Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01109004
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 758
- 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 alanine aminotransferase (ALT) and aspartate aminotransferase (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: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater 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 deep vein thrombosis (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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RVD consolidation lenalidomide, bortezomib and dexamethasone Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Tandem auto transplant Lenalidomide Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide maintenance Lenalidomide Initial autologous transplant followed by lenalidomide maintenance
- Primary Outcome Measures
Name Time Method Percentage of Participants With Progression-free Survival (PFS) 38 months post-randomization Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Disease Progression 38 months post-randomization Disease Progression is defined as progression of multiple myeloma, including one or more of the following:
* A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL
* 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours
* Abnormal free light chain levels of \>10 mg/dl, only in patients without measurable paraprotein in the serum and urine
* At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy
* Definite increase in the size of existing bone lesions or soft tissue plasmacytomas
* Development of new bone lesions or soft tissue plasmacytomas
* Development of hypercalcemia (corrected serum Ca \>11.5 mg/dL or \>2.8 mmol/L) not attributable to any other cause
To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk.Number of Participants With Treatment Response 1 and 2 years post-randomization The number of participants with very good partial response (VGPR) or better \[complete response (CR), near CR (nCR), and stringent CR (sCR)\] according to the International Uniform Response Criteria will be calculated. The "Worse than VGPR" group includes PR, stable disease, and progressive disease.
sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: \< 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR \>=90% reduction in serum PPN plus urine PPN \<100 mg/24hrs, \>= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either \>= 90% or to \<200 mg/24 hours in light chain disease, \>= 50% reduction in the size of soft tissue plasmacytomasPercentage of Participants With Overall Survival (OS) 38 months post-randomization Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization.
FACT-BMT Score Up to 3 years post-randomization The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.
Percentage of Participants With Treatment-related Mortality (TRM) Up to 38 months post-randomization TRM is defined as death prior to progression of multiple myeloma. To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating disease progression as a competing risk.
MOS SF-36 Physical Component Summary Up to 3 years post-randomization The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
MOS SF-36 Mental Component Summary Up to 3 years post-randomization The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
FACT-G Total Score Up to 3 years post-randomization The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being.
FACT-BMT Trial Outcome Index Up to 3 years post-randomization The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being.
Trial Locations
- Locations (54)
Georgia Health Sciences University
🇺🇸Augusta, Georgia, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
UCSD Medical Center
🇺🇸La Jolla, California, United States
Blood and Marrow Transplant Program at Northside Hospital
🇺🇸Atlanta, Georgia, United States
DFCI, Brigham and Womens Hospital
🇺🇸Boston, Massachusetts, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Washington University, Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
Jewish Hospital BMT Program
🇺🇸Cincinnati, Ohio, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
St. Lukes Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Wichita CCOP
🇺🇸Wichita, Kansas, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Ohio State/Arthur G. James Cancer Hospital
🇺🇸Columbus, Ohio, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Penn State College of Medicine, The Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine/The Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas, MD Anderson CRC
🇺🇸Houston, Texas, United States
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Hospital & Clinics
🇺🇸Madison, Wisconsin, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Roswell Park Cancer Center
🇺🇸Buffalo, New York, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
Karmanos Cancer Institute/BMT
🇺🇸Detroit, Michigan, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
University of North Carolina Hospital at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Oklahoma Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Sarah Cannon Blood & Marrow Transplant Program
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
DFCI, Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Christiana Care Health System
🇺🇸Newark, Delaware, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Thompson Cancer Survival Center
🇺🇸Knoxville, Tennessee, United States
North Shore University Hospital
🇺🇸Lake Success, New York, United States