Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.

Further Study Information

The primary objective of the randomized trial is to compare three-year progression-free survival (PFS) between the three treatment arms as a pairwise comparison. Mobilization therapy will not be specified for the study. Randomization to three treatment arms will be done prior to the first transplants. All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive either a second autologous PBSC transplant with the same conditioning regimen as the first transplant or consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40 mg on Days 1, 8 and 15, and bortezomib 1.3mg/m^2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles) or maintenance with lenalidomide (15 mg daily). All patients will also receive maintenance lenalidomide which will start after the second transplant, after the first autologous transplant or after consolidation therapy depending on the treatment arm. Maintenance therapy with lenalidomide will start at 10 mg daily for three months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Eligibility Criteria

Inclusion Criteria:

• Patients meeting the criteria for symptomatic multiple myeloma (MM).

• Patients who are 70 years of age, or younger, at time of enrollment.

• Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.

• Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.

• Hepatic: bilirubin less than 1.5x the upper limit of normal and ALT and AST less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)

• Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.

• Pulmonary: DLCO, FEV1, FVC grater than 50 percent of predicted value (corrected for hemoglobin).

• Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10^6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight.

• Signed informed consent form.

Exclusion Criteria:

• Patients who never fulfill the criteria for symptomatic MM.

• Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques]. Patients with light chain MM detected in the serum by free light chain assay are eligible.

• Patients with plasma cell leukemia.

• Karnofsky performance score less than 70 percent.

• Patients with greater than grade 2 sensory neuropathy (CTCAE).

• Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).

• Patients seropositive for the human immunodeficiency virus (HIV).

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has hypersensitivity to bortezomib, boron or mannitol.

• Patient has received other investigational drugs with 14 days before enrollment.

• Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.

• Female patients who are pregnant (positive B-HCG) or breastfeeding.

• Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.

• Prior allograft or prior autograft.

• Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.

• Patients unable or unwilling to provide informed consent.

• Prior organ transplant requiring immunosuppressive therapy.

• Patients with disease progression prior to enrollment.

• Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation.

• Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.

• Patients unwilling to take DVT prophylaxis.

• Patients who cannot undergo an intervention in any treatment arm due to a priori denial of medical costs coverage by third party payers.

• Patients unable to unwilling to return to the transplant center for their assigned treatments.

