Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
- Conditions
- DS Stage I Multiple MyelomaSmoldering Multiple MyelomaDS Stage II Multiple MyelomaDS Stage III Multiple MyelomaRefractory Multiple Myeloma
- Interventions
- Procedure: Autologous Hematopoietic Stem Cell TransplantationOther: Laboratory Biomarker AnalysisProcedure: Peripheral Blood Stem Cell TransplantationOther: Placebo Administration
- Registration Number
- NCT00114101
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase III trial studies lenalidomide to see how well it works compared to a placebo in treating patients with multiple myeloma who are undergoing autologous stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after autologous stem cell transplant may be an effective treatment for multiple myeloma.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine the efficacy of CC-5013 (lenalidomide) in prolonging time to disease progression in patients with multiple myeloma after autologous stem cell transplant (ASCT).
SECONDARY OBJECTIVES:
I. To determine if CC-5013 will increase the complete response (CR) rate in patients with multiple myeloma following ASCT.
II. To compare the progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma who have undergone ASCT and who then are randomized to either CC-5013 or placebo.
III. To determine the feasibility of long-term administration of CC-5013 to multiple myeloma patients who have undergone ASCT.
OUTLINE:
PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Mobilization of autologous PBSC will be performed according to institutional guidelines.
AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Patients receive melphalan intravenously (IV) over 30-60 minutes on day -2 or -1 or over 2 days on days -3 and -2 or -2 and -1. Patients undergo autologous PBSCT on day 0.
Patients are then randomized to 1 of 2 maintenance treatment arms. (Note: As of 12/17/09, no more patients will be randomized between lenalidomide and placebo. Patients who have not been randomized as of 12/17/09 will be assigned to lenalidomide.)
ARM I: Beginning between day 100-110, patients receive lenalidomide orally (PO) once daily.
ARM II: Beginning between day 100-110, patients receive placebo (PO) once daily.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 460
-
Patients must have active multiple myeloma requiring treatment (Durie-Salmon stage >= 1) and have stable disease or be responsive to at least 2 months of any induction therapy; patients with smoldering myeloma are not eligible unless the disease has progressed to >= stage 1
-
No more than 12 months of any prior therapy, including CC-5013 and thalidomide
-
Within 12 months of initiation of induction therapy
-
No prior progression after initial therapy; in addition, no more than two regimens will be allowed excluding dexamethasone alone
-
No prior peripheral blood, bone marrow, or solid organ transplant
-
Patients must have peripheral blood stem cell collection of >= 2 x 10^6 cluster of differentiation (CD)34+ cells/kg (patient body weight) and preferably 5 x 10^6 cells/kg (patient body weight); stem cells may be collected at any time prior to transplant; peripheral blood stem cell collection may occur before or after registration
-
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
-
Patients must have diffusing capacity of the lung for carbon monoxide (DLCO) > 50% predicted with no symptomatic pulmonary disease
-
Patients must have left ventricular ejection fraction (LVEF) >= 40% by multi gated acquisition scan (MUGA) or echocardiogram
-
Patients must not have uncontrolled diabetes mellitus
-
Patients must not have an active serious infection
-
Patients must not be human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSag), or hepatitis (Hep) C positive
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Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10-14 days prior to registration and repeated within 24 hours prior to the first dose of lenalidomide; in addition, women of childbearing potential taking lenalidomide must have a pregnancy test performed by the doctor weekly during the first 4 weeks of treatment, and then every 4 weeks if menses are regular and every 2 weeks if menses are irregular, and then 30 days following the last dose of lenalidomide; women of childbearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control - one highly effective method (intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (latex condom, diaphragm, or cervical cap) - at the same time, at least 4 weeks before she begins lenalidomide therapy; "women of childbearing" potential is defined as a sexually mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months; men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking lenalidomide and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy
-
Absolute neutrophil count (ANC) >= 1000/uL
-
Platelets >= 100,000/uL
-
Creatinine clearance* >= 40 cc/min
- To be calculated by method of Cockcroft-Gault or after 24-hour urine collection
-
Creatinine =< 2 mg/dL
-
Total bilirubin =< 2 mg/dL
-
Aspartate aminotransferase (AST) =< 3 x upper limits of normal
-
Alkaline phosphatase =< 3 x upper limits of normal
-
Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative (if patient of childbearing potential)
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (melphalan, autologous PBSCT, lenalidomide) Laboratory Biomarker Analysis Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (melphalan, autologous PBSCT, lenalidomide) Autologous Hematopoietic Stem Cell Transplantation Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (melphalan, autologous PBSCT, lenalidomide) Peripheral Blood Stem Cell Transplantation Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (melphalan, autologous PBSCT, placebo) Autologous Hematopoietic Stem Cell Transplantation Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (melphalan, autologous PBSCT, placebo) Laboratory Biomarker Analysis Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (melphalan, autologous PBSCT, lenalidomide) Melphalan Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (melphalan, autologous PBSCT, placebo) Peripheral Blood Stem Cell Transplantation Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (melphalan, autologous PBSCT, placebo) Placebo Administration Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (melphalan, autologous PBSCT, lenalidomide) Lenalidomide Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (melphalan, autologous PBSCT, placebo) Melphalan Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Time to Progression Duration of study (up to 10years) Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method.
