preclude study compliance
• No peripheral neuropathy ≥ grade 2 due to other medical conditions
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent sargramostim (GM-CSF)

Chemotherapy

• Not specified

Endocrine therapy

• No prior glucocorticosteroid therapy for multiple myeloma
• The following treatments for non-malignant disorders are allowed:
• Prior systemic glucocorticosteroids
• Prior or concurrent topical or localized glucocorticosteroids
• Concurrent systemic glucocorticosteroids at a dose of ≤ 10 mg of prednisone per day (or equivalent)

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior palliative and/or localized radiotherapy

Surgery

• Not specified

Other

• No prior systemic therapy for multiple myeloma except bisphosphonates

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
California
      Providence Saint Joseph Medical Center - Burbank, Burbank,  California,  91505,  United States; Recruiting
Colorado
      Boulder Community Hospital, Boulder,  Colorado,  80301-9019,  United States; Recruiting
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States; Recruiting
      Hope Cancer Care Center at Longmont United Hospital, Longmont,  Colorado,  80501,  United States; Recruiting
      Medical Center of Aurora - South Campus, Aurora,  Colorado,  80012-0000,  United States; Recruiting
      North Suburban Medical Center, Thornton,  Colorado,  80229,  United States; Recruiting
      Penrose Cancer Center at Penrose Hospital, Colorado Springs,  Colorado,  80933,  United States; Recruiting
      Porter Adventist Hospital, Denver,  Colorado,  80210,  United States; Recruiting
      Presbyterian - St. Luke's Medical Center, Denver,  Colorado,  80218,  United States; Recruiting
      Rose Medical Center, Denver,  Colorado,  80220,  United States; Recruiting
      Sky Ridge Medical Center, Lone Tree,  Colorado,  80124,  United States; Recruiting
      St. Joseph Hospital, Denver,  Colorado,  80218-1191,  United States; Recruiting
      St. Mary-Corwin Regional Medical Center, Pueblo,  Colorado,  81004,  United States; Recruiting
      Swedish Medical Center, Englewood,  Colorado,  80113,  United States; Recruiting
Connecticut
      Praxair Cancer Center at Danbury Hospital, Danbury,  Connecticut,  06810,  United States; Recruiting
Florida
      Baptist Cancer Institute - Jacksonville, Jacksonville,  Florida,  32207-8554,  United States; Recruiting
      Martin Memorial Cancer Center, Stuart,  Florida,  34994,  United States; Recruiting
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Georgia
      Augusta Oncology Associates, Augusta,  Georgia,  30901,  United States; Recruiting
      Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah,  Georgia,  31403-3089,  United States; Recruiting
Illinois
      Carle Clinic Association, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      Joliet Oncology Hematology Associates, Limited - West, Joliet,  Illinois,  60435,  United States; Recruiting
      Rush-Copley Cancer Care Center, Aurora,  Illinois,  60504-4206,  United States; Recruiting
      Saint Anthony's Hospital at Saint Anthony's Health Center, Alton,  Illinois,  62002,  United States; Recruiting
      Swedish-American Regional Cancer Center, Rockford,  Illinois,  61104-2315,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Center for Cancer Therapy at LaPorte Hospital and Health Services, LaPorte,  Indiana,  46350,  United States; Recruiting
      Elkhart General Hospital, Elkhart,  Indiana,  46514-1329,  United States; Recruiting
      Memorial Hospital of South Bend, South Bend,  Indiana,  46601,  United States; Recruiting
      Saint Anthony Memorial Health Centers, Michigan City,  Indiana,  46360-4358,  United States; Recruiting
      St. Francis Hospital and Health Centers, Beech Grove,  Indiana,  46107,  United States; Recruiting
Iowa
      Alegent Health Community Memorial Hospital, Missouri Valley,  Iowa,  51555-1199,  United States; Recruiting
      Alegent Health Mercy Hospital, Council Bluffs,  Iowa,  51503,  United States; Recruiting
      Burgess Health Center, Onawa,  Iowa,  51040,  United States; Recruiting
      Cancer Center at Ottumwa Regional Health Center, Ottumwa,  Iowa,  52501,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Covenant Medical Center, Waterloo,  Iowa,  50702,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States; Recruiting
      McFarland Clinic, P.C., Ames,  Iowa,  50010,  United States; Recruiting
      Medical Oncology and Hematology Associates - West Des Moines, West Des Moines,  Iowa,  50266,  United States; Recruiting
      Medical Oncology and Hematology Associates at John Stoddard Cancer Center, Des Moines,  Iowa,  50309,  United States; Recruiting
      Medical Oncology and Hematology Associates at Mercy Cancer Center, Des Moines,  Iowa,  50314,  United States; Recruiting
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States; Recruiting
