Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Biomarker/Laboratory analysis, Natural history/Epidemiology, Treatment Active 18 and over NCI ECOG-E1A06 E1A06, NCT00602641

Special Category: CTSU trial

Objectives

Primary

1. To compare progression-free survival between patients receiving melphalan, prednisone, and thalidomide versus melphalan, prednisone, and lenalidomide in newly diagnosed multiple myeloma patients who are not candidates for high-dose therapy.

Secondary

1. To compare overall survival between both arms.
2. To compare response rates and depth of response in these patients.
3. To compare the incidence of toxicities in these patients.
4. To validate the TC classification of myeloma as a prognostic tool using gene expression profiling at diagnosis.

Tertiary

1. To compare quality-of-life (QOL) change between arms based on the FACT-Ntx TOI from baseline to the end of course 24 (maintenance therapy).
2. To examine the impact of differential treatment responses on QOL based on the FACT-Ntx TOI up to course 38.
3. To obtain prospective data on myeloma specific QOL attributes.

Entry Criteria

Disease Characteristics:

• Newly diagnosed multiple myeloma (MM), meeting the following criteria:
  • Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
  • Symptomatic disease with evidence of end-organ damage at initial diagnosis that prompted the initiation of therapy, including ≥ 1 of the following:
    • Anemia
    • Hypercalcemia
    • Bone disease (lytic bone lesions or pathologic fracture)
    • Renal dysfunction



• No smoldering MM, defined by all of the following:
  • Serum monoclonal protein ≥ 3 g/dL
  • Bone marrow plasma cells ≥ 10% or greater
  • Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction



• No monoclonal gammopathy of undetermined significance, defined by all of the following:
  • Serum monoclonal protein < 3 g/dL
  • Bone marrow plasma cells ≤ 10%
  • Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction



• Previously untreated for MM



• Patients 18 to 64 years old must not be a candidate for autologous stem cell transplantation or have declined transplantation or other alternative treatment

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior treatment for myeloma except for either of the following:
  • Prednisone or dexamethasone treatment for myeloma for a duration of less than 4 weeks
  • Prednisone or dexamethasone in combination with thalidomide or lenalidomide for a duration of less than 2 weeks total
• Concurrent bisphosphonates or growth factors (i.e., erythropoietin) for MM allowed
• Concurrent localized radiation therapy is allowed for pain control at the physician’s discretion

Patient Characteristics:

• ECOG performance status 0-2
• Hemoglobin > 7 g/dL
• Platelet count > 75,000/mm³
• ANC > 1,000/mm³
• Creatinine < 2.5 mg/dL
• Direct bilirubin ≤ 1.5 mg/dL
• ALT and AST ≤ 2.5 times upper limit of normal
• No uncontrolled intercurrent illness that would limit compliance with the study including, but not limited to, any of the following:
  • Uncontrolled hypertension
  • Symptomatic congestive heart failure
  • Unstable angina
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled psychiatric illness or social situation
  • Prior history of Stevens Johnson syndrome
• No peripheral neuropathy ≥ grade 2
• No active uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception 4 weeks prior to, during, and 4 weeks after completion of study treatment
• Must be able to take prophylatic aspirin 325mg/day or low-molecular weight heparin or coumadin
• No second active malignancy requiring treatment within the past 2 years, except for basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix

Expected Enrollment

Outcomes

Progression-free survival
Overall survival

Response rates and depth of response comparison
Toxicity
Quality-of-life (QOL) change comparison of arms measured by FACT-Ntx TOI from baseline to course 24
Differential treatment response on QOL measured by FACT-Ntx TOI from baseline to course 38
TC classification validation of myeloma as a prognostic tool using gene expression profiling

Outline

This is a multicenter study. Patients are stratified according to ISS stage (I-II vs III) and age (< 65 vs ≥ 65). Patients are randomized to 1 of 2 treatment arms.

• Arm I:
  • Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance therapy: Patients receive oral thalidomide once daily and continue in the absence of disease progression.



• Arm II:
  • Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance therapy: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression.

Quality of life is assessed at baseline and periodically during treatment.

Peripheral blood and bone marrow samples are collected at baseline for gene expression profiling analysis.

After completion of study treatment, patients will be followed periodically for 10 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

A. Keith Stewart, MD, Protocol chair		Ph: 480-301-4411
S. Rajkumar, MD, Protocol co-chair		Ph: 507-284-8430 Email: rajks@mayo.edu