Trial Contact Information

Trial Lead Organizations/Sponsors

National Heart, Lung, and Blood Institute

Amrita Y. Krishnan

Study Chair

George Somlo

Study Chair

Edward Allen Stadtmauer

Study Chair

Mary Horowitz, MD, MS		Ph: 414-805-0700
		Email: marymh@mcw.edu

U.S.A.
Arizona
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Andrew Yeager, MD	Ph: 520-626-0662
			Email: ayeager@azcc.arizona.edu
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Amrita Krishnan, MD	Ph: 626-256-4673
			Email: akrishnan@coh.org
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Edward Ball, MD	Ph: 858-822-6600
			Email: tball@ucsd.edu
	Stanford
	Stanford Cancer Center
		Ginna Laport, MD	Ph: 650-723-1389
			Email: glaport@stanford.edu
		Wen-Kai Weng, MD
			Email: wkweng@stanford.edu
Colorado
	Denver
	Presbyterian - St. Luke's Medical Center
		Jeffrey Matous, MD	Ph: 303-388-4876
			Email: Jeffrey.Matous@healthonecares.com
Delaware
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Frank Beardell, MD	Ph: 302-737-7700
			Email: fbeardell@dclp.com
Florida
	Gainesville
	University of Florida Shands Cancer Center
		John R Wingard, MD	Ph: 352-273-7760
			Email: wingajr@medicine.ufl.edu
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		Denise Pereira, MD	Ph: 305-243-4909
			Email: dpereira2@med.miami.edu
	Orlando
	Florida Hospital Cancer Institute
		Yasser Khaled	Ph: 407-303-2091
			Email: yasser.khaled.md@flhosp.org
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Taiga Nishihori, MD
			Email: Taiga.Nishihori@moffitt.org
Georgia
	Atlanta
	Blood and Marrow Transplant Program at Northside Hospital
		Asad Bashey, MD, PhD	Ph: 404-851-8238
			Email: abashey@bmtga.com
		Lawrence E. Morris, MD	Ph: 404-255-1930
			Email: lemorris@bmtga.com
	Augusta
	Medical College of Georgia Cancer Center
		Anand Jillella, M.D., FACP	Ph: 215-214-3129
			Email: ajillella@georgiahealth.edu
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		William H Kreisle, MD	Ph: 208-381-2711
			Email: kreislew@slhs.org
Illinois
	Chicago
	Rush Cancer Institute at Rush University Medical Center
		John Maciejewski, MD
			Email: John_Maciejewski@rush.edu
	University of Chicago Cancer Research Center
		Cara Rosenbaum, MD	Ph: 773-702-0167
			Email: Cara.Rosenbaum@uchospitals.edu
	University of Illinois Cancer Center
		Damiano Rondelli, MD	Ph: 312-996-6179
			Email: drond@uic.edu
	Park Ridge
	Advocate Lutheran General Cancer Care Center
		Leonard Klein, MD
			Email: leonard.klein@usoncology.com
Kansas
	Kansas City
	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
		Siddhartha Ganguly, MD
			Email: sganguly@kumc.edu
	Wichita
	CCOP - Wichita
		Shaker Dakhil, MD	Ph: 316-262-4467
			Email: shaker.dakhil@cancercenterofkansas.com
Kentucky
	Lexington
	Lucille P. Markey Cancer Center at University of Kentucky
		Gregory Monohan, MD
			Email: Gpmono0@email.uky.edu
Louisiana
	Shreveport
	Feist-Weiller Cancer Center at Louisiana State University Health Sciences
		Glenn Mills, MD
			Email: gmills@lsuhsc.edu
		Francesco Turturro, MD	Ph: 318-867-8863
			Email: fturtu@lsuhsc.edu
Massachusetts
	Boston
	Dana-Farber/Brigham and Women's Cancer Center
		John Koreth, MBBS, D.Phil	Ph: 617-632-2949
			Email: john_koreth@dfci.harvard.edu
	Massachusetts General Hospital
		Anuj Mahindra, MD
			Email: Amahindra@partners.org
Michigan
	Ann Arbor
	University of Michigan Comprehensive Cancer Center
		Dan Couriel, MD	Ph: 734-936-8785
			Email: dcouriel@umich.edu
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Muneer Abidi	Ph: 313-576-8713
			Email: abidim@karmanos.org
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Brian McClune, DO
			Email: bmcclune@umn.edu
Missouri
	St. Louis
	Saint Louis University Cancer Center
		Steven Pincus, MD, PhD	Ph: 314-577-8854
			Email: pincussm@slu.edu
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		John DiPersio, MD	Ph: 314-454-8306
			Email: jdipersi@im.wustl.edu
Nebraska
	Omaha