      Mercy Cancer Center at Mercy Medical Center - North Iowa, Mason City,  Iowa,  50401,  United States; Recruiting
      Saint Anthony Regional Hospital, Carroll,  Iowa,  51401,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
      St. Luke's Regional Medical Center, Sioux City,  Iowa,  51104,  United States; Recruiting
Maryland
      Cancer Center at Greater Baltimore Medical Center, Baltimore,  Maryland,  21204,  United States; Recruiting
Michigan
      Borgess Medical Center, Kalamazoo,  Michigan,  49001-1666,  United States; Recruiting
      Bronson Methodist Hospital, Kalamazoo,  Michigan,  49007-5364,  United States; Recruiting
      Mercy Memorial Hospital System, Monroe,  Michigan,  48162,  United States; Recruiting
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States; Recruiting
      Cox Medical Center North, Springfield,  Missouri,  65802,  United States; Recruiting
      David C. Pratt Cancer Center at St. John's Mercy, Saint Louis,  Missouri,  63141,  United States; Recruiting
      Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital, Cape Girardeau,  Missouri,  63701,  United States; Recruiting
      St. Francis Medical Center, Cape Girardeau,  Missouri,  63701,  United States; Recruiting
Montana
      Benefis Healthcare Hospital, Great Falls,  Montana,  59405,  United States; Recruiting
      Big Sky Oncology, Great Falls,  Montana,  59405,  United States; Recruiting
      Bozeman Deaconess Hospital, Bozeman,  Montana,  59715,  United States; Recruiting
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
      Community Medical Center, Missoula,  Montana,  59801,  United States; Recruiting
      Deaconess Billings Clinic Cancer Center, Billings,  Montana,  59107-5100,  United States; Recruiting
      Eastern Montana Cancer Center, Miles City,  Montana,  59301,  United States; Recruiting
      Great Falls Clinic, Great Falls,  Montana,  59403,  United States; Recruiting
      Kalispell Regional Medical Center, Kalispell,  Montana,  59901,  United States; Recruiting
      Montana Cancer Center at St. Patrick Hospital and Health Sciences Center, Missoula,  Montana,  59807,  United States; Recruiting
      Northern Rockies Radiation Oncology Center, Billings,  Montana,  59103,  United States; Recruiting
      St. James Community Hospital, Butte,  Montana,  59701,  United States; Recruiting
      St. Peter's Hospital, Helena,  Montana,  59601-4999,  United States; Recruiting
      St. Vincent Healthcare, Billings,  Montana,  59101,  United States; Recruiting
Nebraska
      Alegent Health - Immanuel Medical Center, Omaha,  Nebraska,  68122,  United States; Recruiting
      Bergan Mercy Medical Center, Omaha,  Nebraska,  68124,  United States; Recruiting
      Bryan LGH Medical Center - East, Lincoln,  Nebraska,  68506,  United States; Recruiting
      Bryan LGH Medical Center West, Lincoln,  Nebraska,  68502-3780,  United States; Recruiting
      Cancer Center at Creighton University Medical Center, Omaha,  Nebraska,  68131-2197,  United States; Recruiting
      Cancer Resource Center - Lincoln, Lincoln,  Nebraska,  68510-4844,  United States; Recruiting
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States; Recruiting
      St. Elizabeth Regional Medical Center, Lincoln,  Nebraska,  68510-2494,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      University Medical Center of Southern Nevada, Las Vegas,  Nevada,  89102-2386,  United States; Recruiting
New Jersey
      Booker Cancer Center at Riverview Medical Center, Red Bank,  New Jersey,  07701-9871,  United States; Recruiting
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
      Somerset Medical Center, Somerville,  New Jersey,  08876,  United States; Recruiting
New York
      Comprehensive Cancer Center at Our Lady of Mercy Medical Center, Bronx,  New York,  10466-2604,  United States; Recruiting
North Carolina
      Pardee Memorial Hospital, Hendersonville,  North Carolina,  28791,  United States; Recruiting
North Dakota
      Bismarck Cancer Center, Bismarck,  North Dakota,  58501-4445,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
      Mid Dakota Clinic, P.C., Bismarck,  North Dakota,  58501,  United States; Recruiting
      St. Alexius Medical Center, Bismarck,  North Dakota,  58502,  United States; Recruiting
Ohio
      Licking Memorial Cancer Care Program at Licking Memorial Hospital, Newark,  Ohio,  43055-2899,  United States; Recruiting
      Adena Regional Medical Center, Chillicothe,  Ohio,  45601,  United States; Recruiting
      Akron City Hospital at Summa Health System, Akron,  Ohio,  44309-2090,  United States; Recruiting
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Charles F. Kettering Memorial Hospital, Kettering,  Ohio,  45429,  United States; Recruiting
      Community Hospital of Springfield and Clark County, Springfield,  Ohio,  45505,  United States; Recruiting
