|Phase III||Treatment||Active||70 and under||NCI, NHLBI||690|
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.
- 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.
- 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 Lead Organizations/Sponsors
National Heart, Lung, and Blood InstituteBlood and Marrow Transplant Clinical Trials Network
National Cancer Institute
|Amrita Y. Krishnan||Study Chair|
|George Somlo||Study Chair|
|Edward Allen Stadtmauer||Study Chair|
|Mary Horowitz, MD, MS||Ph: 414-805-0700|
|Arizona Cancer Center at University of Arizona Health Sciences Center|
|Andrew Yeager, MD||Ph: 520-626-0662|
|City of Hope Comprehensive Cancer Center|
|Amrita Krishnan, MD||Ph: 626-256-4673|
|Rebecca and John Moores UCSD Cancer Center|
|Edward Ball, MD||Ph: 858-822-6600|
|Stanford Cancer Center|
|Ginna Laport, MD||Ph: 650-723-1389|
|Wen-Kai Weng, MD|
|Presbyterian - St. Luke's Medical Center|
|Jeffrey Matous, MD||Ph: 303-388-4876|
|Helen F. Graham Cancer Center at Christiana Hospital|
|Frank Beardell, MD||Ph: 302-737-7700|
|University of Florida Shands Cancer Center|
|John R Wingard, MD||Ph: 352-273-7760|
|University of Miami Sylvester Comprehensive Cancer Center - Miami|
|Denise Pereira, MD||Ph: 305-243-4909|
|Florida Hospital Cancer Institute|
|Yasser Khaled||Ph: 407-303-2091|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Taiga Nishihori, MD|
|Blood and Marrow Transplant Program at Northside Hospital|
|Asad Bashey, MD, PhD||Ph: 404-851-8238|
|Lawrence E. Morris, MD||Ph: 404-255-1930|
|Medical College of Georgia Cancer Center|
|Anand Jillella, M.D., FACP||Ph: 215-214-3129|
|Mountain States Tumor Institute at St. Luke's Regional Medical Center|
|William H Kreisle, MD||Ph: 208-381-2711|
|Rush Cancer Institute at Rush University Medical Center|
|John Maciejewski, MD|
|University of Chicago Cancer Research Center|
|Cara Rosenbaum, MD||Ph: 773-702-0167|
|University of Illinois Cancer Center|
|Damiano Rondelli, MD||Ph: 312-996-6179|
|Advocate Lutheran General Cancer Care Center|
|Leonard Klein, MD|
|Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center|
|Siddhartha Ganguly, MD|
|CCOP - Wichita|
|Shaker Dakhil, MD||Ph: 316-262-4467|
|Lucille P. Markey Cancer Center at University of Kentucky|
|Gregory Monohan, MD|
|Feist-Weiller Cancer Center at Louisiana State University Health Sciences|
|Glenn Mills, MD|
|Francesco Turturro, MD||Ph: 318-867-8863|
|Dana-Farber/Brigham and Women's Cancer Center|
|John Koreth, MBBS, D.Phil||Ph: 617-632-2949|
|Massachusetts General Hospital|
|Anuj Mahindra, MD|
|University of Michigan Comprehensive Cancer Center|
|Dan Couriel, MD||Ph: 734-936-8785|
|Barbara Ann Karmanos Cancer Institute|
|Muneer Abidi||Ph: 313-576-8713|
|Masonic Cancer Center at University of Minnesota|
|Brian McClune, DO|
|Saint Louis University Cancer Center|
|Steven Pincus, MD, PhD||Ph: 314-577-8854|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis|
|John DiPersio, MD||Ph: 314-454-8306|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Edward Faber, DO, MS||Ph: 402-559-5520|
|Hackensack University Medical Center Cancer Center|
|Scott Rowley, MD||Ph: 201-996-5828|
|Roswell Park Cancer Institute|
|Hong Liu, MD, PhD||Ph: 716-845-8614|
|Monter Cancer Center of the North Shore-LIJ Health System|
|Ruthee-Lu Bayer, MD||Ph: 516-734-8974|
|Memorial Sloan-Kettering Cancer Center|
|Hugo Castro-Malaspina, MD|
|Heather Landau, MD|
|Mount Sinai Medical Center|
|Luis Isola, MD||Ph: 212-241-6021|
|James P. Wilmot Cancer Center at University of Rochester Medical Center|
|Gordon Phillips, MD|
|SUNY Upstate Medical University Hospital|
|Teresa Gentile, MD, PhD|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Thomas C Shea, MD||Ph: 919-966-7313|
|Duke Cancer Institute|
|Mitchell E Horwitz, MD||Ph: 919-668-1045|
|Wake Forest University Comprehensive Cancer Center|
|David Hurd, MD||Ph: 336-716-7972|
|Jewish Hospital Cancer Center|
|Edward R Broun, MD||Ph: 513-686-3421|
|Seidman Cancer Center at University Hospitals/Case Medical Center|
|Hillard Lazarus, MD||Ph: 216-844-3629|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center|
|Yvonne Efebera, MD|
|Oklahoma University Cancer Institute|
|George Selby, MD||Ph: 405-271-6369|
|George Selby, MD||Ph: 405-271-6369|
|Knight Cancer Institute at Oregon Health and Science University|
|Richard Maziarz, MD|
|Geisinger Cancer Institute at Geisinger Health|
|Edward Gorak, DO||Ph: 570-271-6045|
|Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center|
|Giampaolo Talamo, MD|
|Abramson Cancer Center of the University of Pennsylvania|
|Edward Stadtmauer, MD||Ph: 215-662-7910|
|Thompson Cancer Survival Center|
|Richard Grapski, MD||Ph: 865-541-2161|
|Sarah Cannon Blood & Marrow Transplant Program|
|Jesus Berdeja, MD||Ph: 615-329-0570|
|Vanderbilt-Ingram Cancer Center|
|Adetola Kassim, MD||Ph: 615-343-7893|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas|
|Larry Anderson, MD, PhD||Ph: 214-648-5102|
|Dan L. Duncan Cancer Center at Baylor College of Medicine|
|George Carrum, MD||Ph: 713-441-1450|
|M. D. Anderson Cancer Center at University of Texas|
|Muzzafar Qazilbash, MD||Ph: 713-745-3458|
|Texas Transplant Institute|
|Carlos Bachier, MD||Ph: 210-575-4238|
|Fred Hutchinson Cancer Research Center|
|William Bensinger, MD|
|Mary Babb Randolph Cancer Center at West Virginia University Hospitals|
|Sayed Hamadani, MD|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Natalie Callandar, MD||Ph: 608-262-7202|
|Medical College of Wisconsin Cancer Center|
|Parameswaran Hari, MD, MRC||Ph: 414-805-4604|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01109004
Information obtained from ClinicalTrials.gov on January 30, 2013
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