U.S.A.
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
California
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-5888
Florida
	Fort Lauderdale
	Broward General Medical Center Cancer Center
		Clinical Trials Office - Broward General Medical Center Cancer Center	Ph:  954-355-5346
	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
		Clinical Trials Office - Michael and Dianne Bienes Comprehensive Cancer Center	Ph:  954-776-3239
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Miami Beach
	CCOP - Mount Sinai Medical Center
		Rogerio Lilenbaum, MD	Ph:  305-535-3310
Georgia
	Albany
	Phoebe Cancer Center at Phoebe Putney Memorial Hospital
		Clinical Trials Office - Phoebe Cancer Center	Ph:  229-312-2251
Illinois
	Alton
	Saint Anthony's Hospital at Saint Anthony's Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3019
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3605
	Carthage
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Chicago
	Swedish Covenant Hospital
		Contact Person	Ph:  773-878-8200
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	University of Illinois Cancer Center
		Clinical Trial Office - University of Illinois Cancer Center	Ph:  312-355-3046
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Evanston
	Evanston Northwestern Healthcare - Evanston Hospital
		Clinical Trials Office - Evanston Northwestern Healthcare - Evanston Hospital	Ph:  847-570-1381
	St. Francis Hospital
		K. Joseph Philip, MD	Ph:  773-784-6676
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3605
	Galesburg Cottage Hospital
		John Kugler, MD	Ph:  309-243-3605
	InterCommunity Cancer Center of Western Illinois
		John Kugler, MD	Ph:  309-243-3605
	Havana
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Hinsdale
	Hinsdale Hematology Oncology Associates
		Elyse Schneiderman, MD	Ph:  630-654-1790
	Hopedale
	Hopedale Medical Complex
		John Kugler, MD	Ph:  309-243-3605
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3019
	Kewanee
	Kewanee Hospital
		John Kugler, MD	Ph:  309-243-3605
	La Grange
	La Grange Memorial Hospital
		Clinical Trials Office - La Grange Memorial Hospital	Ph:  630-856-7526
	Macomb
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Moline
		Costas Constantinou, MD	Ph:  563-359-9876
	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
		Costas Constantinou, MD	Ph:  563-359-9876
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Pekin
	Cancer Treatment Center at Pekin Hospital
		John Kugler, MD	Ph:  309-243-3605
	Peoria
	CCOP - Illinois Oncology Research Association
		John Kugler, MD	Ph:  309-243-3605
	Methodist Medical Center of Illinois
		Clinical Trials Office - Methodist Medical Center of Illinois	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		John Kugler, MD	Ph:  309-243-3605
	Proctor Hospital
		John Kugler, MD	Ph:  309-243-3605
	Peru
	Illinois Valley Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Princeton
	Perry Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Spring Valley
	St. Margaret's Hospital
		John Kugler, MD	Ph:  309-243-3605
	Valley Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard Gross, MD	Ph:  937-832-1093
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3019
	Munster
	Community Hospital
		Erwin Robin, MD	Ph:  219-836-2860
	Richmond
	Reid Hospital & Health Care Services
		Howard Gross, MD	Ph:  937-832-1093
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Bettendorf
		Costas Constantinou, MD	Ph:  563-359-9876
	Hematology Oncology Associates of the Quad Cities
		Shobha Chitneni, MD, MBBS	Ph:  563-355-7733
	Davenport
	Genesis Medical Center - West Campus
		George Kovach, MD	Ph:  563-421-1960
	Genesis Regional Cancer Center at Genesis Medical Center
		George Kovach, MD	Ph:  563-421-1960
	Des Moines
	CCOP - Iowa Oncology Research Association
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	John Stoddard Cancer Center at Iowa Lutheran Hospital
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Lutheran Hospital	Ph:  515-241-8704
	John Stoddard Cancer Center at Iowa Methodist Medical Center
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Methodist Medical Center	Ph:  515-241-6727
	Medical Oncology and Hematology Associates at John Stoddard Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Medical Oncology and Hematology Associates at Mercy Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Mercy Cancer Center at Mercy Medical Center - Des Moines
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Mercy Capitol Hospital
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Mason City
	Mercy Cancer Center at Mercy Medical Center - North Iowa
		Clinical Trials Office - Mercy Cancer Center at Mercy Medical Center - North Iowa	Ph:  641-422-6304
	Ottumwa
	McCreery Cancer Center at Ottumwa Regional
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Waterloo
	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue
		Boriana Kamenova	Ph:  319-833-5907
	Covenant Cancer Treatment Center
		Clinical Trials Office - Covenant Cancer Treatment Center	Ph:  319-272-2070
Kansas
	Lawrence
	Lawrence Memorial Hospital
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Topeka
	Cotton-O'Neil Cancer Center
		Clinical Trials Office - Cotton-O'Neil Cancer Center	Ph:  785-270-4963
	Wichita
	Wesley Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
Maine
	Portland
	Mercy Hospital
		Roger Inhorn, MD, PhD	Ph:  207-879-3030
Michigan
	Kalamazoo
	Borgess Medical Center
		Raymond Lord, MD	Ph:  269-373-7458
	Bronson Methodist Hospital
		Raymond Lord, MD	Ph:  269-373-7458
	West Michigan Cancer Center
		Clinical Trials Office - West Michigan Cancer Center	Ph:  269-373-7458
Minnesota
	Bemidji
	MeritCare Bemidji
		Preston Steen, MD	Ph:  701-234-2397
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Hutchinson
	Hutchinson Area Health Care
		Daniel Anderson	Ph:  320-234-5000 800-454-3903
	Maplewood
	HealthEast Cancer Care at St. John's Hospital
		Daniel Anderson	Ph:  651-232-7970
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Hennepin County Medical Center - Minneapolis
		Clinical Trials Office - Hennepin County Medical Center - Minneapolis	Ph:  612-873-5911
	Veterans Affairs Medical Center - Minneapolis
		Clinical Trials Office - Veterans Affairs Medical Center - Minneapolis	Ph:  612-467-2800
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Ph:  763-520-1893
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Saint Louis Park
	CCOP - Metro-Minnesota
		Patrick Flyn