Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma

Recruitment Status: ACTIVE, NOT RECRUITING - HAS RESULTS
(See Contacts and Locations)Verified March 2026 by National Cancer Institute (NCI)
Sponsor: National Cancer Institute (NCI)
Information Provided by (Responsible Party): National Cancer Institute (NCI)

Clinicaltrials.gov Identifier: NCT00098475
Other Study ID Numbers:: NCI-2012-03150

First Submitted: December 6, 2004
First Posted: December 7, 2004
Results First Posted: August 29, 2013
Last Update Posted: May 11, 2026
Last Verified: March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

Study Details

Study Description

PRIMARY OBJECTIVE:

I. To evaluate the response rate and toxicity of lenalidomide (CC-5013) plus dexamethasone (standard dose) versus CC-5013 plus low dose dexamethasone in patients with newly diagnosed myeloma at any time in the first 4 cycles of treatment and to determine if CC-5013 plus low dose dexamethasone will have similar response rate with lower toxicity (First Phase).

SECONDARY OBJECTIVES:

I. To evaluate the response rate of thalidomide plus dexamethasone (Thal/Dex) in patients with newly diagnosed myeloma who do not achieve a complete or partial response at any time in the first 4 cycles with the CC-5013 and dexamethasone combination in either of the two arms (First Phase).

II. To study the effect of CC-5013 on bone marrow microvessel density and angiogenesis grade, on plasma cell labeling index (PCLI), and on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the marrow (First Phase).

III. To study the effect of CC-5013 and dexamethasone on bone marrow mesenchymal progenitor cells (MPCs) (First Phase).

IV. To evaluate in a separate expansion phase the efficacy of aspirin (325 mg/day) versus Coumadin (dose adjusted to maintain a target international normalized ratio \[INR\] of 2-3) in preventing deep vein thrombosis (DVT) in patients with newly diagnosed myeloma receiving CC-5013 plus standard dose dexamethasone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20.

Arm II: Patients receive lenalidomide as in Arm I and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.

In both arms, cycles repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients not responding at any point during the first 4 cycles 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 thalidomide PO QD on days 1-28 and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20.

Arm IV (patients with no response after treatment on Arm II): Patients receive thalidomide as in Arm III and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.

In both salvage therapy arms, cycles repeat every 28 days in the absence of unacceptable toxicity or disease progression. After completion of 4 cycles of therapy, patients may undergo stem cell harvest (using growth factors only) for cryopreservation.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years.

Condition or Disease	Intervention/Treatment
DS Stage I Multiple MyelomaDS Stage II Multiple MyelomaDS Stage III Multiple Myeloma	Drug: DexamethasoneDrug: DexamethasoneDrug: DexamethasoneDrug: Dexamethasone

Study Design

Study Type	Interventional
Actual Enrollment	452 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Double
Primary Purpose	Treatment
Official Title	A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders
Study Start Date	November 2, 2004
Actual Primary Completion Date	November 29, 2008
Actual Study Completion Date	3mos 1w from now

Groups and Cohorts

Group/Cohort	Intervention/Treatment
Arm I (lenalidomide, dexamethasone) Patients receive lenalidomide PO QD on days 1-21 and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20.	Drug: Dexamethasone Given PO
Arm II (lenalidomide, low-dose dexamethasone) Patients receive lenalidomide and acetylsalicylic acid as in Arm I and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.	Drug: Dexamethasone Given PO
Arm III (thalidomide, dexamethasone) Patients with no response after treatment on Arm I: Patients receive thalidomide PO QD on days 1-28 and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20	Drug: Dexamethasone Given PO
Arm IV (thalidomide, low-dose dexamethasone) Patients with no response after treatment on Arm II: Patients receive thalidomide as in arm III and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.	Drug: Dexamethasone Given PO

Outcome Measures

Primary Outcome Measures

Proportion of Patients With Objective Response (First Phase, Step 1)
Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to \<200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response). As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only.

Secondary Outcome Measures

Proportion of Patients With Objective Response (First Phase, Step 2)
Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to \<200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response). As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only.