	UNMC Eppley Cancer Center at the University of Nebraska Medical Center
		Edward Faber, DO, MS	Ph: 402-559-5520
			Email: efaber@unmc.edu
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Scott Rowley, MD	Ph: 201-996-5828
			Email: srowley@humed.com
New York
	Buffalo
	Roswell Park Cancer Institute
		Hong Liu, MD, PhD	Ph: 716-845-8614
			Email: Hong.Liu@roswellpark.org
	Lake Success
	Monter Cancer Center of the North Shore-LIJ Health System
		Ruthee-Lu Bayer, MD	Ph: 516-734-8974
			Email: rbayer@nshs.edu
	New York
	Memorial Sloan-Kettering Cancer Center
		Hugo Castro-Malaspina, MD
			Email: castro-h@mskcc.org
		Heather Landau, MD
			Email: landauh@mskcc.org
	Mount Sinai Medical Center
		Luis Isola, MD	Ph: 212-241-6021
			Email: Luis.Isola@mountsinai.org
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Gordon Phillips, MD
			Email: Gordon_Phillips@urmc.rochester.edu
	Syracuse
	SUNY Upstate Medical University Hospital
		Teresa Gentile, MD, PhD
			Email: gentilet@upstate.edu
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Thomas C Shea, MD	Ph: 919-966-7313
			Email: sheat@med.unc.edu
	Durham
	Duke Cancer Institute
		Mitchell E Horwitz, MD	Ph: 919-668-1045
			Email: Mitchell.horwitz@duke.edu
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		David Hurd, MD	Ph: 336-716-7972
			Email: dhurd@wfubmc.edu
Ohio
	Cincinnati
	Jewish Hospital Cancer Center
		Edward R Broun, MD	Ph: 513-686-3421
			Email: edward.broun@healthall.com
	Cleveland
	Seidman Cancer Center at University Hospitals/Case Medical Center
		Hillard Lazarus, MD	Ph: 216-844-3629
			Email: hillard.lazarus@uhhospitals.org
	Columbus
	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
		Yvonne Efebera, MD
			Email: Yvonne.Efebera@osumc.edu
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		George Selby, MD	Ph: 405-271-6369
			Email: george-selby@ouhsc.edu
		George Selby, MD	Ph: 405-271-6369
			Email: George-selby@ouhsc.edu
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Richard Maziarz, MD
			Email: maziarzr@ohsu.edu
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Edward Gorak, DO	Ph: 570-271-6045
			Email: ejgorak@geisinger.edu
	Hershey
	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
		Giampaolo Talamo, MD
			Email: gtalamo@hmc.psu.edu
	Philadelphia
	Abramson Cancer Center of the University of Pennsylvania
		Edward Stadtmauer, MD	Ph: 215-662-7910
			Email: edward.stadtmauer@uphs.upenn.edu
Tennessee
	Knoxville
	Thompson Cancer Survival Center
		Richard Grapski, MD	Ph: 865-541-2161
	Nashville
	Sarah Cannon Blood & Marrow Transplant Program
		Jesus Berdeja, MD	Ph: 615-329-0570
			Email: jberdeja@tnonc.com
	Vanderbilt-Ingram Cancer Center
		Adetola Kassim, MD	Ph: 615-343-7893
			Email: adetola.kassim@vanderbilt.edu
Texas
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Larry Anderson, MD, PhD	Ph: 214-648-5102
			Email: larry.anderson@utsouthwestern.edu
	Houston
	Dan L. Duncan Cancer Center at Baylor College of Medicine
		George Carrum, MD	Ph: 713-441-1450
			Email: gcarrum@tmhs.org
	M. D. Anderson Cancer Center at University of Texas
		Muzzafar Qazilbash, MD	Ph: 713-745-3458
			Email: mqazilba@mdanderson.org
	San Antonio
	Texas Transplant Institute
		Carlos Bachier, MD	Ph: 210-575-4238
			Email: carlos.bachier@mhshealth.com
Washington
	Seattle
	Fred Hutchinson Cancer Research Center
		William Bensinger, MD
			Email: wbensing@fhcrc.org
West Virginia
	Morgantown
	Mary Babb Randolph Cancer Center at West Virginia University Hospitals
		Sayed Hamadani, MD
			Email: shamadani@hsc.wvu.edu
Wisconsin
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Natalie Callandar, MD	Ph: 608-262-7202
	Milwaukee
	Medical College of Wisconsin Cancer Center
		Parameswaran Hari, MD, MRC	Ph: 414-805-4604
			Email: phari@mcw.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01109004
Information obtained from ClinicalTrials.gov on January 30, 2013

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