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

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

This randomized phase III trial studies 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. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: DS Stage I Multiple Myeloma; DS Stage II Multiple Myeloma; DS Stage III Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Thalidomide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 452
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Huntsville, Alabama, United States, 35801
      • Huntsville Hospital
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Fullerton, California, United States, 92835
      • Saint Jude Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Hospital
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Stuart, Florida, United States, 34997
      • Martin Hospital South
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Putney Memorial Hospital
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates PC-D'Antignac
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Elk Grove Village, Illinois, United States, 60007
      • Ascension Alexian Brothers - Elk Grove Village
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital
    • Joliet, Illinois, United States, 60435
      • Duly Health and Care Joliet
    • Joliet, Illinois, United States, 60432
      • Midwest Center for Hematology Oncology
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Skokie, Illinois, United States, 60076
      • Edward H Kaplan MD and Associates
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Indianapolis
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Lafayette, Indiana, United States, 47904
      • IU Health Arnett Cancer Care
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Bettendorf, Iowa, United States, 52722
      • University of Iowa Healthcare Cancer Services Quad Cities
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Waterloo, Iowa, United States, 50702
      • MercyOne Waterloo Cancer Center
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
  • Massachusetts
    • Leominster, Massachusetts, United States, 01453
      • HealthAlliance Hospital - Leominster
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
  • Montana
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hamilton, New Jersey, United States, 08690
      • The Cancer Institute of New Jersey Hamilton
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Somerville, New Jersey, United States, 08876
      • Robert Wood Johnson University Hospital Somerset
  • New York
    • Middletown, New York, United States, 10940
      • Garnet Health Medical Center
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • New York, New York, United States, 10003
      • Mount Sinai Union Square
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Clinical Oncology Research Consortium NCORP
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58103
      • Essentia Health Cancer Center-South University Clinic
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Philadelphia, Pennsylvania, United States, 19118
      • Chestnut Hill Health System
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group PC-Robert Packer Hospital
    • Sellersville, Pennsylvania, United States, 18960
      • Grand View Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • York, Pennsylvania, United States, 17403
      • WellSpan Health-York Hospital
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Charlottesville, Virginia, United States, 22901
      • Sentara Martha Jefferson Hospital
    • Lynchburg, Virginia, United States, 24501
      • Centra Lynchburg Hematology-Oncology Clinic Inc
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare Regional Cancer Center
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501; Drug: Dexamethasone; Given PO; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Other: Laboratory Biomarker Analysis; Optional correlative studies
Experimental: 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: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501; Drug: Dexamethasone; Given PO; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Other: Laboratory Biomarker Analysis; Optional correlative studies
Active Comparator: 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; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Thalidomide; Given PO; Other Names: Kevadon; Synovir; Thalomid; (+)-Thalidomide; (-)-Thalidomide; .alpha.-Phthalimidoglutarimide; 2, 6-Dioxo-3-phthalimidopiperidine; Alpha-Phthalimidoglutarimide; Contergan; Distaval; N-(2,6-Dioxo-3-piperidyl)phthalimide; N-Phthaloylglutamimide; N-Phthalylglutamic Acid Imide; Neurosedyn; Pantosediv; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)-; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)-; Sedalis; Sedoval K-17; Softenon; Talimol; Sedoval K17
Experimental: 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; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Thalidomide; Given PO; Other Names: Kevadon; Synovir; Thalomid; (+)-Thalidomide; (-)-Thalidomide; .alpha.-Phthalimidoglutarimide; 2, 6-Dioxo-3-phthalimidopiperidine; Alpha-Phthalimidoglutarimide; Contergan; Distaval; N-(2,6-Dioxo-3-piperidyl)phthalimide; N-Phthaloylglutamimide; N-Phthalylglutamic Acid Imide; Neurosedyn; Pantosediv; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)-; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)-; Sedalis; Sedoval K-17; Softenon; Talimol; Sedoval K17

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed every 4 weeks for 16 weeks during Step 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed every 4 weeks for 16 weeks during Step 2

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: S. V Rajkumar, ECOG-ACRIN Cancer Research Group

Publications and helpful links

General 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. Erratum In: Lancet Oncol. 2010 Jan;11(1):14.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2004
• Primary Completion (Actual): November 30, 2008
• Study Completion (Estimated): October 22, 2024

Study Registration Dates

• First Submitted: December 7, 2004
• First Submitted That Met QC Criteria: December 7, 2004
• First Posted (Estimated): December 8, 2004

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dermatologic Agents; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Thalidomide; Lenalidomide; Ichthammol
• Other Study ID Numbers: NCI-2012-03150 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); E4A03 (Other Identifier: CTEP); CDR0000404161