Eligibility Criteria

Ages Eligible for Study	(Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Patients must be diagnosed with symptomatic multiple myeloma within the past 90 days confirmed by the following: Bone marrow plasmacytosis with \>= 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma which must be obtained within 4 weeks prior to randomization Measurable levels of monoclonal protein (M protein): \>= 1.0 g/dL on serum protein electrophoresis or \>= 200 mg of monoclonal light chain on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to randomization; both serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) are required to be performed within 28 days prior to randomization; please note that if both serum and urine m-components are present, both must be followed in order to evaluate response Hemoglobin \> 7 g/dL Platelet count \> 75,000 cells/mm\^3 Absolute neutrophil count \> 1000 cells/mm\^3 Creatinine \< 2.5 mg/dL and creatinine clearance (measured or calculated) \>= 60 mL/min Bilirubin =\< 1.5 mg/dL Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.5 times the upper limit of normal Prior palliative and/or localized radiation therapy is permitted provided at least 4 weeks have passed from date of last radiation therapy to date of registration; patients with prior solitary plasmacytoma treated with radiation therapy with curative intent are eligible if the disease has now progressed to active multiple myeloma meeting all the eligibility criteria for this protocol Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method (intrauterine device \[IUD\], birth control pills, tubal ligation or partner's vasectomy) and one additional effective method (condom, diaphragm or cervical cap); FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy starting 4 weeks prior to and while taking CC5013 or thalidomide and for four weeks after discontinuing this therapy; a FCBP is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months
Exclusion Criteria	No prior systemic therapy with the exception of bisphosphonates for multiple myeloma Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted; prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day; prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson syndrome Patients with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible Patients must not have grade 2 or higher peripheral neuropathy due to other medical conditions at the time of randomization Patients must not have active, uncontrolled infection Patients must not have a history of current or previous deep vein thrombosis or pulmonary embolism regardless of whether or not the patient is receiving anticoagulation therapy For patients registered prior to activation of Addendum # 6; patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or Coumadin For patients registered after activation of Addendum # 6; patients entering the expansion phase of the protocol, which tests anticoagulant prophylaxis, must be able and willing to be randomized between aspirin at 325 mg/day and Coumadin Female patients MUST NOT be pregnant or breastfeeding; due to the potential teratogenic properties of CC 5013, and the known teratogenicity associated with thalidomide, the use of these drugs in this patient population is ABSOLUTELY CONTRAINDICATED