      Doctors Hospital at Ohio Health, Columbus,  Ohio,  43228,  United States; Recruiting
      Fairfield Medical Center, Lancaster,  Ohio,  43130,  United States; Recruiting
      Genesis - Good Samaritan Hospital, Zanesville,  Ohio,  43701,  United States; Recruiting
      Good Samaritan Hospital, Dayton,  Ohio,  45406-1891,  United States; Recruiting
      Grady Memorial Hospital, Delaware,  Ohio,  43015,  United States; Recruiting
      Grandview Hospital, Dayton,  Ohio,  45405,  United States; Recruiting
      Mercy Medical Center Oncology Unit, Springfield,  Ohio,  45501,  United States; Recruiting
      Miami Valley Hospital, Dayton,  Ohio,  45409,  United States; Recruiting
      Middletown Regional Hospital, Middletown,  Ohio,  45044-4898,  United States; Recruiting
      Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital, Westerville,  Ohio,  43081,  United States; Recruiting
      Mount Carmel West Hospital, Columbus,  Ohio,  43222,  United States; Recruiting
      Riverside Methodist Hospital Cancer Care, Columbus,  Ohio,  43214-3998,  United States; Recruiting
      Ruth G. McMillan Cancer Center at Greene Memorial Hospital, Xenia,  Ohio,  45385,  United States; Recruiting
      Samaritan North Cancer Care Center, Dayton,  Ohio,  45415,  United States; Recruiting
      St. Rita's Medical Center, Lima,  Ohio,  45801,  United States; Recruiting
      Strecker Cancer Center at Marietta Memorial Hospital, Marietta,  Ohio,  45750-1635,  United States; Recruiting
      UVMC Cancer Care Center at Upper Valley Medical Center, Troy,  Ohio,  45373-1300,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Pennsylvania
      Abington Memorial Hospital, Abington,  Pennsylvania,  19001,  United States; Recruiting
      Albert Einstein Cancer Center, Philadelphia,  Pennsylvania,  19141,  United States; Recruiting
      Bryn Mawr Hospital, Bryn Mawr,  Pennsylvania,  19010,  United States; Recruiting
      Cancer Center at Paoli Memorial Hospital, Paoli,  Pennsylvania,  19301-1792,  United States; Recruiting
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Guthrie Medical Center - Sayre, Sayre,  Pennsylvania,  18840,  United States; Recruiting
      Joan Karnell Cancer Center at Pennsylvania Hospital, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
      John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105-1556,  United States; Recruiting
      Lankenau Cancer Center at Lankenau Hospital, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Reading Hospital and Medical Center, Reading,  Pennsylvania,  19612-6052,  United States; Recruiting
South Dakota
      Avera McKennan Hospital and University Health Center, Sioux Falls,  South Dakota,  57105-1080,  United States; Recruiting
      Medical X-Ray Center, Sioux Falls,  South Dakota,  57105,  United States; Recruiting
      Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
Vermont
      Community Cancer Center at Rutland Regional Medical Center, Rutland,  Vermont,  05701,  United States; Recruiting
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States; Recruiting
      Lynchburg Hematology-Oncology Clinic, Lynchburg,  Virginia,  24501,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
      Dean Medical Center, Madison,  Wisconsin,  53715,  United States; Recruiting
      Fox Valley Hematology and Oncology, Appleton,  Wisconsin,  54911,  United States; Recruiting
      Green Bay Oncology, Limited - Oconto Falls, Oconto Falls,  Wisconsin,  54154,  United States; Recruiting
      Green Bay Oncology, Limited - Sturgeon Bay, Sturgeon Bay,  Wisconsin,  54235,  United States; Recruiting
      Green Bay Oncology, Limited at St. Mary's Hospital, Green Bay,  Wisconsin,  54303,  United States; Recruiting
      Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse,  Wisconsin,  54601-5494,  United States; Recruiting
      Marshfield Clinic - Lakeland Center, Minocqua,  Wisconsin,  54548,  United States; Recruiting
      Marshfield Clinic - Marshfield Center, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      Oconomowoc Memorial Hospital, Oconomowoc,  Wisconsin,  53066,  United States; Recruiting
      Regional Cancer Center at Sacred Heart Hospital, Eau Claire,  Wisconsin,  54701,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States; Recruiting
      Waukesha Memorial Hospital Regional Cancer Center, Waukesha,  Wisconsin,  53188,  United States; Recruiting
Wyoming
      Cancer Center of Northern Wyoming, Sheridan,  Wyoming,  82801,  United States; Recruiting

Study chairs or principal investigators

S. Vincent Rajkumar, MD,  Study Chair,  Mayo Clinic Cancer Center   
Rafael Fonseca, MD,  Mayo Clinic Scottsdale   
David H. Vesole, MD, PhD,  Medical College of Wisconsin   

Study ID Numbers:  CDR0000404161; ECOG-E4A03; NCT00098475
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  December 7, 2004
ClinicalTrials.gov Identifier:  NCT00098475
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08