Progression was defined per the International Myeloma Working Group definition as one more of the following:
* 25% increase in serum M-component (absolute increase \>= 0.5g/dl)
* 25% increase in urine M-component (absolute increase \>= 200mg/24hour
* 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl)
* 25 % increase in bone marrow plasma cell percentage (absolute increase of \>=10%)
* Definite development of new bone lesion or soft tissue plasmacytomas
* Development of hypercalcemia
- Secondary Outcome Measures
Name Time Method Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100 Day 100 Response was defined according to International Myeloma Working Group criteria (2006)
* Complete Response: Complete disappearance of M-protein from serum \& urine on immunofixation, normalization of Free Light Chain (FLC) ratio \& \<5% plasma cells in bone marrow (BM)
* Partial Response: \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels
* Marginal Response: 25-49% reduction in serum M-component \& urine M-component by 50-89% which still exceeds 200mg/24hour
* Progressive Disease: Defined in primary outcome measure
* Stable Disease: Not meeting any of the criteria above
Trial Locations
- Locations (140)
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
UC San Diego Medical Center - Hillcrest
🇺🇸San Diego, California, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
AdventHealth Porter
🇺🇸Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Saint Joseph Hospital - Cancer Centers of Colorado
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
Western States Cancer Research NCORP
🇺🇸Denver, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸Grand Junction, Colorado, United States
Banner North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Banner McKee Medical Center
🇺🇸Loveland, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Intermountain Health Lutheran Hospital
🇺🇸Wheat Ridge, Colorado, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Saint Francis Hospital - Wilmington
🇺🇸Wilmington, Delaware, United States
George Washington University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
OSF Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Jesse Brown Veterans Affairs Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Heartland Cancer Research NCORP
🇺🇸Decatur, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Carle BroMenn Medical Center
🇺🇸Normal, Illinois, United States
Carle Cancer Institute Normal
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
OSF Saint Francis Radiation Oncology at Pekin
🇺🇸Pekin, Illinois, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Providence Medical Center
🇺🇸Kansas City, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Radiation Oncology Practice Corporation Southwest
🇺🇸Overland Park, Kansas, United States
AdventHealth Shawnee Mission
🇺🇸Shawnee Mission, Kansas, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Christiana Care - Union Hospital
🇺🇸Elkton, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Centerpoint Medical Center LLC
🇺🇸Independence, Missouri, United States
University Health Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Radiation Oncology Practice Corporation South
🇺🇸Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Radiation Oncology Practice Corporation - North
🇺🇸Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
Montefiore Medical Center-Wakefield Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northwell Health NCORP
🇺🇸Lake Success, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
The Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸Hazleton, Pennsylvania, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸Berlin, Vermont, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Virginia Oncology Associates-Hampton
🇺🇸Hampton, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Saint Mary's Medical Center
🇺🇸Huntington, West Virginia, United States
Aurora Cancer Care-Glendale
🇺🇸Glendale, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Aspirus Cancer Care - James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States