Contacts and Locations

Sponsors and Collaborators	National Cancer Institute (NCI)
Locations	University of Alabama at Birmingham Cancer Center \| Birmingham Alabama, United States, 35233Huntsville Hospital \| Huntsville Alabama, United States, 35801Providence Alaska Medical Center \| Anchorage Alaska, United States, 99508Mayo Clinic in Arizona \| Scottsdale Arizona, United States, 85259Providence Saint Joseph Medical Center/Disney Family Cancer Center \| Burbank California, United States, 91505Saint Jude Medical Center \| Fullerton California, United States, 92835El Camino Hospital \| Mountain View California, United States, 94040Kaiser Permanente-San Diego Mission \| San Diego California, United States, 92108The Medical Center of Aurora \| Aurora Colorado, United States, 80012Penrose-Saint Francis Healthcare \| Colorado Springs Colorado, United States, 80907Saint Joseph Hospital - Cancer Centers of Colorado \| Denver Colorado, United States, 80218Swedish Medical Center \| Englewood Colorado, United States, 80113Poudre Valley Hospital \| Fort Collins Colorado, United States, 80524Banner North Colorado Medical Center - Loveland Campus \| Loveland Colorado, United States, 80539Danbury Hospital \| Danbury Connecticut, United States, 06810Eastern Connecticut Hematology and Oncology Associates \| Norwich Connecticut, United States, 06360Holy Cross Hospital \| Fort Lauderdale Florida, United States, 33308UF Health Cancer Institute - Gainesville \| Gainesville Florida, United States, 32610Baptist MD Anderson Cancer Center \| Jacksonville Florida, United States, 32207Mayo Clinic in Florida \| Jacksonville Florida, United States, 32224-9980Martin Hospital South \| Stuart Florida, United States, 34997Phoebe Putney Memorial Hospital \| Albany Georgia, United States, 31701Emory University Hospital/Winship Cancer Institute \| Atlanta Georgia, United States, 30322Atlanta Regional CCOP \| Atlanta Georgia, United States, 30342Augusta Oncology Associates PC-D'Antignac \| Augusta Georgia, United States, 30901Emory Decatur Hospital \| Decatur Georgia, United States, 30033Atrium Health Navicent \| Macon Georgia, United States, 31201Lewis Cancer and Research Pavilion at Saint Joseph's/Candler \| Savannah Georgia, United States, 31405University of Hawaii Cancer Center \| Honolulu Hawaii, United States, 96813Saint Luke's Cancer Institute - Boise \| Boise Idaho, United States, 83712OSF Saint Anthony's Health Center \| Alton Illinois, United States, 62002Northwestern University \| Chicago Illinois, United States, 60611John H Stroger Jr Hospital of Cook County \| Chicago Illinois, United States, 60612Decatur Memorial Hospital \| Decatur Illinois, United States, 62526Ascension Alexian Brothers - Elk Grove Village \| Elk Grove Village Illinois, United States, 60007Edward Hines Jr VA Hospital \| Hines Illinois, United States, 60141Midwest Center for Hematology Oncology \| Joliet Illinois, United States, 60432Duly Health and Care Joliet \| Joliet Illinois, United States, 60435Swedish American Hospital \| Rockford Illinois, United States, 61104UW Health Carbone Cancer Center Rockford \| Rockford Illinois, United States, 61114Edward H Kaplan MD and Associates \| Skokie Illinois, United States, 60076Elkhart General Hospital \| Elkhart Indiana, United States, 46515Fort Wayne Medical Oncology and Hematology Inc-Parkview \| Fort Wayne Indiana, United States, 46845Indiana University/Melvin and Bren Simon Cancer Center \| Indianapolis Indiana, United States, 46202Franciscan Health Indianapolis \| Indianapolis Indiana, United States, 46237IU Health Arnett Cancer Care \| Lafayette Indiana, United States, 47904Saint Joseph Regional Medical Center-Mishawaka \| Mishawaka Indiana, United States, 46545Memorial Hospital of South Bend \| South Bend Indiana, United States, 46601McFarland Clinic - Ames \| Ames Iowa, United States, 50010University of Iowa Healthcare Cancer Services Quad Cities \| Bettendorf Iowa, United States, 52722Iowa Methodist Medical Center \| Des Moines Iowa, United States, 50309Siouxland Regional Cancer Center \| Sioux City Iowa, United States, 51101MercyOne Waterloo Cancer Center \| Waterloo Iowa, United States, 50702Kansas City NCI Community Oncology Research Program \| Prairie Village Kansas, United States, 66208Harold Alfond Center for Cancer Care \| Augusta Maine, United States, 04330Greater Baltimore Medical Center \| Baltimore Maryland, United States, 21204HealthAlliance Hospital - Leominster \| Leominster Massachusetts, United States, 01453Henry Ford Health Saint John Hospital \| Detroit Michigan, United States, 48236West Michigan Cancer Center \| Kalamazoo Michigan, United States, 49007Mercy Hospital \| Coon Rapids Minnesota, United States, 55433Fairview Southdale Hospital \| Edina Minnesota, United States, 55435Unity Hospital \| Fridley Minnesota, United States, 55432Saint John's Hospital - Healtheast \| Maplewood Minnesota, United States, 55109Mayo Clinic in Rochester \| Rochester Minnesota, United States, 55905Regions Hospital \| Saint Paul Minnesota, United States, 55101United Hospital \| Saint Paul Minnesota, United States, 55102Mercy Hospital Saint Louis \| St Louis Missouri, United States, 63141Saint Louis-Cape Girardeau CCOP \| St Louis Missouri, United States, 63141Montana Cancer Consortium NCORP \| Billings Montana, United States, 59102Great Falls Clinic \| Great Falls Montana, United States, 59405Nebraska Cancer Research Center \| Lincoln Nebraska, United States, 68510Nebraska Methodist Hospital \| Omaha Nebraska, United States, 68114Alegent Health Immanuel Medical Center \| Omaha Nebraska, United States, 68122Alegent Health Bergan Mercy Medical Center \| Omaha Nebraska, United States, 68124Midlands Community Hospital \| Papillion Nebraska, United States, 68046Hackensack University Medical Center \| Hackensack New Jersey, United States, 07601The Cancer Institute of New Jersey Hamilton \| Hamilton New Jersey, United States, 08690Morristown Medical Center \| Morristown New Jersey, United States, 07960Virtua Memorial \| Mount Holly New Jersey, United States, 08060Jersey Shore Medical Center \| Neptune City New Jersey, United States, 07753Rutgers Cancer Institute of New Jersey \| New Brunswick New Jersey, United States, 08903Robert Wood Johnson University Hospital Somerset \| Somerville New Jersey, United States, 08876Garnet Health Medical Center \| Middletown New York, United States, 10940NYU Langone Hospital - Long Island \| Mineola New York, United States, 11501Mount Sinai Union Square \| New York New York, United States, 10003Stony Brook University Medical Center \| Stony Brook New York, United States, 11794Mission Hospital \| Asheville North Carolina, United States, 28801Wayne Memorial Hospital \| Goldsboro North Carolina, United States, 27534Southeast Clinical Oncology Research Consortium NCORP \| Winston-Salem North Carolina, United States, 27104Sanford Bismarck Medical Center \| Bismarck North Dakota, United States, 58501Essentia Health Cancer Center-South University Clinic \| Fargo North Dakota, United States, 58103Sanford Broadway Medical Center \| Fargo North Dakota, United States, 58122Summa Health System - Akron Campus \| Akron Ohio, United States, 44304MetroHealth Medical Center \| Cleveland Ohio, United States, 44109Miami Valley Hospital \| Dayton Ohio, United States, 45409Miami Valley Hospital North \| Dayton Ohio, United States, 45415Atrium Medical Center-Middletown Regional Hospital \| Franklin Ohio, United States, 45005-1066Kettering Medical Center \| Kettering Ohio, United States, 45429Saint Charles Hospital \| Oregon Ohio, United States, 43616Firelands Regional Medical Center \| Sandusky Ohio, United States, 44870ProMedica Flower Hospital \| Sylvania Ohio, United States, 43560Mercy Hospital of Tiffin \| Tiffin Ohio, United States, 44883Toledo Community Hospital Oncology Program CCOP \| Toledo Ohio, United States, 43617Toledo Clinic Cancer Centers-Toledo \| Toledo Ohio, United States, 43623Kaiser Permanente Northwest \| Portland Oregon, United States, 97227Jefferson Abington Hospital \| Abington Pennsylvania, United States, 19001Penn State Milton S Hershey Medical Center \| Hershey Pennsylvania, United States, 17033-0850Lancaster General Hospital \| Lancaster Pennsylvania, United States, 17602Saint Mary Medical and Regional Cancer Center \| Langhorne Pennsylvania, United States, 19047University of Pennsylvania/Abramson Cancer Center \| Philadelphia Pennsylvania, United States, 19104Pennsylvania Hospital \| Philadelphia Pennsylvania, United States, 19107Thomas Jefferson University Hospital \| Philadelphia Pennsylvania, United States, 19107Fox Chase Cancer Center \| Philadelphia Pennsylvania, United States, 19111Temple Health - Chestnut Hill Hospital \| Philadelphia Pennsylvania, United States, 19118Einstein Medical Center Philadelphia \| Philadelphia Pennsylvania, United States, 19141Guthrie Medical Group PC-Robert Packer Hospital \| Sayre Pennsylvania, United States, 18840Grand View Hospital \| Sellersville Pennsylvania, United States, 18960Mount Nittany Medical Center \| State College Pennsylvania, United States, 16803Reading Hospital \| West Reading Pennsylvania, United States, 19611Lankenau Medical Center \| Wynnewood Pennsylvania, United States, 19096WellSpan Health-York Hospital \| York Pennsylvania, United States, 17403McLeod Regional Medical Center \| Florence South Carolina, United States, 29506Rapid City Regional Hospital \| Rapid City South Dakota, United States, 57701Sanford Cancer Center Oncology Clinic \| Sioux Falls South Dakota, United States, 57104University of Virginia Cancer Center \| Charlottesville Virginia, United States, 22908Sentara Martha Jefferson Hospital \| Charlottesville Virginia, United States, 22911Centra Alan B Pearson Regional Cancer Center \| Lynchburg Virginia, United States, 24501VCU Massey Comprehensive Cancer Center \| Richmond Virginia, United States, 23298Swedish Medical Center-First Hill \| Seattle Washington, United States, 98122West Virginia University Healthcare \| Morgantown West Virginia, United States, 26506ThedaCare Regional Cancer Center \| Appleton Wisconsin, United States, 54911Gundersen Lutheran Medical Center \| La Crosse Wisconsin, United States, 54601SSM Health Dean Medical Group - South Madison Campus \| Madison Wisconsin, United States, 53715University of Wisconsin Carbone Cancer Center - University Hospital \| Madison Wisconsin, United States, 53792Marshfield Medical Center-Marshfield \| Marshfield Wisconsin, United States, 54449Medical College of Wisconsin \| Milwaukee Wisconsin, United States, 53226ProHealth Oconomowoc Memorial Hospital \| Oconomowoc Wisconsin, United States, 53066ProHealth Waukesha Memorial Hospital \| Waukesha Wisconsin, United States, 53188
Investigators	Principal Investigator: S. V Rajkumar, ECOG-ACRIN Cancer Research Group

More Information

Publications

Baker A, Braggio E, Jacobus S, Jung S, Larson D, Therneau T, Dispenzieri A, Van Wier SA, Ahmann G, Levy J, Perkins L, Kim S, Henderson K, Vesole D, Rajkumar SV, Jelinek DF, Carpten J, Fonseca R. Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach. Blood. 2013 Apr 18;121(16):3147-52. doi: 10.1182/blood-2012-07-443606. Epub 2013 Feb 19. Kumar SK, Uno H, Jacobus SJ, Van Wier SA, Ahmann GJ, Henderson KJ, Callander NS, Haug JL, Siegel DS, Greipp PR, Fonseca R, Rajkumar SV. Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood. 2011 Oct 20;118(16):4359-62. doi: 10.1182/blood-2011-03-342089. Epub 2011 Aug 22. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan;11(1):29-37. doi: 10.1016/S1470-2045(09)70284-0. Epub 2009 Oct 21.